Carcinoma of the Ampulla of Vater 

Updated: May 08, 2018
Author: Nafisa K Kuwajerwala, MD; Chief Editor: N Joseph Espat, MD, MS, FACS 

Overview

Practice Essentials

Carcinoma of the ampulla of Vater, shown in the image below, is a rare malignant tumor arising within 2 cm of the distal end of the common bile duct, where it passes through the wall of the duodenum and ampullary papilla.

Endoscopic view of an ampullary carcinoma. Endoscopic view of an ampullary carcinoma.

The common bile duct merges with the pancreatic duct of Wirsung to form a common channel that exits through the ampulla into the duodenum. The most distal portion of the common bile duct is dilated (ie, forms the ampulla of Vater) and is surrounded by the sphincter of Oddi, which spirals upward around the terminal portion of the duct.

Carcinoma of the ampulla of Vater tends to manifest early due to biliary outflow obstruction, as opposed to pancreatic neoplasms that often are advanced at the time of diagnosis. Clinically, however, ampullary tumors can be virtually indistinguishable from tumors of the distal bile duct or pancreatic head; the point of origin of tumors in this region is typically not determined until the patient undergoes surgery.

Pancreaticoduodenectomy is the standard resection procedure for ampullary carcinoma. When preoperative endoscopic biopsy identifies a lesion as an ampullary adenoma with no high-risk features (eg, high-grade dysplasia), treatment with local resection (ampullectomy) may be considered, if the patient is not a candidate for pancreaticoduodenectomy. However, such patients require surveillance endoscopy to monitor for recurrence.

Surgical resection with curative intent is the only option for long-term survival. Surgical, endoscopic, or radiologic biliary decompression; relief of gastric outlet obstruction; and adequate pain control may improve the quality of life but do not affect overall survival rate.

Pathophysiology

Periampullary carcinoma includes tumors arising in the head, neck, or uncinate process of the pancreas, tumors arising in the distal common bile duct, tumors arising in the duodenum, as well as tumors arising from the ampulla of Vater.

Review of the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute indicates adenocarcinoma is the most frequently identified histology for ampullary cancer. Adenocarcinoma (not otherwise specified [NOS]) was reported in 65% of cases. Carcinoma (NOS) was reported in 8.1%; adenocarcinoma arising from adenoma (adenocarcinoma in villous adenoma, in tubulovillous adenoma, in adenomatous polyp and villous adenocarcinoma) was third most common in 7.5%. Other pathologic diagnoses reported included papillary adenocarcinoma (5.6%), mucinous adenocarcinoma (4.7%), and signet ring cell carcinoma (2%).[1, 2, 3]

Lymph nodes metastases are present in as many as half of patients. Pericanalicular lymph nodes usually are the first to be involved. Nodes along the superior mesenteric, gastroduodenal, common hepatic, and splenic arteries, as well as the celiac trunk, are the second station of lymph nodes. Perineural, vascular, and lymphatic invasion are associated with a poor prognosis. Liver is the most common site (66%) of distant metastasis, followed by lymph nodes (22%). In advanced cases, lung metastasis also may occur.

The concept of ampullary carcinoma as a distinct entity is challenged by the categorization of tumors into intestinal type and biliopancreatic type histologically. A review of 118 adenocarcinomas revealed that the biliopancreatic type had a worse prognosis while the intestinal type may behave more like duodenal carcinoma.[4]

Epidemiology

Frequency

United States

Carcinoma of the ampulla of Vater is an uncommon tumor. Between 1973 and 2005, 5,625 cases were recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. Ampullary cancer accounts for approximately 0.5% of all gastrointestinal tract malignancies.[1] The incidence has been increasing since 1973 at an annual percentage rate of 0.9%.[1] Prior to the recently reported increase, the quoted incidence for ampullary carcinoma was 0.2% of all gastrointestinal malignancies and 6% of all periampullary tumors.[5]

International

Worldwide incidence is not known.

Mortality/Morbidity

Most of these tumors are resectable for cure at diagnosis; however, the 5-year survival rate is only approximately 40%[6, 7, 8] to 67% at best.[5]

Operative mortality rates have decreased significantly over the last decade because of increased surgical experience, improved anesthesia, better preoperative imaging, and better postoperative management.

