Chapter Summary - PANCREAS Final (Schwartz) PDF

 Situated deep in the center of the abdomen and surrounded by numerous important structures and major blood vessels.  A seemingly minor trauma to the pancreas can result in the release of pancreatic enzymes and cause life-threatening pancreatitis. Gross Anatomy  Retroperitoneal organ  Llies in an oblique position  Sloping upward from the C-loop of the duodenum to the splenic hilum.  Weighs 75-100 g and is about 15-20 cm long (adult) The fact that the pancreas is situated so deeply in the abdomen and is sealed in the retroperitoneum explains the poorly localized and sometimes ill-defined nature with which pancreatic pathology presents. Patients with pancreatic CA without bile destruction without bile obstruction usually present after months of vague upper abdominal discomfort, or no antecedent symptoms at all. Due to its retroperitoneal location, pain associated with pancreatitis often is characterized as penetrating through to the back. Regions of the Pancreas Head, Neck, Body and Tail Head  Nestled in the C-loop of the duodenum and is posterior to the transverse mesocolon.  Located posterior to the head: Vena Cava Right Renal Artery Right and Left Renal Vein Neck  Lies directly anterior to the portal vein  At the inferior border of the neck of the pancreas, the superior mesenteric vein joins the splenic vein and then continues toward the porta hepatis as the portal vein. The inferior mesenteric vein often joins the splenic vein near its junction with the portal vein. Sometimes, the inferior mesenteric vein joins the superior mesenteric vein or merges with the superior mesenteric portal venous junction to form a trifurcation.  The superior mesenteric artery lies parallel to and just to the left of the superior mesenteric vein.  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 superior mesenteric vein and superior mesenteric artery.  Venous branches draining the pancreatic head and uncinate process enter along the right lateral and posterior sides of the portal vein.

DocMegz2017

 There are usually no anterior venous tributaries, and a plane can usually be developed between the neck of the pancreas and the portal and superior mesenteric veins during pancreatic resection, unless the tumor is invading the vein anteriorly.  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. Body & Tail  Both lie anterior to the splenic artery and vein. The 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.)  The splenic artery, often tortuous, runs parallel and just superior to the vein alog the posterior superior edge of the body and tail of the pancreas.  The anterior surface of the body of the pancreas is covered by peritoneum. Once the gastrocolic omentum is divided, the body and tail of the pancreas can be seen along the floor of the lesser sac, just posterior to the stomach. Pancreatic pseudocysts commonly develop in this area, and the posterior aspect of the stomach can form the anterior wall of the pseudocyst, allowing drainage to the stomach.  The base of the transverse mesocolon attaches to the inferior margin of the body and tail of the pancreas. The transverse mesocolon often forms the inferior wall of the pancreatic pseudocysts or inflammatory processes, allowing surgical drainage through the transverse mesocolon  The body of the pancreas is anterior to the aorta at the origin of the superior mesenteric artery.  The neck of the pancreas is anterior to the vertebral body of L1 and L2, and blunt anteroposterior trauma can compress the neck of the pancreas against the spine, causing parenchymal and sometimes, ductal injury.  The neck divides the pancreas into approximately two equal halves.  The small portion of the pancreas anterior to the left kidney is referred to As the tail and is nestled in the hilum of the spleen near the splenic flexure of the left colon. Pancreatic Duct Anatomy  The pancreas is formed by the fusion of the ventral and dorsal bud.  The duct from the smaller ventral bud - arises from the hepatic diverticulum, and connects directly to the common bile duct.  The duct from the larger dorsal bud - arises from the duodenum, and drains directly into the duodenum.  The duct of the ventral anlage becomes the duct of Wirsung.  The duct from the dorsal anlage becomes the duct of Santorini.  With gut rotation, the ventral anlage rotates to the right and around the posterior side of the duodenum to fuse with the dorsal bud.  The ventral anlage becomes the inferior portion of the pancreatic head and the uncinate process.  The dorsal anlage becomes the body and tail of the pancreas.

Page 1

 The ducts from each anlage usually fuse together in the pancreatic head such that most of the pancreas drains through the duct of Wirsung or main pancreatic duct, into the common channel formed from the bile duct and pancreatic duct.  The length of the common channel is variable.  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. Pancreas Divisum - the ducts of Wirsung and Santorini fail to fuse resulting to the majority of the pancreas draining through the duct of Santorini and the lesser papilla. The minor papilla can be inadequate to handle the flow of pancreatic juices from the majority of the gland. This relative outflow obstruction can result in pancreatitis and is sometimes treated by sphincteroplasty of the minor papilla.  The main pancreatic duct is usually only 2-3mm in diameter. Pressure in the pancreatic duct is about twice that in the common bile duct to prevent reflux of bile into the pancreatic duct.  The main pancreatic duct joins with the common bile duct and empties at the ampulla of Vater or major papilla, which is nd located on the medial aspect of the 2 portion of the duodenum. Sphincter of Oddi – muscle fibers around the ampulla which controls the flow of pancreatic and biliary secretions into the duodenum. Contraction and relaxation of the sphincter is regulated by complex neural and hormonal factors.  Two (2) cm proximal to the ampulla of Vater lies the lesser papilla from the duct of Santorini. Vascular & Lymphatic Anatomy  Blood supply from the pancreas comes from multiple branches from the celiac and superior mesenteric arteries.  The common hepatic artery gives rise to the gastroduodenal artery before continuing toward the porta hepatis as the proper hepatic artery.  The right gastric artery branches off the gastroduodenal artery just superior to the duodenum. The gastroduodenal artery then travels inferiorly anterior to the neck of the pancreas and posterior to the duodenal bulb. A posterior ulcer in the duodenal bulb can erode into the gastroduodenal artery in this location.  At the inferior border of the duodenum, the gastroduodenal artery gives rise to the right gastroepiploic artert then continues on as the anterior superior pancreaticoduodenal artery, which branches into the anterior and posterior superior pancreaticoduodenal arteries.  As the superior mesenteric artery passes behind the neck of the pancreas, it gives off the inferior pancreaticoduodenal artery at the inferior margin of the neck of the pancreas. This vessel quickly divides into the anterior and posterior pancreaticoduodenal arteries. The superior and inferior pancreaticoduodenal arteries join together within the parenchyma of the anterior and posterior sides of the head

