Ampulla of Vater carcinoma

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.

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, forms the ampulla of Vater,and is surrounded by the sphincter of Oddi, which spirals upward around the terminal portion of the duct.

Most ampullary carcinomas are adenocarcinomas. 

Patients present with symptoms related to biliary obstruction. 

Patients with ampullary cancer generally have better overall survival than patients with pancreatic cancer, but it is a highly lethal disease.

Tends to manifest early due to biliary outflow obstruction, as opposed to pancreatic neoplasms that often are advanced at the time of diagnosis.

The signs and symptoms of ampullary carcinoma are largely related to obstruction of the bile duct or pancreatic duct:

Jaundice secondary to biliary obstruction is the most common clinical presentation

Abdominal pain

Dyspepsia

Malaise

Fever/chills

Anorexia

Pancreatitis

Pruritus—Secondary to biliary obstruction

Nausea

Vomiting

Weight loss

Diarrhea

Upper GI bleed & heme positive stools—May occur due to ulceration of ampullary mass 

Courvoisier gallbladder 

In contrast to pancreatic cancer, vascular involvement of ampullary carcinomas is uncommon, and therefore they are almost always resectable.

Routine laboratory evaluation: include 

Complete blood count

Electrolyte panel

Liver function studies: Prothrombin time, bilirubin (direct and indirect), transaminases, and alkaline phosphatase

CA 19-9:

Carcinoembryonic antigen (CEA): 

Ultrasonography of the abdomen

Abdominal ultrasonography is the initial study to evaluate the common bile duct or pancreatic ducts: Dilatation of these ducts is essentially diagnostic for extrahepatic biliary obstruction.

Biliary or pancreatic ductal dilatation can explain abdominal pain.

CT scanning often demonstrates a mass but is not helpful in differentiating ampullary carcinoma from tumors of the head of the pancreas or periampullary region.

Pancreatic or bile duct dilation may be the only abnormalities noted on the CT scan in small lesions.

High-speed scans obtained during rapid intravenous administration of iodinated contrast material) can reveal tumor involvement of the vasculature.

ERCP can evaluate the ductal architecture. 

PET-CT scans can detect metastases that are too small to be reliably detected on a CT scan

There is an association between ampullary carcinoma and colon cancer.    

Surgical resection with curative intent is the only option for long-term survival.

Bile duct decompression and relief of gastric outlet obstruction by surgical, endoscopic or radiologic means may improve the quality of life but do not affect overall survival rate.

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.

The incidence rates per hundred thousand are 11.7 for pancreatic,, 0.88 bile duct, 0.49 for ampullary and 0.01 for duodenal carcinomas.

Clinical presentation of periampullary carcinomas is similar to that of pancreatic ductal adenocarcinoma.

Approximately 80% of periampullary adenocarcinomas are resectable and comprise around 30-40% of all resections for cancers of the pancreas.

Most commonly an adenocarcinoma.

Lymph nodes metastases are present in as many as half of patients.

Pericanalicular lymph nodes usually are the first to be involved, but lymph nodes along the superior mesenteric, gastroduodenal, common hepatic, and splenic arteries, as well as the celiac trunk, are the second level of lymph nodes involved.

Perineural, vascular, and lymphatic invasion seen on histological evaluation are associated with a poor prognosis.

Liver is the most common site of distant metastasis, followed by lymph nodes.

Accounts for approximately 0.5% of all gastrointestinal tract malignancies.

Incidence has been increasing at an annual percentage rate of 0.9%.

Accounts for 6% of all periampullary tumors.

Most of these tumors are resectable for cure at diagnosis.

The 5-year survival rate is only approximately 40% to 67% at best.

Five-year survival rates after resection of periampullary carcinomas are 37-51% for ampullary, 23-30% for bile duct, and 25-59% for duodenal cancers.

Most common complications are pancreatic fistulas, prolonged gastric emptying, wound complications, intra-abdominal sepsis, thrombophlebitis, and marginal ulceration.