Pancreatic fistulas, prolonged gastric emptying, wound complications, intra-abdominal sepsis, thrombophlebitis, and marginal ulceration are the most common complications.

Postoperative mortality rates in the best centers are 1-2%.

Race-, sex-, and age-related demographics

As follows[1] :

  • Ampullary carcinoma may be more common in whites than blacks.
  • A higher rate of ampullary cancer is observed in men.
  • Ampullary cancer is most often diagnosed in the fifth through the seventh decades of life.
 

Presentation

History

Jaundice is the presenting symptom in 73% of resected patients and in 80% of unresected patients (71% overall) in the 28-year experience published by Talamini et al.[8]

Jaundice may intermittently wax and wane because of central necrosis and sloughing or pressure opening of a minimally obstructed duct. Patients with malignant tumors commonly have jaundice and larger tumors.[9]

Other features are as follows:

  • Progressive weight loss is the second most common symptom in 61%.

  • Abdominal pain and back pain were present in 46%. The abdominal pain usually is dull, aching midepigastric pain or right hypochondriac pain.

  • Back pain may be a sign of advanced stage.

  • Pruritus associated with jaundice in 13-38%.

  • Dyspepsia and vomiting may be present if compromise of the duodenal lumen leads to gastric outlet obstruction.

  • Loss of appetite may be noted.

  • Diarrhea may occur with this tumor due to the absence of lipase within the gut related to pancreatic duct obstruction.

  • Gastrointestinal bleeding occurs in 5% of resected and in 22% of unresected patients.

  • Acute pancreatitis was significantly more common in unresected lesions (28%) compared with resected lesions (2%).[8]

Physical

Physical examination findings may include the following:

  • The Courvoisier sign, painless jaundice associated with a palpable gallbladder, may be present. Unlike that due to a neoplasm, obstructive jaundice due to a stone causes scarring of the gallbladder, precluding its distension.

  • Fever can occur in the setting of ascending cholangitis.

  • Hepatomegaly can occur.

  • Rarely, patients present with features of acute pancreatitis or migratory thrombophlebitis.

  • Palpable fixed epigastric masses or supraclavicular nodes are signs of advanced disease and inoperability.

Causes

The etiology of the disease is poorly understood.

  • Patients with familial adenomatous polyposis (FAP) have an increased risk of both benign and malignant ampullary tumors.[10]

  • As many as 50-90% of patients with FAP develop duodenal adenomas, predominantly concentrated on or around the major papilla.[11]

  • K-ras mutations may be a factor.[12]

  • Microsatellite instability is associated with a better prognosis.

  • Chromosome 17p and 18q loss of heterozygosity are associated with ampullary carcinoma.[13]

 

DDx

 

Workup

Laboratory Studies

Blood biochemistry

 Recommended tests and possible findings include the following:

  • Complete blood cell count (CDB): May show anemia caused by bleeding from the ampullary mass

  • Bilirubin: May show hyperbilirubinemia (conjugated type) due to blockage of the biliary outflow

  • Alkaline phosphatase: May be elevated due to biliary obstruction.

  • Liver function studies: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rise in long-standing obstruction. Elevation of AST is significantly more common in unresectable lesions (83%) than in resected lesions (22%).[8]

  • Serum amylase: A rise in serum amylase level may be seen in 30% of patients.[8]

  • Coagulation profile: Increased prothrombin time and prolonged bleeding and clotting times may be seen in profound obstructive jaundice.

Urine chemistry

Urinalysis may show bile pigments. Absence of urinary urobilinogen signifies complete obstruction.

Tumor markers

Currently, no tumor marker is sensitive or specific enough to serve as reliable screening tools for this carcinoma. Cancer antigen (CA) 19-9 is the most studied and sensitive marker for pancreaticobiliary neoplasms at present; however, a normal serum CA 19-9 level does not rule out pancreaticobiliary malignancy. The following markers have been evaluated and found inaccurate:

  • Carcinoembryonic antigen (CEA)

  • DU-PAN-2

  • Alpha-fetoprotein (AFP)

  • Pancreatic oncofetal antigen (POA) 

Imaging Studies

Abdominal ultrasonography

Advantages of abdominal ultrasonography (US) include the following:

  • Abdominal US is the most useful noninvasive initial investigation for distinguishing medical from surgical causes of jaundice. It is an inexpensive and readily available bedside procedure.

