The Pancreas |Surgery|

Dr. Ma. Dulce Consuerga REGIONS OF THE PANCREAS

Source: Schwartz’s Principles of Surgery 11th ed | Dr. Consuerga’s • Four regions:
lecture o Head
o Neck
Outline o Body
• Anatomy o Tail
• Histology and Physiology
• Acute Pancreatitis
• Chronic Pancreatitis
• Pancreatic Neoplasm
o Neoplasm of the Endocrine Pancreas
o Neoplasm of the Exocrine Pancreas
o PCN
o Lymphoma
• Congenital Abnormality

ANATOMY
• Situated deep in the center of the abdomen,
surrounded by important structures and major BV
• Minor trauma to the pancreas can result in the release
of pancreatic enzymes and cause life-threatening
pancreatitis.
• The pancreas is a retroperitoneal organ that lies in an
oblique position, sloping upward from the C-loop of the
duodenum to the splenic hilum
• Dimensions of the pancreas (adult)
o Weight – 75 to 100 g
o Length – 15 to 20 cm
• Situated so deeply in the abdomen and is sealed in the
retroperitoneum → poorly localized and sometimes ill-
defined nature with which pancreatic pathology
presents
• Retroperitoneal location, thus pain →characterized as
penetrating through to the back.
• The head of the pancreas
o Nestled in the C-loop of the duodenum
o Posterior to the transverse mesocolon
o Just posterior to the head, lie the vena cava,
the right renal artery and both renal veins
• The neck of the pancreas
o Lies directly anterior to the portal vein
o At the inferior border of the neck of the
pancreas, the SMV joins the splenic vein and
then continues toward the porta hepatis as
the portal vein.
o The IMV often joins the splenic vein near its
junction with the portal vein. Sometimes, the
IMV joins the SMV or merges with the superior
mesenteric portal venous junction to form a
trifurcation
o The SMA lies parallel to and just to the left of
the SMV
o The uncinate process and the head of the
pancreas wrap around the right side of the
portal vein and end posteriorly near the space
between the SMV and the SMA
o Venous branches draining the pancreatic
head and uncinate process enter along the
right lateral and posterior sides of the portal
vein.
o There are no anterior venous tributaries.
o A plane can usually be developed between
the neck of the pancreas and the portal and
the SMV during pancreatic resection, unless
the tumor is invading the vein anteriorly
o The common bile duct runs in a deep groove
on the posterior aspect of the pancreatic
head until it passes through the pancreatic
parenchyma to join the main pancreatic duct
at the ampulla of Vater.
• The body and tail of the pancreas
o Lie anterior to the splenic artery and vein
o The splenic vein runs in a groove on the back
of the pancreas and is fed by multiple fragile
venous branches from the pancreatic
parenchyma. These branches must be divided
to perform a spleen-sparing distal
pancreatectomy.
o The splenic artery runs parallel and just superior
to the vein along the posterior superior edge
of the body and tail of the pancreas
o The splenic artery is often tortuous
o Anterior surface of the body of the pancreas:
covered by peritoneum
o Once the gastrocolic omentum is divided, the
body and tail of the pancreas can be seen

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The Pancreas
along the floor of the lesser sac, just posterior
to the stomach.
o Pancreatic pseudocysts commonly develop in
this area, and the posterior aspect of the
stomach can form the anterior wall of the
pseudocyst, allowing drainage into the
stomach.
o The base of the transverse mesocolon
attaches to the inferior margin of the body
and tail of the pancreas.
o The transverse mesocolon often forms the
inferior wall of pancreatic pseudocysts or
inflammatory processes, allowing surgical
drainage through the transverse mesocolon.
o The body of the pancreas is anterior to the
aorta at the origin of the SMA.
o The neck of the pancreas is anterior to the
vertebral body of L1 and L2
o Blunt AP trauma can compress the neck of the
pancreas against the spine, causing
parenchymal and, sometimes, ductal injury.
o The neck divides the pancreas into
approximately two equal halves.
• The tail of the pancreas
o Small portion anterior to the left kidney
o Nestled in the hilum of the spleen near the
splenic flexure of the left colon.
o Awareness of these anatomic relationships is
important to avoid injury to the pancreatic tail
during left colectomy or splenectomy.
|Surgery|
Variations
o In 1/3 of patients, the bile duct and the
pancreatic duct remain distinct to the end of
the papilla
o In another 1/3 the two ducts merge at the end
of the papilla
o In another 1/3, a true common channel is
present for several millimeters
• Commonly, the duct from the dorsal anlage, the duct of
Santorini, persists as the lesser pancreatic duct, and
sometimes drains directly into the duodenum through
the lesser papilla just proximal to the major papilla.
• In approximately 30% of patients, the duct of Santorini
ends as a blind accessory duct and does not empty
into the duodenum.
• Pancreas divisum
o 10%
o Normal anatomical variant
o The ducts of Wirsung and Santorini fail to fuse
o Majority of the pancreas drains through the
duct of Santorini and the lesser papilla, while
the inferior portion of the pancreatic head
and uncinate process drains through the duct
of Wirsung and major papilla.
o In a minority of these patients, the minor
papilla can be inadequate to handle the flow
of pancreatic juices from the majority of the
gland.
o Relative outflow obstruction can result in
pancreatitis and is sometimes treated by
sphincteroplasty of the minor papilla.

PANCREATIC DUCT ANATOMY

• The pancreas is formed by the fusion of a ventral and
dorsal bud
• With gut rotation, the ventral anlage rotates to the right
and around the posterior side of the duodenum to fuse
with the dorsal bud.

• Duct from the ventral bud (smaller)

o Arises from the hepatic diverticulum
o Becomes the duct of Wirsung
o After gut rotation, it becomes the inferior The Main Pancreatic Duct
portion of the pancreatic head and the
uncinate process
• Duct from the dorsal bud
o Arises from the duodenum
o Drains directly to the duodenum
o Becomes the duct of Santorini
o After gut rotation, it becomes the body and
tail of the pancreas

• The ducts from each bud usually fuse together in the

pancreatic head, such that most of the pancreas drains
through the duct or Wirsung, or the main pancreatic
duct, into the common channel formed form the bile
duct and the pancreatic duct
• The length of the common channel varies
• 2-3 mm in diameter
• Runs midway between the superior and inferior borders
of the pancreas, usually closer to the posterior surface

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The Pancreas |Surgery|
• Pressure inside the pancreatic duct is about 2x that in Variations in the arterial anatomy (1 out of 5 patients)
the CBD → prevent reflux of bile into the pancreatic
duct
• The main pancreatic duct joins with the CBD and
empties at the ampulla of Vater or major papilla
located on the medial aspect of the second portion of
the duodenum
• Sphincter of Oddi – muscle fibers around the ampulla →
controls the flow of pancreatic and biliary secretions
into the duodenum.
o Contraction and relaxation are regulated by
complex neural and hormonal factors
• When the accessory pancreatic duct or lesser duct
drains into the duodenum, a lesser papilla can be
• The right hepatic artery, common hepatic artery, or
identified approximately 2 cm proximal to the ampulla
gastroduodenal arteries can arise from the SMA
of Vater.
• In 15% to 20% of patients, the right hepatic artery will
arise from the SMA and travel upwards toward the liver
VASCULAR AND LYMPHATIC ANATOMY
along the posterior aspect of the head of the pancreas
• Blood supply comes from multiple branches from the
→ replaced right hepatic artery
celiac and SMA
o It is important to look for this variation pre-op to
• The common hepatic artery gives rise to the
avoid injury during surgeries
gastroduodenal artery before continuing toward the
• The body and tail of the pancreas → supplied by
porta hepatis as the proper hepatic artery.
multiple branches of the splenic artery.
• The right gastric artery branches off the gastroduodenal
o The splenic artery arises from the celiac trunk
artery just superior to the duodenum.
and travels along the posterior-superior border
• The gastroduodenal artery → supplies the superior
of the body and tail of the pancreas toward
pancreaticoduodenal artery → divides into the anterior
the spleen.
and superior pancreaticoduodenal arteries → travel
• The inferior pancreatic artery usually arises from the SMA
inferiorly within the pancreaticoduodenal groove giving
and runs to the left along the inferior border of the body
off small branches to the duodenum and the head of
and tail of the pancreas, parallel to the splenic artery.
the pancreas
• Dorsal, great, and caudal pancreatic arteries (from
• The superior pancreaticoduodenal arteries join the
medial to lateral order) → run perpendicular to the long
inferior pancreaticoduodenal arteries to complete the
axis of the pancreatic body and tail and connect the
arcade.
splenic artery and inferior pancreatic artery. These
• The inferior pancreaticoduodenal artery is a branch off
arteries form arcades within the body and tail of the
the SMA
pancreas and account for the rich blood supply of the
o It is impossible to resect the head of the
organ.
pancreas without devascularizing the
duodenum, unless a rim of pancreas
VENOUS
containing the pancreaticoduodenal arcade
• The venous drainage of the pancreas follows a pattern
is preserved.
like that of the arterial supply.
o The inferior pancreaticoduodenal artery needs
to be controlled when dissecting the head of
the pancreas off the SMA during a Whipple
procedure.
• The gastroduodenal artery travels inferiorly anterior to
the neck of the pancreas and posterior to the duodenal
bulb
o A posterior ulcer in the duodenal bulb can
erode into the gastroduodenal artery
o At the inferior border, the gastroduodenal
artery gives rise to the right gastroepiploic
artery → then continues to join the inferior
pancreaticoduodenal artery

• The veins are usually superficial to the arteries within the

parenchyma of the pancreas.
• There is an anterior and posterior venous arcade within
the head of the pancreas.
• Typically, the superior vein drains directly into the portal
vein just above the neck of the pancreas and is often a
larger branch of the portal vein → divided during
Whipple procedure.
• The posterior inferior arcade → drains directly into the
IMV at the inferior border of the neck of the pancreas →
also divided during a Whipple procedure.
• The anterior inferior pancreaticoduodenal vein joins the
right gastroepiploic vein and the middle colic vein to
form a common venous trunk → enters the SMV

