Kingdom of Bahrain Arabian Gulf University College of Medicine and Medical Sciences

1. Kingdom of BahrainArabian Gulf UniversityCollege of Medicine and Medical Sciences General Surgery The Pancreas Ali Jassim Alhashli

2. Anatomy and Embryology • Embryology: • Pancreas develop from (duodenal endoderm) at 4th week of gestation. • 2 buds will form, they will rotate and fuse by 8th week: • Ventral pancreatic bud: forms part of the head + uncinate process. • Dorsal pancreatic bud: forms remaining of the head + neck + body + tail. • Anomalies: • Pancreas divisum: failure of ventral and dorsal pancreatic buds to fuse. Therefore, majority of pancreatic drainage occurs via accessory papilla and accessory duct (of Santorini). • Annular pancreas: it results in duodenal obstruction (ring formed around 2nd part of duodenum) which results in post-prandial vomiting.

3. Anatomy: • It is a retroperitoneal organ which is located posterior to the stomach, transverse colon and lesser omentum at the level of L2. • Parts of the pancreas: • Head: includes uncinate process; contained within the curve of 2nd part of duodenum. • Neck: anterior to superior mesenteric vessels. • Body. • Tail: it enters splenorenal ligament this it is adjacent to splenichilum and susceptible to injury during splenectomy. • Blood supply: • Head: • Anterior and posterior superior pancreaticoduodenal arteries → from gastroduodenal artery. • Anterior and posterior inferior pancreaticoduodenal arteries → from superior mesenteric artery. • Neck, body and tail: splenic artery. • Innervation: • Sympathetic: celiac plexus (via splanchnic nerves). • Parasympathetic: vagus nerve. Anatomy and Embryology

4. Histology • Exocrine pancreas: • It secretes 1-2 L/day of clear, isosmotic, alkaline (pH 7.0 – 8.3) fluid containing digestive enzymes (amylase, lipase, trypsin, chymotrypsin and carboxypeptidase). • Endocrine (Islets of Langerhans = 2% of pancreatic weight): • Alpha cells: glucagon (glycogenolysis and release of glucose). • Beta cells: insulin (glucose absorption and storage). • Delta cells: somatostatin (inhibitory functions of GI tract).

5. Acute Pancreatitis • Definition: it is the acute inflammation of the pancreas caused by its autodigestion by proteolytic enzymes. • Causes: PANCREATITIS • P: Posterior perforation of peptic ulcer. • A: Alcohol (50%). • N: Neoplasm. • C: Cholelithiasis (30%). • R: Renal disease (end stage). • E: ERCP. • A: Anorexia (malnutrition). • T: Trauma. • I: Infections. • T: Toxins (drugs = MEDVIPS → Methyldopa/Metronidazole, Estrogen, Didanosine, Valproic acid, Isoniazid, Pentamidine and Sulfonamides). • I: Idiopathic (10%). • S: Surgery/Scorpion bite.

6. Acute Pancreatitis • Signs and symptoms: • Severe, constant epigastric pain radiating to the back and relieved when leaning forward. • Nausea and vomiting. • Cullen’s sign: periumbilical bluish discoloration; Turner’s sign: bluish discoloration of the flank; fox’s sign: bluish discoloration of the inguinal ligament. Notice that these signs indicate severe hemorrhagic pancreatitis. • Diagnosis: • Laboratory investigations: CBC (for leukocytosis), amylase/lipase (lipase is more specific; amylase considered diagnostic if X3 times higher than upper border), LFTs and bilirubin, Urea/creatinine/electrolytes and serum lipids. • Imaging: • AXR: Sentinel loop sign and colon cutoff sign. • Ultrasound. • CT-scan (best): it shows the degree of pancreatitis and if any complications are present (pseudocyst; necrosis: IV contrast is not taken up by dead pancreatic tissue; abscess). • Pancreatic abscess: • Collection of pus in the pancreas. • Patient has unresolving pancreatitis, fever and epigastric mass might be felt. • Do abdominal CT-scan with aspiration and send the sample for Gram stain and culture. • Common organisms are Gram (-) such as E.coli, Pseudomonas and Klebsiella. Gram (+) organisms might also cause abscess such as S.aureus. • Treatment: placement of percutaneous drainage + antibiotics.