DocMegz2017

of the pancreas along the medial aspect of the C-loop of the duodenum and head of the pancreas.  Therefore, it is impossible to resect the head of the pancreas without devascularizing the duodenum, unless a rim of pancreas containing the pancreaticoduodenal arcade is preserved.  The right hepatic artery, common hepatic artery or gastroduodenal arteries can arise from the superior mesenteric artery. Replaced Right Hepatic Artery- the right hepatic artery will arise from the superior mesenteric artery and travel upwards toward the liver along the posterior aspect of the head of the pancreas.  The body and tail of the pancreas are supplied by multiple branches of the splenic artery. The splenic artery arises from the celiac trunk and travels along the posterior-superior border of the body and tail of the pancreas toward the spleen.  The inferior pancreatic artery usually arises from the superior mesenteric artery and runs to the left along the inferior border of the body and tail of the pancreas, parallel to the splenic artery. Three vessels run perpendicular to the long axis of the pancreatic body and tail and connect the splenic artery and inferior pancreatic artery. From medial to lateral.. Dorsal Pancreatic Artery Great Pancreatic Artery Caudal Pancreatic artery  These arteries form arcades within the body and tail of the pancreas, and account for the rich vascular blood supply.  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.  The superior veins drain directly into the portal vein just above the neck of the pancreas.  The posterior inferior arcade drains directly into the inferior mesenteric vein at the inferior border of the neck of the pancreas. These venous tributaries must be 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, which enters into the superior mesenteric veins.  Traction on the transverse colon during colectomy can tear these fragile veins.  There are also 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.  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.  Pancreatic cancer often presents with positive lymph nodes and a high incidence of local recurrence after resection.

Page 2

 Lymph nodes can be 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 the nodes and lymph nodes along the splenic vein and in the hilum of the spleen.

 The pancreatic juice is a combination of acinar cell and duct cell secretions.

Neuroanatomy  The pancreas is innervated by the sympathetic and parasympathetic nervous systems.  The acinar cells responsible for exocrine secretion.  The islets for endocrine secretion.  The islet vasculature are innervated by both systems.  The parasympathetic system stimulates endocrine and exocrine secretion.  The sympathetic system inhibits secretion.

Pancreatic amylase – only pancreatic enzyme secreted in active form; hydrolyzes starch and glycogen to glucose, maltose, maltotriose, and dextrins.

The pancreas is also innervated by neurons that secrete amines and peptides: Somatostatin Vasoactive Intestinal Peptide (VIP) Calcitonin gene-related peptide (CGRP) Galanin  The pancreas also has a rich supply of afferent sensory fibers, which are responsible for the 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 fibers can stop transmission of pain sensation. Histology and Physiology 85% - exocrine function 10% - extracellular matrix 4% - blood vessels and major ducts 2% - endocrine tissue  Although patients can live without a pancreas when insulin and digestive enzyme replacement are administered, the loss of the islet-acinar coordination leads to impairment in digestive function.  Although only approximately 20% of the normal pancreas is required to prevent insufficiency, in many patients undergoing pancreatic resection, the remaining pancreas is not normal, and pancreatic endocrine and exocrine insufficiency can develop with removal of smaller portions of the gland. The Exocrine Pancreas  Secretes approximately 500-800 mL per day of colorless, odorless, alkaline, isosmotic pancreatic juice.

DocMegz2017

Acinar cells – 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. Secretions: Amylase Proteases Lipases

Cholecystokinin (CCK) releasing peptide, CCK and secretin – released by endocrine cells that stimulate the pancreas to secrete enzymes and bicarbonate into the intestine from gastric hydrolysis of protein Proteolytic enzymes – secreted as proenzymes that require activation. Trypsinogen – converted to its active form, Trypsin – by another enzyme, Enterokinase (from duodenal mucosal cells) Trypsin in turn activates other proteolytic enzymes. But its activation is also prevented by the presence of inhibitors that are also secreted by the acinar cells. Familial Pancreatitis - caused by a failure to express a normal trypsinogen inhibitor, Pancreatic Secretory Trypsin Inhibitor (PSTI) aka Serine Protease Inhibitor Kazal Type 1 (SPINK1). Inhibition of trypsinogen activation ensures that enzymes WITHIN the pancreas remain inactive and are activated only within the duodenum. PRSS1 mutation – results in premature, intrapancreatic activation of trypsinogen; accounts for 2/3 of cases of hereditary pancreatitis. Chymotrypsinogen – activated to form chymotrypsin. Elastase, Carboxypeptidase A&B, Phospholipase – also activated by trypsin. Trypsin, Chymotrypsin and Elastase – cleave bonds between amino acids within a target peptide chain Carboxypeptidase A & 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.

Page 3

Pancreatic lipase – hydrolyzes triglycerides to 1-monoglyceride and fatty acid. It is secreted in an active form. Colipase – also secreted by the pancreas and binds to lipase, changing its molecular configuration and increasing its activity. Phospholipase A2 – secreted by the pancreas as a proenzyme that becomes activated by trypsin. It hydrolyzes phospholipids and as with all lipases, requires bile salts for its action. Carboxylic Ester Hydrolase & Cholesterol Esterase – hydrolyze neutral lipid substrates. The hydrolyzed fat is then packaged into micelles for transport into the intestinal epithelial cells, where the fatty acids are reassembled and packaged inside the chylomicrons for transport through the lymphatic system into the bloodstream. Centroacinar and Intercalated duct cells – secrete water and electrolytes present in the pancreatic juice; also contain the enzyme carbonic anhydrase which is needed for bicarbonate secretion. Acinus – composed of 40 acinar cells arranged into a spherical unit with centroacinar cells located in the center. The amount of bicarbonate secreted varies with the pancreatic secretory rate, with greater concentrations of bicarbonate being secreted as the pancreatic secretory rate increases. Chloride secretion varies inversely with bicarbonate secretion. Sodium and potassium concentrations are kept constant. Secretin – hormone released from cells in the duodenal mucosa in response to acidic chime passing through the pylorus in the duodenum; major stimulant for bicarbonate secretion which buffers the acidic fluid entering the duodenum from the stomach. CCK also stimulates bicarbonate secretion but to a much lesser extent than secretin. CCK potentiates secretin-stimulated bicarbonate secretion. Gastrin & Acetylcholine – both stimulants of gastric acid secretion and weak stimulants of pancreatic bicarbonate secretion. Truncal vagotomy reduces bicarbonate and fluid secretion. Inhibits exocrine secretion: Somatostatin Pancreatic polypeptide (PP) Glucagon Destruction of the branching ductal tree from recurrent inflammation, scarring, and deposition of stones eventually contributes to destruction of the exocrine pancreas and exocrine pancreatic insufficiency.