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The Pancreas
• Traction on the transverse colon during colectomy can
tear these fragile veins, which then retract into the
parenchyma of the pancreas, making control tedious.
• There also are numerous small venous branches coming
from the pancreatic parenchyma directly into the
lateral and posterior aspect of the portal vein.
• Venous return from the body and tail of the pancreas
drains into the splenic vein.
LYMPHATICS
• The lymphatic drainage from the pancreas is diffuse
and widespread
• The profuse network of lymphatic vessels and lymph
nodes draining the pancreas provides egress to tumor
cells arising from the pancreas
• This diffuse lymphatic drainage contributes to the fact
that pancreatic cancer often presents with positive
lymph nodes and a high incidence of local recurrence
after resection
• Lymph nodes – palpated along the distal bile duct and
posterior aspect of the head of the pancreas in the
pancreaticoduodenal groove, where the mesenteric
vein passes under the neck of the pancreas, along the
inferior border of the body, at the celiac axis and along
the hepatic artery ascending into the porta hepatis,
and along the splenic artery and vein.
• 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 often
metastasize to these nodes and lymph nodes along the
splenic vein and in the hilum of the spleen.
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|Surgery|
NEUROANATOMY
• Innervated by the sympathetic and parasympathetic
nervous system
• Acinar cells (exocrine secretion, islet cells (endocrine
secretion) and the islet vasculature → innervated by
both systems
• Parasympathetic → stimulates endocrine and exocrine
secretion
• Sympathetic → inhibits secretion
• The pancreas is also innervated by neurons that secrete
amines and peptides such as: somatostatin, VIP,
calcitonin gene-related peptide (CGRP) and galanin
o Exact role uncertain
o They appear to affect both exocrine and
endocrine function
• The pancreas also has a rich supply of afferent sensory
fibers → intense pain associated with advanced
pancreatic cancer, as well as acute and chronic
pancreatitis. These somatic fibers travel superiorly to the
celiac ganglia
• Interruption of these somatic fibers with a celiac plexus
block can stop transmission of pain sensation.
HISTOLOGY AND PHYSIOLOGY
• Pancreatic mass
o 85% Exocrine Pancreas
o 10% Extracellular Matrix
o 4% Vessels and Duct
o 2% Endocrine Pancreas
• The endocrine and exocrine pancreas are sometimes
thought of as functionally separate, but these different
components of the organ are coordinated to allow an
elegant regulatory feedback system for digestive
enzyme and hormone secretion.
• This complex system regulates the type of digestion, its
rate, and the processing and distribution of absorbed
nutrients.
• This coordination is facilitated by the physical
approximation of the islets and the exocrine pancreas,
the presence of specific islet hormone receptors on the
plasma membranes of pancreatic acinar cells, and the
existence of an islet-acinar portal blood system.
• Although patients can live without a pancreas when
insulin and digestive enzyme replacement are
administered, the loss of this islet-acinar coordination
leads to impairments in digestive function.
• The remaining normal pancreas tissue to prevent
pancreatic insufficiency = 20%
EXOCRINE PANCREAS
• Secretes approximately 500 to 800 mL per day of
colorless, odorless, alkaline, isosmotic pancreatic juice
• Pancreatic juice – combination of acinar cell and duct
cell secretion
4
The Pancreas
1-2 L/day
Clear, watery, alkaline (pH 8.0-8.3)
> 20 different digestive enz.
Isoosmotic to plasma
Principal cations : Na & K (~165 mmol/L)
Principal anions : bicarb & Cl
- secrete min : Cl high, bicarb low
- secrete max : Cl low, bicarb high active
transport
Passive exchange of intraductal bicarb for
interstitial Cl at larger pancreatic duct
Digestive enzyme are synthesized and stored in the pancreatic
acinar cells, and released in response to
CCK(cholecystokinin) and vagal cholinergic stimulation
• Proteolytic (trypsin, chymotrypsin, carboxypeptidase,
ribonuclease, deoxyribonuclease, and elastase)
• Lipolytic (lipase, colipase, phospholypase A2)
• Amylolytic (amylase)
Acinar cells
• Secrete
o Amylase
o Proteases
o Lipases
o Enzymes responsible for the digestion of all
three food types – CHO, CHON, fats
• Pyramid-shaped, with their apices facing the lumen of
the acinus.
• Near the apex of each cell are numerous enzyme-
containing zymogen granules that fuse with the apical
cell membrane
• Individual acinar cells secrete all types of enzymes.
• The ratio of the different enzymes released is adjusted to
the composition of digested food through nonparallel
regulation of secretion.
• Pancreatic amylase is secreted in its active form and
completes the digestive process already begun by
salivary amylase.
• Amylase is the only pancreatic enzyme secreted in its
active form
• Amylase hydrolyzes starch and glycogen to glucose,
maltose, maltotriose, and dextrins → these simple sugars
are transported across the brush border of the intestinal
epithelial cells by active transport mechanisms.
• Gastric hydrolysis of protein yields peptides that enter
the intestine and stimulate intestinal endocrine cells to
release cholecystokinin (CCK)-releasing peptide, CCK,
and secretin → stimulate the pancreas to secrete
enzymes and bicarbonate into the intestine.
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|Surgery|
• The proteolytic enzymes are secreted as proenzymes
that require activation
• Trypsinogen → converted by enterokinase (produced
by the duodenal mucosal cells) to its active form trypsin
→ activates other proteolytic enzymes
• Trypsin converts the other zymogens to active forms
• Trypsinogen activation is prevented by the presence of
inhibitors that are also secreted by the acinar cells.
• Inhibition of trypsinogen activation ensures that the
enzymes within the pancreas remain in an inactive
precursor state and are activated only within the
duodenum
• Pancreatic secretory trypsin inhibitor (PSTI) aka serine
protease inhibitor Kazal type 1 (SPINK1) → failure to
express a normal trypsinogen inhibitor – is a cause of
familial pancreatitis.
• Trypsinogen is expressed in several isoforms
• A missense mutation on the cationic trypsinogen, or
PRSS1 → premature, intrapancreatic activation of
trypsinogen → 2/3 of cases of hereditary pancreatitis
• Chymotrypsinogen → activated to form chymotrypsin.
• Elastase, carboxypeptidase A and B, and
phospholipase are also activated by trypsin.
• Trypsin, chymotrypsin, and elastase → cleave bonds
between amino acids within a target peptide chain,
and carboxypeptidase A and B cleave amino acids at
the end of peptide chains. Individual amino acids and
small dipeptides are then actively transported into the
intestinal epithelial cells
• Pancreatic lipase - secreted in an active form →
hydrolyzes triglycerides to 2-monoglyceride and fatty
acid.
• Colipase is also secreted by the pancreas and binds to
lipase, changing its molecular configuration and
increasing its activity.
• Phospholipase A2
o Secreted by the pancreas as a proenzyme
that becomes activated by trypsin
o Hydrolyzes phospholipids and, as with all
lipases, requires bile salts for its action
• Carboxylic ester hydrolase and cholesterol esterase
hydrolyze neutral lipid substrates like esters of
cholesterol, fat-soluble vitamins, and triglycerides.
• The hydrolyzed fat is then packaged into micelles for
transport into the intestinal epithelial cells, where the
fatty acids are reassembled and packaged inside
chylomicrons for transport through the lymphatic system
into the bloodstream
• The centroacinar and intercalated duct cells
o Secrete water and electrolytes present in the
pancreatic juice.
• Acinus - spherical unit; about 40 acinar cells
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The Pancreas |Surgery|

EXOCRINE PANCREATIC INSUFFICIENCY (EPI)

• M/c cause in humans: cystic fibrosis(1st), Shwachman-Diamond
Syndrome(2nd)
• fairly common in diabetes - both type 1 and type 2
• symptoms of malabsorption, malnutrition, vitamim deficiencies,
and weight loss or inability to gain weight in children and is
often associated with steatorrhea
• Treatment: Pancreatic Enzyme Products PEPs , such as
pancrelipase (mixture of three digestive enzymes, amylase,
protease (peptidase), and lipase)
• Tests
o Fecal fat (fat stain)
o Stool trypsin tests
o Trypsinogen (Immunoreactive trypsin)
• Centroacinar cells
o Elastase (in stool)
o Located near the center of the acinus • Non-laboratory tests
o Responsible for fluid and electrolyte secretion o ERCP
o These cells contain the enzyme carbonic o MRCP
anhydrase → needed for HCO3 secretion o Secretin test tube in duodenum : amount of certain
o Amount of HCO3 secreted varies with the enzymes and bicarbonate in the pancreatic
secretion
pancereatic secretory rate. Greater
concentrations of HCO3 secreted as the
pancreatic secretory rate increases
o Chloride secretion varies inversely with ENDOCRINE PANCREAS
bicarbonate secretion
o Sodium and potassium concentrations are
kept constant throughout the spectrum of • Islet of Langerhans
• 1-2% of pancreatic mass
secretory rates
• 20% of total pancreatic blood flow
• Secretin • Insulin: Beta-cell : muscle, liver, fat cells
o Released from cells in the duodenal mucosa in • Glucagon : alpha-cell
response to acidic chyme passing through the • Somatostatin : delta cell
pyloric into the duodenum. • Pancreatic polypeptide : PP cells
o Major stimulant of HCO3 secretion • Acini are exposed to higher conc. of the islet hormones than
o Buffers the acidic fluid entering the duodenum peripheral tissue
from the stomach
• CCK
o Also stimulates HCO3 secretion to a lesser
extent • ~1M islets of Langerhans in the normal adult pancreas
o Potentiates secretin-stimulated HCO3 o Vary in size from 40 to 900 μm
secretion o Larger islets – closer to major arterioles
• Gastric and acetylcholine o Smaller islets – embedded more deeply in the
o Stimulants of gastric secretion parenchyma of the pancreas
o Most islets contain 3000 to 4000 cells of 5 major
o Also weak stimulants of HCO3 secretion in the
types
pancreas
Cell Type Hormone
• Truncal vagotomy produces a myriad of complex
Alpha cells Glucagon
effects on the downstream digestive tract, but the sum
Beta cells Insulin
effect on the exocrine pancreas is a reduction in
Delta cells Somatostatin
bicarbonate and fluid secretion
Epsilon cells Ghrelin
• The endocrine pancreas also influences the adjacent
PP cells PP
exocrine pancreatic secretions
• Enzymes that inhibit exocrine secretion:
o Somatostatin
o Pancreatic polypeptide (PP)
o Glucagon
• The acinar cells release pancreatic enzymes from their
zymogen granules → lumen of the acinus → combine
with water and HCO3 secretions of the centroacinar
cells → the pancreatic juice then travels into the small
interacalcated ducts → interlobular ducts → cells in the
interlobular ducts contribute fluid and electrolytes to
adjust the final concentrations of the pancreatic fluid →
interlobular ducts join to form about 20 secondary ducts
→ empty into the main pancreatic duct.

• Destruction of the branching ductal tree from recurrent

inflammation, scarring, and deposition of stones in
chronic pancreatitis → destruction of the exocrine
pancreas and exocrine pancreatic insufficiency.

