Pancreatic and Periampullary Adenocarcinoma

John P. Christodouleas and Joseph M. Herman

 Background

Approximately how many pancreatic adenocarcinoma (PCA) pts are diagnosed per yr in the U.S.?

The incidence of PCA is ~30,000 cases/yr in the U.S.

Where does PCA rank in cancer incidence in the U.S.? Cancer mortality?

As of 2009, PCA is the 10^th most common cancer Dx but the 4^th most common cause of cancer death in the U.S.

Is there a racial or gender predilection for PCA?

Yes. Blacks are more commonly affected than whites; however, the incidence is similar among males and females.

In what decades of life does PCA incidence peak?

The peak age of PCA is in the 6^th–7 ^th decades of life.

What are 3 environmental exposures associated with PCA?

Most common environmental risk factors for PCA:

1. 
   

   Tobacco smoking

   
   
2. 
   

   2-naphthylamine

   
   
3. 
   

   Benzidine

What % of PCA is familial?

~5% of PCA is familial.

What 2 genetic mutations have most frequently been associated with familial PCA?

p16 and BRCA2 are the 2 most common familial associated genetic changes found in PCA.

Is chronic pancreatitis associated with increased risk of PCA?

No. Chronic pancreatitis is not associated with risk of PCA. Historically, there appeared to be an association, but this can be explained by confounding factors.

What % of PCA arise in the head, body, and tail of the pancreas?

Common PCA sites are 75% in the head, 15% in the body, and 10% in the tail.

What % of PCA pts have metastatic Dz at Dx?

~50% of PCA pts have DM at Dx.

What % of PCA pts have regional node+ Dz at Dx?

~25% of PCA pts have regional node+ Dz at Dx.

For PCA, what are the 3 most common sites of DM?

Common sites of DM for PCA include the liver, peritoneal surface, and lungs.

Is there a role for screening in PCA?

No. There is no current role for PCA screening. There are studies evaluating the role of screening 1^st-degree relatives of PCA with EUS, but this is still experimental.

What % of pancreatic tumors are from the exocrine pancreas?

~95% of PCA are from the exocrine pancreas.

What are the 4 most common pathologic subtypes of exocrine pancreatic tumors?

Most common subtypes of exocrine pancreatic tumors:

1. 
   

   Ductal adenocarcinoma (80%)

   
   
2. 
   

   Mucinous cystadenocarcinoma

   
   
3. 
   

   Acinar cell carcinoma

   
   
4. 
   

   Adenosquamous carcinoma

What is the most common oncogene in PCA?

The K-ras oncogene is present in ~85% of PCA.

What are the 2 most common presenting Sx of PCA?

Common presenting Sx of PCA are pancreatic/biliary duct obstruction, jaundice, and abdominal pain.

What Dz is commonly diagnosed 1–2 yrs prior to a PCA Dx?

60%–80% of PCA pts are diagnosed with diabetes 1–2 yrs prior to Dx. However, only a small proportion of diabetic pts develop PCA.

Periampullary cancers refer to tumors arising from what 3 structures?

Periampullary tumors are those arising from the ampulla of Vater, distal common bile duct (CBD), and adjacent duodenum.

 Workup/Staging

What is the DDx of a pancreatic mass?

The DDx of a pancreatic mass includes exocrine cancer, islet cell/neuroendocrine cancer, cystic adenomas, papillary cystic neoplasms (e.g., intraductal papillary mucinous tumor), lymphoma, acinar cell carcinoma, and metastatic cancer.

Name 4 appropriate procedures for obtaining tissue from a suspicious pancreatic mass.

Procedures to obtain tissue from a suspicious pancreatic mass:

1. 
   

   EUS-guided FNA

   
   
2. 
   

   CT-guided FNA

   
   
3. 
   

   Endoscopic retrograde cholangiopancreatography (ERCP)

   
   
4. 
   