DocMegz2017

Endocrine Pancreas Islets of Langerhans – 1 million in the normal adult pancreas and vary greatly in size from 40 to 900 um. Most islets contain 3000-4000 cells of five major types: Alpha cells – secrete glucagon Beta cells – secret insulin Delta Cells – secrete somatostatin Epsilon Cells – secrete ghrelin PP cells – secrete PP Insulin – 56-amino acid peptide with two chains, alpha and beta chain, joined by two disulfide bridges and a connecting peptide or C peptide. Proinsulin – made in the endoplasmic reticulum and then is transported to the Golgi complex, where it is packaged into granules and the C-peptide is cleaved off. Phases of Insulin Secretion First Phase – lasts about 5 minutes after a glucose challenge Second Phase – longer, sustained release due to ongoing production of new insulin. Beta cell synthesis of insulin is regulated/influenced by the following: Plasma glucose levels Neural signals Paracrine influence of other islet cells Plasma amino acid levels (arginine, lysine, leucine) Free fatty acids Diagnosis: using oral and intravenous (IV) glucose tolerance tests. Oral glucose does not only enters the bloodstream but also stimulates the release of ff enteric hormones: Glucose-dependent Insulinotropic Polypeptide (GIP) Glucagon-like peptide 1 (GLP-1) Incretins Oral glucose tolerance test (OGTT)  Patient is fasted overnight  Basal glucose value is determined  75 g of glucose is given orally over 10 minutes  Blood samples are taken every 30 minutes for 2 hours.  Normal values and criteria for diabetes vary by age, but essentially all values should be GLUCOSE Inhibited by: Glucagon Somatostatin

 Vagal stimulation is the most important regulator of PP secretion. Vagotomy eliminates the rise in PP levels usually seen after a meal. This 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 choleresis (bile secretion) and gallbladder contraction and secretion by the exocrine pancreas.  PP’s most important role is in glucose regulation.  Deficiency in PP secretion is associated with diminished hepatic insulin sensitivity Ghrelin – secreted from Epsilon cells; also present in the gastric fundus in large amounts and stimulates growth hormone secretion; Orexigenic or appetite stimulating; block insulin effects on the liver and inhibits Beta cell response to incretin and glucose. Amylin/Islet Amyloid Polypeptide (IAPP) – found in pancreatic Beta cells stored along with insulin; modulates or counterregulates insulin secretion and function. Pancreastatin – inhibits insulin and possibly somatostatin release; augments glucose release; inhibits pancreatic exocrine secretion. Islet Distribution 70% total islet cell mass - made up of Beta cells located in the center, while the rest are in the periphery 5% - Delta cells 10% - Alpha cells 15% - PP cells  In reality, more than 20 different hormones are secreted by the islets, and the exact functions of this milieau are very complex.  Alpha and Beta cells are evenly distributed throughout the pancreas but islets in the head and uncinate process (ventral anlage) have a higher % of PP cells and fewer Alpha cells  In the body and tail (dorsal anlage), majority are Alpha cells and few PP cells.  Pancreatoduodenectomy removes 95% of PP cells in the pancreas leading to higher incidence of glucose intolerance after the Whipple procedure compared to a distal pancreatectomy with an equivalent amount of tissue resected.

Page 5

Acute Pancreatitis  HALLMARK: Acute pancreatic inflammation associated with little or no fibrosis.  Ranges from mild self-limiting inflammation to critical disease characterized by infected pancreatic necrosis, multiple organ failure, and a high risk of mortality  Smoking – independent risk factor for acute pancreatitis. Etiology  Gallstones (females) and alcohol (males) – 80% of cases; most common  Idiopathic type – characteristic finding of microlithiasis, birefringent crystals on bile microscopy Gallstones Hypothesis for Acute Pancreatitis 1. Common channel hypothesis – it was proposed that a gallstone transiently lodged in the distal common channel of the ampulla of Vater allowed bile to reflux into the pancreatic duct form. 2. Transient incompetence caused by the passage of a stone through the sphincter might allow duodenal fluid and bile to reflux into the pancreatic duct 3. Gallstone obstructing the pancreatic duct leading to ductal hypertension. This backpressure might lead to minor ductal disruption, extravasation of pancreatic juice into the less alkaline interstitium of the pancreas, and promotion of enzyme activation Alcohol  Sustained alcohol ingestion + recurrent acute pancreatitis can lead to chronic pancreatitis (drinking for more than a decade)  Type of alcohol consumed is less important than the amount consumed 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.  Ethanol is a metabolic toxin to pancreatic acinar cells  The secretory burst coupled with ethanol induced spasm of the sphincter of Oddi incited acute pancreatitis  Ethanol also induces ductal permeability  Ethanol also increases protein content of pancreatic juice, decrease bicarbonate levels and trypsin inhibitor concentration  Formation of protein plugs causing obstruction Iatrogenic Pancreatic Biopsy Exploration of the extrahepatic biliary tree and AOV Distal gastrectomy Splenectomy Colectomy Nephrectomy Aortic Aneurysmorraphy Retroperitoneal lymphadenectomy Splanchnic hypoperfusion with cardio-pulmonary bypass