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The Pancreas |Surgery|
Insulin • Insulin deficiency (seen in type 1 and type 3c diabetes)
• The best-studied pancreatic hormone results in an overexpression or upregulation of insulin
• Proinsulin is made in the endoplasmic reticulum → receptors → causes an enhanced sensitivity to insulin in
transported to the Golgi complex, where it is packaged muscle and adipocytes → increases the risk of insulin-
into granules and the C-peptide is cleaved off. induced hypoglycemia
• There are two phases of insulin secretion. • Type 2 DM → downregulation of insulin receptors and
o First phase relative hyperinsulinemia, with resulting insulin
▪ Stored insulin is released resistance.
▪ This phase lasts 5 mins after a glucose • Pancreatogenic or type 3c diabetes (T3cDM) or
challenge maturity-onset diabetes of the young (MODY) →
o Second phase selected impairments of hepatic or peripheral insulin
▪ Longer, sustained release due to receptors
ongoing production of new insulin
• Beta-cell synthesis of insulin is regulated by:
o Plasma glucose levels
o Neural signals
o Pancreatic influence of other islet cells
• The diagnosis of diabetes is made by using oral and IV
glucose tolerance tests
• Oral glucose not only enters the bloodstream
o Stimulates the release of enteric hormones
such as
▪ Gastric inhibitory peptide (aka
glucose-dependent insulinotropic
polypeptide or GIP),
▪ Glucagon-like peptide-1 (GLP-1),
▪ CCK → augment the secretion of
insulin and are therefore referred to
as incretins.
Glucagon
o Oral glucose is a more vigorous stimulus to
• 29-AA, single-chain peptide
insulin secretion than IV glucose
• Promotes hepatic glycogenolysis and gluconeogenesis
• OGTT
and counteracts the effects of insulin through its
o Fasted overnight, and a basal glucose value is
hyperglycemic action
determined
• Glucose is the primary regulator of glucagon secretion,
▪ 40 g/m2 or 75 g of glucose is given
as it is with insulin → INHIBITORY EFFECT
orally over 10 mins
• Glucagon release is stimulated by hypoglycemia and
▪ Blood samples are taken q 30 min for
by the AA arginine and alanine
2h
• GLP-1 inhibits glucagon secretion in vivo
• Normal values and criteria for diabetes vary by age, but
• Insulin and Somatostatin inhibit glucagon secretion in a
essentially all values should be <200 mg/dL, and the
paracrine fashion within the islet
120-minute value should be <140 mg/dL.
• The same neural impulses that regulate insulin secretion
• Insulin secretion by the beta-cell is also influenced by
also regulate glucagon secretion – the two hormones
plasma levels of amino acids such as arginine, lysine,
work together in a balance of actions to maintain
leucine, and free fatty acids.
glucose levels.
• Cholinergic and alpha sympathetic fibers stimulate
Stimulates insulin release Inhibits insulin release glucagon release
Glucagon Somatostatin • Beta sympathetic fibers inhibit glucagon release
GIP Amylin • In pancreatogenic or type 3c diabetes, glucagon
GLP-1 Pancreastatin responsiveness to a fall in blood glucose is lost →
CCK Beta-sympathetic fibers increasing the risk for hypoglycemia
Cholinergic fibers
Alpha-sympathetic fibers Stimulates glucagon release Inhibits glucagon release
Hypoglycemia Glucose
• Insulin functions Arginine GLP-1
o Inhibit endogenous (hepatic) glucose Alanine Insulin
production and to facilitate glucose transport Cholinergic fibers Somatostatin
into cells → lowering plasma glucose levels. Alpha-sympathetic fibers Beta-sympathetic fibers
o Inhibits glycogenolysis
o Inhibits fatty acid breakdown Somatostatin
o Inhibits ketone formation
• Originally isolated from the hypothalamus, but now
o Stimulates protein synthesis known to have a wide anatomic distribution, not only in
• There is a considerable amount of functional reserve in neurons but also in the pancreas, gut, and other tissues
insulin secretory capacity.
• It is a highly conserved peptide hormone
• If the remaining portion of the pancreas is healthy, • Of fundamental importance in regulatory processes
about 80% of the pancreas can be resected without the throughout the body
patient becoming diabetic • One gene encodes for a common precursor that is
• In patients with chronic pancreatitis, or other conditions
differentially processed to generate tissue-specific
in which much of the gland is diseased, resection of a amounts of two bioactive products, somatostatin-14,
smaller fraction of the pancreas can result in and somatostatin-28.
pancreatogenic, or type 3c diabetes • These peptides inhibit endocrine and exocrine secretion
• Insulin receptors are dimeric, tyrosine kinase–containing
and affect neurotransmission, GI and biliary motility,
transmembrane proteins that are located on all cells.

