Pancreatic neoplasms by Dr. Sreenath

1. PANCREATIC NEOPLASMS
Dr K Sreenath
Junior Resident, Dept of Surgery
RIMS Imphal

2. PANCREAS
 Weighs between 75 and 125 g and measures 10 to
20 cm.
 Lies in the retroperitoneum just anterior to the first
lumbar vertebrae
 Divided into four portions, the head, neck, body
and tail.

3. PANCREAS ANATOMY

4. ARTERIAL SUPPLY
 Multiple arcades in the
head and body of the
pancreas provide a rich
blood supply.
 The head of the pancreas
cannot be resected
without devascularizing
the duodenum unless a
rim of pancreas
containing the
pancreaticoduodenal
arcade is preserved

5. VENOUS DRAINAGE
 Follows a pattern
similar to the arterial
supply
 Veins usually
superficial to the
arteries

6. LYMPHATIC DRAINAGE
 The lymphatic drainage
from the pancreas is diffuse
and widespread, which
explains the high incidence
of lymph node metastases
and local recurrence of
pancreatic cancer.
 The pancreatic lymphatics
also communicate with
lymph nodes in the
transverse mesocolon
and mesentery of the
proximal jejunum.
 Tumors in the body and tail
of the pancreas are often
unresectable because they
metastasize to these lymph
nodes

7. INNERVATION
 The pancreas has a
rich supply of
afferent sensory
fibers that travel
superiorly to the
celiac ganglia.
 Interruption of
these somatic fibers
with a celiac plexus
block can interfere
with transmission of
pancreatic pain

8. TYPES OF PANCREATIC NEOPLASMS
 Neoplasms of exocrine pancreas
Cystic neoplasms account for <1% of
pancreatic cancers
Ductal adenocarcinoma >90% of pancreatic
cancers
 Neoplasms of endocrine pancreas
Neuroendocrine tumors or islet-cell tumors,
rare

9. CARCINOMA EXOCRINE PANCREAS

10.  MC – Ductal adenocarcinoma
 Ninth most common cancer diagnosis
 Fourth in cancer deaths
 Men> women (1.3 : 1)
 African Americans have a slightly higher risk
 Mean age at diagnosis is 72 years
 Incidence lowest in Middle East and in India

11. RISK FACTORS-ENVIRONMENTAL
 Smoking
 C/C Pancreatitis
 Occuopational exposure
 Diabetes
 Obesity
 Diet ( Rich in protein and fat)
 Infectious - H pylori or HBV ?
 Genetic
 Alcohol , coffee and Radiation ..No Risk
(Maingot’s 12th edn p. 1188)

12. RISK FACTORS-HEREDITARY

13. PATHOGENESIS
 Most cases are sporadic.
 Sequential pathway has been observed in the development
of PDAC from pancreatic intraepithelial neoplasia (PanIN) to
invasive cancer.
 Genes identified- PDX1, KRAS2, CDKN2A/p16, P53, and
DPC4 (SMAD4).
 KRAS2 oncogene is activated (by point mutation ) 95% of
pancreatic cancers
 Earliest event in tumorigenesis.

14. PanIN :
Progressive abnormality of the ductal epithelium from
columnar metaplasia (PanIN-1A) through carcinoma in
situ (PanIN-3).
PanIN-1A : Presence of columnar, mucin-producing ductal
epithelium
PanIN-1B : The development of papillary architecture
PanIN-2 : Evidence of nuclear atypia
PanIN-3 (carcinoma in situ): marked cytologic atypia,
complete loss of polarity

15. MOLECULAR GENETIC PROGRESSION FROM PANIN TO
INVASIVE DUCTAL ADENOCARCINOMA.

16. PERIAMPULLARY CARCINOMA
 Adenocarcinomas of the
 Head of the pancreas
 Ampulla of Vater ,
 Distal bile duct (cholangiocarcinoma),
 Duodenum .
 Less commonly, acinar cell carcinomas or
pancreatic endocrine neoplasms occur in the
periampullary region of the pancreas

