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Evaluation and Management of a

Jaundiced Patient
Alex A. Erasmo, MD, FACS, FPCS
Professor 2, Faculty of Medicine and Surgery
University of Santo Tomas
Jaundice
• Normal serum bilirubin: 0.5-1.3 mg/dl
• Clinical jaundice: bilirubin >2.0 mg/dl
• Causes
• Medical jaundice

• Surgical jaundice
Differential diagnosis of jaundice
Abnormality in Predominant
Examples
bilirubin metabolism hyperbilirubinemia

Multiple transfusions, sepsis,


Increased production Unconjugated
hemolysis

Impaired uptake or Gilbert’s disease, Crigler-


Unconjugated
conjugation Najjar, neonatal jaundice

Impaired transport and Dubin-Johnson, Rotor’s,


Conjugated
excretion cirrhosis, hepatitis

Choledocholithiasis, benign
stricture, periampullary
Biliary obstruction Conjugated
cancer, cholangiocarcinoma,
chronic pancreatitis
Workup algorithm for jaundice

Direct/indirect bilirubin
AST, ALT, Alkaline Phosphatase
Hepatitis serologies
Ultrasound

No intrahepatic dilatation Intra/ extrahepatic


ductal dilatation No extrahepatic dilatation ductal dilatation

Medical Jaundice Hilar obstruction Distal obstruction


Algorithm for intra- and extrahepatic duct dilatation

Stones

ERCP

Cholecystectomy
and CBDE
Choledocholithiasis
• Epidemiology and pathogenesis
– Usually formed in the GB and pass to the
CBD
– Secondary stones
• Cholesterol or hard black pigmented stones
– Primary stones
• asso. w/ biliary stasis and infection
• brown pigment, soft, crushable
Clinical features
• Signs/symptoms

– RUQ pain, jaundice, clay-colored stools, dark urine

– Charcot’s triad for acute cholangitis

• Intermittent fever, jaundice, RUQ pain

– Reynold’s pentad

• Charcot’s triad and hypotension, and CNS changes


Diagnosis
• Transabdominal ultrasound
– Non-invasive
– First imaging modality
– Sensitivity for detection of a dilated CBD, 55-
90%
– Sensitivity for detection of CBD stones, 25%
• EUS
– Accuracy of ~98%
– Preferred method of investigation
Diagnosis
• MRCP
– Non-invasive ; expensive
– Accuracy is not as good as EUS
• Stones <6 mm in size are often missed

• ERCP
– Diagnostic and therapeutic
– Invasive : acute pancreatitis, bleeding, perforation

• IOC
– Performed at time of cholecystectomy
Treatment
• Get Prothrombin time

• Parenteral Vit K (phytonadione)

• Acute cholangitis

– iv antibiotics – coverage against aerobic and


anaerobic organisms
Management of patients with CBD stones

Stone and jaundice

No Sepsis Sepsis

ERCP Open ERCP with


LC and
followed by cholecystectomy drainage
CBDE
LC and CBDE

Laparoscopic Open
Cholecystectomy cholecystectomy
and CBDE and CBDE
Surgical removal of CBD stone
Secondary stones
ERCP with stone extraction
Endoscopic removal using
choledoscope
Workup algorithm for jaundice

Direct/indirect bilirubin
AST, ALT, Alkaline Phosphatase
Hepatitis serologies
Ultrasound

No intrahepatic dilatation Intra/ extrahepatic


ductal dilatation No extrahepatic dilatation ductal dilatation

Medical Jaundice Hilar obstruction Distal obstruction


Algorithm for intra- and extrahepatic duct dilatation
Pancreatic Cancer - Epidemiology

• Worldwide 250,000 new cases/year


• Overall crude incidence: 7.8 per 100 000
• Peak age incidence: 65-75 years old

• USA: 28,000–30,300 new cases/year


– approx. equal number of deaths/year
Pancreatic cancer
• Location
– Head 80%, body 15%, tail 5%
• Types
• Ductal adenocarcinoma, most common
• Intraductal papillary mucinous neoplasm
• Mucinous cystadenocarcinoma
Pancreatic Cancer
• Upon diagnosis
– 40-45% locally advanced; 40-45% metastatic; 10-20%
localized resectable