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The Pancreas
intestinal absorption, vascular tone, and cell
proliferation
• Five different somatostatin receptors (SSTRs) have been
cloned and the biologic properties of each are
different.
• Hexapeptide and octapeptide analogues such as
octreotide bind only to SSTR2, SSTR3, and SSTR5 – these
analogues have a longer serum half-life and their potent
inhibitory effect has been used clinically to treat both
endocrine and exocrine disorders
• Octreotide → decrease fistula output and speed the
time it takes for enteric and pancreatic fistulas to close.
• Endocrine release of somatostatin occurs during a meal
Stimulates somatostatin release Inhibits somatostatin release
Intraluminal fat* Acetylcholine
Acidification of gastric and Cholinergic neurons
duodenal mucosa
Pancreatic polypeptide (PP)
• 36-amino-acid, straight chain peptide
• Discovered during the process of insulin purification
• Protein is the most potent eneteral stimulator of PP
release, closely followed by fat, whereas glucose has a
weaker effect
• Hypoglycemia, whether insulin induced or not, strongly
stimulates PP secretion through cholinergic stimulation
• Phenylalanine, tryptophan, and fatty acids in the
duodenum stimulate PP release, probably by inducing
CCK, GIP, and secretin release
• Vagal stimulation of the pancreas is the most important
regulator of PP secretion
o Vagotomy eliminates the rise in PP levels
usually seen after a meal
o Can be used as a test for the completeness of
a surgical vagotomy or for the presence of
diabetic autonomic neuropathy.
• PP has been shown to inhibit
o Choleresis (bile secretion)
o Gallbladder contraction
o Secretion by the exocrine pancreas
• PP most important role: glucose regulation – through its
regulation of hepatic insulin receptor gene expression
• Deficiency in PP secretion d/t proximal
pancreatectomy, severe chronic pancreatitis of cystic
fibrosis is assoc. w diminished hepatic insulin sensitivity
d/t reduced hepatic insulin receptor availability →
REVERSED BY PP ADMINISTRATION
Stimulates PP release
Protein* – most potent
Fats
Glucose – weak effect
Hypoglycemia through
cholinergic stimulation
Phenylalanine,
tryptophan, and
fatty acids in the duodenum
Ghrelin
• Epsilon cells
• Also present in the gastric fundus in large amounts
• Stimulates growth hormone secretion via GH-RH release
from the pituitary
• It is an orexigenic or appetite-stimulating
• Increased in obesity
• Block insulin effects on liver
• Inhibits the beta-cell response to incretin hormones and
glucose
• Ghrelin secretion from and within the islet may
modulate the responses of other islet cells to nutrient
and hormonal stimuli
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In addition to the five main peptides secreted by the pancreas,
there are other peptide products of the islet cells:
• Amylin
• Peptide YY (PYY)
• Pancreastatin
• Neuropeptides:
o VIP, galanin, and serotonin
Amylin or islet amyloid peptide (IAPP)
• 37-AA polypeptide
• Predominantly expressed by the pancreatic beta-cells
• Stored along with insulin in secretory granules
• Function: modulation or counter-regulation of insulin
secretion and function
Pancreastatin
• Inhibits insulin and possible somatostatin release
• Augments glucagon release
• Inhibits pancreatic exocrine secretion
Peptide YY (PYY)
• Structurally related to PP
• Initially found in hormone-secreting “L” cells of the small
intestine, where it colocalizes with GLP-1
• Recently, localized to the islets
• Regulate insulin secretion through an autocrine
mechanism
ISLET DISTRIBUTION
• Beta cells located in the central portion of each islet →
about 70% of the total islet cell mass
• The other cell types are located predominantly in the
periphery
• Delta cells 5%
• Alpha-cells 10%
• PP cells 15%
• Islet cells specialize in the secretion of predominantly
one hormone; but individual islet cells can secrete
multiple hormones
• Beta cells → secrete both insulin and amylin, which
counter regulates the action of insulin
• >20 diff hormones are secreted by the islets, exact
functions are very complex
• Beta and delta cells are evenly distributed throughout
the pancreas
• Islets in the head and uncinate process (ventral anlage)
→ higher % PP cells, fewer alpha cells
• Islets in the body and tail (dorsal anlage) → majority
alpha cells and a few PP cells
• Pancreatoduodenectomy removes 95% of the PP cells
in the pancreas → higher incidence of glucose
intolerance after a Whipple procedure compared to a
distal pancreatectomy with an equivalent amount of
tissue resected
• Chronic pancreatitis, which disproportionately affects
the pancreatic head → PP deficiency and
pancreatogenic diabetes.
• The relative preponderance of alpha cells in the body
and tail of the pancreas explains the typical location of
glucagonomas.
ACUTE PANCREATITIS
Definition, Incidence, and Epidemiology
• Inflammatory disorder of the pancreas characterized by
edema, and when severe, necrosis
• Can develop local and systemic complications
8
The Pancreas
• Ranges from a mild, self-limiting inflammation of the
pancreas to severe and critical disease characterized
by infected pancreatic necrosis, multiple organ failure
and a high mortality.
• Traditional view: acute pancreatitis completely resolves
with no morphological, functional, or symptomatic
sequelae.
• Necrotizing pancreatitis can leave significant scarring,
strictures, and impairment of exocrine and endocrine
pancreatic function.
• Acute pancreatitis is the most common inpatient
principal GI discharge diagnosis in the US, with an
increasing incidence and is associated with the highest
aggregate in patient costs
• About 300,000 case/yr in US
• 10-20% = severe
• About 4,000 Deaths/yr + more than $2billion cost
• Crude mortality rate 1 per 100,000 population
• 14th most common overall and the 9th most common
noncancer cause of GI deaths
• Worldwide incidence 5 to 80 per 100,000 population,
with the highest incidence recorded in Finland and US
• The incidence of acute pancreatitis also shows
significant variation related to the prevalence of
etiological factors and ethnicity.
• Smoking is an independent risk factor for acute
pancreatitis.
Etiology
• Many factors are causally r/t the onset of acute
pancreatitis
• Most common causes: gallstones and alcohol –
accounting for up to 80% of cases, but it is not
uncommon to diagnose acute pancreatitis in the
absence of these factors (“idiopathic acute
pancreatitis”)
• Median age varies with etiology
o Alcohol- and drug- induced pancreatitis → 3rd
or 4th decade
o Gallstone and trauma → 6th decade
• Gender difference: more related to etiology
o Males – alcohol
o Females – gallstones
Gallstones
• Evidence that passage of a gallstone is related to the
onset of acute pancreatitis comes from the
characteristic transient derangement of liver function
tests and the high retrieval rate of gallstones from feces
within 10 days of an attack of acute pancreatitis
compared with those without acute pancreatitis (88%
vs. 11%).
• Mechanism not clear
• Hypotheses:
o Common-Channel hypothesis
o Incompetent Sphincter of Oddi (after passing
GS)
o Pancreatic Duct blockage: Helminth, Tumor
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• When gallstones and other etiological factors cannot
be identified, there is still the possibility of finding
microlithiasis, seen as birefringent crystals, on bile
microscopy.
• Occult microlithiasis is probably responsible for up to half
of those with idiopathic acute pancreatitis
Alcohol
• At least 2yr drink, commonly
• Dx : Hx expose ethanol + absence of other cause
• Mechanism
o “Secretion with Blockage” Mechanism
o Increase Ductal Permeability → premature
activation of enzymes → causes damage to
parenchyma
o Improper enzyme leaking to surrounding tissue
→ d/t increase in the protein content of
pancreatic juice and the decrease in HCO3
levels and trypsin inhibitor concentration
o Dec Pancreatic Blood flow
• Alcohol ingestion – associated with acute pancreatitis
• Sustained alcohol ingestion – assoc. with recurrent
acute pancreatitis and dev’t of chronic pancreatitis in
susceptible individuals who have been drinking for more
than a decade
• The type of alcohol consumed is less important than the
amount consumed (100-150 grams/d) and the pattern
of drinking
• It is common for patients with alcohol-associated acute
pancreatitis to have a history of excess alcohol
consumption prior to the first attack.
Iatrogenic
• Acute pancreatitis can occur due to trauma to the
ducts or parenchyma after surgical procedures,
including:
o biopsy
o bile duct exploration
o distal gastrectomy
o splenectomy
• Any sugery that causes Low System Perfusion
o Cardiopulmonary bypass
o Cardiac transplant
o Hemorrhagic shock
o Major trauma
• ERCP (most common) 5-10%
o Direct Injury or Intraductal Hypertension
o 3rd most common identified etiological factor
o The risk of post-ERCP acute pancreatitis is
increased if the contrast agent is infused
repeatedly under high pressure by the
endoscopist and in patients with sphincter of
Oddi dysfunction.
• Recent evidence demonstrates that the risk can be
decreased with prophylactic rectal nonsteroidal drugs
→ better strategy than prophylactic pancreatic duct
stenting.
9
The Pancreas
Hereditary Pancreatitis
• AD disorder
• r/t mutations of the cationic trypsinogen gene (PRSS1)
→ premature activation of trypsinogen to trypsin and
causes abnormalities of ductal secretion → promote
acute pancreatitis
• Mutations in the SPINK1 protein → blocks the active
binding site of trypsin → predisposes to acute
pancreatitis
• Variations in penetration and phenotype are common,
and there are many other mutations that have been
implicated
• Mutant enzymes activated within acinar cells can
overwhelm the first line of defense – pancreatic
secretory trypsin inhibitor – and resist backup defenses
(e.g., proteolytic degradation, enzyme Y, and trypsin
itself) → allows activated mutant cationic trypsin to
trigger the entire zymogen activation cascade
Tumors
• 1-2% of Pancreatitis found Pancreatic carcinoma
o An episode of acute pancreatitis can be the
first clinical indicator.
• Periampullary Tumor
• Common in patients over 50 yo
• Mechanism :
o Blockage of secreted juice
• Cross-sectional imaging after the resolution of the acute
pancreatitis is required.
Hyperlipidemia
• Caused by hypertriglyceridemia but not by
hypercholesterolemia
• Serum triglycerides must rise above 1000 mg/dL
• Primary Hypertriglyceridemia
o Types I, IV, and V are associated with acute
pancreatitis
• Secondary Hypertriglyceridemia
o Alcohol
o Diabetes
o Pregnancy
o Drugs:
▪ Loop and thiazide diuretics,
▪ tamoxifen,
▪ retinoids,
▪ beta-blockers etc.
• Lipase is thought to liberate toxic FAs into the
pancreatic microcirculation → microcirculatory
impairment and ischemia.
• Dietary modifications and drug treatment are used to
lower triglycerides.
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Drugs
• Thiazide diuretics
• Furosemide
• Estrogen replacement therapy
• Steroid therapy in children
• Chemotherapy agents and anti-immune drugs
• Lipid-based drug or solutions, such as propofol
Miscellaneous Causes
• Hypercalcemia (both acute & chronic Pancreatitis)
o Hypersecretion & Calcified causing obstruction
• Ascaris Lumbricoides / Clonorchis sinensis
o Oriental Cholangitis , CHCA , PD obstruction
• Hereditary Pancreatitis :
o Mutation of Trypsinogen gene à Cationic
Trypsinogen (PRSS1)
• Pancreatic Divisum
• Azotemia
• Vasculitis
• Scorpion venom : surge of cholinergic n. effect
▪ (as same as Antiacetylcholinesterase
inhibitor agent)
• Idiopathic pancreatitis
Infection
• Mumps, Coxsackievirus , Mycoplasma pneumoniae
• Found from rising of Antibody titer in about 30% of Pt
with pancreatitis with No other cause
• No direct evidence that isolated from diseases of the
pancreas
PATHOPHYSIOLOGY
• Occurs in varying degrees of severity
• Determinants are multifactorial
• Prevalent belief: Activation of digestive zymogens inside
acinar cells → cause acinar cell injury
• Ultimate severity of the resulting pancreatitis may be
determined by the events that occur after acinar cell
injury.
o Inflammatory cell recruitment and activation
o Generation and release of cytokines and other
chemical mediators that cause systemic
inflammation and multiple organ
dysfunction/failure
10
The Pancreas
INTRAPANCREATIC EVENTS
SYSTEMIC EVENTS
PRECIPITATING EVENTS
• Chiari: pancreatitis was d/t premature, intrapancreatic
activation of digestive enzymes → resulting in “auto-
digestion” of the organ
• The role of trypsin activation in the pathophysiology of
acute pancreatitis has also been suggested by clinical
studies.
• Hereditary pancreatitis is associated with mutations that
lead to elevated intracellular trypsin activation and
activation of trypsinogen causes clinical pancreatitis.
• Under physiologic conditions, several protective
mechanisms have evolved to prevent autodigestion of
the pancreas by these enzymes
o Synthesis of enzymes as inactive precursors,
o Separation of the site of production, and
o Activation of the enzymes
o Presence of trypsin inhibitors
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• It is thought that acute pancreatitis occurs when these
protective mechanisms are overwhelmed with
erroneously activated enzymes → causing injury
• Intra-acinar activation of trypsinogen goes hand-in-
hand with inhibition of acinar secretion.
• Although intra-acinar events initiate acute pancreatitis,
events occurring subsequent to acinar cell injury
determine the severity of pancreatitis.
• Activated neutrophils are attracted and activated
• in the pancreas → releasing superoxide (the respiratory
burst) and proteolytic enzymes (cathepsins, elastase,
and collagenase) → further pancreatic injury.
• In addition, macrophages release cytokines (including
tumor necrosis factor-alpha (TNF-α) and interleukins (IL-
1, IL-2, IL-6, and IL-8) → mediate local and systemic
inflammation.
• Inflammatory mediators cause:
o Increased pancreatic vascular permeability →
hemorrhage, edema, microthrombi
• Fluid may collect in and around the pancreas
• Failure of the pancreatic microcirculation – feature of
more severe acute pancreatitis → results in pancreatic
hypoperfusion and necrosis.
• Interstitial edematous pancreatitis – acute inflammation
of the pancreatic parenchyma and peripancreatic
tissues, but with no recognizable necrosis
• Necrotizing pancreatitis – when necrosis is present →
pancreatic hypoperfusion with contrast
• The NFκB-dependent inflammatory pathway is an
important mechanism by which events occurring in the
pancreas can induce systemic inflammation
• Once activated, NFκB regulates synthesis of multiple
cytokines and chemokines → recruitment of various
inflammatory cells that then magnify and propagate
systemic inflammation
• The infiltrating neutrophils can also further augment the
pancreatic injury
• Organ failure can develop at any stage of acute
pancreatitis, associated with an overwhelming
proinflammatory response early, or later secondary to
the development of infected local complications.
• The drivers of the systemic response are poorly
understood, although factors include the elaboration of
proinflammatory cytokines
• Mesenteric lymph, bypassing the liver and containing
these constituents, may contribute to the development
of organ failure
• The development of pancreatic necrosis, the
breakdown of the intestinal barrier, and the suppression
of the immune response through the compensatory
inflammatory response → contribute to the
development of infected pancreatic necrosis → peaks
in the third to fourth week
• It is assoc. w deterioration of patient’s condition and
with the late development of the systemic inflammatory
response syndrome (SIRS) and multiorgan dysfunction
syndrome/failure (MODS/F).
• Organ failure is scored using the Marshall or Sequential
Organ Failure Assessment (SOFA) systems
11
The Pancreas
• Three organ systems most frequently involved are
cardiovascular, respiratory, and renal.
• Multiple organ failure is defined as two or more organs
registering two or more points on these scoring systems
• Monitoring organ failure over time and in response to
treatment is important in the care and timing of
intervention in these patients.
|Surgery|
• Guarding (both Voluntary/Involuntary)
• Dec. BS / Absent
• May have abd distended with intraperitoneal fluid
• May have Pleural Effusion (often on Lt side)
• Cullen/s sign , Grey Turner’s sign : indicate for
Necrotizing (Hemorrhagic) Pancreatitis

