Pancreatic and peri-ampullary CA

Ductal adenoCA most common primary

malignant disease of pancreas and periampullary region
Accounts for more than 75% of all nonendocrine tumors in this region
Ranks 11th among all cancers

Pancreatic and peri-ampullary CA

Most lethal CA overall 5-yr survival rate <3%

5th leading cause of cancer death
Ampullary, distal CBD, duodenal adenoCA
less common than pancreatic tumor; accounts
for 15-20% of all peri-ampullary malignant
disease.

Pancreatic and peri-ampullary CA

Pancreatic and peri-ampullary CA

Peri-ampullary CA (ampulla, distal CBD,

duodenum) associated with increased age,
HNPCC, Peutz-Jeghers syndrome, familial
adenomatous polyposis, Gardners syndrome.

Pancreatic and peri-ampullary CA

Can be broadly classified as primary, metastatic, or

systemic
Primary cancers can demonstrate either endocrine or
nonendocrine differentiation
Most common malignant diseases that metastasize to
the pancreas are renal cell, breast, colorectal, small cell
lung and melanoma
Systemic malignant conditions involving the pancreas
include leukemia and lymphoma

Pancreatic and peri-ampullary CA

Ductal AdenoCA (1o solid non-endocrine

epithelial tumor)
By far the most common peri-ampullary malignant
disease
Typically aggressive; most resected adenoCA have
already metastasize to regional lymph nodes
Papillary ductal lesion are 3x more common in
patients with pancreatic CA than in normal pancreas
Display k-ras, p53, p16 mutation

Pancreatic and peri-ampullary CA

Adenosquamous CA variant of adenoCA; occurs
in patients with history of chemoradiation
Giant cell CA accounts for <5% of solid
pancreatic malignant tumors
Acinar cell CA distinct histologic appearance
(often greater than 10cm)
Pancreatoblastoma or pancreatic cancer of infancy;
occur in children up to the age of 15yrs.

Clinical Presentation

Vague symptoms early the course

Develop obstructive jaundice secondary to
obstruction of the intrapancreatic portion of the
CBD
Jaundice often associated with pruritus, acholic
stools and dark urine
Pain described as vague upper abdominal,
epigastric or back discomfort

Staging

Palliative Therapy

Non-operative palliation
Most peri-ampullary adenoCA have unresectable
tumors at presentation
Palliation is aimed at three major symptoms:
obstructive jaundice, duodenal or gastric outlet
obstruction and tumor-associated pain
Patients found to have distant metastases,
unresectable local disease, or disseminated intraabdominal tumors are appropriate candidates for
non-operative therapy
Age alone is not a contraindication to surgical
resection or palliation

Palliative Therapy

Biliary obstruction
Biliary decompression can be achieved by either
endoscopic or percutaneous transhepatic technique
PBD first reported in 1974; catheter exchanges done
every 3mos to prevent cholangitis and recurrent
jaundice secondary to stent occlusion
Endoscopic approach is the method of choice
because of lower procedure-related morbidity and
mortality; removal and replacement of stent every 36mos to prevent recurrent jaundice and cholangitis

Palliative Therapy

Pain

Pain associated with pancreatic cancer is unremitting and

often poorly managed
Postulated causes include tumor infiltration into the celiac
plexus, pain associated with early satiety, gastroduodenal
obstruction and gallbladder or biliary obstruction, increased
parenchymal pressure caused by pancreatic duct obstruction,
and pancreatic inflammation
Tumor-associated pain is best treated with long-acting oral
analgesic in appropriate dosage, pain management specialist
may be required to help manage this problem
For pain intractable to typical narcotic regimens, CT guided
percutaneous celiac nerve block, external beam radiation
therapy, and thoracoscopic or endoscopic chemical
splanchnicectomy maybe done.

