Approach to Obstructive Jaundice & Pancreatic Cancer

1. Approach to Obstructive Jaundice & Pancreatic Cancer MO TEACHING – JULY 21, 2015

2. Learning Points • Obstructive Jaundice • Definition of Jaundice • Bilirubin Cycle • Anatomy • Causes • Investigations • Management • Pancreatic Cancer • Incidence • Risk Factors, Clinical Signs & Symptoms • Staging, Prognosis • Investigations • Management • MCQ

3. DEFINITION • Jaundice: • Yellowish  pigmentation of the skin, the conjunctival membranes over the sclerae and other mucous membranes caused by hyperbilirubinemia and subsequently causes increased levels of bilirubin in extracellular fluids. • Normal Serum Bilirubin is 0.3 to 1.0 mg • Concentration higher than approx. 3 mg/dL (>50µmol/L) leads to jaundice

4. RBC Cycle RBC life span in blood stream is 90-120 days Old RBCs are phagocytosed and/or lysed Lysis occurs extravascularly in the RE system subsequent to RBC phagocytosis Intravascular Hemolysis of young RBC This is due to hemolytic diseases of RBC

5. E V Pathway for RBC Liver, Spleen & Bone marrow Phagocytosis & Lysis Hemoglobin Bilirubin Globin Heme Fe2+ Amino acids Through Liver Excreted Amino acid pool 7

6. BILIRUBIN CYCLE

7. Bilirubin handling in Kidney Unconjugated bilirubin(UCB):because of its lipid solubility and not water soluble, it is not excreted in urine. Conjugated bilirubin (CB): is water soluble, so it is filtered at the glomerulus and appears in the urine. 9

8. Anatomy of biliary system

9. Causes of jaundice

10. ANATOMY

12. EVALUATION History Examination Investigations

13. Presentation Hallmarks of obstructive jaundice: Icterus, dark urine, pale stools and generalized pruritus Hx of fever, biliary colic and intermittent jaundice (charcot’s triad) is suggestive of cholangitis/choledocholithiasis Painless, progressive, persistent, pruritic jaundice associated with weight loss, anorexia, and abdominal mass is suggestive of periampullary cancer Melena/anaemia usually associated with periampullary cancer

14. HISTORY • Patients commonly complain of: • pale stools • dark urine • yellowness of the eye • pruritus. • Age • Jaundice (duration ,onset, progresion) • Presence of abdominal pain( location and characteristics of the pain) • The presence of systemic symptoms (eg, fever, weight loss) • Symptoms of gastric stasis (eg, early satiety, vomiting, belching) • Previous malignancy • Known gallstone disease • Gastrointestinal bleeding • Hepatitis • Previous biliary surgery/procedure • Use of alcohol, drugs, and medications, Travel history

15. CLINICAL EXAMINATION • Physical examination findings typically include jaundice and right upper quadrant tenderness. • Charcot's triad set of three common findings: abdominal pain, jaundice, & fever. • Anaemia - hemolysis, cancer , cirrhosis • Gross weight loss-malignancy • Hunched up position-chronic pancreatitis or ca pancreas • Fetor, flapping tremors, personality changes-impending hepatic coma • Skin changes: • Bruising • purpuric spots • spider naevI • palmar erythema • white nails, • Loss of secondary sexual characters

16. ABDOMINAL EXAMINATION • Dilated peri umbilical veins- cirrhosis & portal collateral circulation • Ascitis-Cirrhosis or malignant disease • Nodular liver • Courvoisier’s Law • presence of an enlarged gallbladder which is nontender and accompanied with mild jaundice, the cause is unlikely to be gallstones

17. LABAROTORY STUDIES FBC: anemia, infection,Hgbpathy Serum U/E/Cr Urinalysis : bilirubin, urobilinogen Stool for ocult blood: ca ampula Stool microscopy for ova and parasites Clotting profile Hepatitis serology: HbsAg, HCV LFT: see next slide