• Cullen’s sign – bruise-like discoloration around the

umbilicus
• Grey Turner’s sign - discoloration in the flanks
MANAGEMENT OF ACUTE PANCREATITIS
• Rare sign: tetany d/t hypocalcemia
General Considerations
• All patients with suspected acute pancreatitis should be
Investigation
admitted to hospital.
• Hemoconcentration
• Mild acute pancreatitis – less than a week
• Azotemia – Rising BUN, Creatinine
• Severe and critical acute pancreatitis – many weeks or
• Hyperglycemia
months of intensive treatment
• Hypoalbuminemia
• Risk of mortality
• Hypocalcemia
o <1% mild disease
• hyperglycemia
o Increasing to 10% moderate disease
o 20-40% severe disease
Serum marker
o >50% critical disease
• Serum Amylase
• The earlier identification of these high-risk categories
o Early rising: Peak within several hours, remain 3-
and their transfer to specialized centers is an important
5 days
priority of management
o Not related to severity
• Mgt: multidisciplinary
o Urine Amylase
• Essential requirements for mgt:
o May elevated 2-3 days after serum amylase
o Accurate diagnosis
o False Positive
o Appropriate triage
▪ small bowel obstruction,
o High-quality supportive care
▪ perforated duodenal ulcer,
o Monitoring and treatment of complications
▪ other intra-abdominal inflammatory
conditions
CLINICAL DIAGNOSIS
o A patient with acute pancreatitis can have a
Diagnosis of acute pancreatitis requires the patient to present
normal serum amylase level
with:
o Patients with hyperlipidemia → values may
• Abdominal Pain:
appear normal bc of interference with
o Severe constant epigastric (can occur
chemical determination of serum amylase by
anywhere in thoracoabdomen)
lipids
o Acute onset
o In some cases, urinary clearance of
o Often radiates through the midback
pancreatic enzymes from the circulation
o Knifing, boring through
increases during pancreatitis → urinary levels
o Relieved by leaning forward
may be more sensitive than serum levels. → It is
• Elevation of serum amylase or lipase (>3x upper limit of
recommended that amylase concentrations
normal)
also be measured in the urine
• Imaging (usually by contrast-enhanced CT scanning) is
o Urinary amylase → remain elevated for several
only required for the diagnosis of acute pancreatitis
days after serum levels have returned to
when these diagnostic criteria are not met.
normal
• Because of the many causes of hyperamylasemia, it is
o Severe pancreatitis assoc. with necrosis →
important to use either the pancreatic isoenzyme of
pancreas may not have the capacity to
amylase or lipase
release large amounts of enzymes into the
circulation
• N/V (later presentation) that do not relieve pain
o Severe disease → hemoconcentration from
third space fluid loss → can effect serum
PE
concentration
• Abdominal tenderness, often with signs of peritonitis
• Tachycardia
• Tachypnea
• Hypotension
• Hyperthermia
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The Pancreas |Surgery|
• P-amylase : Pancreatic specific amylase • Clinical sign
o More specific (88-93%) – Fever
o If >3 times of normal level - reliable for Dx – Shock
Pancreatitis – respiratory failure
o May False Negative – Anuria
o Esp. in alcoholic pancreatitis , HyperTG – neurologic disturbance
pancreatitis – Ileus
o Normal Serum Amylase, NOT EXCLUDE ACUTE – palpable abdominal mass
PANCREATITIS – abdominal compartment syndrome > 25 mmHg
» (>15 mmHg = Abdominal Hypertension)
• Serum lipase
o Indicate for Highest probability of the disease
o Positive in 75-80% of case
o Persistence than Amylase
o >3 times of normal level = Diagnosis
o Normal level : vary upon the laboratory
method
o Sensitivity & Specificity (100%) : Cameron

PAIN MANAGEMENT
• Pain: cardinal symptom
• Pain relief is a clinical priority
• Analgesia should be administered IV, at least at the
outset and before oral intake has been established
• Mild pain → NSAIDs (Metamizole 2g q 8h IV
• Severe pain → Opioid analgesia (Buprenorphine 0.3mg
q 4h IV)
• Administration of buprenorphine, pentazocine, procaine
hydrochloride, and meperidine are all of value in
controlling abdominal pain.
• Morphine is to be avoided because of its potential to
cause sphincter of Oddi spasm.

PREDICTING SEVERITY
• Predicting pancreatitis severity is important in making
triage decisions whether a patient should be transferred
to a tertiary hospital or an ICU and in making decisions
about fluid therapy and whether an ERCP is indicated,
etc
• Most widely used: Ranson’s criteria or modified Glasgow
criteria
o Both use clinical and biochemical parameters
scored over the first 48 hours of admission.
o Three or more positive criteria → “predicted
severe.”

1. Clinical Risk factor

• Ages and Comorbidity
• Clinical sign
2. Scoring Systems
• Ranson score
• APACHE-II
• Other : Imrie/Gasglow score , SOFA
3. Biological marker (not routinely used)
• C-reacitive Protein (CRP) : >150 at 48hr confirm
Ac Severe Pan.
• IL-6 , PMN elastase , Trypsinogen Activation
Peptide (TAP)
4. CT severity Index (CTSI)
• Balthazar
• Necrosis

Clinical Risk Factor

• Ages and Comorbidity
– Age > 70 yr
– BMI >30 kg/m2
– Cardiovascular disease
– DM

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 The Pancreas |Surgery|
CLASSIFICATION OF SEVERITY
• The key determinants of severity are
o local complications (absent, sterile, or infected) and
o systemic complications (absent, transient organ
failure, persistent organ failure).
• Two classification systems
o Three grades (mild, moderately severe, and severe)
Revised Atlanta Criteria (RAC)
o Four categories (mild, moderate, severe, critical) of
the Determinants Based Classification (DBC)

SUMMARY OF THE INTERNATIONAL SYMPOSIUM ON

ACUTE PANCREATITIS (ATLANTA, 1992)

Definition
• Acute Fluid Collections.
• Occur early
• Found 30-50% of Pt
• lack a wall of granulation or fibrous tissue
• more than half regress spontaneously
• Pancreatic and Peripancreatic Necrosis
• areas of nonviable pancreatic or
peripancreatic tissue
• Either sterile / infected
• Fat necrosis +/- tissue necrosis : puttylike or
pastelike
• may evolve into pseudocysts ,(late fibrosis)
• Pancreatic Pseudocyst
• collections of pancreatic juice
• enclosed by a nonepithelialized wall
composed of fibrous and granulation tissue
• Intrapancreatic / Extrapancreatic (more
common , esp in lesser sac)
• not present before 4 to 6 weeks after the onset
of an attack
• If infected à Pancreatic abscess
• If rupture into peritoneal cavity à Pancreatic
Ascites
• If rupture into pleral space à
Pancreaticopleural fistula
• Pancreatic Abscess and Infected Pancreatic Necrosis

DETERMINING ETIOLOGY
• The history of alcohol ingestion must be ascertained
and confirmed with blood ethanol levels.
• Gallstones -- ultrasonography.
• A gallstone etiology – more likely in females over the
age of 50 with an elevation of
o alkaline phosphatase (>300 iu/L),
o alanine transferase(>100 iu/L), and
o amylase (>4000 iu/L).

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The Pancreas |Surgery|
• In the absence of gallstones and alcohol → a THERAPEUTIC ENDOSCOPIC RETROGRADE
systematic approach to the identification of another CHOLANGIOPANCRETOGRAPHY
factor will include taking a history of drugs, trauma, • RTs have demonstrated that early ERCP (within 24-48h of
ERCP, infection, and measuring serum triglycerides, admission) reduce complications, but not mortality, in
calcium, and others patients with predicted severe gallstone associated
acute pancreatitis
IMAGING • More recent evidence has suggested that early ERCP
• Plain Film Abdomen confers no benefit in the absence of concomitant
• Finding Colon Cutoff sign cholangitis, as the offending common duct stone
• abrupt termination of gas within the usually passes before ERCP can be performed → this
proximal colon at the level of the may be evidenced by improvement in the liver function
radiographic splenic flexure tests over the first 2 to 3 days.
• Sentinel Loop • If there is persistent cholestasis, an MRCP can be used to
• Localized Bowel ileus detect a common duct stone and can be used as a
• Generalized Bowel ileus prerequisite for attempting an ERCP.
• Other • Persistent cholestasis without cholangitis may require an
• Soft tissue Density at Epigastrium ERCP but not usually in the acute setting.
• Pancreatic Calcification
• Opaque GS DIFFERENTIAL DIAGNOSIS
• Lt Pleural Effusion • Bowel obstruction
• Cholecystitis or cholangitis
• Mesenteric ischemia or infarction
• Perforated hollow viscus

PRINCIPLES OF TREATMENT
1. Adequate Monitoring
2. Adequate Resuscitation: Fluid & Electrolyte
• Not too much/too low
• Hypocalcemia , Met. Acidosis ,
Hypoalbuminemia
• HypoMg.
3. Pancreatic Rest : NPO
4. Adequate Pain Control : dec. cholinergic n. stimuli
• Ultrasound
• Best noninvasive for confirm GS
• Can detect Extrapancreatic duct dilatation
• Pancreatic edema , swelling & Peripancreatic
Fluid collection
• 20% of pt may not give info. due to bowel gas

• Contrast-Enhanced CT scan
• Gold standard
• Used in detect complication and
access severity
• Indication for use
1. Suspected of Diagnosis
2. Acute Pancreatitis , that Clinically did
not improve in 48-72 hr
3. Suspected of Complication from Acute
pancreatitis
• Peripancreatic collection
• Pancreatic Necrosis
• Pancreatic Pseudocyst
(late)

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The Pancreas |Surgery|

TREATMENT OF BILIARY PANCREATITIS

• Controversial point : Timing (48-72hr , >72hr)
• ERCP , Cholecystectomy with CBD clearance
• Indication : for Early ERCP
o Obstructive Jx with Cholangitis
o Severe pancreatitis
o Pancreatitis with obstructive Jx >24hr
• Routine Early ERCP : not recommended

PANCREATIC NECROSIS
• Occur about 20% of Pancreatitis pt.
• Severe Necrotizing Pancreatitis
• Sterile vs Infected : ceCT with FNA
o “Air Bubble” found 20% of Infected PN (IPN)
o Mortality
TREATMENT o <1% in sterile PN
• Decompressive Nasogastric Tube o About 40% in IPN
• H2-Blocker • Clinical :
• Secretion-inhibiting Drugs o Fever, Leukocytosis, clinical not imp. In 72hr
• Atropine , Calcitonin , Somatostatin , • Treatment
Glucagon , Fluorouracil o Antibiotic
• Protease-inhibiting Drugs o Drainage
• Aprotinin , Gabexate masylate , Camostate , ▪ Catheter-bases Therapy
Phospholipase A2 inh. ▪ Surgical Debridement
• Anti-inflammatory response Therapy • For Life-Threatening only
• Indomethacin & Prostaglandin inhibitors
• PAF (Platelet-activating factor ) antagonist :
PAF acetylhydrolase , Lexipafant
• Peritoneal Lavage

SEVERE PANCREATITIS
Dx when :
1. Ranson score ≥ 3
2. APACHE-2 ≥ 8
3. Dev. Local/Systemic complication
• MOF
• Pseudocyst , necrosis , abscess

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The Pancreas |Surgery|
OPEN NECROSECTOMY
• Indication
o Infected Pancreatic and/or peripancreatic
necrosis
o Sterile necrosis with progressive clinical
deterioration under Maximum Medical Tx :
Controversial
o Massive hemorrhage or bowel perforation
(colon, duodenum).
• Timing : “as late as possible”
• Preparation
o Empirical Antibiotic
o CT : for road map
o Prepare For massive Blood loss
o G/M PRC 4-6 u
o Invasive monitoring : Central line / Swan-Ganz
catheter

CHOLECYSTECTOMY
• Widely accepted that cholecystectomy is essential to
prevent recurrent gallstone associated pancreatitis
• Important question: Timing?
• Index cholecystectomy
o Done in the same admission and prior to
discharge
o Appears safe
o Can almost always be accomplished
laparoscopically.
o Not suitable for all patients → those who have
had local pancreatic complications, which
includes a large inflammatory mass that
extends into the porta hepatis.
▪ These patients may require an
interval cholecystectomy after
resolution of the inflammatory
process.
• If surgery is required for the management of local
complications, then a cholecystectomy is often
performed at that time.