DocMegz2017

Hereditary Pancreatitis PRSS1 cationic trypsinogen gene mutation – premature activation of trypsinogen SPINK1 protein mutation from which blocks the binding site of trypsin Tumors Pancreatic or periampullary tumor Hyperlipidemia Patients with Type I and V hyperlipoproteinemia with marked hypertriglyceridemia Lipase liberates toxic fatty acids into the pancreatic microcirculation leading to impairment and ischemia Tx: Clofibrate, Dietary modification Drugs & Miscellaneous Thiazide diuretics Azathioprine Furosemide Estrogens 1-asparaginase Methyldopa 6-mercaptopurine Tetracycline Sulfonamides Pentamidine Procainamide Nitrofurantoin Dideoxyinosine Valproic acid AChe inhibitors Hypercalcemia from hyperparathyroidism Ascaris lumbricoides Clonorchis sinensis causing Oriental cholengitis Azotemia Vasculitis Sting of the Trinidadian scorpion Pathophysiology Pancreatitis begins with the activation of digestive zymogens inside acinar cells, which cause acinar injury Precipitating Initial Events A. Acinar Cell Events Pancreatitis is essentially the premature, intrapancreatic activation of digestive enzymes, resulting to autodigestion. There is intra-acinar activation of trypsinogen from injurious stimuli. Several Protective mechanisms: 1. Enzymes are synthesized as inactive precursors called proenzymes or zymogens. The activation occurs safely in the duodenum where the brush border enteropeptidases (aka enterokinase) activates the trypsinogen and the resulting trypsin activates other zymogens. 2. Synthesis of trypsin inhibitors which are transported and stored along with the digestive enzyme zymogens to inhibit prematurely activated trypsinogen within the pancreatic acinar cells. 3. Acute Pancreatitis can occur locally (within the gland) with Cathepsin B which is located in the cytoplasmic vacuole of the

Page 6

cells. It activates trypsinogen. Cathepsin once activated and in the cytosol, initiates apoptotic death. There is release of Cytochrome C that initiates apoptotic cascade. Inhibition of cathepsin B by pharmacological inhibitors or by genetic depletion of cathepsin B eliminates trypsin activation. 4. Injurious stimuli leads to sustained cytosolic Calcium increase. Blocking the Calcium increase prevents co-localization and activation of trypsin. Pre-ERCP (Endoscopic Retrograde Cholangipnacreatography) supplementation of Magnesium, antagonist of Calicum is currently evaluated. B. Intrapancreatic Events 1. Activated Neutrophils in tissue injury release superoxides (“respiratory burst”) and proteolytic enzymes (cathepsins, elastase, and collagenase) which cause further injury. 2. Macrophage release cytokines (TNF Alpha, IL6, IL8) which mediate local and systemic inflammatory response leading to pancreatic vascular permeability resulting to edema, hemorrhage and microthrombi. Failure of pancreatic microcirculation results in hypoperfusion and necrosis. Interstitial Edematous Pancreatitis – is acute inflammation of the pancreatic parenchyma and peripancreatic tissues but without recognizable necrosis. Necrotizing Pancreatitis – term when necrosis is present, should be evidenced by pancreatic hypoperfusion with contrast CT. C. Systemic Events 1. There is systemic inflammation and multiorgan failure. 2. The NFkB-dependent inflammatory pathway is the KEY pathway. It activates typsin independently from sustained Calcium increase. Once activated, it synthesizes multiple cytokines and chemokines leading to recruitment of various inflammatory cells. TAKE NOTE that although intra-acinar events initiate acute pancreatitis, events occurring SUBSEQUENT to acinar cell injury will determine the SEVERITY. Elucidation of inflammatory mediators (TNF A, IL1, IL2, IL6) can modulate the course of severe acute pancreatitis. 3. Organ failure can develop at any stage of acute pancreatitis associated with an overwhelming proinflammatory response. The proinflammatory constituents can appear in the mesenteric lymph bypassing the liver may contribute to the development of organ failure. 4. The development of Pancreatic Necrosis, breakdown of intestinal barrier, suppression of the immune response (peak in rd th the 3 to 4 week) may cause deterioration in the patient and may result to late development of Systemic Inflammatory Response Syndrome (SIRS) and Multiorgan Dysfunction syndrome/failure (MODS/F)

Organ systems frequently involved: Cardiovascular Respiratory Renal Management of the Patient General Considerations    

Mild acute pancreatitis – less than a week in the hosp Severe/Critical type – weeks or months The risk of mortality reflects the spectrum of severity. THE EARLIER IDENTIFICATION OF HIGH RISK CATEGORIES AND TRANSFER OF PATIENTS TO SPECIALIZED CENTERS IS AN IMPORTANT PRIORITY OF MANAGEMENT.  Use Ranson’s Criteria to identify high risk patients. Diagnosis  Acute onset of severe constant epigastric pain which often radiates through to the mid back  Elevation of serum amylase or lipase (>3x upper limit of normal) – to rule out hyperamylasemia  Imaging (usually by contrast enhanced CT scanning) is ONLY required for the diagnosis of acute pancreatitis when these diagnostic criteria are NOT MET.  Serum Amylase conc increases almost immediately with the onset of disease and peaks within several hours. It remains elevated for 3-5 days before returning to normal.  There is NO significant correlation between the magnitude of serum amylase elevation and severity of pancreatitis.  Hyperamylasemia can occur NOT INVOLVING the pancreatitis. (Small bowel obstruction, perforated duodenal ulcer)  In patients with hyperlipidemia, serum amylase can be NORMAL because of the interference of lipids with chemical determination of serum amylase.  Urinary clearance levels of pancreatic enzymes is a more sensitive marker than serum levels in pancreatitis! It is recommended that amylase concentrations also be measured in the urine. Urinary amylase levels usually remain elevated for several days after serum levels have returned to normal.. even in patients with severe pancreatitis associated with significant necrotic damage where the pancreas may not release large amounts of enzymes into the circulation.  With increasing severity of disease, the intravascular fluid loss may become life-threatening as a result of sequestration of edematous fluid in the retroperitoneum.  There may also be bleeding into the retroperitoneum or peritoneal cavity. Blood from necrotizing pancreatitis may dissect through soft tissues and manifest as a bluish discoloration around the umbilicus (CULLEN’s SIGN) or in the flanks (GREY TURNER’S SIGN)  Severe fluid loss may lead to prerenal azotemia, hyperglycemia, hypoalbuminemia, and hypocalcemia to produce tetany.