17. CLINICAL PRESENTATION

18. CARCINOMA BODY AND TAIL
 Late presentation
 Pain and weight loss are more common
 Rare
 Poor prognosis

19. SIGNS
 A palpable distended gallbladder (Courvoisier’s law)
 Left supraclavicular node (Virchow’s node & Troisier’s
sign )
 Periumbilical lymphadenopathy may be palpable
(Sister Mary Joseph’s node).
 Peritoneal dissemination and perirectal tumor
involvement may be palpable via digital rectal
examination (Blumer’s shelf)
 Migratory suprficial thrombophlebitis (Trousseau ‘s sign)

20. LABORATORY EVALUATION
 Hepatic function evaluation
 Coagulation profile
 Nutritional assessment.
 Tumor markers : CEA, CA19-9
 CA19-9
Most sensitive most reliable tumor marker
for pretreatment evaluation and post-
treatment surveillance

21. IMAGING STUDIES
Ultrasound abdomen
Initial ivestigation
Multiphase Multidetector CT
- The imaging study of choice
- Three-phase (noncontrast, arterial,
and portal venous) CT scan with 3-
mm slices and coronal and 3 D
reconstruction
- Extension to SMA, Celiac axis, SMV-PV complex
and contiguous structures can be determined
- Metastasis can be asessed
- Resectability can be predicted

22. US is often the initial test in symptomatic patients.
US is used for diagnosis rather than staging, although liver metastasis and
ascites may be seen.
Ultrasound
normal anatomy

23. CT Findings
Axial CT image shows stage
T1 pancreatic ductal
adenocarcinoma
Drawing shows T1 tumor, which is
defined as being equal to or smaller
than 2 cm in maximum diameter and
confined to pancreas, and T2 tumor,
larger than 2 cm and confined to
pancreas

24. CT Findings
Drawing shows T3 tumor, defined as
tumor that may extend beyond
pancreas but without involvement of
celiac axis or superior mesenteric
artery.
Contrast-enhanced axial CT image shows T3 tumor that
has involved common bile duct, requiring a stent, and that
extends medially beyond confines of pancreatic head.
Tumor is separated from superior mesenteric vein (long
arrow) and superior mesenteric artery (short arrow) by fat
plane (type A relationship). Note that tumor involves
duodenum (arrowhead).

25. CT Findings
Drawing shows T4 tumor, defined as
primary tumor involving either
superior mesenteric artery or celiac
axis.
Contrast-enhanced axial CT image shows
pancreatic tumor (white arrows) engulfing
celiac axis. Short black arrow = splenic
artery, long black arrow = common
hepatic artery.

26. Endoscopic US
To provide tissue diagnosis of suspected tumors through FNA prior to
initiating systemic therapy.
Beneficial for identifying small tumors smaller than 2 cm
A 2.5cm round, hypoechoic
tumor is identified in the the
region of the genu. The
superior mesenteric vein can
be seen separate from the
tumor.
Invasion of the dilated CBD
by a large irregular
hypoechoic tumor located in
the head of pancreas.
A large hypoechoic tumor is seen to
invade the portal vein (arrow), with
loss of tumor-vessel interface and
tumor extension into vessel lumen.
The dilated CBD contains echogenic
sludge.

27. MRI Findings
The role of MRI in pancreatic cancer has been less well studied than the role of
CT scanning. It does not appear to be superior to spiral CT scanning.
The ability of MRI to demonstrate pancreatic adenocarcinoma largely depends on
the demonstration of deformity of the gland, as reflected in its size, shape, contour,
and signal intensity characteristics.
Thin-section helical CT image obtained during
pancreatic phase reveals large pancreatic
tumor with tumor surrounding celiac trunk and
hepatic artery.
Extent of vascular encasement is better
depicted by CT scan than by MR images.
T1 contT1

28. MRI Findings
Transverse T1-weighted fat-
suppressed image shows
verified adenocarcinoma of
the pancreatic head
Adenocarcinoma was visible
as a low-signal-intensity
tumor.
The normal pancreas is of
low signal intensity on T1-
weighted images and of
intermediate signal on T2-
weighted images, with a
variable amount of fat in the
gland parenchyma.

