data from randomized trials failed to show any advantage of somatostatin analogs for accelerating

fistula closure after pancreatic surgery.39

Pancreatic Polypeptide Synthesis, Secretion, and Action

Pancreatic polypeptide is a 36-amino-acid polypeptide secreted by the F cells of the pancreatic islet. The

physiologic role of pancreatic polypeptide remains unclear. It has been shown to inhibit pancreatic

exocrine secretion and gallbladder emptying. Cholinergic innervation predominantly regulates

pancreatic polypeptide secretion. In diabetes and normal aging pancreatic polypeptide secretion is

increased resulting in increased circulating pancreatic polypeptide levels.

Other Peptide Products

Other peptides are secreted within the pancreatic islet. These include neuropeptides such as VIP,

galanin, amylin, pancreastatin, chromogranin A, and serotonin, which are believed to play a role in the

regulation of islet cell secretion. Amylin, a 36-amino-acid polypeptide, is secreted by the B cells, but not

in equimolar amounts to proinsulin. Amylin inhibits secretion of insulin and its uptake in the periphery.

Amylin has been found to be deposited in the pancreas of patients with type II diabetes and has been

implicated in the pathogenesis of the disease. Pancreastatin is another peptide found in large amounts in

the pancreas. It is a derivative of chromogranin A, but its physiologic significance is unknown.

Chromogranin A is produced by most neuroendocrine tumors and is a good marker for diagnosis and

recurrence of pancreatic neuroendocrine tumors.

Tests of Pancreatic Endocrine Function

The most widely used tests of pancreatic endocrine function measure the body’s ability to utilize

glucose. The oral glucose tolerance test provides an indirect assessment of the insulin response to an

oral glucose load; it measures the glucose profile and not the actual insulin response. After an overnight

fast, two basal blood samples are drawn and glucose levels are analyzed. Patients are then given an oral

glucose load of 40 g/m2 over 10 minutes. Blood samples are then drawn every 30 minutes for 2 hours.

The fasting glucose level should be less than 110 mg/dL. Fasting levels between 110 and 126 mg/dL are

considered borderline, and fasting levels above 126 mg/dL are diagnostic of diabetes. The 2-hour

glucose level should be below 140 mg/dL. Two-hour levels between 140 and 200 mg/dL are borderline,

and 2-hour levels over 200 mg/dL are again diagnostic of diabetes mellitus. The test takes into account

the gastrointestinal influences of glucose metabolism and can be affected by antecedent diet, drug use,

exercise, and patient age.

The intravenous glucose tolerance test can be used to eliminate gastrointestinal influences on glucose

metabolism. After basal glucose levels are obtained, this test is performed in similar fashion to the oral

glucose tolerance test, except the glucose load is delivered as an intravenous bolus of 0.5 g/kg over 2 to

5 minutes. Blood is then drawn every 10 minutes for an hour. The disappearance of glucose per minute

(K value) is calculated. A K value of 1.5 or higher is normal. The results are age adjusted, as the

response to the intravenous glucose load decreases with age.

An insulinoma is a pancreatic neuroendocrine tumor that secretes insulin. The gold standard for

diagnosis of insulinoma is the 72-hour monitored fast. This test documents Whipple triad of

hypoglycemia, neuroglycopenic symptoms concurrent with hypoglycemia, and resolution of symptoms

with administration of glucose. It also allows the clinic to rule out surreptitious administration of

exogenous insulin. Within the B cell, proinsulin is cleaved into insulin and C-peptide prior to secretion.

Therefore, both insulin and C-peptide levels can be measured in the blood stream and should be present

in a 1:1 ratio. Surreptitious administration of exogenous insulin can be differentiated from insulinoma

by the absence of C-peptide in the case of the exogenously administered insulin. Patients are fasted in a

monitored setting. All nonessential medications are stopped and patients can only drink water, black,

decaffeinated coffee, and diet sodas. Glucose and insulin levels as well as neuroglycopenic symptoms

are closely monitored. The criteria for discontinuing the fast include serum glucose levels less than 45

mg/dL and the patient must be symptomatic. The 72-hour fast is highly sensitive for insulinoma and a

patient rarely finishes this test without an unequivocal diagnosis. Urine should also be screened for the

presence of sulfonylureas and other oral hypoglycemic medications.

The intravenous arginine test and tolbutamide response test are used to help in diagnosis of more rare

hormone-secreting pancreatic neuroendocrine tumors. After an overnight fast, a patient is given a 30-

minute intravenous infusion of 0.5 g/kg of arginine, which stimulates secretion of islet cell hormones.

Blood samples are taken every 10 minutes and radioimmunoassays are performed for the hormone in

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question. This test is most useful for glucagon-secreting tumors and is not commonly used. Elevations of

plasma glucagon levels to over 400 pg/mL are diagnostic for glucagonoma.

Tolbutamide is a sulfonylurea that stimulates insulin secretion and secretion of other pancreatic

endocrine hormones. After fasting overnight, blood samples are drawn and a patient is given 1 g of

tolbutamide intravenously. Blood glucose is monitored for 1 hour and blood samples are drawn to

determine levels of the hormone of interest. Sustained hypoglycemia with hypersecretion of insulin is

diagnostic of insulinoma. Somatostatin levels more than twice as high as the normal values of the

particular assay used are considered diagnostic of somatostatinoma.

