Carcinoma of the Ampulla of Vater Treatment & Management

Hepatic metastasis, serosal implants, ascites, lymph node involvement outside the resectional field, and major vessel invasion all are contraindications to surgical resection. Treatment options for advanced or unresectable stages are discussed below. The role of adjuvant therapy remains controversial.

Willett and colleagues reported their experience with adjuvant radiotherapy (40-50 gray [Gy], with or without concurrent 5-fluorouracil as a radiosensitizer) for high-risk tumors of the ampulla of Vater. Compared to surgery alone, the radiotherapy group demonstrated a trend toward better locoregional control; however, no advantage in survival was seen.^[14]

Bhatia et al published the Mayo Clinic experience in 2006 concluding that 5-fluorouracil and radiotherapy (median, 50.4 Gy in 28 fractions) improved overall survival (3.4 y vs 1.6 y with surgery alone, p=0.01) in patients with lymph node involvement but not necessarily in those with locally advanced tumors.^[15]

Barton and Copeland reported on the M.D. Anderson Cancer Center experience of using postoperative chemotherapy for carcinoma of the ampulla of Vater. No combination of drugs prolonged life.^[16] Krishnan and colleagues updated the M.D. Anderson experience in 2008. This series suggested an overall survival benefit with adjuvant fluorouracil or capecitabine following pancreaticoduodenectomy, although their study was inadequately powered with 54 patients to reach statistical significance. This group also suggested that locally advanced tumor stages (T3/T4) may warrant the addition of adjuvant chemoradiation therapy, as this was an independent poor prognostic indicator.^[17]

Kim and colleagues reported their series of 118 patients, 41 of whom received adjuvant chemoradiation therapy with 5-fluorouracil and total radiation dose up to 40 Gy. Their results revealed improved locoregional relapse-free survival, and possibly also an overall survival advantage, although statistical significance was not achieved.^[18]

A Phase II study evaluating capecitabine and oxaliplatin (CAPOX) in patients with advanced adenocarcinoma of the small bowel or ampulla reported improved overall survival in comparison to other reported regimens (20.4 vs 15.5 months in patients with metastasis). The primary site of disease was the ampulla of Vater in 12 of 30 patients.^[19]

Yeung and colleagues used neoadjuvant chemoradiotherapy in 4 patients with duodenal/ampullary carcinomas. No residual tumor was found in pancreaticoduodenectomy specimens of these 4 patients.^[20]

Gemcitabine has shown promise in cases of biliary tract cancer. These results may be extrapolated to include gemcitabine, alone or in combination, in chemotherapy regimens, especially in cases where a periampullary primary is difficult to characterize, but has pancreaticobiliary features.

Surgical resection in an ampullary carcinoma is the primary modality of treatment. The highest cure rates are achieved if the tumor is localized to the ampullary region and complete resection is achieved[R0].

Diagnostic staging laparoscopy may be indicated to avoid laparotomy in the setting of advanced disease with distant occult metastasis.

Pancreaticoduodenectomy (Whipple) is the standard procedure.^[7] Pylorus preserving pancreaticoduodenectomy or classic Whipple can be performed depending on extent of tumor and surgeon preference. With improvement in postoperative management and surgical technique, operative mortality rates are as low as 1% in experienced centers.^[4] Resectability rates for ampullary carcinoma were up to 96% in the 1990s.^[6]

Local resection (ampullectomy) may be considered for patients with an ampullary adenoma with absence of dysplasia on preoperative biopsies who are inappropriate candidates for pancreaticoduodenectomy. Recurrence rate is high in this population; therefore, surveillance endoscopy is indicated.^[21]

Extensive preoperative assessment of cardiac, respiratory, renal, and cerebral functions should be performed in older patients or those with comorbid conditions.

Toh et al reported 25 patients (13 men, 12 women) with a median age of 65 years who had an ampullary tumor. The resectability rate was 88%, with no operative mortality. The 5-year actuarial survival rate of patients who underwent radical resection was 49%. They concluded that local resection is recommended only for small, benign tumors and for patients who may be unfit for radical surgery; otherwise, pylorus-preserving pancreaticoduodenectomy is safe and the most effective procedure.^[22]

Preoperative details include the following:

• Assessment of nutritional status and supplementation when necessary (Fortunately, most of these patients do not have any nutritional problems.)
• Standard mechanical and oral antibiotic bowel preparation may be considered, but it is not essential for pancreaticoduodenectomy.
• Assessment of coagulation profile and correction of decreased prothrombin time by administration of vitamin K in patients with advanced jaundice
• Intravenous antibiotic prophylaxis
• Preoperative biliary drainage in jaundiced patients is indicated in patients with cholangitis and those with profound hyperbilirubinemia as this may impact coagulation status and wound healing. Preoperative stenting may be associated with increased postoperative infectious complications.
• Fluid and electrolyte correction
• Assessment of cardiac, renal, and pulmonary status