DIABETES
• Prediabetes and diabetes are common after acute
pancreatitis and occur in nearly 40% of patients after
hospital discharge
• Prevalence of newly diagnosed diabetes → higher after
acute pancreatitis (23%) vs prevalence of diabetes in
the general population (4–9%).
• The risk of diabetes increases by at least twofold after 5
years as compared with 12 months
• The severity of acute pancreatitis appears to have
minimal effect on risk of diabetes.

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The Pancreas |Surgery|
CHRONIC PANCREATITIS
• is an incurable, chronic inflammatory condition that is
multifactorial in its etiology, highly variable in its presentation,
and a challenge to treat successfully.
• Permanent loss of pancreatic exocrine & endocrine function
→ pancreatic insufficiency
• Autopsy studies indicate that evidence of chronic
inflammation, such as fibrosis, duct ectasia, and acinar
atrophy is seen in up to 5% of the population, although these
data are difficult to interpret because many of these
changes are also present in asymptomatic elderly patients.

ETIOLOGY
• Genetic mutations - autosomal dominance which cause
excessive production of trypsinogen
• Alcohol exposure
• Duct obstruction due to trauma
• Gallstones
• Tumors
• Metabolic diseases such as hyperlipidemia and
hyperparathyroidism
• Autoimmune disease

CLASSIFICATION
• A major impediment to a better understanding of the
etiology, frequency, and severity of chronic pancreatitis has
been the difficulty with which investigators and clinicians
have struggled to identify a useful classification system.
• The TIGAR-O scheme categorizes chronic pancreatitis
according to risk factors and etiologies, such as:
a. Toxic-metabolic
b. Idiopathic
c. Genetic
d. Autoimmune
e. Recurrent and severe acute pancreatitis
f. Obstructive

A recent classification system based on histopathology as well as

etiology was delineated by Singer and Chari.
A. Chronic Calcific (Lithogenic) Pancreatitis
• This type is the largest subgroup and includes patients
with calcific pancreatitis of most etiologies.
• majority of patients have a history of alcohol abuse,
stone formation and parenchymal calcification can
develop in a variety of etiologic subgroups; hereditary
pancreatitis and tropical pancreatitis are particularly
noteworthy for the formation of stone disease.

B. Chronic Obstructive Pancreatitis

• compression or occlusion of the proximal ductal system
by tumor, gallstone, posttraumatic scar, or inadequate
duct caliber (as in pancreas divisum).
• Obstruction of the main pancreatic duct by
inflammatory (posttraumatic) or neoplastic processes
can result in diffuse fibrosis, dilated main and secondary
pancreatic ducts, and acinar atrophy.
• The patient may have little in the way of pain symptoms
or may present with signs of exocrine insufficiency.

Pancreas divisum
→ represents a special case of obstructive pancreatitis.
→ It is the most common congenital anomaly involving the
pancreas and occurs in up to 10% of children.

Bea x Abby 18
The Pancreas
→ It is thought to predispose the pancreas to recurrent
acute pancreatitis and chronic pancreatitis, due to
functional obstruction of a diminutive duct of Santorini
that fails to communicate with Wirsung’s duct.
|Surgery|
E. Asymptomatic Pancreatic Fibrosis
• seen in some asymptomatic elderly patients, in tropical
populations, or in asymptomatic alcohol users.
• There is diffuse perilobar fibrosis and a loss of acinar cell
mass, but there is not a main ductular component.
• usually asymptomatic in terms of typical pancreatic pain,
and a recent histopathologic study of patients with
typical chronic pancreatitis and “diabetic exocrine
pancreatopathy” reveals significant differences in
morphology, including a virtual absence of duct distortion
or obstruction

F. Idiopathic Pancreatitis
• When a definable cause for chronic pancreatitis is
lacking, the term idiopathic is used to categorize the
illness.
• includes young adults and adolescents who lack a family
history of pancreatitis but who may represent individuals
with spontaneous gene mutations encoding regulatory
proteins in the pancreas.
• A variable percentage of SPINK1 and CFTR mutations
have been described in various studies.

C. Chronic Inflammatory Pancreatitis
• characterized by diffuse fibrosis and a loss of acinar
elements with a predominant mononuclear cell infiltration
throughout the gland.
• This type, referred to as autoimmune pancreatitis (AIP), is
associated with a variety of illnesses with suspected or
proven autoimmune etiology, such as Sjögren’s
syndrome, rheumatoid arthritis, and type 1 diabetes
mellitus.
• AIP has been characterized as either type I, with
accompanying systemic or multiorgan dysfunction, or
type II, which is restricted to the pancreas.
PATHOLOGY
• Fibrosis
o A common feature of ALL forms of chronic pancreatitis
is the perilobular fibrosis that forms surrounding individual
acini, then propagates to surround small lobules, and
eventually coalesces to replace larger areas of acinar
tissue due to activation of pancreatic stellate cells
(PSCs) that are found adjacent to acini and small
arteries.

D. Tropical (Nutritional) Pancreatitis

• highly prevalent among adolescents and young adults in
Indonesia, southern India, and tropical Africa.
• Abdominal pain develops in adolescence, followed by
the development of a brittle form of pancreatogenic
diabetes.
• Due to protein-caloric malnutrition, toxic products of some
indigenous foodstuffs have also been thought to
contribute to the disease.
• Because of the geographic concentration of this
earlyonset form of chronic pancreatitis, it has been
termed tropical pancreatitis, although the exact etiology
remains unclear.
• Clinically, tropical pancreatitis presents much like
hereditary pancreatitis, and a familial pattern among
cases is not unusual.
• SPINK1 mutations have been documented in 20% to 55%
of patients with tropical pancreatitis, and CFTR mutations
have been reported as well.
• The accelerated deterioration of endocrine and exocrine
function, the chronic pain due to obstructive disease, and
the recurrence of symptoms despite decompressive • Stone Formation
procedures characterize the course of disease. o Pancreatic stones are composed largely of calcium
carbonate crystals trapped in a matrix of fibrillar and
other material.

Bea x Abby 19
The Pancreas
o The fibrillar center of most stones contains no calcium but
rather a mixture of other metals.
o stones form from an initial noncalcified protein
precipitate, which serves as a focus for layered calcium
carbonate precipitation
o pancreatic stones are composed largely of calcium
carbonate crystals trapped in a matrix of fibrillar and
other material
CLINICAL PRESENTATION
• Abdominal pain
o the most common symptom of chronic pancreatitis.
o midepigastric in location but may localize or involve either
the left or right upper quadrant of the abdomen.
o Occasionally, it is perceived in the lower midabdomen but
is frequently described as penetrating through to the back
o The pain is typically steady and boring, but not colicky.
o It persists for hours or days and may be chronic with
exacerbations caused by eating fatty foods or drinking
alcohol.
o Chronic alcoholics also describe a steady, constant pain
that is temporarily relieved by alcohol, followed by a
more severe recurrence hours later.
o Patients with chronic pancreatic pain typically flex their
abdomen and either sit or lie with their hips flexed, or lie
on their side in a fetal position
o Strategies to relieve pain are therefore based on three
approaches:
▪ Reducing secretion and/or decompress the secretory
compartment
▪ Resecting the focus of chronic inflammatory change,
or
▪ Interrupting the transmission of afferent neural impulses
through neural ablative procedures.
o A trial of antisecretory therapy or endoscopic duct
drainage may select those patients who will benefit
preferentially from a decompressive procedure.
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• Diarrhea
o Bulky, foul-smelling, loose (but not watery) stool that
may be pale in color and float on the sirface of toilet
water
• Steatorrhea
o A greasy or oily appearance to the stool, or may describe
an “oily slick” on the waters surface.
o In severe streatorrhea, an orange, oily stool is often seen
o As exocrine deficiency increases, symptoms of
steatorrhea are often accompanied by weight loss.
o Patients may describe a good appetite despite weight
loss or diminished food intake due to abdominal pain.
• Anorexia or Nausea
o When pancreatic exocrine capacity falls below 10% of
normal, diarrhea and steatorrhea develop
o The combination of decreased food intake and
malabsorption of nutrients usually results in chronic weight
loss → below ideal body weight
o Sometimes the anorexia is secondary to the avoidance of
the pain
DIAGNOSTICS
• The diagnosis of chronic pancreatitis depends on the clinical
presentation, a limited number of indirect measurements that
correlate with pancreatic function, and selected imaging
studies
• The direct measurement of pancreatic enzymes (e.g., lipase
and amylase) by blood test is highly sensitive and fairly
specific in acute pancreatitis but is seldom helpful in the
diagnosis of chronic pancreatitis.
• Pancreatic polypeptide (PP)
o The pancreatic endocrine product that correlates most
strongly with chronic pancreatitis is the PP response to a
test meal
o Severe chronic pancreatitis is associated with a blunted
or absent PP response to feeding but, as with many
other tests, a normal PP response does not rule out the
presence of early disease.
• The measurement of pancreatic exocrine secretion requires
aspiration of pancreatic juice from the duodenum after
nutrient (Lundh test meal) or hormonal (CCK or secretin)
stimulation
20
The Pancreas |Surgery|
o Direct aspiration of pancreatic juice by endoscopic
cannulation of the duct is performed in some centers,
but it is not risk free, comfortable for the patient, or more
sensitive than luminal intubation methods.
• Fecal levels of chymotrypsin and elastase have been
proposed as simpler, less expensive tests of exocrine function
and correlate well with loss of pancreatic function