29. MRCP
Assessment of luminal pancreatobiliary anatomy
Usefull for cystic lesions of the pancreas
ERCP
- To perform a biopsy and palliate
jaundice (biliary stenting)
Signs
Abrupt block
PD encasement
Dubble duct sign
Scrambled egg appearance

30. ERCP has a sensitivity of 95% and a
specificity of 85% for pancreatic
malignancy.
Most pancreatic carcinomas arise from
the ductal epithelium and produce
complete or partial ductal obstruction.
ERCP image
shows dilated
biliary tree and
obstruction of
common bile
duct associated
with tumor in
pancreatic
head.
Endoscopic retrograde cholangiopancreatography (ERCP)

31. ERCP image shows
slight narrowing of
pancreatic duct and
ductal dilatation.
Sphincterotomy was
performed, and
pancreatic stent was
placed.
Contrast-enhanced CT
scan fails to depict
tumor (arrow) around
stent in dilated common
bile duct.
Unenhanced T1-weighted MR
image shows inhomogeneity of
pancreatic head, but does not
show tumor.
Compared with other modalities, MRI appears to be more valuable for staging the
extent and spread of pancreatic carcinoma than for tumor detection of lesions
smaller than 2 cm.

32. Magnetic resonance cholangiopancreatography (MRCP)
MRCP is as sensitive as ERCP and may prevent inappropriate explorations of
the pancreatic and bile ducts in patients with suspected pancreatic carcinoma in
whom interventional endoscopic therapy is unlikely
Coronal image from MRCP
shows double-duct sign
caused by obstruction by
tumor.
Dilated common bile duct and
dilated pancreatic duct are
seen proximal to abrupt
cutoff.

33. Magnetic resonance cholangiopancreatography (MRCP)
MR pancreatogram reveals a dilated
pancreatic duct proximal to the
obstructing pancreatic head mass.
ERCP helps confirm the dilatation of the
pancreatic duct in the body and the distal
stricture.

34. MRI Findings
Coronal oblique MRCP demonstrates
pancreatic duct obstruction in the head
with proximal dilatation of both pancreatic
duct (PD) and common bile duct (CBD),
which is referred to as the double duct
sign.
Coronal MR angiogram in the venous phase
shows vascular infiltration of the portal vein
and venous confluens. Note the consecutive
mesenteric collateral formation.

35. >The medial margin of the
descending duodenum may be pulled
medially at the level of the ampulla,
forming a reversed-3 appearance.
This is known as Frostberg 3 sign.
>Rose thorn appearance
Duodenal invasion at
the level of papilla major
demonstrated by upper
GI endoscopy

36. Upper GI barium studies may
reveal an extrinsic impression of
the mass on the posteroinferior
aspect of the antrum of the
stomach, widened C loop of
duodenum
This is known as antral pad
sign”.

37. Percutaneous transhepatic cholangiogram(PTC)
>Percutaneous
transhepatic
cholangiogram showing a
catheter in a dilated
common bile duct with an
abrupt, irregular
stricture at the lower
end, indicative of a
pancreatic cancer
>Not used routinely due
to other less invasive
imaging modalities

38. STAGING

40.  Following CT imaging, patients are classified into resectable,
borderline resectable, or unresectable.
 Resectable tumors -
 Localized to the pancreas, with no evidence of SMV or portal
vein involvement and a preserved fat plane
 Borderline resectable
 (1) severe unilateral or bilateral SMV-portal impingement;
 (2) less than 180-degree tumor abutment on the SMA
 (3) abutment or encasement of hepatic artery, if reconstructible
 (4) SMV occlusion, if of a short segment, and reconstructible.
 Unresectable tumors -
 Those that exhibit metastasis, including lymph node metastasis
outside the field of resection, ascites, or vascular involvement

42. STAGING LAPROSCOPY
Indications
 Large tumors (>3 cm)
 Significantly elevated CA19-9 level (>100 U/mL)
 Uncertain findings on CT
 Body or tail tumors

