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

2. Learning Points Obstructive Jaundice Pancreatic Cancer MCQ
Definition of Jaundice
Bilirubin Cycle
Anatomy
Causes
Investigations
Management
Pancreatic Cancer
Incidence
Risk Factors, Clinical Signs & Symptoms
Staging, Prognosis
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 Fe2+ Liver, Spleen & Bone marrow Hemoglobin
Phagocytosis & Lysis
Hemoglobin
Globin
Bilirubin
Heme
Amino acids
Fe2+
Through Liver
Amino acid pool
Excreted 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: Age
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. MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY (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 4) Choledochal cyst
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 ducts If 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 resection If the tumor has begun to spread into the liver, the affected part of the liver is removed, along with the bile ducts.
Whipple procedure If 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: Location of tumor: - 60% head - 25% body - 15% tail
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:
Radiation/Chemotherapy

44. Whipples procedure:

45. Unresectable Tumour Extra-pancreatic involvement: Direct 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

51. Answer 2 (D)

52. Questions 3

53. Answer 3

54. Question 4

55. Answer 4
ERCP

56. Question 5

57. Answer 5

58. a. Palliative Chemotherapy b. Liver resection followed by chemotherapy
A 59 year old man is diagnosed as having carcinoma of the pancreas with two malignant deposits in the right lobe of the liver. What is the most appropriate treatment?
a. Palliative Chemotherapy
b. Liver resection followed by chemotherapy
c. Simultaneous resection of liver metastasis and en bloc segmental pancreatic resection
d. Pancreatic resection followed by liver resection once recovered
e. Radical radiotherapy followed by surgery 58

59. a. Palliative Chemotherapy b. Liver resection followed by chemotherapy
A 59 year old man is diagnosed as having carcinoma of the pancreas with two malignant deposits in the right lobe of the liver. What is the most appropriate treatment?
a. Palliative Chemotherapy
b. Liver resection followed by chemotherapy
c. Simultaneous resection of liver metastasis and en bloc segmental pancreatic resection
d. Pancreatic resection followed by liver resection once recovered
e. Radical radiotherapy followed by surgery 59

60. Answer: a
Pancreatic cancer has a poor prognosis and most cases have metastatic disease at presentation. There is no role in pancreatic cancer for liver resection together with pancreatic surgery as there is no survival benefit. Most centres will offer palliative chemotherapy which has improved both longevity and quality of life. 60

61. a. ERCP and placement of metallic stent b. ERCP alone
A 43 year old lady presents with jaundice and is diagnosed as having a carcinoma of the head of the pancreas. Although she is deeply jaundiced, her staging investigations are negative for metastatic disease. What is the best method of biliary decompression in this case?
a. ERCP and placement of metallic stent
b. ERCP alone
c. ERCP and placement of plastic stent
d. Cholecystectomy
e. Choledochoduodenostomy 61

62. a. ERCP and placement of metallic stent b. ERCP alone
A 43 year old lady presents with jaundice and is diagnosed as having a carcinoma of the head of the pancreas. Although she is deeply jaundiced, her staging investigations are negative for metastatic disease. What is the best method of biliary decompression in this case?
a. ERCP and placement of metallic stent
b. ERCP alone
c. ERCP and placement of plastic stent
d. Cholecystectomy
e. Choledochoduodenostomy 62

63. Answer: c
A plastic stent is the best option for biliary decompression in resectable disease. Surgical bypasses have no place in the management of operable malignancy as a bridge to definitive surgery. 63

64. Thank You