PANCREATIC ANATOMY

The pancreas lies in the retroperitoneum at the level of the second lumbar vertebrae. It lies obliquely

and transversely from its most caudal point at the duodenal C-loop on the right to its most cranial point

in the splenic hilum on the left. The pancreas is composed of four anatomic parts: the head (including

the uncinate process), the neck, the body, and the tail (Fig. 52-7).

Figure 52-7. Normal pancreatic anatomy. The pancreatic head lies within the C-loop of the duodenum. The main pancreatic duct

and common bile duct run through the head of the pancreas and drain into the duodenum at the ampulla of Vater. The superior

mesenteric artery and vein lie posterior to the pancreatic neck.

Relationship to Adjacent Structures

The pancreatic head is further subdivided into the head and uncinate process. The head and uncinate

process lie within the C-loop of the duodenum and include all the pancreatic parenchyma to the right of

the superior mesenteric vessels. The pancreatic head is attached to the medial aspect of the descending

and third portion of the duodenum and the two organs share a blood supply. The uncinate process

projects from the inferior portion of the pancreatic head medially to the left, then posterior to the

superior mesenteric vessels. The inferior vena cava, right renal artery and vein, and left renal vein lie

posterior to the uncinate process and pancreatic head. The bile duct runs through the posterior and

superior aspect of the pancreatic head, joining the pancreatic duct and draining into the duodenum

medially at the ampulla of Vater (Fig. 52-7).

The pancreatic neck is the portion of pancreatic tissue that overlies the superior mesenteric artery and

vein anteriorly. The anterior surface of the pancreatic neck lies directly posterior to the pylorus of the

stomach. The body of the pancreas continues left from the pancreatic neck. The anterior surface of the

pancreatic neck, body, and tail are covered with peritoneum and forms the floor of the omental bursa

within the lesser sac. The stomach overlies the pancreatic body/lesser sac anteriorly. The posterior

surface of the pancreatic body is not peritonealized and directly contacts the aorta, left adrenal gland,

left kidney, and left renal artery and vein. The body of the pancreas is the portion overlying the second

lumbar vertebrae. The tail of the pancreas begins anterior to the left kidney and extends superolaterally

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to the hilum of the spleen. The splenic artery and vein run along the posterior surface of the pancreas.

The tail of the pancreas is in close proximity to the spleen and splenic flexure of the colon.

Pancreatic Ductal Anatomy

The main pancreatic duct, or duct of Wirsung, begins in the pancreatic tail. It most commonly runs

within the posterior aspect of the pancreatic parenchyma, midway between the superior and inferior

border of the gland. In the head of the pancreas, the pancreatic duct turns inferiorly at the genu of the

pancreatic duct and joins the common bile duct, draining into the second portion of the duodenum at

the ampulla of Vater. A common channel may exist between the common bile duct and main pancreatic

duct and it varies in length across the population. At the level of the ampulla of Vater, the pancreatic

duct is anterior and inferior to the common bile duct. At the ampulla of Vater, the sphincter of Oddi

prevents reflux of duodenal contents into the bile duct and pancreatic duct. This sphincter of Oddi is

controlled by a variety of neural and hormonal factors that regulate relaxation and constriction.

A normal main pancreatic duct is 2 to 4 mm in diameter and has a ductal pressure of approximately

15 to 30 mm Hg. This is higher than the pressure in the common bile duct (7 to 17 mm Hg) and serves

to prevent reflux of bile into the pancreatic ductal system. There are over 20 side branches of the main

pancreatic duct throughout the pancreas providing drainage of acinar units. The accessory pancreatic

duct, or duct of Santorini, is more variable than the main pancreatic duct. It typically drains the

uncinate process and inferior portion of the pancreatic head into the duodenum at the minor papilla,

proximal to the ampulla of Vater.

Arterial Blood Supply

The pancreatic blood supply arises from the celiac axis and superior mesenteric artery. The celiac axis

arises from the abdominal aorta and most commonly gives rise to the splenic artery, the left gastric

artery, and the common hepatic artery (Fig. 52-8A). The splenic artery courses along the posterior

surface of the pancreatic body and tail and gives rise to more than 10 branches which supply the

pancreatic body and tail. The first branch of the splenic artery is the dorsal pancreatic artery; it arises

close to the origin of the splenic artery and supplies blood to the proximal body. Further distally, the

great pancreatic artery supplies the midportion of the body and the caudal pancreatic artery supplies the

pancreatic tail.

The head of the pancreas is supplied by both the celiac and superior mesenteric artery (SMA). The

gastroduodenal artery is the first branch off the common hepatic artery. Distal to the first portion of the

duodenum, the gastroduodenal artery becomes the superior pancreaticoduodenal artery and divides into

anterior and posterior branches. The SMA gives rise to the inferior pancreaticoduodenal artery, which

also divides into anterior and posterior branches. The inferior and superior pancreaticoduodenal arcades

form an extensive collateral network with the superior pancreaticoduodenal arcades, supplying both the

duodenum and head of the pancreas. Anteriorly these arcades lie in the groove between the pancreas

and duodenum. Posteriorly, they cross the common bile duct. The arterial blood supply of ampulla of

Vater is from three pedicles off the superior and inferior pancreaticoduodenal arteries. The posterior

pedicle, located at 11 o’clock, arises from the superior pancreaticoduodenal artery. The ventral

commissural pedicle, located at 1 o’clock, arises from both arcades. Finally, the inferior pedicle at 6

o’clock arises from the anterior branch of the inferior pancreaticoduodenal artery. Near the head of the

pancreas, branches arising from the splenic artery form collaterals with the inferior pancreaticoduodenal

arcades.

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