7. Acute Pancreatitis

8. Acute Pancreatitis • Differential diagnosis: • Acute cholecystitis. • Peptic ulcer disease (± perforation). • Myocardial infarction (inferior wall). • Treatment: • Bed rest and NPO. • Analgesia (don’t use morphine). • Fluid resuscitation and monitoring of electrolytes. • Antibiotics are given when patient has necrotizing pancreatitis (CT-guided aspiration). • Surgery indicated when there are complications of pancreatitis: hemorrhage, pseudocyst or infected necrosis. • Prognosis: Ranson’s criteria

9. Chronic Pancreatitis • Definition: it is the chronic inflammation of the pancreas which results in pancreatic shrinkage, fibrosis and calcification thus exocrine and endocrine functions are lost. • Causes: commonly associated with alcohol abuse (in 70% of cases). This chronic inflammation might result from recurrent attacks of acute pancreatitis. Notice that gallstones are not a common cause for chronic pancreatitis. • Signs and symptoms: • Recurrent or constant epigastric pain which may or may not radiate to the back. • Malabsorption and malnutrition. Therefore, patient has steatorrhea (25% of cases) and deficiency of fat-soluble vitamins (A, D, K and E). • New onset of type-I diabetes mellitus (1/3 of cases). • Diagnosis: • AXR: pancreatic calcifications. • CT-scan: atrophy and calcifications. • ERCP: chain-of-lakes pattern (ductal irregularities with dilation and stenosis). • Fecal fat analysis: for elastase levels. • Indications for surgery: • Pseudocyst: it is a nonepithelialized, encapsulated pancreatic fluid collection. Chance of spontaneous recovery is less when pseudocyst is larger than 5 cm → internal drainage is required via percutaneous drain, operative drainage or cyst gastrostomy (if it is adherent to the stomach). Surgery is indicated when there is: rupture, infection, hemorrhage or it is enlarging. • Persistent pain. • GI or biliary obstruction. • Treatment: • Medical: analgesia + insulin + replacement of pancreatic enzymes. • Surgical: • Pain relief: celiac plexus block. • Ampullary procedures: ERCP with endoscopic sphincterotomy. • Resection of portions of pancreas: • Whipple procedure: pancreaticoduodenoctomy with hepatojejunostomy, pancreaticojejunostomy and gastrojejunostomy.

10. Chronic Pancreatitis

11. Pancreatic Adenocarcinoma • Pancreatic cancer arises from exocrine pancreas. 2/3 of tumors occur in the head of pancreas thus patients will present early as this causes biliary obstruction. • Risk factors: • Increased age (< 60 years). • Male gender. • African-Americans. • Smoking (doubles the risk). • Diabetes. • Chronic pancreatitis. • Alcohol abuse. • Signs and symptoms: • Epigastric pain radiating to the back. • Weight loss and anorexia. • New onset of diabetes. • Malnutrition with steatorrhea. • Painless jaundice (due to ampullary obstruction). This results in what is known as Courvoisier’s sign (palpable, nontender, distended gallbladder). • Migratory thrombophlebitis (Trousseau’s syndrome): vessel inflammation –due to blood clot- which is recurrent or appearing in different locations over time.