19. Investigations ( urine)

20. Investigation ( imaging & procedure) • Goals of Imaging: • To confirm presence of extrahepatic obstruction • Identify specific Cause of Obstruction • Determine level of obstruction • AXR • U/S HBS • Stones, CBD diameter • More sensitive than CT to pick up stones and gallbladder pathology • CT abdomen • ERCP/MRCP • EUS • Percutaneous transhepatic cholangiogram

21. AXR May show: Calcifed gallstones Porcelain gallbladder Air in biliary tract or gallbladder wall

22. Ultrasound Usually most commonly used initial investigation Tell us size of bile duct (intra and extra hepatic) Stones: Gallbladder/CBD stone (less sensitive) Hepatic metastasis Peripancreatic/hilar lymphadenopathy Ascites Differentiate between solid or cystic lesion Disadvantage unreliable for small CBD stones and biliary strictures

23. CT Most useful diagnostic and staging modality in patients suspected in periampullary/pancreatic ca Provides more accurate and complete image of pancreatic mass along with extent and relation to other structures Allows to see primary tumours/mets Provides info about adjacent vascular structures as portal, sup mesenteric and splenic veins as well as sup mesenteric and celiac artery Periampullary node and retroperitoneal structure involvement may be seen

24. MAGNETICRESONANCECHOLANGIOPANCREATOGRAPHY (MRCP) Noninvasive test to visualize the hepatobiliary tree and pancreatic duct Indicated when both intra and extrahepatic ductal system is dilated but no discrete mass lesion is found on CT Vascular structures can be visualized by using contrast agen gadolinium Disadvantage: purely diangostic and no intervention can be done MRCP is better to determine the extent and type of tumor as compared to ERCP

25. Endoscopic retrograde cholangiogram (ERCP) Invasive procedure to provide direct visualization of level biliary obstruction Advantage: can also be used for endoscopic stone retrieval and papillary stenting in same stenting Most useful when pancreatic duct obstruction is present but no mass is seen on CT or MRI – in this situation to differentiate chronic pancreatitis vs pancreatic ca Direct visualization of biliary tree/pancreatic duct both therapeutic and diagnostic Allows biopsy or brush cytology, Stone extraction or stenting Double duct sign: cut off of both pancreatic and distal bile duct around pancreatic mass Complications: Cholangitis, bleeding, pancreatitis, biliary leakage

26. ENDOSCOPIC ULTRASOUND (EUS) Useful for detection and staging of ampullary tumours, detection of microlithiasis, choledocholithias and biliary strictures Enables aspiration of cysts and biopsy of solid lesions Allows diagnostic tissue sampling via EUS guided fine-needle aspiration (EUS-FNA) The sensitivity of EUS for the identification of focal mass lesions in pancreas has been reported to be superior to that of CT scanning Compared to MRCP for the diagnosis of biliary stricture, EUS has been reported to be more specific (100% vs 76%)

27. Percutaneous Transhepatic Cholangiogram (PTC) Previously used invasive procedure to visualize biliary tree especially the proximal part Percutaneous biliary drain can be left in place for biliary decompression Disadvantage: more invasive, can cause bleeding, hemobilia, discomfort, and inability to visualize pancreatic duct PTC is indicated when percutaneous intervention is needed and ERCP either is inappropriate or has failed. Can be used to drain biliary obstructions.

28. Management Perioperative management of obstructive jaundice • Extrahepatic biliary obstruction due to any cause requires mechanical decompression • Achieved: Resection of obstructing lesions, surgical bypass if lesion is not resectable, endoscopic/percutaneous stenting • Preoperative biliary decompression improves postoperative morbidity • usually cause increased hemorrhage & infections • Indicated in severe jaundice or when there are signs of impending liver failure/severe sepsis • Bladder catheterization to monitor output • Broad spectrum antibiotic prophylaxis • Parenteral vitamin K +/- fresh frozen plasma • Need careful post operative fluid balance to correct dehydration • Antihistamine for symptomatic relief of pruritus • Consider given mannitol preop, intraop and post op for diuresis to prevent hepatorenal syndrome

