3ANATOMY:-Retroperitoneal-Regions:*Head: Adjacent to C-loop and posterior totransverse mesocolon, anterior tovena cava, right renal artery, andrenal veins. CBD transverses thepancreatic head and joins the mainpancreatic duct at the ampulla ofVater*Neck: Anterior to portal vein*Uncinate process: Wraps around portal vein and ends posteriorly in the spacebetween the SMA and SMV*Body & Tail: Anterior to splenic artery and vein. Located in floor of lesser sacposterior to stomach. Covered by gastrocolic omentum.
4Embryology:-The pancreas forms from two diverticulae of the endodermal lining of the foregut in a region which later becomes the duodenum.-The dorsal pancreatic bud passes anterior to the portal vein (forms head,neck, body, & tail).-The ventral pancreatic bud is smaller and rotates around behind the duodenum (forms caudate part of the head & the uncinate process.-Both buds then usually fuse (~8 weeks).-Ducts develop in both buds and fuse.-Pancreatic duct is usually 2-3 mm in diameter.
5-Duct of Wirsung starts at the tail and extends to the head -Duct of Wirsung starts at the tail and extends to the head. It terminates atthe papilla of Vater. It is derived from the ventral pancreatic bud.-Duct of Santorini (accessory pancreatic duct) drains a smallupper portion of the pancreatic head and terminates in the duodenum as asmall accessory papilla. It is derived from the dorsal pancreatic bud.
6PANCREAS DIVISUM:-In 10% of patients, the ducts of Wirsung and Santorini fail to fuse.-Most of the pancreas is then drained through the duct of Santorini and the minor papilla.-In some of these patients, the minor papilla is unable to handle the volume of pancreatic juices produced by the gland, resulting in a relative outflow obstruction.-Can result in pancreatitis.-Treatment: Sphincteroplasty of minor papilla.
7SPHINCTER OF ODDI:-The main pancreatic duct joins with the common bile duct and emptiesinto the ampulla of vater in the second portion of the duodenum.-Muscle fibers around the ampulla form the Sphincter of Oddi.-Contraction and relaxation of the Sphincter of Oddi are regulated by hormones and neuronal control.
8ARTERIAL SUPPLY:-Celiac axis gives off common hepatic, which gives riseto GDA, which becomes superior pancreaticoduodenalartery as it passes behind the 1st portion of theduodenum. This branches into the anterior andposterior superior pancreaticoduodenal arteries.-The SMA gives off the inferior pancreaticoduodenalartery as it passes behind the neck of the pancreas.This divides into the anterior and posterior inferiorpancreaticoduodenal arteries.The superior and inferior pancreaticoduodenal arteries join together to form an arcade of blood vessels supplying the pancreatic parenchyma and duodenum.The dorsal, great, and pancreatic arteries form connections between the splenic artery and the inferior pancreaticoduodenal artery.
9-Venous drainage tends to follow arterial supply. -Lymphatic drainage is diffuse and widespread. Lymphatics connect with the lymph nodes draining the jejunum and transverse mesocolon. There are also lymph nodes adjacent to the head of the pancreas as well as the hilum of the spleen.***The extensive lymphatics explain why pancreatic cancer often presents with positive lymph nodes and a high incidence of recurrence after resection.***
10NEURAL CONTROL OF PANCREATIC SECRETIONS: -Parasympathetics: Stimulate secretion of endocrine & exocrine pancreas.-Sympathetics: Inhibit secreation.-Rich supply of afferent sensory fibers, which are responsible for intense pain associated with pancreatitis and pancreatic cancer.
11EXOCRINE PANCREAS:-Secretes cc/day-Acinar cells contain zymogen granules, which fusewith the membrane and secrete a variety ofenzymes into a ductal system-These enzymes are responsible fordigestion of food.
