neoplasms of pancreas

1. Neoplasms of the Pancreas
Dr.Prabhakara Rao.Y M.S,McH
Professor of surgery

2. Introduction
• 4th
leading cause of cancer death.
• Non-specific symptoms, inaccessibility to
examination, aggressiveness, technical
difficulties associated with surgery.

3. 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

4. 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.

5. Epidemiology/Risk Factors
• A protective effect for dietary fiber, vitamin C.
fruits and veggies.
• Long standing diabetes is not a risk factor.

6. Epidemiology/Risk Factors
• Chronic pancreatitis of any cause has been
associated 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.

7. Epidemiology/Risk Factors
• Six genetic syndromes associated with an
increased risk of pancreatic cancer are:
• HNCC, BRCA-2 associated familial breast cancer,
Peutz-Jeghers syndrome, ataxia-telangietasia,
hereditary pancreatitis, familial mole-melanoma
syndrome.

8. Molecular Genetics
• Tumor suppressor genes: p53, p16, DPC4,
BCA2.
• P53 is inactivated in 75% of all pancreatic
cancers.

9. 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.

10. The tumours of the pancreas can be -
A. Non-Endocrine neoplasms
B. Endocrine neoplasms
TUMOURS OF THE PANCREAS

11. NON-ENDOCRINE NEOPLASMS:
 Benign non-endocrine neoplasms of
pancreas. Includes:-
(adenoma, cystadenoma, lipomas, fibromas,
haemingoma, lymphangioma and neuromas).
They are extremely rare and no clinical
significance unless they become palpable or
give pressure to adjacent structures and cause
symptoms. Can be solid or cystic or both. The
diagnosis should be made after exclusion of
more frequent malignant tumours.

12.  Malignant non-endocrine neoplasms.
The most common are:-
1. Ductal adenocarcinoma
2. Cystadenocarcinoma
NOTE: Periampullary carcinoma is term used for
juxta-pancreatic carcinomas. They are three forms:-
 Carcinoma of the ampulla
 Carcinoma of the lower CBD
 Duodenal carcinoma
Exocrine
cell of
pancreas

13. ENDOCRINE NEOPLASMS:
These are less common than non-endocrine tumours
and generally benign and sometimes multiple. They
includes:
 Insulinoma
 Glucogonomas
 Others:
- Gastrinomas
- Somatostatatinomas
- Vipomas (Vasoactive Intestinal
Polypeptide)
common

14. Pathology
• 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.

15. 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.

16. 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).

17. Pathologic Classification of Cystic
Neoplasms of the Pancreas
• Serous cystic neoplasm (SCN)
Microcystic adenoma
Oligocystic adenoma
• Mucinous cystic neoplasm (MCN)
Mucinous cystadenoma
Mucinous cystic tumour borderline
Mucinous cystadenocarcinoma
Noninvasive (carcinoma-in-situ)
Invasive

18. • Intraductal papillary mucinous neoplasm
(IPMN)
Adenoma
Borderline
Carcinoma-in-situ
Invasive carcinoma

19. SEROUS CYSTIC NEOPLASMS
• always benign
• occur in women in the sixth decade of life.
• abdominal pain and the presence of a
palpable mass were the most common
complaints among symptomatic patients.
• predilection for the pancreatic body and tail
• Enucleation

20. MUCINOUS CYSTIC NEOPLASMS
• 20-30% of cystic neoplasms of the pancreas
• more common in females than males, with
over 90% of patients being female.
• mean age at presentation being 48-52 years.
• most commonly occur in the body or tail of
the pancreas

21. • MCNs contain large septated cysts with thick
irregular walls that may be well-detailed on
CT, MRI, or ultrasound evaluation.
• Papillary projections from the epithelium
often extend into the cystic cavities and may
be visible, particularly on endoscopic
ultrasound imaging.

22. • MCNs have been shown to be rich in CEA and
low in amylase.
• Other tumor markers such as CA 72-4, CA 19-
9, CA 125, and CA 15-3 have been investigated
as adjuncts to diagnosis

23. • Segmental pancreatic resections for lesions in
the pancreatic neck and body (central
pancreatectomy) or tail (spleen-preserving
distal pancreatectomy) should be performed
cautiously

24. INTRADUCTAL PAPILLARY MUCINOUS
NEOPLASMS
• significant malignant potential.
• Characteristic features include a tall,
columnar epithelium with marked mucin
production, and cystic transformation of
either the main pancreatic duct or one of its
side branches.
• IPMN tend to be older, with a mean age of
approximately 65 years.