43. PREOPERATIVE PREPARATION
 Correction of anemia
 Replenishment of glycogen store
 Correction of dehydration
 Injection of vitamin K
 Adequate IV fluids and mannitol to ensure
adequate diuresis
 Broad spctrum antibiotics 1-2 days prior
 Enteral or parenteral nutrition
 Pulmonary physiotherapy
 Preoperative biliary drainage – contraversial

44. TREATMENT
Head of the pancreas
> Pancreaticoduodenectomy is the
procedure of choice.
(Either Wipple’s or Traverso and Longmire)
> Laparoscopic Pancreaticoduodenectomy
Body and Tail of the Pancreas
Distal pancreatectomy and en
bloc splenectomy

45. PANCREATICODUODENECTOMY – 6 STEPS
1. A Cattell-Braasch maneuver
2. Extended Kocher maneuver
3. Portal dissection
4. Transect stomech
5. Transect jejunum
6. Transect pancreas and
complete retroperitoneal
dissection

46. PANCREATICODUODENECTOMY-
RECONSTRUCTIONS
1. End to side PJ
2. End to side HJ
3. End to side GJ
( antecolic)

47. STRUCTURES REMOVED
 Distal stomach
 Gall bladder
 CBD
 Head of Pancreas
 Duodenum
 Proximal jejunum
 Regional lymphatics

49. ADJUVANT THERAPY

50. PALLIATIVE THERAPY
 Biliary Obstruction
 ERCP with metal stent placement
 Surgical biliary-enteric bypass (Roux-en-Y
hepaticojejunostomy)

51. Gastric Outlet Obstruction
 Endoscopic luminal stenting
 Double bypass consisting of a Roux-en-Y
hepaticojejunostomy and gastrojejunostomy
Pain Relief
 NSAIDS or long acting opioids
 Celiac nerve block
 Neurolysis

52. RECENT ADVANCES
 Immunotherapy
 Allogenic tumor cell vaccine under phase 2 trial
 Angiogenesis inhibitors
 Becacizumab (anti VEGF) with gemcitabine under
phase 3 trial
 K ras inhibitors
 Tipifarnib ( farnesyl transferase inhibitor)- studied and
showed no improvement in outcome
 EGFR inhibitors
 EKB 569 and erlotinib
 Erlotinib approved for treatment of unresectable
cancer( study by NCI of Canada)

53. CYSTIC NEOPLASMS OF THE PANCREAS

54. CYSTIC NEOPLASMS OF THE PANCREAS
 Second most common exocrine pancreatic
neoplasm next to adenocarcinoma.
 Types
Mucinous
Serous
IPMN

55. MUCINOUS CYSTIC NEOPLASM
 Most common cystic neoplasms of the
pancreas.
 Young women, Men are rarely affected.
 Fifth decade.
 Typically found in the body and tail of the
pancreas

56.  Contain mucin-producing epithelium
 Presence of mucin-rich cells and ovarian-like stroma
 CT scan –
 solitary , fine septations, surrounded by a rim of calcification
 Predictors of malignancy
 Eggshell calcification,
 larger tumor size
 mural nodule on cross-sectional imaging

57.  EUS and cyst fluid analyses demonstrate
mucin-rich aspirate and
high CEA levels (>192 ng/mL)
low levels of amylase
 Standard treatment - Pancreatic resection

58. SEROUS CYSTIC NEOPLASM
 Predilection for the head of the pancreas
 Vague abdominal pain and less frequently with weight
loss and obstructive jaundice
 Large , wellcircumscribed masses.
 Microscopy - multiloculated, glycogen-rich small cysts.

59.  CT Scan-
Central calcification, with radiating septa giving the
sunburst appearance (10-20%)
 Large (>4 cm) or rapidly growing, symptomatic lesion
 Treatment is Resection
 Small (<4 cm) , asyptomatic can be observed.

60. INTRADUCTAL PAPILLARY MUCINOUS
NEOPLASM
 First described by Ohashi
 Several names—
Mucin secreting carcinoma
Villous adenoma of the duct of Wirsung
Diffuse intraductal papillary adenocarcinoma
Intraductal cystadenoma
Mucinous duct ectasia, and
Intraductal papillary mucinous tumor.