• Advanced disease
– OMS <6 months; 5-year SR 0.4-5%

• 2.6-9% undergo pancreatic resection


– OMS 11-20 months; 5-year SR 7-25%

• All patients die within 7 years of diagnosis


The Kaplan-Meier estimate of overall survival by disease extent

----- locally advanced


metastatic disease
Risk factors
• Tobacco smoking
• Familial background
– Peutz-Jeghers syndrome
– Familial atypical multiple mole melanoma
– Hereditary non-polyposis colon cancer
– Ataxia telangiectasia
– Li-Fraumeni syndrome
– Familial adenomatous polyposis
– Cystic fibrosis
• Chronic pancreatitis
• Hereditary pancreatitis
Clinical Presentation
• Jaundice, pruritus
• Anorexia, weight loss
• Back pain
• Late-onset diabetes
• Vomiting due to duodenal obstruction
• Palpable GB (Courvoisier’s sign)
• Virchow’s node, Sister Joseph’s sign
• Migratory thrombophlebitis
Diagnosis
• CA 19-9

• CT scan

• ERCP

• MRCP

• EUS

• Diagnostic laparoscopy

• PET scan
CA 19-9
• Gold standard serologic marker for pancreatic cancer
– Sensitivity 90%
– Specificity 98%
• Elevated in benign diseases
• Values >200 IU/ml
– Diagnostic of pancreatic cancer
• Values >300 IU/ml
– Unresectable tumor
• Independent predictor of recurrence and survival
• Response to therapy
CT Scan
• Diagnostic and staging modality of choice
• Multidetector CT
– Dual-phase imaging (arterial/venous phase)

– H2O, oral contrast; nonionic contrast per IV

– 1.25 mm slices in one 20-second breath hold

– 3D viewing
CT Scan
A. tumor pancreatic head; B. dilated pancreatic duct
CT signs of unresectability
• Distant extrapancreatic spread
• liver, peritoneal implants
• Ascites
• Encasement of SMA
• Occlusion of the SMV-PV confluence
CT scan of APC
Encasement of confluence of the SMV and PV
Accuracy of 3D-CT
Unresectable Margin-positive
Periamp Ca(%) resection(%)

Sensitivity 90 54

Specificity 95 93

PPV 78 72

NPV 98 86

Overall accuracy 94 83

J GASTROINTEST SURG 2004;8:280-288


MRI in pancreatic cancer

• For vascular assessment and tumor detection


– No advantage over CT scan

• No advantage in obtaining both MRI and CT


MRCP
• MRI with MRCP
– Dx of pancreatic malignancies
– Resectability
– Preventing unnecessary preoperative ERCP
• Feature of pancreatic head
adenocarcinoma
– “double duct sign”
MRCP
Endoscopic Ultrasound(EUS)

• Detects small pancreatic lesions

• Localize lymph node metastases or vascular tumor


infiltration with high sensitivity

• EUS-guided FNA
– Sensitivity 60%-90%

• Major limitations
– Operator dependence

– Liver and peritoneal mets


Detection of Vascular Involvement
EUS vs. Angiography

Method Sensitivity Specificity PPV NPV

EUS 86% 71% 86% 71%

Angiography 21% 71% 60% 31%

J of Clin Gastroenterol 2001


EUS - no PV involvement
EUS : (+) PV involvement
Staging Laparoscopy

• Rationale: identify mets not seen by CT, MRI, EUS


• Sites of mets
– Small liver nodules(<1 cm)
– Peritoneal implants
• Incidence
– 15%-20% pancreatic head
– 50% body and tail

• Neoadjuvant CRT
Laparoscopic Staging
(Conlon KC Ann Surg, Feb 1996)