  • Abdominal US can identify dilated ducts, liver metastasis (in almost 90% of cases), ascites, and nodal metastasis.

  • Doppler US can be used to assess vascular involvement.

  • The level of obstruction can be assessed in 90% of patients.

  • US-guided fine-needle aspiration (FNA) can be performed.

Limitations of abdominal US are as follows:

  • Effectiveness is related to the skill of the user.

  • Very superficial lesions and very deep lesions may be missed. Distinguishing a metastasis from a hemangioma may be difficult.

  • Sensitivity is 80-90%, and information is inferior to that obtained by CT scan or MRI. Poor bowel preparation may obscure the important pathology.

  • It has been found to be diagnostic of carcinoma of ampulla of Vater only in 23.8% cases.

Endoscopic ultrasonography and transpapillary ultrasonography

Endoscopic ultrasonography (EUS) is performed through a peroral route. EUS remains highly operator dependent. It offers an additional option for biopsy. The test is highly sensitive in detecting major vascular involvement, which can prevent unnecessary surgery.[14]

EUS may identify tumors less than 1 cm in size. EUS is the most sensitive tool for diagnosis and staging of carcinoma of the ampulla of Vater. The sensitivity for detection is 97%, for T staging, 72%; for nodal staging, 47%; and for determining vascular involvement, 100%. However, the presence of biliary stent can decrease the accuracy to some extent. It can also be coupled along with biliary stenting. However, the sensitivity is low for determining distant metastasis.

Laparoscopic sonography can detect occult liver metastasis. Staging laparoscopy with laparoscopic ultrasonography may be more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% vs 50% and 65%, respectively[15] ).

Computed tomography

Advantages are as follows: 

  • CT is noninvasive.

  • CT scan is superior to US but inferior to EUS for carcinoma of the ampulla of Vater unless extensive tumor is present.

  • CT scan is better in evaluating resectability and preoperative staging. It gives better assessment of invasion, encasement, or compression of vessels and adjacent organs.

  • CT-guided biopsy may be obtained when mass lesions are present, but endoscopic biopsy is preferred.

  • Simultaneous dilatation of the common bile duct and the pancreatic duct (the double duct sign) may be seen in obstruction from ampulla of Vater cancer, but is not specific for this disease[49] ; see the images below.

    Double duct sign of periampullary cancers. Note th Double duct sign of periampullary cancers. Note the dilated common bile duct as well as the pancreatic duct. Liver metastatic lesion is also seen.
    Distended gall bladder with double duct sign in a Distended gall bladder with double duct sign in a patient with periampullary cancer.

Disadvantages of CT are as follows:

  • Very ill patients may be unable to lie still or arrest respiration for the long periods required for high-quality imaging.

  • CT scan is more expensive than US and requires expertise in interpretation.

  • Potential radiation hazards exist for patients and staff.

  • Rare contrast reactions or contrast nephropathy may occur.

  • Metal, stents, and clips may cause artifacts.

  • Very small tumors (<1 cm) may be missed.

Magnetic resonance imaging

MRI is the most informative noninvasive method of evaluation currently available. MRI cholangiopancreatography (MRCP) provides 94% accuracy in identifying the cause and extent of the pathology. Results are reproducible. An MRCP revealing a resectable mass may preclude the need for endoscopic retrograde cholangiopancreatography (ERCP).

Radiography

Chest radiography is performed to exclude pulmonary metastasis and other pulmonary diseases.

Other Tests

An electrocardiogram should be performed to assess cardiac status, since surgery will be considered as a means of treatment. Nutritional studies should be ordered in preparation for surgery.

Procedures

Endoscopic retrograde cholangiopancreatography

Advantages of this procedure are are as follows: 

  • ERCP allows diagnostic and therapeutic access to both the common bile duct and pancreatic duct.