61.  Sixth to seventh decade of life.
 Commonly in head region.
 Wide spectrum
ranging from benign adenoma, borderline, carcinoma in
situ, and invasive adenocarcinoma.
 Types-
Side branch or branch duct IPMN,
Main duct IPMNs,
Mixed -type IPMNs

62. SIDE BRANCH IPMN
 Involves dilation of the pancreatic duct side branches
that communicate with but do not involve the main
pancreatic duct.
 Focal (involving a single side branch) or multifocal
 Risk of malignant transformation directly related to the
size of the cystic dilation
 Others - mural nodules or general thickening of the cyst
wall symptoms like jaundice, pain, and diabetes

63.  Small (<1 cm) IPMNs:-
Surveillance with CT or MRI in 1 year
 Asymptomatic cysts ,1 -3 cm:-
Imaging at 6 months followed by
annual evaluation if no change in size.
 Cysts larger than 3 cm:-
Surgical resection (Partial
pancreatectomy)
 Risk of invasive malignancy- 10% to 15%

65. MAIN DUCT IPMN
 Abnormal cystic dilation of the main pancreatic duct with
columnar metaplasia
 Endoscopy –
thick mucinous secretions oozing from patulous papilla
 May be focal or diffuse
 30% to 50% risk of harboring invasive pancreatic cancer at the
time of presentation.

66.  Treatment- Surgical resection
(Risk of malignant transforamtion)
 Predictors of malignancy-
Jaundice,
Elevated serum alkaline phosphatase
Mural nodules,
Diabetes
Main pancreatic duct diameter of 7 mm
 Elevation of the CEA level is not predictive of invasive
malignancy

67.  CT scans –
dilated main pancreatic duct, cysts of varying sizes,
and possibly mural nodules.
 MRCP-
localization of mural nodules and pretreatment
classification of suspected side branch or main duct
types of IPMN
 Aspirated fluid is typically viscous and clear, contains
mucin and columnar mucinous cells with variable atypia
 Elevated CEA level (>192 ng/mL; log scale)

68. MIXED-TYPE IPMN
 Side branch IPMN that has extended to involve the
main pancreatic duct
 Risk of invasive malignancy at the time of
presentation (30% to 50%)
 Surgical resection is indicated for the treatment

70. NEOPLASMS OF ENDOCRINE PANCREAS

71.  Paul Langerhans medical student, in
1869
pale staining cells within the
pancreas
 Alpha (A) – Glucagon
 Beta (B) – Insulin and amylin
 Delta (D) – Somatostatin and
vasoactive intestinal
peptide (VIP)
 F cells – Pancreatic
polypeptide (PP)
 Gastrin-producing cells are
normally present in the fetal
pancreas only.

72. ISLET CELL TUMORS
 Very rare
 Most are benign and
nonfunctional.
 The incidence of malignancy varies from 10% in
insulinomas to almost 100% in glucagonomas.
 Insulinomas, glucagonomas, and VIPomas arise
from the pancreas, whereas most gastrinomas
occur in the duodenum.

73. MOLECULAR GENETICS
 Distinct from that of pancreatic adenocarcinoma.
 Transcriptional silencing is believed to play a
role in islet cell tumorigenesis.
 Loss of heterozygosity (LOH) 11q is common in
functional pancreatic endocrine tumors
 LOH 6q is associated with the development of
nonfunctional tumors.

74. INSULINOMA
 Most common functioning tumor
 Equal distribution in the head, body, and tail.
 97% are located in the pancreas, remaining 3% are
located in the duodenum, splenic hilum, or gastrocolic
ligament
 Whipple’s triad
 fasting-induced neuroglyopenic symptoms of hypoglycemia
 low blood glucose levels (40 to 50 mg/dL),
 relief of symptoms after the administration of glucose.

75.  72 hour fast test
 High level of serum
insulin (>5 µU/mL)
 Insulin-to-glucose ratio
higher than 0.3
 C peptide levels higher
than 1.2 µg/mL
 CECT or MRI
 Hyperattenuating
because of their rich
vascular supply

76. GASTRINOMA
 Second most common functional pancreatic
endocrine tumor
 Cell of origin is not clear, because the normal adult
pancreas has no gastrin-producing cells.
 More common in men
 Produce Zollinger-Ellison syndrome (ZES)
 Hypergastrinemia , subsequent severe peptic
ulceration, severe diarrhea.