Intraoperative details include the following:

• Laparoscopic assessment is obtained for peritoneal metastasis; hepatic metastases; and extensive lymphatic, vascular, or surrounding organ invasion.
• Resectability of the primary tumor is determined by mobilizing the head of the pancreas (ie, Kocher maneuver), opening the lesser sac, and exposing and inspecting the confluence of the splenic vein and superior mesenteric vein. Involvement of the retropancreatic portal vein is not a universal contraindication, as this segment of portal vein may be resected en bloc and subsequent reconstruction of the vein performed (this is shown in the image below). Kocherization of the duodenum. For ampullary malignancies greater than 1 cm in size, pancreaticoduodenectomy is the preferred operation. This figure demonstrates the process of kocherization of the duodenum. The second and third portions of the duodenum are mobilized en bloc with the periduodenal nodal tissue. The authors prefer to expose the inferior vena cava (IVC) and remove alveolar tissue, which lies above the IVC en bloc with the specimen.
• Intraoperatively, a transduodenal FNA or core biopsy is the preferred method for pathologic confirmation of the diagnosis. In about 10% of cases, these methods do not permit intraoperative confirmation of carcinoma. Resection should be performed in such cases based on preoperative and intraoperative findings.
• Resectability may be a subjective phenomenon based on the experience and skill of the surgeon.^[23]
• A feeding jejunostomy or a nasojejunal tube insertion may be considered during the procedure to permit early resumption of enteral feeding; however, this is rarely necessary.

Pancreaticoduodenectomy

Pancreaticoduodenectomy is the standard resection procedure for ampullary carcinoma.

In this operation, the pancreas is transected anterior to the portal vein to resect the pancreatic head and uncinate process with the specimen. The duodenum and gastric antrum are resected with the pancreatic head in the classic Whipple procedure. The gallbladder and distal bile duct are also resected. Peripancreatic lymph nodes are included with the resection.

Intraoperative frozen section of the bile duct and pancreatic margins are confirmed negative prior to reconstruction.

Restoration of the gastrointestinal continuity is completed with pancreaticojejunostomy or pancreaticogastrostomy, hepaticojejunostomy, and gastrojejunostomy (these are depicted in the illustration below).

Pylorus-preserving pancreaticoduodenectomy

Pylorus-preserving pancreaticoduodenectomy preserves the entire pylorus, along with 1-2 cm of the first part of the duodenum. GI continuity is restored with a duodenojejunostomy. This, in theory, represents a more physiologically acceptable procedure, with similar survival rates. Postgastrectomy complications, such as dumping and marginal ulceration, are reduced. Delayed gastric emptying may be exacerbated.

Postprandial release of gastrin and secretin is nearly normal in patients who undergo this procedure.

Transduodenal (laparoscopic or open) or endoscopic excision of ampullary tumors

Transduodenal excision may be considered in the setting of adenoma if preoperative biopsy specimens reveal no dysplasia, but it is reserved for elderly patients, patients with significant comorbid conditions, and those with favorable tumors (generally < 2-3 cm, pedunculated).

Palliative surgery

Palliative surgery is reserved for patients with unresectable tumors but who are good candidates for surgery. The goal is to alleviate biliary obstruction, duodenal obstruction, or pain. Either cholecystojejunostomy or hepaticojejunostomy bypass is performed. Duodenal obstruction may require gastrojejunostomy.

Prophylactic gastrojejunostomy should be performed, even in a duodenum unobstructed at the time of laparotomy, because as many as one third of patients develop obstruction later. However, prophylactic gastrojejunostomy adds significant morbidity risk to the procedure.

Chemical splanchnicectomy, using either 6% phenol or 50% ethanol, can be performed intraoperatively. This procedure controls pain in 80% of patients.

• Nutritionist to provide patient education regarding postgastrectomy diet or diabetic diet when appropriate
• Endocrinologist, rarely, when pharmacologic management of blood glucose is required
• Physiotherapist, rarely, for patients experiencing postoperative deconditioning (These patients most commonly experienced postoperative complications or had preexisting conditions.)

• Nasogastric decompression is discontinued based on the reconstruction performed.
• Clear liquid diet usually begins between the second and fifth postoperative day.
• Regular diet may resume usually between the fifth and seventh postoperative day.
• Delayed gastric emptying is defined, in part, by an inability to tolerate a solid diet by 8-10 days postoperatively. Use of motility agents, such as erythromycin, which is a motilin agonist, may be considered.

• The patient should ambulate from the first postoperative day.
• Early ambulation and chest physiotherapy reduce morbidity.