   Pancreatic resection (i.e., histologic Dx is not required before surgery)

What is the major advantage of EUS-guided FNA over CT-guided FNA of a pancreatic mass?

EUS-guided FNA is associated with lower risk of peritoneal seeding (2% vs. 16%).

What is the workup for suspected PCA?

Suspected PCA workup: H&P, CBC, CMP, CA 19-9, triphasic thin-sliced CT abdomen (pancreas protocol), chest imaging, +/− ERCP/EUS FNA for Dx and/or stent placement

In what circumstance will a PCA pt not excrete any CA 19-9?

If a pt is red cell Lewis antigen A–B negative, then the pt cannot excrete CA 19-9. The Lewis antigen negative phenotype is present in 5%–10% of the population.

What is the significance of a post-resection CA 19-9 >90 U/mL?

In RTOG 9704, 53 pts (14%) had CA 19-9 >90 U/mL, and only 2 of these pts survived up to 3 yrs.

What is the NCCN 2010 classification scheme for PCA?

PCA are classified in 4 categories (and per AJCC staging):

1. 
   

   Resectable (T1-3N0 or N+) (stages I–II)

   
   
2. 
   

   Borderline resectable (T4NX) (stage III)

   
   
3. 
   

   Locally advanced (T4NX) (stage III)

   
   
4. 
   

   Metastatic (TXNXM1) (stage IV)

What is the AJCC 7^th edition (2009) T and N staging for PCA?

1. 
   

   T1: limited to pancreas and ≤2 cm

   
   
2. 
   

   T2: limited to pancreas and >2 cm

   
   
3. 
   

   T3: extends beyond pancreas but without celiac axis or superior mesenteric artery (SMA) involvement

   
   
4. 
   

   T4: celiac axis or SMA involvement

   
   
5. 
   

   N1: regional node involvement

What are the AJCC 7^th edition (2009) stage groupings for PCA?

1. 
   

   Stage 0: Tis

   
   
2. 
   

   Stage IA: T1N0M0

   
   
3. 
   

   Stage IB: T2N0M0

   
   
4. 
   

   Stage IIA: T3N0M0

   
   
5. 
   

   Stage IIB: T1-3N1M0

   
   
6. 
   

   Stage III: T4NXM0

   
   
7. 
   

   Stage IV: TXNXM1

Per the NCCN, what 3 criteria are necessary for a primary pancreatic tumor to be resectable?

NCCN resectability for PCA is defined as follows:

1. 
   

   Patent superior mesenteric vein (SMV)/portal vein confluence

   
   
2. 
   

   Clear fat plane around celiac artery and SMA

   
   
3. 
   

   No nodal mets or other mets beyond field of resection

Per the NCCN, what pancreatic head/body lesions are considered “borderline resectable”?

NCCN definition of borderline resectability for PCA:

1. 
   

   Severe unilat SMV/portal confluence impingement

   
   
2. 
   

   Tumor abutment on SMA

   
   
3. 
   

   Gastroduodenal artery encasement up to hepatic artery

   
   
4. 
   

   Tumors with limited involvement of IVC

   
   
5. 
   

   Short segment SMV occlusion with patent vein both proximally and distally

   
   
6. 
   

   Colon or mesocolon invasion

What pancreatic tail lesions are considered “borderline resectable”?

Invasion into the adrenal gland, colon, mesocolon, or kidney are considered borderline resectable for PCA tail lesions.

What location of PCA is associated with higher rates of resectability: head, body, or tail?

PCA head tumors are more resectable b/c they cause Sx early (and therefore present with earlier-stage Dz).

What % of pts with resectable PCA tumors by CT imaging will be resectable at the time of surgery?

~80% of PCA pts deemed resectable by CT are resectable at the time of surgery.

What is the stage of a PCA pt with positive cytology at time of laparoscopy?

Positive cytology is stage IV (M1).

Does the AJCC 7^th edition (2009) TNM staging for periampullary adenocarcinoma differ from PCA?

Yes

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