77.  Abdominal pain (75%)
 Diarrhea releived by nasogastric
aspiration
 Symptoms of GERD
 Gastrinoma triangle (90%)
 The cystic duct CBD junction
 The jn between the second and
third portions of the duodenum
 Junction between the neck and
body of the pancreas

78.  Presence of hypergastrinemia in the presence of
increased secretion of gastric acid.
 An elevated serum gastrin level coupled with a pH
lower than 2 in the gastric aspirate
 Fasting levels of gastrin. higher than 1000 pg/mL
(upper limit of normal of 100 pg/mL)
 An increase of more than 200 pg/mL in the gastrin
value after administration of secretin

79. VIPOMAS
 Release high levels of VIP
 Verner-Morrison syndrome
 Also known as WDHA syndrome (watery diarrhea,
hypokalemia, achlorhydria) or pancreatic cholera.
 Solitory , larger than 3 cm ; 75% body and tail
 Hypokalemia, hypomagnesemia, hypo or achlorhydria,
hypercalcemia.

80. GLUCAGONOMAS
 Very rare
 Tend to be larger, averaging 5 to 10 cm in size
 Most are malignant
 Almost always arise in the pancreas and 65% to 75%
are found in the body or tail.
 A fasting glucagon level higher than 50 pmol/L is
considered diagnostic.
 The glucagonoma syndrome:
 4Ds: diabetes, dermatitis, deep vein thrombosis, and
depression

82. SOMATOSTATINOMAS
 Usually solitary and 85% are larger than 2 cm.
 Mostly at head of pancreas
 Ninety percent are malignant
 Steatorrhea , diabetes mellitus, hypochlorhydria, and
gallstones
 Fasting somatostatin level higher than 14 mol/liter
 Associated with von Recklinghausen’s disease and
pheochromocytomas

83. NONFUNCTIONAL NEUROENDOCRINE TUMORS
 Defined as a pancreatic tumor of endocrine origin,
with no definable hormonal syndrome.
 Late in seeking help hence most tumors are
malignant and metastasized at the time of
presentation
 Identified by positive immunostaining for
chromogranin A or synaptophysin.

84. LOCALIZATION
 Cross -sectional imaging with CT or MRI
 first step in localization.
 sensitivity is 71% to 82% and is directly related to
the size of the tumor.
 vascular blush in the arterial phase is critical
 lesions smaller than 1cm cannot be identified.
 Endoscopic ultrasound (EUS)
 Overall sensitivity of 93%
 Greater sensitivity when compared with CT and MRI for
detecting tumors < 3 cm
 Allows for fine-needle aspiration (FNA) of tumors

85.  Somatostatin receptor scintigraphy (SRS)
 Not useful for insulinoma
 The sensitivity for SRS is over 80% for all pancreatic
endocrine tumors excluding insulinomas
 It has an overall sensitivity of 80% to 100% and
specificity higher than 90% for gastrinomas.
 SRS may not show the exact location of a tumor
indicates its vicinity within a few centimeters
 Angiographic techniques and portal venous
sampling (sensitivity higher than 90%)
 Blind exploration with intraoperative ultrasound

88. TREATMENT
 The treatment of endocrine tumors is surgical.
(pancreatic head resection, distal pancreatic resection, or
enucleation.)
 Performed by open or laparoscopic approaches
 Insulinoma – Enucleation
 Metastatic _ Streptozotocin, with or without 5-fluorouracil
 Gastrinoma
 Small well encapsulated _ Enucleation
 Large unencapsulated _ Require segmental resection,
including distal pancreatectomy or
pancreaticoduodenectomy.
 Radiation therapy and chemotherapy are ineffective.

89.  VIPomas, glucagonomas, somatostatinomas, and
nonfunctional pancreatic endocrine tumors-
Resection is the treatment of choice for and
remains the only curative option.
 Dacarbazine is uniquely effective against glucagonoma.

90. THANK YOU