Organ failure is scored using the Marshall or Sequential Organ Failure Assessment (SOFA) systems.

DocMegz2017

Page 7

Pain Management  PAIN is the CARDINAL SYMPTOM of acute pancreatitis  Those with mild pain can usually be managed with NSAID  Severe pain are best managed with Opioid analgesia

 MR is superior to CT scanning in detecting any sold component within collections  Arterial Phase CT Scan (CTa) is useful in detecting pseudoaneurysm, active bleeding and/or hematoma.

Buprenorphione Pentazocine Procaine Hydrochloride Meperidine

Therapeutic Endoscopic Retrograde Cholangiopancreatography (ERCP)  Early ERCP reduces complications but not mortality in patients with severe gallstone-associated acute pancreatitis.  The benefits of this may be offset however there is risk in the procedure – increase severity of pancreatitis, bleeding, cholangitis, and duodenal perforation.

*Morphine – is AVOIDED due to its potential to cause sphincter of Oddi spasm. Predicting Severity  Accurately predicting acute pancreatitis severity is important in making triage decisions.  Use Ranson’s criteria or modified Glasgow criteria  When 3 or more positive criteria, the disease is considered “predicted severe” Determining the Etiology  History of alcohol ingestion and blood ethanol levels  Gallstones by ultrasonography (females over age 50 with elevated ALP >300 IU/L, ALT >100 IU/L and Amylase >4000 IU/L)  In the absence of gallstone and alcohol, include history of drug abuse, trauma, ERCP, infection, measure serum Triglycerides, Calcium, Fluid Resuscitation  Fluid therapy to restore and maintain circulating blood volume is the most important intervention in the early management of acute pancreatitis.  It is best to resuscitate with a balanced crystalloid and to restore normal blood volume, blood pressure, and urine output. Lactated Ringer’s solution may be superior to normal saline in reducing systemic inflammatory response.  Caution in patients with cardiac and renal disease and in the elderly. Nutritional support  It is no longer acceptable to “rest the pancreas” by avoiding enteral nutrition, and parenteral nutrition should only be offered. Enteral nutrition should be commenced after initial fluid resuscitation and within the first 24 hours of admission.  A delay in commencing early enteral nutrition may contribute to the development of intestinal ileus and feeding intolerance.  Aggressive early enteral feeding particularly prior to adequate resuscitation may put the patient at risk of nonocclusive mesenteric ischemia. Cross-Sectional Imaging  It may be necessary to perform CT Scan to diagnose acute pancreatitis in patients who are severely ill, undifferentiated abdominal pain.  The primary purpose of cross sectional imagine is the diagnosis of local complications, extent of pancreatic necrosis, or presence of different fluid collections.

DocMegz2017

Antibiotics  The use of broad-spectrum antibiotics to treat established infection in acute pancreatitis is well-established practice but not as prophylactic antibiotic. Managing Local Complications  Vigilance is required for the timely and accurate diagnosis of local complications.  The decision to intervene is based on the clinical status and trajectory of the patient.  Close monitoring: regular measurement of inflammatory markers and pancreatic protocol CT Scan if local complication is suspected.  In practice, intervention is DELAYED in order to allow demarcation of necrosis, and a reduced risk of bleeding, disseminated infection and collateral damage to adjacent organs. Percutaneous Catheter drainage – used in pxn with suspected infected complications; prefer than Fine Needle Aspiration since it “buys time,” lesion becomes more walled, and safer to treat.  Surgical technique should only be considered in those who fail to respond to the “step-up approach” that is prior percutaneous drainage and minimally invasive intervention.  Pseudocyst is usually conservative since half of these will resolve spontaneously. In pseudocyst, percutaneous drainage should be avoided for the risk of external pancreatic fistula. Transpapillary Pancreatic Duct Stenting is the preferred approach. Managing Organ Failure The responsiveness of orgain failure to resuscitation over the first 48 hours is an important prognostic clue. Cholecystectomy While it is widely accepted that cholecystectomy is essential to prevent gallstone pancreatitis recurrence, the timing is important. Index cholecystectomy – appears safe and accomplished laparoscopically but not suitable for all patients, particulary who had local complications which include a large phlegmon that extends into the porta hepatis.

Page 8

Chronic Pancreatitis Incurable, chronic, multifactorial cause, highly variable in presentation and difficult to treat. Etiology Genetic Mutations Alcohol exposure Duct obstruction due to trauma, gallstones and tumors Metabolic diseases (hyperlipidemia, hyperparathyroidism, autoimmune) Nutritional (Tropical Pancreatitis) Idiopathic Genetic Causes  Patients first present in childhood or adolescence with abdominal pain and are found to have chronic calcific pancreatitis on imaging studies.  Progressive pancreatic dysfunction is common  Increase risk of subsequent carcinoma but typically at the age >50 y/o  Autosomal dominant pattern of inheritance (80% penetrance)  Incidence is equal in both sexes PRSS1 mutation - gain-of-function missense mutation in an Arg to His substitution at position 117 at chromosome 7q35 resulting to proteolysis of trypsin and excess production of trypsinogen R122H and N291 – additional mutations of PRSS1 PRSS2 – gain of function mutation in the anionic typsinogen gene SPINK1 mutation – loss-of-function of inhibiting trypsin action by competitively blocking the active site of the enzyme; associated with familial and idiopathic forms of chronic pancreatitis, and tropical pancreatitis. Cystic Fibrosis Transmembrane Receptor (CFTR) – present in pancreatic duct cells and controls the amount of chloride and bicarbonate secreted into the normally alkaline pancreatic juice; CFTR mutations are associated with Cystic Fibrosis, Classic Pulmonary disease (F508), Chronic idiopathic Pancreatitis, Autoimmune Pancreatitis CLDN2 gene – encodes a tight junction protein normally present in ductal cells; In chronic pancreatitis, CLDN protein is abnormally expressed in acinar cells, and may alter the secretory dynamics of enzyme release. Men with only one X chromosome have no protection if they inherit a CLDN2 mutation unlike in women. This helps to explain the high prevalence of alcoholic chronic pancreatitis among men.