12ENZYMES: *Amylase: Only pancreatic enzyme secreted in its active form Hydrolyzes starch and glycogen*Gastric hydrolysis of proteins causes peptides to enter the small intestine and releasecholecystokinin and secretin, which stimulate the pancreas to release enzymes andbicarbonate. Cl- secretion is inversely related to bicarbonate secretion.*The enzymes are secreted as proenzymes, which are then activated byenterokinase, located in the small intestine. Thisexplains why autodigestion of the pancreas doesnot occur.
13ENDOCRINE PANCREAS:* ~1 million islets of Langerhans (spherical collections of cells scattered throughoutthe pancreatic parenchyma)* Contain a variety of cells, which secrete a variety of hormones into the bloodstream
14Hormone Islet Cell Functions IAPP = islet amyloid polypeptide.Table 32-2 Pancreatic Islet Peptide ProductsHormoneIslet CellFunctionsInsulin (beta cell)Decreased gluconeogenesis, glycogenolysis, fatty acid breakdown and ketogenesisIncreased glycogenesis, protein synthesisGlucagon (alpha cell)Opposite effects of insulin; increased hepatic glycogenolysis and gluconeogenesisSomatostatin (delta cell)Inhibits gastrointestinal secretionInhibits secretion and action of all gastrointestinal endocrine peptidesInhibits cell growthPancreatic polypeptidePP (PP cell)Inhibits pancreatic exocrine secretion and secretion of insulinFacilitates hepatic effect of insulinAmylin (IAPP)Counterregulates insulin secretion and functionPancreastatinDecreases insulin and somatostatin releaseIncreases glucagon releaseDecreases pancreatic exocrine secretion
16ACUTE PANCREATITIS:*Inflammation of the pancreas with little or no fibrosis of the gland*Due to: AlcoholBiliary tract disease VasculitisHyperlipidemia Pancreatic duct obstructionHeredity NeoplasmsHypercalcemia Pancreas divisumTrauma Ampullary and duodenal lesionsSurgical InfectionsERCP Venom (scorpion)Ischemia Drugs (thiazides, lasix, estrogens,Hypoperfusion azathioprine, methyldopa, 6-MP, etc)Embolic Idiopathic
18ALCOHOL:-Pancreatitis may occur after a single use, but more often occurs in patients who have used g/day of alcohol >2 years. (10-15%)-Can be recurrent after continued alcohol abuse.-Mechanism:*Ethanol causes sphincter of Oddi spasm. (Blockage)*Ethanol is a metabolic toxin to pancreatic acinar cells, which interferes withenzyme synthesis and secretion.*Get initial secretory increase followed by inhibition. Enzymes and calciumprecipitate within the pancreatic duct, resulting in multiple obstructions.*Ethanol increases ductal permeability. Enzymes leak out into surroundingtissue.*Ethanol transiently decreases pancreatic blood flow, causing focal ischemia.
19Pathophysiology of acute pancreatitis: ***Ultimate severity of pancreatitis depends on the extent of the systemic inflammatory response and cytokines that play a role in activation and migration of inflammatory cells.***
20DIAGNOSIS:*Diagnosis of exclusion—Rule out perforated peptic ulcer, gangrenous small bowelobstruction, and cholecystitis. (Require immediate intervention)-Abdominal pain (usually epigastric), usually after a meal.-”Knifing” or “boring” pain through to the back—relieved by leaning forward.-Nausea and vomiting, with continued retching after stomach is emptied. Vomitingdoes not relieve the pain.-Tachycardia, tachypnea, hypotension, fever-Voluntary/Involuntary guarding-Decreased or absent bowel sounds-Abdomen may be distended with intraperitoneal fluid-Blood from necrotizing pancreatitis dissects through soft tissues and causes a bluishdiscoloration around the umbilicus (Cullen’s sign) or flanks (Gray Turnersign)
21Pancreatic-specific amylase: -More specific for pancreatitis (88-93%) Serum amylase:-usually increases immediately with onset of pancreatitis & peaks within a few hours (However, may be normal in pancreatitis)-remains elevated 3-5 days-no correlation between magnitude of elevation & severity of pancreatitis-can also be elevated with SBO, perforated duodenal ulcer, other intra-abdominal inflammatory conditionsUrine amylase:-may be more sensitive than serum amylase in detection of pancreatitis (lipids may interfere with measurement of serum amylase)-levels remain elevated for several days longer than serum amylasePancreatic-specific amylase:-More specific for pancreatitis (88-93%)Serum lipase:-Remains elevated longer than serum amylase.
