Neoplasms of the exocrine pancreas

Other conditions for which a possible connection to pancreatic cancer are: thyroid cancer, cystic fibrosis, pernicious anemia.. Activating point mutations in the k-ras oncogene is the

Neoplasms of the Pancreas

Vic V Vernenkar, D.O

St Barnabas HospitalDept Of SurgeryFrom Greenfield’s Surgery 2006

4th edition

• Estimates:33000 cases, 32000 die in 2005

• 4th leading cause of cancer death

• Non-specific symptoms, inaccessibility to examination, aggressiveness, technical

difficulties associated with surgery

• More than 80% of cases between 60-80

years of age, rare under 40

• African-American of both sexes

Epidemiology/Risk Factors

• Men over women

• Cigarette smoking increased risk 1.5-5 times

• Increased consumption of total calories, CHO, cholesterol, meat, salt, fried food, refined sugar, soy beans, nitrosamines

Epidemiology/Risk Factors

• A protective effect for dietary fiber, vitamin

C fruits and veggies

• Long standing diabetes is not a risk factor

Epidemiology/Risk Factors

• Chronic pancreatitis of any cause has been

associated with a 25-year cumulative risk of 4% Other conditions for which a possible connection

to pancreatic cancer are: thyroid cancer, cystic fibrosis, pernicious anemia.

• Most cases of pancreatic cancer have no

predisposing factors, however it is estimated that between 5-10% arise because of a familial

disposition.

melanoma syndrome.

Molecular Genetics

• DPC4 is on Chromosome 18q The Chromosome

is missing in 90% of all pancreatic cancers, the

gene inactive in 50% The mutations are more

specific for pancreatic cancer than p53 or p16

mutations.

• Oncogenes, when over expressed encode proteins

with transforming qualities Activating point

mutations in the k-ras oncogene is the most

common genetic alteration in pancreatic cancer, found in 80-90% of pancreatic cancers.

• Classified based on cell of origin Most

common are ductal adenocarcinomas

• 65% of ductal cancers arise in the head,

neck, or uncinate process; 15% originate in the body or tail; 20% diffuse

Solid Epithelial Tumors

• Adenocarcinomas: 75%, white yellow,

poorly defined, often obstruct bile duct or main pancreatic duct

• Often associated with a desmoplastic

reaction that causes fibrosis and chronic pancreatitis

Solid Epithelial Tumors

• Infiltrate into vascular, lymphatic, perineural

spaces At resection, most mets to lymph nodes.

• Mets to liver (80%), peritoneum (60%), lungs and pleura (50-70%), adrenal (25%) Direct invasion of adjacent organs as well.

• Others include adenosquamous, acinar cell (1%, better prognosis), giant cell (5%, poorer

prognosis), pancreatoblastoma (children 1-15

years, more favorable).

Cystic Epithelial Tumors

• Less common than ductal, more in women, throughout the gland

• Vast majority of cysts are benign

pseudocysts

Cystic Epithelial Tumors

• Important to recognize cystic neoplasms

because management is very different from non-neoplastic cysts Many can have

malignant potential

Cystic Epithelial Tumors

• Serous Cystic Neoplasms more common in women (2:1).Uniform cuboidal, glycogen

rich cells 30% asymptomatic, most have

symptoms of pain, N/V Can be anywhere in the gland, does not communicate with

ducts Most are benign Symptomatic cysts that cannot be differentiated from other

potentially malignant cysts should be

excised

Cystic Epithelial Tumors

• Mucinous Cystic Neoplasms (MCN) are mucin producing epithelial cells associated with an ovarian-type stroma Most in body and tail Columnar mucin producing cells 1/3 associated with invasive cancer Lesions should be completely resected as invasive and in-situ carcinomas can be very focal So cannot say benign on biopsy alone Benign can progress to malignancy as well

Cystic Epithelial Tumors

• Intraductal Papillary-Mucinous Neoplasms

(IPMN) extensively involve the main pancreatic duct and branches Lack ovarian type stroma, more

common in men Older patient 60-80 Symptoms of pain, weight loss, steatorrhea, jaundice, diabetes,

chronic pancreatitis More common in head and neck

On endoscopy, mucin can be seen oozing from

ampulla ERCP for ductal communication Progress from benign to malignant Goal is complete surgical excision of benign and malignant lesions with

negative margins.

• Inability to make diagnosis at early stage

• Specific symptoms occur after invasion of adjacent structures

• Most occur at the head, obstructs the bile

duct that is intrapancreatic, causing

jaundice, dark stools, dark urine, abdominal

or back pain that is usually ignored by the patient Pain may also be caused by

invasion of splanchnic plexus and

retroperitoneum

• New onset of diabetes (10-15%), acute

pancreatitis Jaundice is most

common(87%), hepatomegaly(83%),

palpable gallbladder(29%) may be present Cachexia, muscle wasting, nodular liver, Virchow’s node, SMJ node, ascites (15%)

• Amylase, lipase normal, other labs like

obstructive jaundice

• Ca 19-9, when upper level cutoff is used

>200U/mL, accuracy is 95% in diagnosing pancreatic cancer With CT, ERCP, US and Ca19-9 together, it approaches 100%

• Higher levels correlate with prognosis and tumor recurrence, unresectability

• CT has replaced US On CT appears as an area of enlargement with a localized

hypodense lesion Do thin cuts thru

pancreas and liver CT is used to determine size of lesion and involvement of adjacent structures, mets

• MRI offers no advantage MRCP promising in

terms of duct evaluations.