  • The procedure displays the details of ductal anatomy and accurately demonstrates the level and nature of the obstruction. Anatomical variations in ducts can be evaluated carefully.

    Endoscopic view of an ampullary carcinoma. Endoscopic view of an ampullary carcinoma.
  • ERCP allows therapeutic procedures, such as sphincterotomy, stenting, and nasobiliary drainage.

  • It permits sampling of pancreatic juice, bile, and brush/grasp biopsy.

  • Endoscopic excision of small periampullary tumors is gaining in popularity.

Disadvantages

  • ERCP is an invasive procedure that requires an expert endoscopist/radiologist and a cooperative patient.

  • Very small tumors (< 1 cm) can be missed.

  • ERCP is not possible if access to the duodenal papilla is difficult to obtain because of diverticula, anatomical ductal variations, or prior surgical bypass.

  • This procedure can precipitate pancreatitis and cholangitis.

  • Perforation and hemorrhage are 2 of the more serious complications.

  • Ahn et al reported that preoperative ERCP was an independent risk factor for postoperative recurrence in patients with ampulla of Vater cancer; ERCP was associated with a significantly higher rate of early distant metastasis within 1 year, especially in patients with early-stage disease.[48]

Percutaneous transhepatic cholangiography

Indications for percutaneous transhepatic cholangiography (PTC), which is highly invasive, are very limited. PTC is most useful when ERCP is unavailable or technically not feasible.

PTC can be useful in severely jaundiced patients when laparotomy or ERCP is not possible. Percutaneous transhepatic biliary drainage or transhepatic stenting may be the only option for some patients. Biliary leakage may lead to peritonitis. Excessive bleeding from the puncture site and pneumothorax represent significant, but uncommon, complications.

Histologic Findings

In the Surveillance, Epidemiology, and End Results (SEER) database, adenocarcinoma is the most frequently identified histology for ampullary cancer. Histologic types and frequency were as follows[1] :

  1. Adenocarcinoma not otherwise specified (NOS): 65% of cases
  2. Carcinoma (NOS): 8.1%
  3. Adenocarcinoma arising from adenoma (adenocarcinoma in villous adenoma, in tubulovillous adenoma, in adenomatous polyp and villous adenocarcinoma): 7.5%.
  4. Papillary adenocarcinoma: 5.6%
  5. Mucinous adenocarcinoma: 4.7%
  6. Signet ring cell carcinoma: 2%

Adenocarcinoma is categorized as intestinal type or biliopancreatic type, which may have prognostic implications. Intestinal type has columnar cells organized into tubular or cribriform glands. Biliopancreatic type consist of cuboidal or low columnar cells arranged into simple glands or papillary or micropapillary structures.[4]

Staging

The tumor, node, metastases (TNM) classification and stage grouping is based on the Union Internationale Contre Cancrum (UICC) system, established in 1977, with separate classifications for pancreatic and periampullary carcinomas. The staging is important only to communicate a uniform definition of extent of disease. 

T (primary tumor) classification is as follows:

  • Tx - The primary tumor cannot be assessed

  • T0 - No sign of primary tumor

  • Tis - Carcinoma in situ

  • T1 - Tumor limited to the ampulla or sphincter of Oddi

  • T2 - Tumor invading the wall of the duodenum

  • T3 - Tumor invasion into the pancreas 2 cm or less

  • T4 - More than 2 cm tumor invasion into the pancreas or any other adjacent organ

Peripancreatic tissue includes the surrounding retroperitoneal fatty tissue (retroperitoneal soft tissue or retroperitoneal space), including the mesentery (mesenteric fat), mesocolon, greater and lesser omentum, and peritoneum. Direct invasion of the bile ducts and the duodenum includes involvement of the ampulla.

Adjacent large vessels include the portal vein, the celiac trunk, the superior mesenteric artery, and the common hepatic artery, and vein (not the splenic vessels).

N (regional lymph nodes) classification is as follows:

  • NX - Regional lymph nodes cannot be assessed

  • N0 - No regional lymph node metastases

  • N1 - Regional lymph node metastases

Subclassification of the category N1 into N1a (only 1 metastatic lymph node) and N1b (2 or more lymph nodes affected by metastases) is recommended, as the 2 categories appear to have marked prognostic differences. Total number of peripancreatic lymph nodes found in the surgical specimen must be documented.