22Imaging:*CT: uniform enhancement of pancreas*Ultrasound
23APACHE II score: (acute physiology & chronic health evalutation) RANSEN’S CRITERIACriteria for acute pancreatitis not due to gallstones At admissionDuring the initial 48 h Age >55 y Hematocrit fall >10 points WBC >16,000/mm3 BUN elevation >5 mg/dL Blood glucose >200 mg/dL Serum calcium <8 mg/dL Serum LDH >350 IU/L Arterial PO2 <60 mm Hg Serum AST >250 U/dL Base deficit >4 mEq/L Estimated fluid sequestration >6LCriteria for acute gallstone pancreatitis Age >70 y WBC >18,000/mm3 BUN elevation >2 mg/dL Blood glucose >220 mg/dL Serum LDH >400 IU/L Base deficit >5 mEq/L Estimated fluid sequestration >4LPrognosis:<2: Mortality-03-5: Mortality 10-20%>7: Mortality >50%*Only useful for 1st 48hAPACHE II score: (acute physiology &chronic health evalutation)-uses vital signs, labs, age, andchronic health status of patient- >8 is severe
24TREATMENT:*Mild pancreatitis: (no systemic complications, low Ranson’s & Apache II score)-IVF resuscitation/maintenance-Pain management (avoid morphine due to Sphicter of Oddi contraction)-Supportive (rest the pancreas)-NPO-NGT-H2 blockers*No abx unless suspect infection-Slow feeding after pain subsides, amylase decreases, patient feels hungry
25Severe Pancreatitis: (Ranson’s >7, Apache II Severe Pancreatitis: (Ranson’s >7, Apache II >8, systemic symptoms)-ICU & Supportive Care-TPN vs jejunal feeds-If necrotizing: Flagyl, Imipenim, 3rd gen cephalosporin, Diflucan prophylaxis-If necrotizing & septic: Consider necrosectomy
26Biliary Pancreatitis: -Treatment controversial-Cholecystectomy once pancreatitis improves before discharge home-If patient still has pancreatitis, but CBD is obstructed, ERCP with sphincterotomy & stone extraction is indicated-Routine ERCP is not indicated due to risk of post-ERCP pancreatitis
28-Pain:MidepigastricRUQ or LUQPenetrating through to the backSteady & boring (not colicky)Often exacerbated by eating & drinking-Pain causes patient to lay still-Nausea/Vomiting-Anorexia, malabsorption, weight loss-Diarrhea/Steatorrhea due to pancreatic exocrine dysfunction-Diabetes due to pancreatic endocrine insufficiency
29CHRONIC PANCREATITIS: Incurable, chronic, inflammatory condition -Associated with ETOH in 70% of casesMultiple hit theory: Multiple episodes of acute pancreatitis cause inflammatory changes that result in chronic inflammation & scarring
30Chronic Calcific Pancreatitis Chronic Obstructive PancreatitisChronic Inflammatory PancreatitisChronic Autoimmune PancreatitisAsymptomatic Pancreatic FibrosisAlcoholPancreatic tumorsUnknownAssociated with autoimmune disorders (e.g., primary sclerosing cholangitis)Chronic alcoholicHereditaryDuctal strictureEndemic in asymptomatic residents in tropical climatesTropicalGallstone- or trauma-induced pancreas divisumHyperlipidemiaSjögren's syndromeHypercalcemiaPrimary biliary cirrhosisDrug-inducedIdiopathic
31Histology: Induration, nodular scarring, fibrosis, mononuclear cell infiltrates, patchy areas of necrosis, reduced islet size and number(Sheets of fibrosis & loss of acinar tissue)(Mononuclear cell infiltrate)
32***Mostly a clinical diagnosis!*** I. Measurement of pancreatic products in blood A. Enzymes B. Pancreatic polypeptideII. Measurement of pancreatic exocrine secretion A. Direct measurements 1. Enzymes 2. Bicarbonate B. Indirect measurement 1. Bentiromide test 2. Schilling test 3. Fecal fat, chymotrypsin, or elastase concentration 4. [14C]-olein absorption III. Imaging techniques A. Plain film radiography of abdomen B. Ultrasonography C. Computed tomography D. Endoscopic retrograde cholangiopancreatography E. Magnetic resonance cholangiopancreatography F. Endoscopic ultrasonographyTests for ChronicPancreatitis:***Mostly a clinical diagnosis!***