RADIOLOGY
• Using of Imaging for Chronic pancreatitis
o Diagnosis
o The evaluation of severity of disease – Cambridge
classification
o Detection of complications
o Assistance in determining treatment option
• Transabdominal ultrasonography PROGNOSIS
- frequently used as an initial imaging method in patients • Depends on:
with abdominal symptoms, and changes consistent with o Etiology of disease
pancreatic duct dilatation, intraductal filling defects, o Complication
cystic changes, and a heterogeneous texture are seen in o Age
chronic pancreatitis o Socioeconomic status
• Magnetic Resonance Cholangiopancreatography (MRCP) • Progressive, cumulative increase risk of cancer
- Used to select patients who are candidates for the most
invasive imaging method, ERCP. COMPLICATIONS
- It can disclose ductal abnormalities that correlates closely Pseudocyst
with the contrast-filled ducts • A chronic collection of pancreatic fluid surrounded by a
• Helical CT Scan nonepithelialized wall of granulation tissue and fibrosis
- used to visualize the nature, extent, location, and • Pseudocysts occur in up to 10% of patients with acute
relative relationships of pancreatic structures and lesions pancreatitis, and in 20% to 38% of patients with chronic
is possible with great clarity pancreatitis, and thus, they comprise the most common
• MRI: disclose fluid-filled ducts and cystic lesions, has added complication of chronic pancreatitis
greatly to the imaging options for chronic pancreatitis • The identification and treatment of pseudocysts requires
• ERCP: Gold standard in diagnosis and staging of chronic definition of the various forms of pancreatic fluid collections
pancreatitis that occur

• Endoscopic Ultrasound (EUS)
- more sensitive than ERCP
- is now frequently used as a preliminary step in the
evaluation of patients with pancreatic disease
- provides not only imaging capability but also adds the
capacity to obtain cytologic and chemical samples of
tissue and fluid aspirated with linear array monitoring
• Natural History:
o For acute pseudocyst (or <6week): 40% solve
spontaneous , 20% develop complication
o For Chronic pseudocyst (7weeks up): about 5 % solve
spontaneously; 50-60% develop complication
o No malignant potential : af <6cm/asymptomatic, no
complication: surveillance
• Indication for surgery
o Symptomatic: often occur in Pseudocyst size > 6cm.
- early satiety, gastric outlet obstruction, jaundice, pain,
thrombosis
-
PATHOGENESIS
• In chronic pancreatitis, a pancreatic duct leak with
extravasation of pancreatic juice results in a peripancreatic
fluid collection (PPFC).

Bea x Abby 21
The Pancreas |Surgery|
• Over a period of 3 to 4 weeks, the PPFC is sealed by an o Surgical options include a cystogastrostomy (picture
inflammatory reaction that leads to development of a wall of below), a Roux-en-Y cystojejunostomy, or a
acute granulation tissue without much fibrosis. cystoduodenostomy.
• This is referred to as an acute pseudocyst.
• Acute pseudocysts may resolve spontaneously in up to 50% of
cases, over a course of 6 weeks or longer.
• Pseudocysts >6 cm resolve less frequently than smaller ones
but may regress over a period of weeks to months.
• Pseudocysts are multiple in 17% of patients, or they may be
multilobulated.
• They may occur intrapancreatically or extend beyond the
region of the pancreas into other cavities or compartments o Cystojejunostomy is the most versatile method, and it can
be applied to pseudocysts that penetrate into the
TREATMENT FOR PSEUDOCYST transverse mesocolon, the paracolic gutters, or the lesser
• Rule sac.
1. Cystic neoplasm must not be treated as a pseudocyst o Cystogastrostomy can be performed endoscopically
2. Elective external drainage must not be done (picture below), laparoscopically, or by a combined
- If not correct of downstream obstruction laparoscopic-endoscopic method.
• Point of consideration
- The thickness of the pseudocyst wall: after 4-6week
- The location of the pseudocyst: near Stomach,
Duodenum
- The contents of the pseudocyst: Blood, pus
- The pancreas and the pancreatic duct need separate
consideration in planning the treatment of a pseudocyst

SUMMARY OF TREATMENT
Cystagastrostomy If lying posterior to
stomach
Cystojejunostomy Ideal for internal
drainage
OPEN If located at body and
SURGERY tail
• The timing and method of treatment requires careful
Not adhere to stomach,
consideration.
Bulging through the
• Pitfalls in the management of pseudocysts result from the
colon
incorrect (presumptive) diagnosis of a cystic neoplasm
Cystoduodenostomy If located at head of
masquerading as a pseudocyst, a failure to appreciate the
pancreas
solid or debris-filled contents of a pseudocyst that appears to
Distal pancreatectomy Extent of resection,
be fluid filled on CT scan, and a failure to document true
depend on ERCP
adherence with an adjacent portion of the stomach before
findings
attempting transgastric internal drainage.
External drainage Only if no occlusion of
• If the pseudocyst has failed to resolve with conservative
PD
therapy and symptoms persist, internal drainage is usually
Cystogastrostomy
preferred to external drainage to avoid the complication of a
Cystoduodenostomy
pancreaticocutaneous fistula.
o Pseudocysts communicate with the pancreatic ductal Roux-en-Y
LAPAROSCOPIC cystijejunostomy
system in up to 80% of cases, so external drainage creates
a pathway for pancreatic duct leakage to and through Distal pancreatectomy ±
the catheter exit site. splenectomy
o Internal drainage may be performed with either External drainage
endoscopic methods (transgastric or transduodenal Percutaneous drainage
puncture and multiple stent placements, with or without a RADIOLOGIC Percutaneous
nasocystic irrigation catheter), or surgical methods (a true transgastric drainage
cystoenterostomy, biopsy of cyst wall, and evacuation of Transpapillary
all debris and contents). pancreatic duct stent
ENDOSCOPIC Transgastric stent
Transduodenal stent