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

May be more common in Caucasians than in African Americans, and a higher rate in men.

Most often is seen in the fifth through the seventh decades of life.

Jaundice is the presenting symptom in 73% of patients.

Pruritus is associated with jaundice in 13-38% of cases

Jaundice may be intermittent due to central necrosis, sloughing and changing pressures at an obstructed duct.

Weight loss is the second most common symptom at 61%.

Abdominal pain and back pain are present in 46% of cases.

Abdominal pain usually is dull, aching and in the midepigastrium or right hypochondriac area.

Back pain may indicate the presence of advanced disease.

Nausea and vomiting may be present due to gastric outlet obstruction.

Anorexia, and diarrhea may occur.

Gastrointestinal bleeding and acute pancreatitis may occur.

The Courvoisier sign may be present, as may hepatomegaly.

Ascending cholangitis can occur.

Rarely, patients present with migratory thrombophlebitis.

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

Chromosome 17p and 18q loss of heterozygosity are associated with ampullary carcinoma.

A rise in serum amylase level may be seen in 30%.

Absence of urinary urobilinogen signifies complete obstruction.

No tumor marker is sensitive or specific enough to serve as screening test.

Abdominal ultrasonography is the most useful noninvasive initial investigation for distinguishing causes of jaundice, and can identify dilated ducts, liver metastasis, ascites, nodal metastases, vascular involvement, and the level of obstruction.

Abdominal US-guided fine-needle aspiration (FNA) can be performed for diagnostic purposes.

Abdominal ultrasound sensitivity is 80-90%, but the information is inferior to that obtained by CT scan or MRI.

Abdominal US diagnostic of carcinoma of ampulla of Vater only in less than 24% of cases.

EUS may identify tumors less than 1 cm in size and is the most sensitive tool for diagnosis and staging of carcinoma of the ampulla of Vater.

Endoscopic ultrasonography (EUS) allows for biopsy and is highly sensitive in detecting major vascular involvement, which can prevent unnecessary surgery.

Endoscopic ultrasonography (EUS) sensitivity for detection of ampulla of Vater carcinoma is 97%, for tumor staging, 72%, for nodal staging, 47%, and for determining the presence of vascular involvement, 100%.

Endoscopic ultrasonography (EUS) accuracy is diminished by the presence of a biliary stent.

Staging laparoscopy with laparoscopic ultrasonography is highly accurate in predicting tumor resectability.

CT scan is superior to US but inferior to EUS for the diagnosis of carcinoma of the ampulla of Vater.

CT scan of the abdomen is beneficial for evaluating resectability and preoperative staging.

CT scan of the abdomen allows for assessment of invasion, encasement, or compression of vessels and adjacent organs by the cancer.

While CT-guided biopsy may be obtained when mass lesions are present, endoscopic biopsy is pref2242ed.

The presence of metal, stents, or clips may cause artifactual changes with abdominal CT.

MRI cholangiopancreatography (MRCP) provides 94% accuracy in identifying the cause of obstructive jaundice and extent of the underlying pathology.

ERCP allows diagnostic and therapeutic access to both the common bile duct and pancreatic duct by displaying the details of ductal anatomy and demonstrates the level and type of the obstruction.

ERCP allows therapeutic procedures, such as sphincterotomy, stenting, and biliary drainage, and for sampling of pancreatic juice, bile, acquiring brush and tissue biopsies.

ERCP can precipitate pancreatitis and cholangitis.

Percutaneous transhepatic cholangiography is highly invasive, but may be useful in severely jaundiced patients when laparotomy or ERCP is not possible.

Percutaneous transhepatic biliary drainage may be the only option for some patients.

Adenocarcinoma is the most frequently identified histology for ampullary cancer.

Adenocarcinoma arising from adenomas, tubulovillous adenocarcinoma, mucinous adenocarcinoma, and signet ring cell carcinomas are other types of lesions associated with ampullary carcinomas.

Ampullary adenocarcinoma can also be categorized as intestinal type or biliopancreatic type.

Intestinal type has columnar cells organized into tubular or cribriform glands.