DocMegz2017

Alcohol  Drunkard’s Pancreas  There is a linear relationship between exposure to alcohol and the development of chronic pancreatitis.  Although the risk of disease is dose related and highest in heavy (>150 g/d) drinkers, the prevalence of chronic pancreatitis among confirmed alcohol abusers is only 5 to 15%  However, the duration of alcohol consumption is definitely associated with the development of pancreatic disease.  The onset occurs between ages 35 to 40 years after 16-20 years of alcoholic consumption.  Recurrent episodes of acute pancreatitis are typically followed by chronic symptoms after 4 or 5 years  It was proposed that chronic pancreatitis was the result of multiple episodes of acute inflammation, with residual and progressively increasing chronic inflammation.  Others proposed that initial acute inflammation was not necessarily linked to chronic changes in the pancreas. Other additional factors were necessary for repeated exposure  Regardless, the concept of multiple episodes of pancreatic injury ultimately leads to chronic disease is widely accepted as the pathophysiologic sequence.  Repeated or severe episodes of toxin-induced injury activates a cascade of cytokines, which, in turn, induces pancreatic stellate cells (PSCs) to produce collagen and cause fibrosis  Alcohol may interfere with intracellular transport and discharge of digestive enzymes and may contribute to the colocalization of digestive enzymes and lysosomal hydrolase within acinar cells leading to autodigestion.  High protein, low bicarbonate, low volume secretory output is seen in chronic alcohol exposure. Calcium is complexed to protein plugs that in the end promotes an inflammatory response.  Cigarette smoking has been strongly associated with chronic pancreatitis but until recently it was unclear whether this was a causative factor. Recently, smoking accelerates the development of alcoholic pancreatitis, and the risk of cancer in chronic pancreatitis is increased significantly. Smoking appears to be an independent risk factor. Hyperparathyroidism  Hypercalcemia is a known cause of pancreatic hypersecretion, and chronic hypercalcemia caused by untreated hyperparathyroidism is associated with chronic calcific pancreatitis, calculus formation, and obstructive pancreatopathy.  Treatment: Correction of hyperparathyroidism Hyperlipidemia  Predisposing factor in women when they receive estrogen replacement therapy  Aggressive therapy of hyperlipidemia is important in peri- or postmenopausal patients

Page 9

Classification TIGAR-O Categorizing Scheme T- Toxic metabolic I- Idiopathic G – Genetic A – Autoimmune R – Recurrent and severe acute pancreatitis O – Obstructive Chronic Calcific (Lithogenic) Pancreatitis  Includes patients with calcific pancreatitis of most etiologies  Although the majority of patients with calcific pancreatitis has a history of alcohol abuse, stone formation and parenchymal classification can develop in a variety of etiologic subgroups.  The clinician should therefore avoid the assumption that calcific pancreatitis confirms the diagnosis of alcohol abuse Chronic Obstructive Pancreatitis Refers to chronic inflammatory changes that are caused by the compression or occlusion of the proximal ductal system by tumor, gallstone, posttraumatic scar, or inadequate duct caliber. (Recall Pancreas Divisum) Chronic Inflammatory Pancreatitis  Diffuse fibrosis and loss of acinar elements with a predominant mononuclear cell infiltration  Increased levels of serum B-globulin or IgG4 are also present.  Steroid therapy is uniformly successful. Autoimmune Pancreatitis – a variant of chronic pancreatitis that is nonobstructive, diffusely infiltrative disease associated with fibrosis, a mononuclear cell infiltrate (lymphocyte, plasma cell or eosinophil), and an increased titer of one or more autoantibodies; associated with Sjogren’s syndrome, RA, Type I DM Types: Type 1 AIP – with accompanying systemic or multiorgan dysfunction Type 2 – restricted to the pancreas only

Tropical (Nutritional) Pancreatitis – adolescent and young adults; brittle form of pancreatogenic diabetes. Patients appear malnourished, characteristic cyanotic coloration of the lips; with SPINK1 mutation (20-55% of pxn) and CFTR mutations; the accelerated deterioration of endocrine and exocrine function, the chronic pain due to obstructive disease, and the recurrence of symptoms despite decompressive procedures characterize the course of the disease. Asymptomatic Pancreatic Fibrosis – elderly pxn; diffuse perilobular fibrosis and a loss of acinar cell mass but without a main ductular component.

DocMegz2017

Idiopathic Pancreatitis – lacks definable cause; young adults and adolescents without family history of pancreatitis; SPINK 1 and CFTR mutations; also found in the elderly with biliary tract disease. Pathology Histology  Unevenly distributed, induration, nodular scarring, lobular regions of fibrosis  As disease progress there is loss of normal lobulation with thicker sheets of fibrosis  Ductular epithelium is usually atypical, with dysplasia  Cuboidal cells with hyperplastic feature  Areas of mononuclear cell infiltrates or patchy areas of necrosis  Cystic changes seen  Tropical pancreatitis and hereditary pancreatitis are histologically indistinguishable from chronic alcoholic pancreatitis.  In obstructive chronic pancreatitis, calculi are absent  In pancreatic lobular fibrosis seen in the elderly, small ducts are dilated, sometimes with small calculi trapped within Fibrosis  Common feature of all forms of chronic pancreatitis is the perilobular fibrosis the forms surrounding acini, then propagates to surround small lobules, and eventually coalesces to replace larger areas of acinar tissue.  Pathogenesis involves the activation of pancreatic stellate cells (PSCs)  In response to pancreatic injury, the PSCs become activated and proliferate, lose their lipid vesicles and transform into myofibroblast-like cells. These cells respond to proliferative factors (TGF Beta, PDGF), and synthesize and secrete Type I and III collagen, fibronectin

Stone Formation Pancreatic stones are composed largely of calcium carbonate crystals trapped in a matrix of fibrillar and other material The fibrillar center contains no calcium but a mixture of other metals. This suggests that stones form from an initial noncalcified protein precipitation. The same low MW protein is present in stones and protein plugs and was initially named Pancreatic Stone Protein (PSP) PSP was found to be a potent inhibitor of Calcium carbonate crystal growth and has subsequently been renamed Lithostanthine Independently, Pancreatic Thread protein has been shown to be homologous with lithostanthine. Finally, reg protein was subsequently found to be homologous with lithostanthine

Page 10

The PSP/Pancreatic Thread Protein/reg/Lithostathine gene codes for a 166-amino acid product that undergoes post translational modification to produce isoforms present in pancreatic juice. High concentrations found in pyramidal neurons in Alzheimer’s disease and Down Syndrome, and also found in renal tubules which is consistent with its biologic action of preventing calcium carbonate precipitation.

