neoplasms of the exocrine pancreas-1
TRANSCRIPT
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
1/56
Neoplasms of the Pancreas
Vic V. Vernenkar, D.O.
St. Barnabas HospitalDept. Of Surgery
From Greenfields Surgery 2006
4th edition
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
2/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
3/56
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
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
4/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
5/56
Epidemiology/Risk Factors
A protective effect for dietary fiber, vitamin
C. fruits and veggies.
Long standing diabetes is not a risk factor.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
6/56
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 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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
7/56
Epidemiology/Risk Factors
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
8/56
Molecular Genetics
Tumor suppressor genes: p53, p16, DPC4,
BCA2.
P53 is inactivated in 75% of all pancreatic
cancers.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
9/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
10/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
11/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
12/56
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).
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
13/56
Cystic Epithelial Tumors
Less common than ductal, more in women,
throughout the gland.
Vast majority of cysts are benign
pseudocysts.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
14/56
Cystic Epithelial Tumors
Important to recognize cystic neoplasms
because management is very different from
non-neoplastic cysts. Many can havemalignant potential.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
15/56
Cystic Epithelial Tumors
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
16/56
Cystic Epithelial Tumors
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
17/56
Cystic Epithelial Tumors
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
18/56
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
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
19/56
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%.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
20/56
Diagnosis
Inability to make diagnosis at early stage.
Specific symptoms occur after invasion of
adjacent structures.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
21/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
22/56
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%).
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
23/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
24/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
25/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
26/56
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
27/56
Preoperative Staging
Determine feasibility of surgery and optimal
treatment for each individual patient.
In many cases only CT scan is necessary.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
28/56
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
29/56
Preoperative Staging
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
30/56
Preoperative Staging
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
31/56
Preoperative Staging
Endoscopic US useful for small lesions,
lymph nodes, vascular invasion, EU guided
FNA may avoid seeding.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
32/56
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
33/56
Preoperative Staging
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
34/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
35/56
Preoperative Staging
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
36/56
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
37/56
Resection of Pancreatic
Carcinoma Head, Neck, Uncinate: 1912 Kaush first
successsful resection of duodenum and
portion of pancreas for ampullary cancer.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
38/56
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 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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
39/56
Resection of Pancreatic
Carcinoma Operative management of pancreatic
cancer consists oftwo phases: first
assessing tumor resectability, secondcompleting a pancreaticiduodenectomy
and restoring GI continuity.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
40/56
Resection of Pancreatic
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
41/56
Resection of Pancreatic
Carcinoma3. Dissect out SMV and Portal vein to rule
out tumor invasion.
4. Once this is negative go topancreaticoduodenectomy (pylorus
preserving or classic).
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
42/56
Kocherizing
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
43/56
Determining Resectability
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
44/56
Resected Head
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
45/56
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
46/56
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
47/56
Pylorus Preserving
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
48/56
Postoperative Results
During the 1960s and 1970s, many centers
reported operative mortality in range of 20-
40%, with postoperative morbidity rates of40-60%.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
49/56
Postoperative Results
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
50/56
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
51/56
Postoperative Results
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
52/56
Long-term Survival
Historically, 5% 5-year survival post
resection. More recent studies suggest
improved survival.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
53/56
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 (
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
54/56
Adjuvant Therapy
Radiation
5-FU
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
55/56
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.
-
7/29/2019 Neoplasms of the Exocrine Pancreas-1
56/56
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.