Biliary pancreatic type consist of cuboidal or low columnar cells arranged into simple glands or papillary or micropapillary structures.

Surgical resection, if possible is the pref2242ed treatment, whereas serosal disease, ascites, vascular invasion and liver metastases are contraindications to such surgery.

Adjuvant radiotherapy, compared to surgery alone, trends to improved locoregional control, without a survival advantagei (Willett et al)

Mayo clinic report demonstrated radiation plus chemotherapy with 5-FU can improve overall survival 3.4 years vs 1.6 for surgery alone in patients with nodal involvement (Bhatia et al)..

Postoperative chemotherapy for carcinoma of the ampulla of does not significantly prolong life.

Locally advanced tumor stages (T3/T4) warrant the addition of adjuvant chemoradiation therapy, as this is independent poor prognostic process.

Capecitabine and oxaliplatin (CAPOX) in patients with advanced adenocarcinoma of the ampulla associated with improved overall survival in comparison to other regimens.

Gemcitabine has efficacy in cases of pancreatic carcinoma and is to be considered in periampullary cancer.

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.

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

Pancreaticoduodenectomy is the standard procedure surgical procedure, with an operative mortality rates are as low as 1% in experienced centers.

Pylorus sparing pancreaticoduodenectomy is the pref2242ed procedure.

Pylorus-preserving pancreaticoduodenectomy preserves the entire pylorus, along with 1-2 cm of the first part of the duodenum.

GI continuity is preserved with a duodenojejunostomy, with reduction in postgastrectomy complications, such as dumping and marginal ulceration.

Resection rates for ampullary carcinoma are up to 96%.

The 5-year actuarial survival rate of patients who undergo radical resection is about 49%.

Preoperative biliary drainage in jaundiced patients is indicated, to prevent coagulation and wound healing problems.

Resectability of the primary tumor is determined by mobilizing the head of the pancreas, a procedure known as the Kocher maneuver, by opening the lesser sac, and exposing and inspecting the confluence of the splenic vein and superior mesenteric vein.

Pancreaticoduodenectomy procedure for periampullary cancer transacts the pancreas anterior to the portal vein to resect the pancreatic head and uncinate process, duodenum and gastric antrum, gallbladder, distal bile duct and peri pancreatic lymph nodes.

Bile duct and pancreatic margins are confirmed negative by frozen section diring the procedure and prior to reconstruction.

Palliative surgery for patients with unresectable tumors, is to alleviate biliary obstruction, duodenal obstruction, or pain with either a cholecystectomy or hepaticojejunostomy bypass or gastrojejunostomy.

Gastrojejunostomy should be performed, because as many as one third of patients develop obstruction later.

Prophylactic gastrojejunostomy adds significant morbidity to the procedure.

Chemical splanchnicectomy can be performed intraoperatively to control pain.

Recurrent disease is not curable.

Patients with familial adenomatous polyposis have as much as 50-90% chance of patients developing duodenal adenomas, and such patients should receive close endoscopic surveillance.

Morbidity remains high for pancreaticoduodenectomy, with rates of 41 and 47% reported in two series.

The most common complications of pancreaticoduodenectomy are leak and fistulas (12%), wound infection (7-11%), and delayed gastric emptying (7-18%).

Other complications include intraabdominal abscess, hemorrhage, dehiscence, prolonged ileus, biliary anastomotic leak, thrombophlebitis, and marginal ulceration.

Postoperative mortality following pancreaticoduodenectomy is 1-2% today in experienced centers.

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.

Survival after surgical resection is related to the extent of local invasion of the primary lesion, lymph node involvement, vascular invasion, perineural invasion, cellular differentiation, surgical margins, and perioperative blood transfusion.

38% reported 5 year survival for resected patients (Talamini et al).

Among patients with resected periampullary adenocarcinoma adjuvant chemotherapy (5-FU plus folinic acid or gemcitabine) compared with observation, was not associated with significant survival benefit (European Study Group for Pancreatic Cancer).