Palliative Therapy

Duodenal obstruction
Surgical gastrojejunostomy or feeding tube insertion
maybe done
Endoluminal approaches with biliary-type
expandable metallic stents are now being tested

Operative palliation
Tertiary centers report resectability rates for periampullary cancers ranging from 67-89%
Palliative surgery is indicated in patients whose
tumors are found to be unresectable at the time of
laparotomy intended for curative resection

Operative Palliation

Obstructive jaundice

Most commonly performed surgical procedure for relief of

obstructive jaundice include hepaticojejunostomy or
choledochojejunostomy, choledochoduodenostomy and
cholecystojejunostomy

Pain

Chemical splanchnicectomy can be performed to alleviate the

debilitating pain at the time of operative palliation; performed
by injecting 20ml of 50% alcohol through a spinal needle on
either side of the aorta at the level of celiac plexus

Resectional Therapy

Pancreaticoduodenectomy for peri-ampullary tumors

Halsted performed the first successful resection of a periampullary tumor in 1898

Kausch performed the first successful en bloc resection using
two-stage approach
Whipple and colleagues popularized the procedure in the
1930s and 1940s
Pylorus-preserving pancreaticoduodenectomy is now the
fovored procedure because the gastric reservoir and the
pyloric mechanism are kept intact

Resectional Therapy

Operative technique

If the tumor is localized to the periampullary region

or head, neck, or uncinate process of the pancreas,
with no evidence of distant metastatic disease of the
pancreas or major vascular involvement, the surgeon
proceeds with resection

Resectional Therapy

Complications

Operative mortality rate for pancreaticoduodenectomy is

currently less than 3% in centers specializing in pancreatic
surgery
Despite this rate, incidence of post-operative complications
remains as high as 40-50%
Two leading causes of morbidity are early delayed gastric
emptying and disruption or leak at the pancreatic anastomosis
(pancreatic fistula); the cause is likely multifactorial
Erythromycin has been shown to improve gastric emptying
after surgery
By definition, pancreatic fistula occurs 7 or more days postop, when the drain output contains milky, amylase-rich fluid
in excess of 50ml/day

Prognostic Factors

Prognostic factors

Determined by multiple factors including tumor stage,

biologic features, molecular genetics, post-op factors and the
use of adjuvant chemoradiation
Peri-ampullary tumors including distal bile duct, ampullary,
and duodenal adenoCA are less common, overall 5-yr
survival rate is better
In long term survivors with resected peri-ampullary
adenoCA, the site specific 5-yr actual survival rates were 15%
for pancreatic CA, 27% for distal bile duct CA, 39% for
ampullary CA, and 59% for duodenal CA
Well-differentiated tumors, negative resection margins, and
negative nodal status were indicators of a better prognosis for
all peri-ampullary cancers.

Prognostic Factors

For Pancreatic CA

Patients with diploid tumors fared significantly better than

aneuploid tumors
Tumors with p53 mutations have worse prognosis
Tumors with DNA mismatch repair mutations, so-called
RER+ tumors, are associated with improved prognosis
Post-op adjuvant chemotx and radiation tx has been shown
to improve survival
5-FU and external beam radiation tx appear to be indicated
after pancreaticoduodenectomy for pancreatic adenoCA

Prognostic Factors

Bile duct CA or cholangiocarcinoma

Medial survival was 22mos for distal bile duct tumors, with a
5-yr survival of 28%
Surgical resection, negative microscopic margins, pre-op
nutritional status, and absence of post-op sepsis were the best
predictors of improve outcome
Adjuvant chemoradiation does not appear to prolong survival

AdenoCA of the ampulla of Vater

2nd most common peri-ampullary malignancy, has a higher

resectability rate and a better prognosis
Actuarial 5-yr survival rate at 38%
Favorable factors: no peri-op BT, negative lymph node
status, and well-differentiated or moderately differentiated
tumors

Prognostic Factors

AdenoCA of the duodenum

Least common of the peri-ampullary neoplasm
Associated with the best prognosis
5-yr survival rate of 69%
Negative resection margins and tumors located in
the first and second portion of the duodenum
appear to influence survival favorably

Thank You!