TUMORS OF THE AMPULLA OF VATER

1. TUMORS OF THE AMPULLA OF VATER Aswad H. Al.Obeidy FICMS, FICMS GE&Hep Kirkuk General Hospital

2. TUMORS OF THE AMPULLA OF VATER • Has the highest incidence of neoplastic transformation and malignancy. • Production of local carcinogens through the combined interactions of the components of bile, pancreatic juice, and duodenal contents. • Both benign and malignant tumors of the ampulla of Vater occur. • The benign tumors include adenomas, gastrointestinal stromal tumors (GISTs) , lipomas, and neuroendocrine tumors. • Tumors metastatic from other primary sites have also been reported

3. ADENOMA AND ADENOCARCINOMA • Most common malignant tumor of the ampulla of Vater • less than 10% of all periampullary adenocarcinomas • Up to 25% of such tumors that are resectable. • Arise from the mucosal cells of the ampulla of Vater and undergo an adenoma–carcinoma progression sequence • Benign adenomas may become dysplastic, with subsequent progression to adenocarcinoma. • 80% to 90% of adenocarcinomas were surrounded by benign adenomas • In many cases evolution from benign to malignant histology was noted. • Risk factors for ampullary adenocarcinoma include familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome. FAP have higher frequency of ampullary adenomas, 50% to 86%

4. Clinical Features • The average age of patients with ampullary adenoma is the mid-50s • For ampullary adenocarcinoma is the mid-60s. • Present most commonly with obstructive jaundice, in 80% • Weight loss occurs in 75% of patients • Abdominal pain in 50% • Occult gastrointestinal bleeding is common, in one third of patients • Nonspecific symptoms such as anorexia, dyspepsia, and malaise • Rarely, with pancreatitis secondary to pancreatic duct obstruction • With features of sphincter of Oddi dysfunction • Physical examination include conjunctival or cutaneous icterus and, less commonly, hepatomegaly, a distended gall-bladder • Positive fecal occult blood test result • Very rarely distinctive silver stools, which result from a combination of the absence of bilirubin and the presence of blood.

5. Diagnosis • The earliest and most common laboratory abnormality is an increase in the serum alkaline phosphatase level • Followed by hyperbilirubinemia as the tumor obstructs the bile duct. • No tumor markers have been identified that are either sensitive or specific • The first imaging modality should be ultrasonography or CT to determine the level of biliary obstruction. • Dual-contrast helical CT is the most informative and cost-effective imaging technique • CT can detect a periampullary mass larger than 1cm,the level of biliary obstruction, the relationship of the mass with surrounding vascular structures, and the presence or absence of liver metastases. • Endoscopy to visualize duodenal mucosal abnormalities • ERCP is often the next procedure for patients with a suspected ampullary malignancy • EUS has been reported to be both reliable and accurate in the diagnosis and staging

6. Staging • Primary Tumor (T Stage) • T1 Tumor limited to ampulla of Vater • T2 Tumor invades duodenal wall • T3 Tumor invades ≤2 cm into pancreas • T4 Tumor invades >2 cm into pancreas and/or adjacent organs • Regional Lymph Nodes (N Stage) • N0 No regional lymph node metastasis • N1 Regional lymph node metastasis • Distant Metastasis (M Stage) • M0 No distant metastasis • M1 Distant metastasis • TNM Stage Grouping • Stage I T1 N0 M0 • Stage II T2-3 N0 M0 • Stage III T1-3 N1 M0 • Stage IVA T4 N0-1 M0 • Stage IVB T1-4 N0-1 M1

7. Management • Local Excision • The first local surgical resection of an ampullary tumor was performed by William S. Halsted in 1899. • Currently, local resection of ampullary tumors is reserved for patients with a benign adenoma or ampullary neuroendocrine tumor and for highly selected patients with ampullary adenocarcinoma • The options for local treatment are endoscopic snare removal, endoscopic ablation, and surgical ampullectomy. • Pedunculated tubular adenomas smaller than 1 cm without severe dysplasia can be managed endoscopically, usually with snare excision, sphincterotomy, and temporary placement of a pancreatic duct stent,the risk of incomplete resection and recurrence is as high as 20% with this method. • Operative resection • For adenomas larger than 1 cm, operative resection is indicated once metastatic disease is excluded. • Postoperative morbidity after local ampullectomy is low, and mortality rates lower than 2% have been reported.

8. Review of the literature • Beger and colleagues identified 62 patients who had undergone ampullectomy for benign neoplasms. After a follow-up period ranging from 1 to 156 months, all were free of disease. • Branum and associates reported that of 19 patients with benign neoplasms resected with ampullectomy, disease recurred in 5 at a mean of 35 months (range, 8 to 72 months); two of these patients also had FAP. • Mayo Clinic suggesting that such patients may be at risk for the development of adenocarcinoma at the site of recurrence. Fifty patients with benign villous ampullary tumor were treated with local excision, and 17 tumors recurred, with actuarial recurrence rates of 32% at 5 years and 43% at 10 years. Four of the recurrences (24%) were adenocarcinomas

9. Whipple's procedure • Treatment of choice for patients with ampullary adenocarcinoma • Classic pancreaticoduodenectomy, which includes a distal gastrectomy, and the pylorus-preserving modification • Local lymph node resection is adequate because there are no data to support an extended lymph node dissection for ampullary adenocarcinoma. • Many centers reporting operative mortality rates of less than 5% • Morbidity rates associated with this procedure remain high, from 25% to 50% • In 1997, the group at the Johns Hopkins Hospital reported the largest single-institution experience in the management of adenocarcinoma of the ampulla of Vater • One hundred twenty patients with adenocarcinoma were treated over a 28-year period. Resection was performed in 106 patients (88%), 105 of whom (99%) underwent either a pancreaticoduodenectomy (n = 103) or total pancreatectomy (n = 2). The overall operative mortality rate was 3.8%. One or more complications occurred in 49 patients, for an overall morbidity rate of 47%. The most common complication was pancreatic fistula, which occurred in 23 patients (25%).

10. Chemotherapy and Radiation Therapy and palliation • There are no data to support use adjuvant chemoradiation for ampullary adenocarcinoma. • Limited data demonstrate that adjuvant chemotherapy with 5-FU, doxorubicin, and mitomycin C delays tumor recurrence in patients with ampullary adenocarcinoma • Operative palliation of obstructive jaundice with a Roux-en-Y hepaticojejunostomy is appropriate. • A gastrojejunostomy also should be performed in patients with a compromised duodenal lumen to prevent gastric outlet obstruction before death. • If the tumor is determined preoperatively to be unresectable, biliary decompression can be ac-complished by means of endoscopic or percutaneous techniques.

11. Prognosis • Survival in patients with unresectable ampullary adenocarcinoma is 5 to 9 months. • The overall 5-year survival rate for patients with resected ampullary cancer ranges from 25% to 55% • The 5-year survival rate is significantly better than that for patients with pancreatic adenocarcinoma • In the 1997 Johns Hopkins series, lymph node status, degree of differentiation, and operative blood loss were significant predictors of survival • Tumor diameter had no effect on survival, nor did adjuvant therapy • In a series of 101 patients who underwent resection for ampullary adenocarcinoma at Memorial Sloan-Kettering Cancer Center, the 5-year survival rate was 46%, and resection margin status, nodal status, and tumor differentiation were predictive of survival