• Next step is ERCP to get anatomy and specimens Sensitivity of ERCP to diagnose cancer is 90%

Look for long irregular stricture in an otherwise normal duct is highly suggestive Obstruction with

no distal filling Don’t need on everybody Do it if suspect cancer but no mass seen on CT Or

symptomatic but no jaundice and no mass, chronic pancreatitis patients with development of mass.

• For tumors of the neck, head, uncinate

process, occlusion of the SMA or portal vein along with presence of periportal collateral vessels is a sign of unresectability

Preoperative Staging

• In contrast tumors of the body and tail,

occlusion of the splenic vein with perigastric collaterals does not always preclude resection.

• The extent of further staging depends on the patient and surgeon If findings of staging can prevent an operation and lead to non-operative palliation, these efforts are worthwhile.

Preoperative Staging

• Endoscopic US useful for small lesions,

lymph nodes, vascular invasion, EU guided FNA may avoid seeding

potential for seeding along tract or intraperitoneally FNA should be done on patients deemed unresectable for direction of chemotherapy, or patients in whom neoadjuvant chemo is being considered Currently

EUS is the preferred technique for this in these

situations.

Preoperative Staging

• At the time of diagnosis, only 10% tumors confined to pancreas 40% have locally

advanced disease, 50% distant spread

Overall only 10-20% of all patients are candidates for pancreatic resection.

Preoperative Staging

• Diagnostic laparoscopy on potentially

resectable patients may find mets to liver and peritoneum not seen on CT because

they are small 50% of tumors of body and tail will have unexpected mets to

peritoneum, whereas in head and neck, only 15% unexpected mets seen

Resection of Pancreatic

Carcinoma

• Head, Neck, Uncinate: 1912 Kaush first successsful resection of duodenum and portion of pancreas for ampullary cancer

Resection of Pancreatic

Carcinoma

• 1935- Whipple described a technique for radical

excision of a periampullary cancer Was originally performed in two stages, first stage was a

cholecystogastrostomy and gastrojejunostomy

Second stage was done after nutritional status

better and jaundice improved was en-bloc

resection of second portion of duodenum, head of pancreas without reestablishing pancreas-GI

continuity Since then many modifications done.

Resection of Pancreatic

Carcinoma

• Operative management of pancreatic

cancer consists of two phases: first

assessing tumor resectability, second completing a pancreaticiduodenectomy and restoring GI continuity

Resection of Pancreatic

Carcinoma

1 Search first for mets, extrapancreatic involvement

Send frozen sections on suspect lesions.

2 Assess primary tumor, for resectabilty, look for

IVC, Aorta, SMA, SMV, Portal vein To do this

you do a Kocher maneuver to mobilize duodenum and head from IVC and aorta, once mobilized can

assess relationship of tumor to SMA Inability to find a plane between pulsation of SMA and

tumor means unresectable.

Resection of Pancreatic

Carcinoma

3 Dissect out SMV and Portal vein to rule

out tumor invasion

4 Once this is negative go to

pancreaticoduodenectomy (pylorus

preserving or classic)

Kocherizing

Determining Resectability

Resected Head

Pylorus Preserving

Postoperative Results

• During the 1960s and 1970s, many centers reported operative mortality in range of 20-40%, with postoperative morbidity rates of 40-60%

Postoperative Results

• During last two decades rates reported

down to 2-3% mortality Reasons why

fewer, more experienced surgeons are

performing the operation on a more frequent basis, pre and post op care has improved,

anesthesia has improved, large number of

patients are being treated at high volume

centers

Postoperative Results

• Complication rates remain high (30%)

Pancreatic fistula remains the most frequent serious complication (5-15%) The

mortality from this has decreased though

• Other common complications include

delayed gastric emptying, abscess, bleeding, infection, diabetes, exocrine insufficiency

Long-term Survival

• Historically, 5% 5-year survival post resection More recent studies suggest improved survival

Long-term Survival

• In 2000, Sohn, et al on 616 patients resected with

a 17% 5-year survival, median survival of 17

months Factors found to be important predictors

of survival included tumor diameter (<3cm),

negative resection margin, well/mod tumor

differentiation, postop chemoradiatioin treatment.

• Most favorable were small tumors, margin

negative, node negative resections, median

survival was 33 months and 5-year survival was 31%.

Adjuvant Therapy

• Radiation

• 5-FU

• Jaundice : Choledochojejunostomy,

cholecystojejunostomy Stent placement.

• With stents, may need frequent exchanges, may migrate, recurrent jaundice is higher Metallic

stents stay open longer Lower complication rates with respect to surgical palliation.

• Surgical palliation for patients expected to live longer than 6 months only.

• Duodenal Obstruction:Gastrojejunostomy

do it or not if the patient is not obstructed Studies say do it No difference in length of stay post op, morbidity, mortality

• Pain: Long-acting morphine derivatives,

percutaneous blocks are successful at

eliminating pain in majority