Presentation, Natural History, and Complications Presenting Signs & Symptoms  Pain is the most common symptom of chronic pancreatitis.  Midepigastric but may localize or involve either the left or right upper quadrant of the abdomen  Occasionally it is perceived in the lower midabdomen  Frequently described as penetrating through to the back  Persists for hours or days  May be chronic with exacerbation caused by eating/drinking alcohol  Chronic alcoholic also describe a steady, constant pain temporarily relieved by alcohol, followed by more severe recurrence hours later  Patients with chronic pancreatic pain typically flex their abdomen  Either sit or lie with hips flexed of in a fetal position  The pain causes the patient to be still  Nausea/vomiting may accompany the pain  Anorexia is the most common assoc symptom

1.

2.

3.

Etiologies Ductal hypertension due to strictures or stones, may predispose to pain that is initiated or exacerbated by eating. A chronic pain without exacerbation may be related to parenchymal disease or retroperitoneal inflammation with persistent neural involvement. Acute exacerbations of pain in the setting of chronic pain may be due to acute increase in duct pressure or recurrent episodes of acute inflammation in the setting of chronic parenchymal disease.

 Pain that is found in association with ductal hypertension is most readily relieved by pancreatic duct decompression, through endoscopic stenting or surgical decompression.  The surgical relief of pain due to obstructive pancreatopathy may be dependent on the degree of underlying fibrosis rather than the presence of ductal obstruction

 The role of chronic inflammation and development of nerve damage in the diseased gland also thought to contribute to pain.  Chronic inflammation results in the infiltration of tissue by macrophages which secrete prostaglandins and other nociceptive agents  Inflammatory damage to the perineural layers surrounding the unmyelinated pancreatic nerves and a focal infiltration of inflammatory cells around nerves suggest that neural fibers are a target for cellular response to inflammation in the pancreas

1. 2. 3.

Malabsorption and Weight Loss  Pancreatic exocrine capacity falls 25 g/L and a markedly elevated amylase level. Serum albumin may be low. ERCP is most helpful

 Pseudocysts may become secondarily infected, in which they become abscesses.  They can compress or obstruct adjacent organs or structure leading the superior mesenteric vein thrombosis or splenic vein thrombosis.  They can erode into visceral arteries and cause pseudoaneurysms  They can perforate and cause peritonitis or intraperitoneal bleeding  Pseudocysts usually cause symptoms of pain, fullness or early satiety  Sometimes pseudocysts resemble cystadenoma and cystadenocarcinoma radiographically and should be examined by EUS and aspirate to determine whether it is a true neoplasm or pseudocyst.  If infection is suspected, the pseudocyst should be aspirated (NOT drained) by CT or US-guided FNA and the contents examined for organisms by Gram’s stain and culture.  If pseudocyst failed to resolve with conservative therapy, internal drainage is usually preferred to avoid complication of a pancreaticocutaneous fistula.

Pancreatic-Enteric Fistula - the erosion of a pancreatic pseudocyst into an adjacent hollow viscus can result in a pancreatic-enteric fistula.

Internal drainage may be performed with: Percutaneous catheter-based methods (Transgastric puncture and stent Placement Endoscopic methods (Transgastric or transduodenal puncture and multiple stent placements, with or without a nasocystic irrigation catheter) Surgery (True cystoenterostomy, biopsy of cyst wall, and evacuation of all debris and contents – cystogastrostomy, Rouxen-Y cystojejunostomy, or cystoduodenostomy) Transductal drainage may be a safe and effective approach to the management of pseudocystic disease. Complications of endoscopic or radiologic drainage: Bleeding from cystoeneterostomy Incoulation of a pseudocyst with failure of resolution Persistence of infection Pancreatic Ascites When a disrupted pancreatic duct leads to pancreatic fluid extravasation that does not become sequestered as a pseudocyst, but drains freely into the peritoneal cavity, pancreatic ascites occurs.

DocMegz2017

The most common site – transverse colon or splenic flexure Fistula presents with evidence of GI or colonic bleeding and sepsis Head-of-Pancreas Mass Inflammatory mass in the head of the pancreas in advanced chronic pancreatitis Clinical Presentation Severe pain Stenosis of the distal common bile duct Duodenal stenosis Compression of Portal vein Stenosis of the proximal main pancreatic duct An accelerated transformation from hyperplasia to dysplasia exist in patients with pancreatic head enlargement (also, mutation and polymorphisms of p53) Splenic and Portal Vein Thrombosis Left sided or Sinistral Portal Hypertension – formation of variceal as a consequence of either portal or splenic venous occlusion and splenic vein thrombosis Treatment Medical Therapy Analgesics Cessation of alcohol use Oral enzyme therapy Selective use of antisecretory therapy Analgesia Oral analgesics are prescribed as needed, alone or with analgesia-enhancing agents (gabapentin). Narcotics for adequate pain control Essential to abstain from alcohol Enzyme Therapy Pancreatic enzyme administration serves to reverse the effects of pancreatic exocrine insufficiency. All patients with chronic pancreatitis pain begin with nonenteric-coated enzyme supplement together with acidsuppressive medication.