M (distant metastases) classification is as follows:

  • MX - Distant metastases cannot be assessed

  • M0 - No distant metastases

  • M1 - Distant metastases

Note: The splenic lymph nodes and those at the tail of the pancreas are not regional; metastases in these lymph nodes are classified as distant metastases (M1).

Stage grouping of periampullary carcinoma is as follows:

  • Stage 1 - T1 N0 M0

  • Stage 2 - T2 N0 M0; T3 N0 M0

  • Stage 3 - T1 N1 M0; T2 NI M0; T3 N1 M0

  • Stage 4 - T4 any N any M; any T any N  M1

Martin proposed a 4-stage system, as follows:

  • Stage I - Vegetating tumor limited to the epithelium, with no involvement of the Oddi sphincter

  • Stage II - Tumor localized in the duodenal submucosa without involvement of the duodenal muscularis propria but possible involvement of the sphincter of Oddi

  • Stage III - Tumor involving the duodenal muscularis propria

  • Stage IV - Tumor involving the periduodenal area or the pancreas, with proximal or distal lymph node involvement

 

Treatment

Medical Care

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.[16]

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.[17]

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.[18, 19]

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.[20] 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.[21]

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.[22]

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.[23]

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.[24]

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 Care

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].[25, 26]

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.[9] 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.[6] Resectability rates for ampullary carcinoma were up to 96% in the 1990s.[8]

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.[27]

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.[28]

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 malig 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.[29]

  • 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.

Periampullary malignancy. Transected pancreas with Periampullary malignancy. Transected pancreas with head. Pancreaticoduodenectomy is the preferred treatment for most periampullary tumors. This picture depicts transection of the pancreas at the pancreatic neck. This particular patient presented with a periampullary malignancy accompanied by jaundice and pancreatitis. A preoperative pancreatic stent (usually unnecessary) is seen within the pancreatic duct.

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).

Carcinoma of the ampulla of Vater. Roux-en-Y recon Carcinoma of the ampulla of Vater. Roux-en-Y reconstruction following completion of a standard pancreaticoduodenectomy.

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).[30]

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.[31]

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.

Consultations

See the list below:

  • 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.)

Diet

See the list below:

  • 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.

Activity

See the list below:

  • The patient should ambulate from the first postoperative day.

  • Early ambulation and chest physiotherapy reduce morbidity.

 

Medication

Medication Summary

Prophylactic and postoperative antibiotics are given according to hospital protocol.

Chemotherapeutic Agents

Class Summary

Fluorouracil can be used as a radiosensitizer for high-risk tumors of the ampulla of Vater.

Fluorouracil (Adrucil)

Fluorinated pyrimidine antimetabolite that inhibits thymidylate synthase and interferes with RNA synthesis and function. Has some effect on DNA. Useful in symptom palliation for patients with progressive disease.

Antibiotics

Class Summary

Initial empiric antimicrobial therapy must be comprehensive and should cover both aerobic and anaerobic gram-negative organisms.

Cefoxitin (Mefoxin)

Second-generation cephalosporin indicated for gram-positive cocci and gram-negative rod infections. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.

Any second-generation cephalosporin may be used instead of cefoxitin.

 

Follow-up

Further Outpatient Care

Sonography, CT scan of the abdomen, and liver function tests may be used to detect recurrence and manage complications. However, these examinations should not be carried out on a routine basis, as early diagnosis of recurrent disease apparently offers no therapeutic benefit.

Recurrent disease is not considered curable; therefore, follow-up is limited principally to palliative considerations, such as the following:

  • Reducing pain
  • Relieving biliary or gastroenteric obstruction
  • Managing evident or latent exocrine or endocrine pancreatic insufficiency

Further Inpatient Care

Postoperative care includes the following:

  • Broad-spectrum antibiotic coverage for 24 hours is indicated.

  • Continuous nasogastric aspiration usually is maintained for the first 24 hours.

  • Oral feeding may be considered on the second postoperative day.

  • Subcutaneous heparin and pneumatic compression stockings are used to prevent deep vein thrombosis (DVT).

