Neoplasms of the Exocrine Pancreas-1

7/29/2019 Neoplasms of the Exocrine Pancreas-1

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Neoplasms of the Pancreas

Vic V. Vernenkar, D.O.

St. Barnabas HospitalDept. Of Surgery

From Greenfields Surgery 2006

4th edition


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Introduction

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.


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Epidemiology/Risk Factors

Increase threefold since the beginning of the

century.

Age, race, sex, tobacco, diet, specific

genetic syndromes.

More than 80% of cases between 60-80

years of age, rare under 40.

African-American of both sexes


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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.


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A protective effect for dietary fiber, vitamin

C. fruits and veggies.

Long standing diabetes is not a risk factor.


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Chronic pancreatitis of any cause has been

associated with a 25-year cumulative risk of 4%.

Other conditions for which a possible connectionto pancreatic cancer are: thyroid cancer, cystic

fibrosis, pernicious anemia.

Most cases of pancreatic cancer have no

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

disposition.


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Six genetic syndromes associated with an

increased risk of pancreatic cancer are:

HNCC, BRCA-2 associated familial breast

cancer, PJ syndrome, ataxia-telangietasia,

hereditary pancreatitis, familial mole-

melanoma syndrome.


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Molecular Genetics

Tumor suppressor genes: p53, p16, DPC4,

BCA2.

P53 is inactivated in 75% of all pancreatic

cancers.


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Molecular Genetics

DPC4 is on Chromosome 18q. The Chromosomeis missing in 90% of all pancreatic cancers, thegene inactive in 50%. The mutations are morespecific for pancreatic cancer than p53 or p16mutations.

Oncogenes, when over expressed encode proteinswith transforming qualities. Activating pointmutations in the k-ras oncogene is the mostcommon genetic alteration in pancreatic cancer,found in 80-90% of pancreatic cancers.


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Pathology

Classified based on cell of origin. Most

common are ductaladenocarcinomas.

65% of ductal cancers arise in the head,

neck, or uncinate process; 15% originate in

the body or tail; 20% diffuse.


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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.


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Solid Epithelial Tumors

Infiltrate into vascular, lymphatic, perineural

spaces. At resection, most mets to lymph nodes.

Mets to liver (80%), peritoneum (60%), lungs andpleura (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).


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Cystic Epithelial Tumors

Less common than ductal, more in women,

throughout the gland.

Vast majority of cysts are benign

pseudocysts.


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Important to recognize cystic neoplasms

because management is very different from

non-neoplastic cysts. Many can havemalignant potential.


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Serous Cystic Neoplasms more common inwomen (2:1).Uniform cuboidal, glycogen

rich cells. 30% asymptomatic, most havesymptoms of pain, N/V. Can be anywherein the gland, does not communicate withducts. Most are benign. Symptomatic cysts

that cannot be differentiated from otherpotentially malignant cysts should beexcised.


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Mucinous Cystic Neoplasms (MCN) aremucin producing epithelial cells associated

with an ovarian-type stroma. Most in bodyand tail. Columnar mucin producing cells.1/3 associated with invasive cancer. Lesionsshould be completely resected as invasive

and in-situ carcinomas can be very focal. Socannot say benign on biopsy alone. Benigncan progress to malignancy as well.


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Intraductal Papillary-Mucinous Neoplasms(IPMN) extensively involve the main pancreaticduct and branches. Lack ovarian type stroma,more common in men. Older patient 60-80.Symptoms of pain, weight loss, steatorrhea,

jaundice, diabetes, chronic pancreatitis. Morecommon in head and neck. On endoscopy, mucin

can be seen oozing from ampulla. ERCP for ductalcommunication. Progress from benign tomalignant. Goal is complete surgical excision of

benign and malignant lesions with negative

margins.


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Staging

T1 limited to pancreas, 2cm or less in size.

T2 limited to pancreas, >2cm.

T3 extends beyond pancreas, but not celiac

or SMA.

T4 involves celiac or SMA (unresectable).

N0, N1

M0, M1


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5-Year Survival

Stage 1A, 1B (T1-T2, N0, M0)20-30%.

Stage 1B (T2, N0,M0) 20-30%.

Stage 2A (T3, N0,M0) 10-25%.

Stage 2B (T1, T2, T3, N1, M0)10-15%.

Stage 3 (T4, any N, M0) 0-5%.

Stage 4 (Any T, any N, M1) 0%.


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Diagnosis

Inability to make diagnosis at early stage.

Specific symptoms occur after invasion of

adjacent structures.


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Diagnosis

Most occur at the head, obstructs the bile

duct that is intrapancreatic, causing

jaundice, dark stools, dark urine, abdominalor back pain that is usually ignored by the

patient. Pain may also be caused by

invasion of splanchnic plexus andretroperitoneum.


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Diagnosis

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,

Virchows node, SMJ node, ascites (15%).


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Diagnosis

Amylase, lipase normal, other labs likeobstructive jaundice.