33Dilated pancreatic duct with intraductal stones & parenchymal calcification EUS, MRCP, ERCP, transabdominal US
34Treatment: -Analgesics, celiac plexus block -Cessation of ETOH -Oral enzyme therapy-Selective use of antisecretory therapy (Octreotide)-Some benefit from ERCP with sphincterotoy/stenting (proximal panc duct stenosis)-Surgery
35TRANSDUODENAL SPHINCTEROPLASTY: -Incision of the ampullary, bile duct, & pancreatic duct sphincters-Suture apposition of mucosal edges of the incision-Used for obstruction & inflammation isolated to this region
36Puestow: (Lateral pancreaticojejunostomy) -Permits extensive drainage of the pancreatic duct-Drainage procedure for “chain of lakes” (segmental narrowings & dilations of the duct)-Good for pancreatic duct >6mm
37Distal pancreatectomy: -Good for inflammatory changes isolated to body & tail-Good for patients without ductal dilation-Leaves pancreas behind– high rate of recurrence
39Beger: (Duodenum sparing pancreatic head resection)
40Frey Procedure: Resection of the pancreatic head with longitudinal pancreaticojejunostomy (provides complete decompression of the entire ductal system)
41Islet Cell Autotransplantation: -Used to prevent diabetes in pancreatic resection-Need 2-3 million islet cells-Islets are infused into the portal venous system for intrahepatic grafting-Limited by ability to harvest enough islet cells from a sclerotic gland
42Complications of chronic pancreatitis: -Pseudocyst: Chronic collection of pancreatic fluid surrounded by a nonepithelialized wall of granulation tissue & fibrosis
43-Acute pseudocyst (acute fluid collection): Usually due to pancreatic duct leak with extravasation of pancreatic juice.-Wall of granulation tissue without fibrosis forms around the fluid collection after 3-4 weeks & seals it-50% resolve spontaneously (usually those <6cm)
44Treatment: If asymptomatic: expectant -If symptomatic or enlarging: ERCP with stent, cystenterostomy (endoscopically, laparoscopically, or open)-Infected: aspirate/drain***ANY PSEUDOCYST WITHOUT PRECEEDING ACUTE PANCREATITIS NEEDS INVESTIGATION TO DETERMINE THE ETIOLOGY***
45Pancreatic abscess: Pseudocysts that become secondarily infected -Can lead to venous thrombosis, pseudoaneurysms, or hemorrhage
46Other complications:-Splenic/portal vein thrombosis (can get gastric varices). Tx: splenectomy-Pancreatic ascites/effusion Tx: octreotide, bowel rest, TPN-Pancreatic-enteric fistula-Inflammatory mass in head of pancreas
48INSULINOMA: -Most common type of islet cell tumor -Arise from pancreatic beta cells-Most common cause of fasting hypoglycemia in adults-83-92% are single, 8-17% are multiple (MEN)-84% benign, 16% malignant (metastatic)-90% sporadic, 10% associated with MEN I-Physiology:Tumor secretes excessive insulinResults in hypoglycemiaThe brain reacts with initial excitation (convulsion)Eventually results in neurologic depression (coma)
49Signs/Symptoms (often due to the release of epinephrine as a response to hypoglycemia) Loss of consciousness TremorConfusion HungerWeakness/Fatigue Positive Babinski signDeep coma ParesthesiasSweating IrritabilityDrowsiness/stupor Transient hemiplegiaLightheadedness Abdominal painVisual disturbances PalpitationsAmnesiaClonic convulsionsHeadache***It is not possible to differentiate benign from malignant lesions based on symptoms.***It is not possible to correlate the size of the tumor with the extent of symptoms.