29. Treatment of Common Obstructive Jaundice Causes Choledocholithiasis Ca Head of Pancreas / Periampullary Carcinoma/malignancy of lower 3rd of CBD Gallbladder Ca Choledochal Cyst Cholangiocarcinoma Strictures

30. 1. Choledocholithiasis (gallstones) • Treatment of choice is stone extraction through ERCP/endoscopic sphinterotomyy with extraction of stones by dormia basket catheter or balloon catheter followed by lap chole • Success rate is 90%, complications include perforation, bleeding, pancreatitis b)Mechanical lithotripsy – through modified dormia basket • If stone large, can be crushed in situ c) Open exploration of common bile duct is indicated in • Presence of multiple stones (more than 5) and Stones > 1 cm • Multiple intra hepatic stones • Distal bile duct strictures • Failure of ERCP • Recurrence of CBD stones • T Tube inserted, after 8-10 days T Tube cholangiogram is done, if dye goes freely into duodenum without any filling defect, T Tube is removed after 2 weeks

31. 2. Periampullary Carcinoma Surgical Excision mainstay treatment Assessment of resectability and preoperative staging is crucial If tumour is resectable: procedure of choice is pancreaticoduodenectomy/Whipple’s operation If not operable then Endoscopic sphincterotomy + stenting with percutaneous transhepatic biliary drainage Structres removed are: Head and neck of Pancreas including uncinate process Whole duodenum up to 10cm of proximal jejunum Partial gastrectomy Lower end of CBD Gallbladder Pericholedochal, periduodenal and peripancreatic lymph nodes Followed by : Choledochojejunostomy Pancreaticojejuonostomy Gastrojejuonostomy

32. 3) Gallbladder Ca a) if involving CBD then whipple resection is done b) And in case of inoperable cases Endoscopic / Radiological stenting is done 4)Choledochal cyst • Surgical excision of the cyst with Reconstruction of the extra hepatic biliary tree • Long term follow up is necessary because of complications like cholangitis , lithiasis , anastomotic stricture

33. 5) Cholangiocarcinoma Epithelial cancer of cholangiocytes Can be intrahepatic, hilar, and distal bile duct tumours Hilar accounts for 2/3 of all extra hepatic carcinomas Surgical resection remains only chance for cure Removal of the bile ductsIf the tumor is at a very early stage (Stage 1), just the bile ducts containing the cancer are removed. The remaining ducts in the liver are then joined to the small bowel, allowing the bile to flow again. Partial liver resectionIf the tumor has begun to spread into the liver, the affected part of the liver is removed, along with the bile ducts. Whipple procedureIf the tumor is larger and has spread into nearby structures, the bile ducts, part of the stomach, part of the small bowel (duodenum), the pancreas, gall bladder and the surrounding lymph nodes are all removed If surgery to remove the tumour is not possible, it may be possible to relieve the blockage through stents through ERCP or PTC

34. 6)Strictures • Can be benign/malignant • 80% benign strictures are iatrogenic/hepatobilary • 20% benign due to inflammatory: • Chronic pancreatitis, choledocholithiasis, cholangitis, stenosis of sphincter of Oddi, biliary tract infections • Treatment done 3 ways: • Percutaneous dilation and stenting • Endoscopic dilation and stenting • Therefore, surgery should probably be reserved for those patients with complete ductal obstruction or for those in whom endoscopic therapy has failed. Surgery with Roux-en-Y choledochojejunostomy or hepaticojejunostomy is the standard of care with good or excellent results in 80 to 90% of patients. • All have relapse rates of 15-45%

35. Pancreatic Cancer

36. Epidemiology • 6th leading cause of cancer-related death in SG • 8th in men and 9th in women Worldwide • 10th incidence of cancer in Singapore • Incidence rises sharply after age of 45 • Male > Female: 1.3 / 1 • Black > White