Laparoscopic Resected Unresectable


Assessment

Resectable(n=67) 61 6

Unresectable(n=41) 0 41

Sens : 86.5% PPV : 98.8%


Spec : 99.2% NPV : 90.4%
Positron Emission Tomography
(PET) Scan
• Principle
– FDG
• Clinical applications
– Dx of new cancers
– Staging
– Evaluation of tx
– Assess recurrent disease
• Recurrent pancreatic carcinoma
– ↑ CA 19–9
– Localize the disease: equiv. CT findings
Endoscopic Retrograde
Cholangiopancreatography (ERCP) for
Diagnosis and Therapy

National Institutes of Health


State-of-the-Science Conference Statement
January 14-16, 2002
What is the role of ERCP in pancreatic
and biliary malignancy?
• ERCP is unnecessary for the diagnosis of cancer in a
patient presenting with a localized pancreatic mass
initially seen on a CT scan, if the patient is a candidate
for surgery.

• Preoperative stenting and staging by ERCP in such cases


confers no measurable advantage and is not supported
by evidence from clinical trials.
What is the role of ERCP in pancreatic
and biliary malignancy?
• Preoperative ERCP may complicate or preclude
surgical intervention.

• Contrast-enhanced CT or MRI scanning performed


with a pancreaticobiliary protocol is usually sufficient
for staging prior to surgical intervention.

• ERCP is the best available means for direct


visualization to diagnose and biopsy ampullary
malignancies.
2. What is the role of ERCP in
pancreatic and biliary malignancy?

• If ERCP and stenting are used, metal stents

remain patent longer than plastic.

• Metal stents may be preferred in patients who

are expected to survive longer than 6 months.


ERCP

Pancreatic head cancer “double


duct sign”
Treatment for Localized Resectable
Pancreatic Head Cancer
• Good-risk

– Whipple’s procedure

– Pylorus-preserving PD (PPPD)

• Poor-risk

– Endoscopic drainage
Pancreaticoduodenectomy
Resectable Lesion
whipples
stomach
pancreas
• whipples
CHD
PV
IVC

kidney
Specimen after Whipple’s Operation -
pancreatic head carcinoma

GB

P
Whipple’s procedure-
ampullary carcinoma
PPPD - duodenal carcinoma
Reconstruction after PPPD
Contraindications to Surgical Resection of
Pancreatic Cancer
Metastases to the liver, peritoneum, omentum, or any extra-abdominal site

Encasement of celiac axis, hepatic artery, or SMA

Involvement of splenoportal confluence

Involvement of bowel mesentery

Involvement of SMV or portal vein


Treatment of Advanced Pancreatic Cancer (APC)

• Poor-risk
– ERCP
– PTBD
• Good-risk
– Bypass surgery
• Cholecysto- or hepaticojejunostomy with
gastrojejunostomy
– Endoscopic biliary drainage
• Neoadjuvant chemotx/radiotx (?)
Treatment for APC
Surgical Bypass vs. Endoscopic Stenting
Methods
• 204 patients with periamp tumors
• Randomized: endoscopic stent or surgical bypass
Results
• Success rate: no difference ( 94 pts vs. 95 pts)
• Lower procedure-related mortality in stented group
(3% vs. 14%)
• Late GOO higher in stented group (17% vs. 7%)

Lancet 344:1655-1660 1994


Endoscopic Retrograde
Cholangiopancreatography (ERCP) for
Diagnosis and Therapy

National Institutes of Health


State-of-the-Science Conference Statement
January 14-16, 2002
What is the role of ERCP in pancreatic
and biliary malignancy?
• Palliative intervention for obstructive jaundice in
pancreatic and biliary cancer may involve ERCP with
stenting or surgery.

• The available evidence does not indicate a major


advantage to either alternative, so the choice may be
made depending on clinical availability and patient or
practitioner preference.
Advanced Pancreatic Cancer

Liver metastases PV Invasion


APC - Endoscopic Stenting
Plastic stent SEMS
APC - PTBD
Treatment of Advanced Pancreatic Cancer (APC)

• Poor-risk
– ERCP
– PTBD
• Good-risk
– Bypass surgery
• Cholecysto- or hepaticojejunostomy with
gastrojejunostomy
– Endoscopic biliary drainage
• Neoadjuvant chemotx/radiotx (?)
Annals of Surgical Oncology 8:758-765 (2001) 2001