Bea x Abby 22
The Pancreas
MANAGEMENT OF CHRONIC PANCREATITIS
• Analgesia
o Oral analgesics are prescribed as needed, alone or with
analgesia-enhancing agents such as gabapentin.
o Adequate pain control usually requires the use of
narcotics, but these should be titrated to achieve pain
relief with the lowest effective dose.
o Opioid addiction is common, and the use of long-
acting analgesics by transdermal patch together with
oral agents for pain exacerbations slightly reduces the
sedative effects of highdose oral narcotics.
o It is essential for patients to abstain from alcohol.
o In addition to removing the causative agent, alcohol
abstention results in pain reduction or relief in 60% to
75% of patients with chronic pancreatitis.
• Enzyme Therapy
o Pancreatic enzyme administration serves to reverse the
effects of pancreatic exocrine insufficiency.
o Adequate pancreatic enzyme replacement reverses
the exocrine insufficiency seen in most patients, and it
prevents secondary complications such as metabolic
bone disease due to inadequate absorption of the fat-
soluble vitamins A, D, E, and K.
• Antisecretory Therapy
o Somatostatin administration has been shown to inhibit
pancreatic exocrine secretion and CCK release
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|Surgery|
o The somatostatin analogue octreotide acetate has
therefore been investigated for pain relief in patients
with chronic pancreatitis
SURGICAL THERAPY
• Sphincteroplasty
o The sphincter of Oddi and the pancreatic duct
sphincter serve as gatekeepers for the passage of
pancreatic juice into the duodenum (Fig. 33-48).
o Stenosis of either sphincter
(sclerosing papillitis), due to
scarring from pancreatitis or from
the passage of gallstones, may
result in obstruction of the
pancreatic duct and chronic
pain.
o Transduodenal sphincteroplasty
with incision of the septum
between the pancreatic duct
and common bile duct may
offer significant relief for the rare
patient with a focal obstruction
and inflammation isolated to this
region
• Drainage Procedures
o After the early reports of success with pancreatostomy
for the relief of symptoms of chronic pancreatitis, Cattell
described pancreaticojejunostomy for relief of pain in
unresectable pancreatic carcinoma
o Shortly thereafter, Duval and, separately, Zollinger and
associates described the caudal Roux-en-Y
pancreaticojejunostomy for the treatment of chronic
pancreatitis in 1954 (picture below)
o The so-called Duval procedure was used for decades
by some surgeons, but it almost invariably failed due to
23
The Pancreas
restenosis and segmental obstruction of the pancreas
due to progressive scarring.
o In 1958, Puestow and Gillesby described these
segmental narrowings and dilatations of the ductal
system as a “chain of lakes,” and proposed a
longitudinal decompression of the body and tail of the
pancreas into a Roux limb of jejunum (picture below)
o Four of Puestow and Gillesby’s 21 initial cases were side-
to-side anastomoses, and 2 years after their report,
Partington and Rochelle described a much simpler
version of the longitudinal, or side-to-side Rouxen-Y
pancreaticojejunostomy that became universally
known as the Puestow procedure (picture below)
• Hybrid Procedures
• Resectional Procedures
o Distal Pancreatectomy
- For patients with focal inflammatory changes
localized to the body and tail, or in whom no
significant ductal dilatation exists, the technique of
partial (40–80%) distal pancreatectomy has been
advocated
- Although distal pancreatectomy is less morbid than
more extensive resectional procedures, the
operation leaves untreated a major portion of the
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gland, and is therefore associated with a significant
risk of symptomatic recurrence
- long-term outcomes reveal good pain relief in only
60% of patients, with completion pancreatectomy
required for pain relief in 13% of patients.
o Proximal Pancreatectomy (Whipples procedure)
- Proximal pancreaticoduodenectomy or total
pancreatectomy or with or without pylorus
preservation
- pain relief 4 to 6 years after operation was found in
71% to 89% of patients.
- However, mortality ranged from 1.5% to 3%, and
major complications occurred in 25% to 38%
o Total Pancreatectomy
- surgeons who used total pancreatectomy found
that the operation produces no better pain relief
for their patients than pancreaticoduodenectomy
(about 80–85%).
- Moreover, the metabolic consequences of total
pancreatectomy in the absence of islet cell
transplantation can be profound and life-
threatening.
o PANCREATIC HEAD RESECTION OR DPPHR
- requires the careful dissection of the
gastroduodenal artery and the creation of two
anastomoses and it carries a similar complication
risk as the Whipple procedure due to the risk of
pancreatic leakage and intra-abdominal fluid
collections.
- Pain relief was reportedly maintained in chronic
91%, mortality was <1%, and diabetes developed in
21%, with 11% demonstrating a reversal of their
preoperative diabetic status
24
The Pancreas
PANCREATIC NEOPLASMS
• relatively uncommon but do occur with enough frequency
• The cells of the endocrine pancreas, or islet cells, originate
from neural crest cells, also referred to as amine precursor
uptake and decarboxylation cells.
• Multiple endocrine neoplasia (MEN) syndromes occur when
these cells cause tumors in multiple sites.
• The MEN1 syndrome involves pituitary tumors, parathyroid
hyperplasia, and pancreatic neoplasms.
INSULINOMA
• Insulinomas are the most common functional pancreatic
endocrine neoplasms and present with a typical clinical
syndrome known as Whipple’s triad.
• The triad consists of:
o symptomatic fasting hypoglycemia
o a documented serum glucose level <50mg/dL
o relief of symptoms with the administration of glucose
• Patients can present with a profound syncopal episode or less
severe symptoms that are averted by frequent eating.
• Common symptoms include:
o Palpitations
o Trembling
o Diaphoresis
o Confusion or obtundation, and seizure
o Family members may report that the patient has
undergone a personality change
• Laboratory: Elevated serum insulin and C-peptide levels
• Diagnosis:
o Can be clinched with a monitored fast in which blood is
sampled every 4 to 6 hours for glucose and insulin levels
until the patient becomes symptomatic. However, this
can be dangerous and must be done with close
supervision.
o CT Scan and EUS
▪ Majority (90%) of insulinomas are benign and 10%
are malignant
• Treatment:
o They are typically cured by simple enucleation.
o However, tumors located close to the main pancreatic
duct and large (>2 cm) tumors may require a distal
pancreatectomy or pancreaticoduodenectomy.
GASTRINOMA
• Zollinger-Ellison syndrome (ZES) is caused by a gastrinoma, an
endocrine tumor that secretes gastrin → acid hypersecretion
and peptic ulceration
• Common symptoms:
o Abdominal pain
o Peptic ulcer disease
o Severe esophagitis
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|Surgery|
• However, in the era of effective antacid therapy, the
presentation can be less dramatic.
• Although most of the ulcers are solitary, multiple ulcers in
atypical locations that fail to respond to antacids should raise
suspicion for ZES and prompt a workup.
• At the time of diagnosis, 21% of patients with gastrinoma have
diarrhea.
• Laboratory: Serum gastrin level >1000 PG/ML
• Diagnosis: SSTR (Octreotide) Scintigraphy in combination with
CT Scan
• Treatment:
o Highly selective vagotomy if unresectable disease is
identified or if the gastrinoma cannot be localized
o If hepatic metastases are identified, resection is justified if
the primary gastrinoma is controlled and the metastases
can be safely and completely removed
VASOACTIVE INTESTINAL PEPTIDE-SECRETING TUMOR
• The classic clinical syndrome associated with this pancreatic
endocrine neoplasm consists of:
o severe intermittent watery diarrhea leading to
dehydration
o weakness from fluid and electrolyte losses.
• Large amounts of potassium are lost in the stool.
• The vasoactive intestinal peptide-secreting tumor (VIPoma)
syndrome is also called WDHA syndrome due to the presence
of watery diarrhea, hypokalemia, and achlorhydria.
• The massive (5 L/d) and episodic nature of the diarrhea
associated with the appropriate electrolyte abnormalities
should raise suspicion of the diagnosis.
• Laboratory: Serum VIP levels must be measured on multiple
occasions because the excess secretion of VIP is episodic
and single measurements might be normal and misleading.
• Diagnosis:
o CT scan localizes most VIPomas
o EUS is the most sensitive imaging method with all islet cell
tumors.
• Treatment:
o Somatostatin analogues are helpful in controlling the
diarrhea and allowing replacement of fluid and
electrolytes.
o Palliative debulking operations can sometimes improve
symptoms for a period, along with somatostatin
analogues.
o Hepatic artery embolization also has been reported as
a potentially beneficial treatment.
GLUCAGONOMA
• Diabetes in association with dermatitis should raise the
suspicion of a glucagonoma.
• The diabetes usually is mild.
• The classic necrolytic migratory erythema manifests as cyclic
migrations of lesions with spreading margins and healing
centers typically on the lower abdomen, perineum, perioral
area, and feet. Patients also complain of an enlarged,
sensitive tongue.
• Laboratory: confirmed by measuring serum glucagon levels
usually >500 pg/mL.
• Glucagon is a catabolic hormone, and most patients present
with malnutrition.
25
The Pancreas |Surgery|
• The rash associated with glucagonoma is thought to be • Systematic histologic evaluation of areas surrounding
caused by low levels of amino acids pancreatic cancers has revealed the presence of precursor
• Treatment: control of the diabetes, parenteral nutrition, lesions that have been named pancreatic intraepithelial
octreotide, and debulking operations are recommended in neoplasia
good operative candidates to relieve symptoms. • Lesions demonstrate the same oncogene mutations and loss
of tumor-suppressor genes found in invasive cancers, the
SOMATOSTATINOMA frequency of these abnormalities increasing with progressive
• Because somatostatin inhibits pancreatic and biliary cellular atypia and architectural disarray.
secretions, patients with a somatostatinoma present with:
o Gallstones → due to bile stasis
o Diabetes → due to inhibition of insulin secretion
o Steatorrhea → due to inhibition of pancreatic exocrine
secretion and bile secretion.
• Most somatostatinomas originate in the proximal pancreas or
the pancreatoduodenal groove, with the ampulla and
periampullary area as the most common site (60%).
• The most common presentations are:
o Abdominal pain
o Jaundice
o Cholelithiasis
• Laboratory: Elevated serum somatostatin levels >10 ng/mL.
• Treatment: complete excision of the tumor and
cholecystectomy is warranted in fit patients.

NEOPLASMS OF THE EXOCRINE PANCREAS

• Overall, pancreatic cancer has the worst prognosis of all
malignancies with a 5-year survival rate of only 7.2%
• It is the third leading cause of cancer death behind lung and
colorectal cancer.
• Pancreatic cancer is more common in older adults with most
patients being 75 to 84 years old.
• Pancreatic cancer is more common in African Americans
and slightly more common in men than women
• The risk of developing pancreatic cancer is two to three times
higher if a parent or sibling had the disease.
• Another risk factor that is consistently linked to pancreatic
cancer is cigarette smoking.
o Smoking increases the risk of developing pancreatic
cancer by at least twofold due to the carcinogens in
cigarette smoke.
• Coffee and alcohol consumption have been investigated as
possible risk factors, but the data are inconsistent
• Diabetes has been known to be associated with pancreatic
cancer for many years.
GENETICS OF PANCREATIC CANCER
• The K-ras oncogene is currently thought to be the most
commonly mutated gene in pancreatic cancer, with
approximately 90% of tumors having a mutation
• Multiple tumor-suppressor genes are deleted and/or mutated
in pancreatic cancer, including p53, p16, and DPC4 (Smad
4), and in a minority of cases, BRCA2
• Tumors in the pancreatic body and tail are generally larger at
the time of diagnosis, and therefore, less commonly
resectable.
• Tumors in the head of the pancreas are typically diagnosed
earlier because they cause obstructive jaundice.
• Ampullary carcinomas, carcinomas of the distal bile duct,
and periampullary duodenal adenocarcinomas present in a
similar fashion to pancreatic head cancer but have a slightly
better prognosis, probably because early obstruction of the
bile duct and jaundice leads to the diagnosis
DIAGNOSIS AND STAGING
• Abdominal MRI provides essentially the same information as
CT scanning
• PET scan in locally advanced lesions may help rule out distal
metastasis
• EUS can be used to detect small pancreatic masses that
could be missed by CT scanning and is commonly used when
there is a high suspicion for pancreatic cancer but no mass is
identified by the CT scan
• CT Scan (Pancreatic Protocol) is probably the single most
versatile and cost-effective tool for the diagnosis and staging
of pancreatic cancer

PATHOLOGY
• About two-thirds of pancreatic adenocarcinomas arise within
the head or uncinate process of the pancreas; 15% are in the
body, and 10% are in the tail, with the remaining tumors
demonstrating diffuse involvement of the gland.
• Pancreatic cancer probably arises through a stepwise
progression of cellular changes, just as colon cancer
progresses by stages from hyperplastic polyp to invasive
cancer.

Bea x Abby 26
The Pancreas |Surgery|
o Duodenal obstruction
→ Endoscopic metallic duodenal stents
→ Duodenum: gastrojejunostomy or Enteric bypass
→ Double bypass

CHEMOTHERAPY AND RADIATION FOR LOCALLY ADVANCED/

METASTATIC DISEASE
• RT may slow the progression of local disease and possibly
alleviate or prevent symptoms including pain, biliary
obstruction, bleeding, and bowel obstruction.
• However, the likelihood of micrometastatic distant disease is
high, treatment is not expected to be curative, and radiation
can result in toxicity
• Folfirinox, a combination of three chemotherapy drugs (5-
FU/leucovorin, irinotecan, and oxaliplatin) is now commonly
used as first-line treatment for metastatic pancreatic
adenocarcinoma in patients with a relatively good
performance status.
• Stereotactic body radiotherapy (SBRT) has been used to limit
toxicity by targeting high-dose short-course radiation to
enhance local response prior to surgery
• 5-FU or Capecitabine (Xeloda)
• Erlotinib (Tarceva)

SURGICAL RESECTION: PANCREATICODUODENECTOMY

• Appropriate clinical and/or imaging indications of pancreatic
cancer
• Tissue diagnosis before performing a
pancreaticoduodenectomy is not essential
• In the face of clinical and radiologic preoperative indications
of pancreatic cancer, a negative biopsy should not preclude
resection

DIAGNOSTIC AND TREATMENT ALGORITHM

• If with metastases already: biopsy for a tissue diagnosis
o may be candidates for palliative chemotherapy trials
• Performed through a midline incision from xiphoid to
umbilicus or through a bilateral subcostal incision
• Initial portion of the procedure to assessment of resectability
o Liver and visceral and parietal peritoneal surfaces
o Gastrohepatic omentum is opened, and the celiac axis
area
o Base of the transverse mesocolon to the right of the
middle colic vessels
o Portal hepatis

TREATMENT
• Patients with pancreatic cancer (85-90%) have disease that
clearly precludes surgical resection
• Three clinical problems in advanced pancreatic cancer that
require palliation.
o Pain
→ Oral narcotics
→ Sustained-release preparations of morphine
→ Celiac nerve block
o Jaundice
→ Endoscopic biliary stent
→ If we cannot do endoscopic stenting the best way to
address the jaundice is to do an
hepaticojejunostomy procedure or
choledocojejunustomy procedure in order to bypass
the flow of the bile

Bea x Abby 27
The Pancreas |Surgery|
POSTOPERATIVE SURVEILLANCE
• Recurrence after successful resection usually manifests as
hepatic metastases
• After adjuvant chemoradiation with 5-FU and external beam
radiation, Gemcitabine is usually administered on a weekly
basis for 6 months
• Clinical history and PE every 3 months for the first 2 years, 6-12
months for the next 3 years
• Get a serial measurements of CA-19 and CT scan

Bea x Abby 28