50Check insulin to glucose ratio while patient is having symptoms. Diagnosis:Check insulin to glucose ratio while patient is having symptoms.-Low glucose, but elevated insulinCheck C-Peptide levels (to rule out exogenous insulin)-elevated3. Check Urine sulfonylureas
51Preoperative localization: CT and EUS -100% of insulinomas are located in the pancreas.-Most tumors are <1cm-Best localization test is intraoperative ultrasound.
52Treatment: RESECTION-1/3 found in head and uncinate process,1/3 found in body, 1/3 found in tail-Enucleation is usually best for tumors of thehead and body-Spleen sparing distal pancreatectomy is usually best for lesions in the very distal pancreas.
53-Lymph node dissection is not necessary -For malignant (metastatic) insulinoma, perform appropriate pancreatic resection and liver resection.-Radiofrequency ablation can be used to address unresectable lesions in the liver.-Post-op:-Often get rebound hyperglycemia (~ ) for 24-48h. Glucose should return to normal after that.-Insulin supplementation is usually not required.-Medical tx: Diazoxide or octreotide
54GASTRINOMA: (Zollinger-Ellison Syndrome) -Most common islet cell tumor in MEN I syndrome-May be sporadic (75%) or familial (as in MEN I syndrome) (25%)-Autosomal dominant inheritance-Often is metastatic at time of diagnosis
55Symptoms:Abdominal painUlcerations in the upper GI tractDiarrheaGERDSuspect…Recurrent ulcer after medical or surgical treatmentPostbulbar ulcerFamily history of ulcer diseaseUlcer with diarrheaProlonged undiagnosed diarrheaMEN I in familyNongastrinoma pancreatic endocrine tumorsProminent gastric rugal folds on UGI
56DIAGNOSIS:-Fasting serum gastrin level >200pg/ml-Levels >1000 with hyperacidity and ulcer disease are pathognomonic for gastrinoma
57Differentiate between Gastrinoma, G-cell hyperplasia, G-cell hyperfunction, etc. -SECRETIN TEST: (normally, secretin inhibits gastrin release)-Draw baseline gastrin level-Give 2units/kg of secretin IV-Collect gastrin levels at 5 minute intervals for 30min-Increase in gastrin level by >200pg/ml indicates gastrinoma-MEAL TEST:-Measure serum gastrin response to a standard meal-Should see little change in gastrinoma patients-Should be increased in patients with antral G-cell hyperplasia*Once gastrinoma is diagnosed, next step is to treat with H2-blockers or PPI’s
58Localize:-CT abdomen/pelvis-Somatostatin receptor scintigraphy study (Octreotide Scan)-MRI-EUS*Most are located within the Gastrinoma Triangle (Passaro’s Triangle) (Junction of cystic duct to common bile duct, third portion of duodenum, neck of pancreas)
59Treatment: -Complete resection: -Enucleation in head of pancreas -Full thickness excision of duodenal lesions-Full lymph node dissection-Resection or radiofrequency ablation of liver mets-Use intraoperative ultrasound to help locate tumor-Whipple if unable to find tumorRetropancreatic,Transverse mesocolic,Sybpyloric,Hepatic,Celiac lymph nodes
60-For metastatic disease (usually to liver or bone) -Radiation therapy-Chemotherapy (Streptozocin and fluorouracil or etoposide and cisplatinum)-Somatostatin analogs
61GLUCAGONOMA: -Produced by alpha cells of pancreatic islets -Produce excessive glucagon*SYMPTOMS:DiabetesNecrolytic migratory erythema (skin rash)Tendency to develop DVTsStomatitisGlossitisCheilosisHypoaminoacidemia
62DIAGNOSIS:-Elevated fasting plasma level of glucagon->1000pg/ml is diagnosticpg/ml is suggestive-Could biopsy skin lesions