Page 13

Antisecretory Therapy Somatostatin administration – inhibit pancreatic exocrine secretion and CCK release Octreotide Acetate – somatostatin analogue Neurolytic Therapy Cardiac plexus neurolysis with alcohol injection has been an effective form of analagesic treatment in patients with pancreatic carcinoma; short-acting Endoscopic Management Pancreatic Duct Stenting – used for treatment of proximal pancreatic duct stenosis, decompression of a pancreatic duct leak, and for drainage of pancreatic pseudocysts that can be catheterized through the main pancreatic duct Extracorporeal shock wave Lithotripsy (ESWL) – used for pancreatic duct stones, together with endoscopic stenting and stone removal. Surgical Therapy  Surgery should be considered only when the medical therapy of symptoms has failed.  The choice of operation and the timing of surgery are based on each patient’s pancreatic anatomy, the likelihood that further medical and endoscopic therapy will halt the symptoms of the disease, and the chance that a good result will be obtained with the lowest risk of morbidity and mortality.  Preparation for surgery should include restoration of proteincaloric homeostasis, abstinence from alcohol and tobacco. Sphincteroplasty  The Sphincter of Oddi and the pancreatic duct sphincter serve as gatekeeper for the passage of pancreatic juice into the duodenum.  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  Transduodenal sphincterectomy with incision of the septum between the pancreatic duct and common bile duct appear to offer significant relief. Drainage Procedures (see pictures on separate page) Pancreaticojejunostomy Duval Procedure / Caudal Roux-en-Y pancreaticojejunostomy Puestow Procedure / Longitudinal or side-to-side Roux-en-Y Pancreatojejunostomy – effective for pain relief when the maximum duct diameter is 6 mm; preferred method Resectional Procedures Distal Pancreatectomy - for patients with focal inflammatory changes localized to the body and tail, or in whom no significant ductal dilatation exists; risk for recurrence 95% Distal Pancreatectomy – intended for patients with sclerotic (small duct) disease, and which attempted to avoid the morbidity of total pancreatectomy by preserving the rim of

DocMegz2017

pancreas in the pancreaticoduodenal groove along with its associated blood vessels and distal common bile duct; disadv: high risk of brittle diabetes, hypoglycemia and malnutririon Proximal Pancreatectomy/ Pancreatojejunostomy/ Whipple’s Procedure – widely used, pain relief for 4-6 years, high rate of symptomatic relief that outweighs metabolic consequences and mortality risk Total pancreatectomy – disadvantage: brittle diabetes, lethal episodes of hypoglycemia, hypoglycemic unresponsiveness due to absence of pancreatic glucagon, iatrogenic hypoglycemia; rarely used for the tx of refractory chronic pancreatitis Duodenum-preserving Pancreatic Head Resection (DPPHR)/ Beger’s Procedure – requires careful dissection of the gastroduodenal artery and the creation of two anastomoses; risk of pancreatic leakage and intra-abdominal fluid collections. Local Resection of the Pancreatic Head with Longitudinal Pancreaticojejunostomy (LR-LPJ)/ Frey’s procedure – excavation of pancreatic head, including the ductal structures in continuity with a long dichotomy of the dorsal duct; decompression of the the head as well as the body and tail of the gland; preservation of the neck and the capsule of the posterior pancreatic head; ZERO mortality rate; less complications than Whipple’s and DPPHR. Organ-Preserving Pancreatic Head Resection (OPPHR) – excavating the core of the pancreatic head and draining with Lateral Pancreaticojejunostomy but without any effort to include the dorsal duct. Berne Modification of DPPHR – served as an alternative to DPPHR procedure in patients with portal hypertension; operative time and length of stay of patients were shorter. The removal of the central portion of the head of the gland is the key to the successful resolution of pain long term. Total Pancreatectomy with Islet Auto-Transplantation – for tx of diabetes in adjunct to pancreatic surgery from benign pancreatic disease. The ability to recover a sufficient quantity of islets from a sclerotic gland is dependent on the degree of fibrotic disease present. Pancreatic Neoplasms Endocrine Neoplasms Islet Cells originate from neural crest cells (amine precursor uptake and decarboxylation cells. MEN1 Syndrome – involves pituitary tumors, parathyroid hyperplasia, pancreatic neoplasms Insulinoma – most common functional pancreatic endocrine neoplasm and present with typical clinical syndrome known as WHIPPLE’S TRIAD; pxn present with profound syncopal episode; common sx include palpitations, trembling, diaphoresis, confusion orobtundation, seizure, personality

Page 14

change, elevated C-peptide levels, serum insulin elevated; 90% benign and solitary

malnutrition. Debulking operations are recommended in good operative candidates to relieve symptoms

Whipple’s Triad: Symptomatic fasting hypoglycemia Serum glucose level 60 years old; more common in men and African Americans; risk is 2-3x higher if parent or sibling has the disease Cigarette smoking – risk factor consistently linked to pancreatic cancer; 2-fold increase due to carcinogens present  Coffee and alcohol consumption are possible risk factors  Diets high in fat, low in fiber, fruits, and vegetable are increased risk  Diabetes has been known to be associated with pancreatic cancer  The new onset of diabetes, or sudden increase in insulin requirement in an elderly patient with pre-existing diabetes should provoke concern for the presence of pancreatic cancer. Genetics KRAS Oncogene – present in most cases of pancreatic cancer Her2/Neu Oncogene – homologous to Epidermal growth Factor receptor (EGFr) is overexpressed in pancreatic cancer Multiple Tumor Supressor genes: p53, p16, SMAD4, and in minority, BRCA2. Pathology Pancreatic Intraepithelial Neoplasia (PaIN) – precursor lesion

Page 15

THE ABILITY TO DETECT THESE PRECURSOR LESIONS IN HUMANS AT A STAGE WHERE THE CANCER CAN STILL BE PREVENTED OR CURED IS AN IMPORTANT GOAL OF CURRENT PANCEATIC CANCER RESEARCH! About 2/3 of pancreatic adenocarcinomas arise within the head or uncinate process of the pancreas. Tumors in the pancreatic body and tail are generally larger at the time of diagnosis,and therefore, less commonly resectable. Tumors in the head are typically diagnosed earlier because they cause obstructive jaundice. Acinar cell carcinoma – uncommon type that usually presents with a large tumor, often 10cm or more but prognosis is better. Diagnosis & Staging (refer to the table for TNM staging)

GOD BLESS SA ATING LAHAT!  #RoadtoVNeck -DocMegz

DocMegz2017

Page 16

DocMegz2017

Page 17

DocMegz2017

Page 18

DocMegz2017

Page 19