Ca 19-9, when upper level cutoff is used>200U/mL, accuracy is 95% in diagnosingpancreatic cancer. With CT, ERCP, US andCa19-9 together, it approaches 100%.

Higher levels correlate with prognosis andtumor recurrence, unresectability.


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Radiology

CT has replaced US. On CT appears as an

area of enlargement with a localized

hypodense lesion. Do thin cuts thrupancreas and liver. CT is used to determine

size of lesion and involvement of adjacent

structures, mets.


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Radiology

MRI offers no advantage. MRCP promising interms 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 otherwisenormal duct is highly suggestive. Obstruction withno distal filling. Dont need on everybody. Do it ifsuspect cancer but no mass seen on CT. Orsymptomatic but no jaundice and no mass, chronic

pancreatitis patients with development of mass.


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Preoperative Staging

Determine feasibility of surgery and optimal

treatment for each individual patient.

In many cases only CT scan is necessary.


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Absence of metastases, patent SMV-portal

vein confluence, no direct extension to

celiac axis or SMA accuracy forresectability 85%.

Fortumors of the neck, head, uncinate

process, occlusion of the SMA or portalvein along with presence of periportal

collateral vessels is a sign of unresectability.


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In contrast tumors of the body andtail,

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.


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Endoscopic US useful for small lesions,

lymph nodes, vascular invasion, EU guided

FNA may avoid seeding.


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Percutaneous FNA should not be used onpotentially resectable tumors for two reasons. Firsteven if the result is negative it does not rule out

malignancy, in fact the small, potentially curablelesions will be the ones that are missed by theneedle. Second is potential for seeding along tractor intraperitoneally. FNA should be done on

patients deemed unresectable for direction ofchemotherapy, or patients in whom neoadjuvantchemo is being considered. Currently EUS is the

preferred technique for this in these situations.


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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.


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Diagnostic laparoscopy on potentially

resectable patients may find mets to liver

and peritoneum not seen on CT becausethey are small. 50% of tumors of body and

tail will have unexpected mets to

peritoneum, whereas in head and neck, only15% unexpected mets seen.


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Resection of Pancreatic

Carcinoma Head, Neck, Uncinate: 1912 Kaush first

successsful resection of duodenum and

portion of pancreas for ampullary cancer.


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Carcinoma 1935- Whipple described a technique for radical

excision of a periampullary cancer. Was originally

performed in two stages, first stage was acholecystogastrostomy and gastrojejunostomy.

Second stage was done after nutritional status

better and jaundice improved was en-bloc

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

continuity. Since then many modifications done.


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Carcinoma Operative management of pancreatic

cancer consists oftwo phases: first

assessing tumor resectability, secondcompleting a pancreaticiduodenectomy

and restoring GI continuity.


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Carcinoma1. Search first for mets, extrapancreatic

involvement. Send frozen sections on suspectlesions.

2. Assess primary tumor, for resectabilty, look forIVC, Aorta, SMA, SMV, Portal vein. To do thisyou do a Kocher maneuver to mobilizeduodenum and head from IVC and aorta, once

mobilized can assess relationship of tumor toSMA. Inability to find a plane betweenpulsation of SMA and tumor meansunresectable.


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Carcinoma3. Dissect out SMV and Portal vein to rule

out tumor invasion.

4. Once this is negative go topancreaticoduodenectomy (pylorus

preserving or classic).


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Kocherizing


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Determining Resectability


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Resected Head


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Pylorus Preserving


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Postoperative Results

During the 1960s and 1970s, many centers

reported operative mortality in range of 20-

40%, with postoperative morbidity rates of40-60%.


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During last two decades rates reported

down to 2-3% mortality. Reasons why

fewer, more experienced surgeons areperforming the operation on a more frequent

basis, pre and post op care has improved,

anesthesia has improved, large number ofpatients are being treated at high volume

centers.


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Complication rates remain high (30%).

Pancreatic fistula remains the most frequent

serious complication (5-15%). Themortality from this has decreased though.

Other common complications include

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


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Long-term Survival

Historically, 5% 5-year survival post

resection. More recent studies suggest

improved survival.


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Long-term Survival

In 2000, Sohn, et al. on 616 patients resected witha 17% 5-year survival, median survival of 17months. Factors found to be important predictors

of survival included tumor diameter (


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Adjuvant Therapy

Radiation

5-FU


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Palliation

Jaundice: Choledochojejunostomy,

cholecystojejunostomy. Stent placement.

With stents, may need frequent exchanges, maymigrate, recurrent jaundice is higher. Metallic

stents stay open longer. Lower complication rates

with respect to surgical palliation.

Surgical palliation for patients expected to livelonger than 6 months only.


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Palliation

Duodenal Obstruction:Gastrojejunostomy

do it or not if the patient is not obstructed.

Studies say do it. No difference in length ofstay post op, morbidity, mortality.

Pain: Long-acting morphine derivatives,

percutaneous blocks are successful ateliminating pain in majority.

Neoplasms of the Exocrine Pancreas-1

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