63LOCALIZATION:-Always located within the pancreas-Usually large at presentation-CT scan-Somatostatin receptor scintigraphy-Intraoperative ultrasound**Usually are malignant and may have lymph node and liver mets
64TREATMENT:-Complete resection:-Resect primary disease, regional lymph nodes, and metastatic sites-If can’t completely resect…debulk-Octreotide can be useful in controlling symptoms in incurable disease
65VIPoma: (Verner-Morrison Syndrome) -Tumors mostly located in body/tail of pancreas and occasionally in duodenum-SYMPTOMS:Watery secretory diarrhea that persists even during fastingHypokalemia (due to fecal loss of large amounts of potassium)Achlorhydria (because inhibits gastric acid secretion)Lethargy, muscle weakness, & nausea (due to hypokalemia)Metabolic acidosis (due to loss of bicarb in stool)HyperglycemiaHypercalcemiaCutaneous flushing
66Diagnosis:-Rule out other causes of diarrhea-Elevated plasma VIP in the presence of diarrhea (usually >3L/day) and does not resolve when patient fastsLocalization:-Generally, VIPomas are large tumors-CT scan-Ultrasound (EUS)- Somatostatin receptor scintigraphy
67Treatment:-Compete resection-Resection of appropriate portion of pancreas, lymph node dissection, resection of any metastatic disease-Cholecystectomy , regardless of disease stage, to facilitate later treatment with a somatostatin analog (can case gallstones)-Octreotide can be used to control diarrhea in unresectable disease
68SOMATOSTATINOMA:-Rare neuroendocrine tumors of D-cell origin-Secrete excessive amounts of somatostatin-Symptoms: (Pancreatic somatostatinoma)Mild diabetes (inhibits insulin and glucagon)Cholelithiasis (inhibits cholecystokinin with dec. gallbladder contractility)Diarrhea (inhibits pancreatic enzyme and bicarb secretion that leads to impaired intestinal absorption of lipids)*Duodenal somatostatinomas usually have symptoms due to local mass effect rather than the actions of the hormones.
69-Most are found within the pancreas (head), although there have been -Most are found within the pancreas (head), although there have been reports of somatostatinomas elsewhere (duodenum and jejunum).-Diagnosis: Serum somatostatin levels >100pg/ml (may reach as high as 10ng/ml)-Difficult to diagnose due to nonspecific symptoms, and often there are liver metastasis upon diagnosis.TREATMENT:-Treat hyperglycemia and malnutrition-Localization studies-Resection and debulking-Cholecystectomy due to cholelithiasis due to hypersomatostatinemia.
71-Worst prognosis of all cancers (5% 5yr survival) -Risk factors: ->60yrs old-African American-Women-Relative with pancreatic ca. (2-3X inc risk)-Smoking (doubles risk)-Diet high in fat & low in fiber & veggies-Diabetes-Chronic pancreatitis-k-ras mutation
72DIAGNOSIS:- “Painless jaundice” (but, pain is often 1st sx)-US-CT-CA 19-9-EUS when suspect malignancy, but can’t see on CT scan or when need biopsy-Diagnostic laparoscopy when suspect resectable
73Treatment:-Resection vs palliation-Chemotherapy, radiation-Stenting, biliary-enteric bypass*Highly individual*
74INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM -Arises from pancreatic ducts-Mucin production causes cystic dilation of the ducts-Atrophic pancreatic parenchyma due to duct obstruction->70yrs old, chronic pancreatitis due to duct obstruction, pancreatic insufficiency-Tx: Resection (malignancy determined by invasion)-50% 10 year survival