12. Pancreatic Adenocarcinoma • Diagnosis: • Labs: increased LFTs, alkaline phosphatase and direct bilirubin. • Study of choice: abdominal CT-scan with IV contrast. • You can follow up the patient with the tumor marker CA 19-9. • Treatment: • Tumors of the head of pancreas: Whipple procedure (although most tumors cannot be resected at time of diagnosis!). • Tumors of body/tail of pancreas: near-total pancreatectomy. • Post-operatively: chemotherapy (5-FU) + external-beam radiation. • If tumor cannot be surgically removed → palliative treatment to relieve symptoms: • Relieve biliary obstruction: ERCP with biliarystenting. • Relieve duodenal obstruction: gastrojejunostomy – bypass procedure. • To control the pain: splanchnic nerve block. • Prognosis: • Resectable tumor: 12 months with 5-year survival rate = 15%. • Unresectable tumor: 6 months with 5-year survival rate = > 3%

13. Pancreatic Adenocarcinoma

14. Islet Cell Tumors • Insulinoma: • Definition: It is a benign neoplasm of beta-cell of Islet of Langerhans which results in increased production of insulin. It is the most common islet cell tumor. • Most of these tumors are solitary but if they are associated with MEN-1 (Parathyroid, Pancreas, Pituitary) → they can be multiple. • Symptoms related to hypoglycemia triggered catecholamine release. Insulinoma is characterized by Whipple’s triad: • Symptoms of hypoglycemia with fasting. • Relief of symptoms with eating. • Fasting glucose > 50 mg/dL • Diagnosis: • Fasting serum insulin < 10 µU/ml. • Fasting insulin-to-glucose ratio < 0.3 • C-peptide levels should be measured to rule out exogenous administration of insulin. • Abdominal CT-scan or MRI. • Treatment: surgical resection of the tumor. Diazoxide (potassium channel activator) can be used to relief symptoms of hypoglycemia as it blocks the release of insulin from pancreas.

15. Islet Cell Tumors • Gastrinoma (also known as Zolinger-Ellison syndrome): • Definition: it is a tumor which results in increased production of gastrin. It is the 2nd most common islet cell tumor. • This tumor is usually multiple and 60% are malignant. It is located in gastrinoma triangle which is bordered by: • Junction of 2nd and 3rd parts of the duodenum. • Superior mesenteric artery. • Cystic duct. • Signs and symptoms (mostly those of PUD): • Epigastric pain which becomes worst after eating food. • Profuse watery diarrhea. • Diagnosis: • Fasting serum gastrin< 500 pg/ml • Secretin stimulation test causes paradoxical increase in gastrin level. • Ulcers in unusual locations (3rd part of duodenum or jejunum). • Octreotide scan: most gastrinomas over-express somatostatin receptor type-II which can be targeted by In-III labeled octreotide. • Treatment: • PPI (to relieve symptoms of PUD). • Surgical resection. • Chemotherapy.

16. Islet Cell Tumors • Vipoma: • Definition: malignant neoplasm in which there is increased production of (VIP: Vasoactive Intestinal Peptide). At time of diagnosis, most patients have metastasis to lymph nodes and liver. • It is also known as WDHA syndrome: • WD: Watery Diarrhea. • H: Hypokalemia (which results in arrhythmias, muscle fasiculations and tetany). • A: Achlorhydria. • Diagnosis: • Fasting serum VIP < 800 pg/ml. • Treatment: • Control diarrhea with octreotide. • Surgical removal of the tumor with chemotherapy. • Glocagonoma: • Definition: it is a rare malignant tumor of alpha cell of islet of Langerhans resulting in increased production of glucagon. Most patients have metastasis to lymph nodes and liver at time of diagnosis. • Signs and symptoms: • Hyperglycemia. • Weight loss (duo to low amino acid levels). • Necrolytic migratory erythema: necrosis of superficial epidermis and swollen epidermal cells. • Mucositis: painful inflammation and ulceration of mucous membranes lining the digestive tract. • Anemia. • Diagnosis: • Fasting serum glucagon < 1000 pg/ml. • Skin biopsy to confirm presence of necrolytic migratory erythema. • Treatment: • Octreotide: to inhibit release of glucagon. • Surgical resection and chemotherapy.