37. Risk factors • Cigarette Smoking • High Body Mass Index • Non-hereditary chronic pancreatitis • 5% link to 1st degree relatives • Pancreatic cysts • BRCA1, BRCA2, STK11 • Hereditary Pancreatitis

38. Pathology: mostly ductal adenocarcinoma (metastasizes early; presents late) Location of tumor: - 60% head - 25% body - 15% tail

39. Clinical Symptoms & Signs • Asthenia • Weight loss • Anorexia • Abdominal & epigastric pain • Dark urine, Jaundice • Nausea, Vomitting, Diarrhea • Back pain • Steatorrhea • Clinical Manifestations: Jaundice, Hepatomegaly, RUQ mass, Cachexia, Courvosier’s sign, ascites, pain

40. Investigations • Transabdominal Ultrasound • Abdominal CT • ERCP: sensitivity 92%, specificity 96% • MRCP • EUS-guided or percutaneous biopsy • CA19-9: sensitivity 70-92%, specificity 68-92%

43. Surgical Treatment • Tumours in the head/uncinate process: • Standard operation: pancreaticoduodenectomy • Total pancreatectomy • Tumours of the tail/body: • distal pancreatectomy with laparoscopic exploration TRO peritoneal mets. • Tumours involving the entire gland: • Total pancreatectomy • Radiation/Chemotherapy

44. Whipples procedure:

45. Unresectable Tumour Extra-pancreatic involvement: extensive peri-pancreatic lymphatic involvement nodal involvement beyond the peri-pancreatic tissues distant metastases Direct involvement: superior mesenteric artery (SMA), inferior vena cava, aorta, celiac axis, or hepatic artery (defined by the absence of a fat plane between the low density tumour and these structures on CT scan)

46. Prognosis Poor, as diagnosed late Mean Survival <6 months usually 5 year survival < 2% After Whipple, survival 5-14% Slightly better prognosis: Tumour <3 cm No nodes involved Negative resection margins Ampullary/islet cell tumours

47. Questions

48. Question 1 A 62-year-old woman presents for evaluation ofsudden-onset, severe, painless jaundice. The patienthas developed anorexia with a 20-lb weight loss over a 3-month period and recently was diagnosed with diabetes mellitus. FBC is normal, total bilirubin is 8.9 mg/dL, direct serum bilirubin is 8.3 mg/dL, alkaline phosphatase is 550 U/L, AST is 120 U/L, and ALT is 134 U/L. ERCP is performed, which reveals significant intra- and extrahepatic ductal dilation and a tight distal biliary stricture (Figure ). What is thispatient’s most likely diagnosis? (A) Ampullary cancer (B) Cholangiocarcinoma (C) Cholecystitis (D) Pancreatic adenocarcinoma (E) Postoperative biliary stricture

49. Answer 1 (D) Pancreatic adenocarcinoma. The patient presents with classic signs of pancreatic adenocarcinoma—painless jaundice, weight loss, and anorexia in the setting of recently diagnosed diabetes. The cholangiogram demonstrates a long, tight distal CBD stricture. The distal CBD runs through the head of the pancreas (the most common site for pancreatic adenocarcinoma), and in this patient, the CBD is extrinsically compressed by a tumor mass. Cholangiocarcinoma at this site is possible but markedly less common. Although a postoperative biliary stricture is possible, it is very unlikely to develop in the intrapancreatic portion of the CBD due to its limited accessibility. Ampullary cancer could present with similar symptoms and laboratory profile but would likely demonstrate a site of obstruction in the most distal portion of the CBD at the level of the ampulla/duodenal wall and not higher up the duct, as seen in this patient. Cholecystitis is not possible in this patient, as she has undergone cholecystectomy, evidenced by the absence of a gallbladder and the postsurgical clip seen on the cholangiogram.

50. Questions 2 In obstructive jaundice, urinary examination shows: No urobilinogen, no bilirubin Increased urobilinogen, increased bilirubin Increased urobilinogen, no bilirubin No urobilinogen, increased bilirubin