25. • Tall mucin-producing columnar epithelial cells that
remain well differentiated characterize IPMN
adenoma.
• IPMN borderline lesions are described as lesions with
moderate epithelial dysplasia, moderate loss of
polarity, changes in nuclear morphology, and
pseudopapillary formation
• IPMNs with carcinoma-in-situ have severe dysplastic
changes. These lesions may be papillary or
micropapillary, and severely dysplastic lesions may
lose the ability to secrete mucin.

26. • malignant potential of IPMNs involving the
main pancreatic ductal system appears to be
greater than that of lesions involving only
secondary ducts.

27. UNUSUAL PANCREATIC CYSTIC
NEOPLASMS
• Solid Pseudopapillary Tumor
• Cystic Neuroendocrine Tumor
• Cystic Acinar Cell Tumor
• Cystic Degeneration of Ductal
Adenocarcinoma

28. 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

29. 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%.

30.  Spread of pancreatic tumours:
A. Local Invasion
B. Lymphatic
C. Blood
D. Via peritoneal & omentum
causing ascites

31. CLINICAL FEATURES:
 The diagnosis of pancreatic cancer
varies from the simple and clinically
obvious to the most difficult and almost
impossible the initial symptoms and
signs depend on the site and extent of
the pancreatic cancer.

32.  Modes of presentation:
 Weight loss
 Pain
 Jaundice
 Steatorrhoea
 Diabetes Mellitus
 Acute Pancreatitis
 Malignant Ascites
 Gastric Outlet Obstruction

33.  Approach to Investigations:
(Selective Investigations)
 Ultrasound Scan
 C.T. Scan
 MR Imaging Scan
 ERCP
 Histology & Cytology
 Angiography (Coeliac, Superior -
Mesenteric)
 Laparoscopy

34. DELAY IN DIAGNOSIS:
 Over 90% of patient with pancreatic cancer
present in the late stage of theirdisease. At time
no chance of cure.
 The factors responsible forlate diagnosis
A. Tumour is asymptomatic in the early
stage.
B. Patient delay.
C. Physician delay.
D. The patient may not have ready and easy
access to competent diagnostic centre.

35. Diagnosis
• 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.

36. 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, Virchow’s node,
SMJ node, ascites (15%).

37. Diagnosis
• 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.

38. Radiology
• 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.

39. Radiology
• 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.

40. MANAGEMENT OF PANCREATIC CANCER:
A. Surgical Treatment
B. Non Surgical Treatment

41. Preoperative Staging
• Determine feasibility of surgery and optimal
treatment for each individual patient.
• In many cases only CT scan is necessary.

43. Preoperative Staging
• Absence of metastases, patent SMV-portal
vein confluence, no direct extension to celiac
axis or SMA accuracy for resectability 85%.
• 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.

44. 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.

45. Preoperative Staging
• Endoscopic US useful for small lesions, lymph
nodes, vascular invasion, EU guided FNA may
avoid seeding.

47. Preoperative Staging
• Percutaneous FNA should not be used on potentially
resectable tumors for two reasons. First even if the
result is negative it does not rule out malignancy, in
fact the small, potentially curable lesions will be the
ones that are missed by the needle. Second is
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.

48. 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.

49. 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.

51. Resection of Pancreatic Carcinoma
• Head, Neck, Uncinate: 1912 Kaush first
successsful resection of duodenum and
portion of pancreas for ampullary cancer.

52. 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.

53. 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.

54. 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.

55. 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).

56. Kocherizing

57. Determining Resectability

58. Resected Head

61. Pylorus Preserving

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

63. 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.

64. 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.

65. Long-term Survival
• Historically, 5% 5-year survival post resection.
More recent studies suggest improved
survival.

66. 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%.

67. Adjuvant Therapy
• Radiation
• 5-FU

68. Palliation
• 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.

69. Palliation
• 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.