  • Adequate blood replacement is necessary in cases of intraoperative blood loss.

  • Early ambulation and chest physiotherapy reduce morbidity.

  • Serum electrolytes, renal function, and liver function should be monitored.

  • Blood glucose level should be monitored after pancreatectomy.

  • Abdominal drains can be removed after 3-5 days if no evidence of pancreatic fistula exists or after resuming a solid diet if pancreaticogastrostomy was performed.

  • Tachycardia and tachypnea may at times be the earliest signs of a leak.

Deterrence/Prevention

Patients with familial adenomatous polyposis (FAP) and their family members should be counseled about the possibility of acquiring ampullary carcinoma. As many as 50-90% of patients with FAP develop duodenal adenomas, concentrated predominantly on or around the major papilla.[11] Such patients should receive close endoscopic surveillance.

Patients who have undergone local resection of an ampullary adenoma should receive endoscopic surveillance for recurrence.

Complications

Complications of surgery for ampulla of Vater cancer include the following:

  • Morbidity remains high for pancreaticoduodenectomy, with rates of 41% and 47% reported in two series.[6, 32]

  • Pancreatic anastomotic leak and fistula (12%), wound infection (7-11%), and delayed gastric emptying (7-18%) are the most common complications.[6, 32]

  • Differing definitions of pancreatic fistula contribute to the wide range of reported occurrence, which have reached as high as 27%. The International Study Group on Pancreatic Fistula (ISGPF) first set out a definition of pancreatic fistula in 2005, and in 2016 redefined it as "a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula."[50]  The ISGPF also stratified postoperative pancreatic fistula fistulas into 3 grades according to clinical impact: grade A  has no clinical importance and has been redefined as a "biochemical leak" rather than a true pancreatic fistula; grade B requires a change in the postoperative management, with drains either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures; grade C requires reoperation to prevent possible organ failure and/or mortality.

  • Intra-abdominal sepsis or abscess, hemorrhage, fascial dehiscence, prolonged ileus, biliary anastomotic leak, thrombophlebitis, and marginal ulceration all can manifest as complications of the surgery. Dumping syndrome can be seen in patients who have had a significant part of their stomach removed.

  • Reoperation is uncommon, but it is indicated most commonly for bleeding, intra-abdominal infection, and uncontrolled pancreatic anastomotic dehiscence.

  • A dramatic reduction has been seen in postoperative mortality following pancreaticoduodenectomy from 17-25% before 1985 to 1-2% today in experienced centers. This can be attributed to growing surgical experience, improved anesthesia, better preoperative imaging, and refined postoperative management.

  • More than 40 reconstruction procedures are described in the literature to reduce the risk of pancreatic leak, including occlusion of the residual pancreas with Ethibloc or fibrin (as a means to avoid complications secondary to anastomosis) or temporary occlusion with a fibrin adhesive and subsequent anastomosis (in order to avoid 4-6 days of secretion and the risk of damage to the anastomosis).

Prognosis

Prognostic features include the following:

  • The surgical mortality rate has progressively decreased to as low as 1% in experienced centers.[6]

  • Most patients with carcinoma of the ampulla of Vater die of recurrent disease. Treatment fails in nearly three fourths of patients with poor prognostic features.

  • el-Ghazzawy et al reviewed their experience from 1987-1991 with 123 patients who had ampullary cancer. In the group that underwent surgical resection, survival was not influenced independently by perineural invasion, microlymphatic invasion, vascular invasion, or tumor differentiation when the tumors were controlled for stage.[33]

  • Talamini et al reported a 38% 5-year survival rate for resected patients with ampullary adenocarcinoma in 106 patients from 1969-1996.[8]

  • Carter et al reviewed 118 adenocarcinomas and found that biliopancreatic type had a worse prognosis while intestinal type may behave more like duodenal carcinoma.[4]

  • Review of the SEER data reveals stratification of survival by tumor stage. Five-year survival rates for local, regional, unknown, and distant stages were 45%, 31%, 14%, and 4%, respectively.[1]

Patient Education

Those with FAP, and their family members, should be counseled about the possibility of acquiring ampullary carcinoma.