Neoadjuvant Chemoradiation for Localized


Adenocarcinoma of the Pancreas

• Rebekah R. White, MD, Herbert I. Hurwitz, MD, Michael A. Morse, MD,


Catherine Lee, MD, Mitchell S. Anscher, MD, Erik K. Paulson, MD, Marcia R.
Gottfried, MD, John Baillie, MB, ChB, Malcolm S. Branch, MD, Paul S. Jowell,
MB, ChB, Kevin M. McGrath, MD, Bryan M. Clary, MD, Theodore N. Pappas,
MD and Douglas S. Tyler, MD
• Departments of Surgery (RRW, BMC, TNP, DST), Medicine (HIH, MAM, JB, MSB, PSJ, KMM), Radiation
Oncology (CL, MSA), Radiology (EKP), and Pathology (MRG); Duke University Medical Center,
Durham, North Carolina
Methods
• 111 Pts
– Radiographically localized, pathologically confirmed
pancreatic adenocarcinoma

• Neoadjuvant external beam radiation therapy


(EBRT; median, 4500 cGy) and
• 5-flourouracil-based chemotherapy
• Tumors
– Potentially resectable (PR, n = 53)
– Locally advanced (LA, n = 58)
Results

• Resected after CRT


– 28 pts(53%) with initially PR tumors

– 11 pts (19%) with initially LA tumors

• 2 complete pathological responses

• Negative surgical margins : 72%

• Negative lymph nodes: 70%


CT Scan

Pre-CRT Post-CRT
Ampullary, bile duct, and duodenal tumors

• Adenocarcinomas
• Present similar manner to pancreatic head cancer
• Progress from benign adenoma to invasive
adenocarcinoma
• Long-term survival better than pancreatic ductal carcinoma
• 5-year survival rate
– Ampulla, 50%
– Bile duct, 30%
– Duodenum, 25%
Survival Rate

Pancreatic Cancer Periampullary Cancer

Jeekel H et al Ann Surg 2004


Biliary strictures
• Causes
– Iatrogenic (injury to bile ducts)
• Open cholecystectomy
• Laparoscopic cholecystectomy
– Inflammatory or infection
• Sclerosing cholangitis
• Tuberculosis
• Cholangiocarcinoma
Iatrogenic Biliary Strictures
• Early or late
• Causes Grade I Grade II

 Devascularization
 Thermal injury
 Direct injury
 Infections
 Technical problems Grade III Grade IV

• Bismuth
classification
Bile Duct Injuries - Incidence
• Open cholecystectomy
1 in 300 to 500 procedures(0.2% to 0.3%)

• Laparoscopic cholecystectomy
0.6% or 2x that of open cholecystectomy
Bile Duct Injuries - Spectrum
• Bile leaks
• Bile duct lacerations, transections, and
excisions
1. Cystic duct injuries
2. Extrahepatic bile duct injuries
3. Intrahepatic bile duct injuries
Bile Leaks
• Radiology literature – 25% subhepatic fluid collections
 30% to 45% with bile

• Overwhelming majority are clinically insignificant


• Major bile leak
 Biliary fistula

 Bilomas

 Ascites

 Bile peritonitis
Cystic duct injuries
• Cystic duct leak
 Most common biliary injury associated with LC

 Causes
• Failure to ligate or clip the cystic duct

• Inadequate application of clips or endoloops

• Unrecognized cystic duct injury

 Diagnosis and treatment


• ERCP with nasobiliary drainage
Bile duct lacerations, transections, and
excisions
• Most serious complication after
cholecystectomy
• Types
1. Extrahepatic bile duct injuries – most
common
2. Intrahepatic bile duct injuries
Bile duct injuries
• Clinical presentation
– Jaundice after surgery
– Abdominal pain, tenderness, distension
– Fever
• Lab works
– Elevated total bil. and conj. bil.
– Elevated alk phos.
Imaging studies
• Ultrasound
• ERCP
• MRCP
• PTC
ERCP
PTC
MRCP
Treatment
• Bile duct transections and excisions
– Reconstruction
• Intraoperative diagnosis
– Primary repair over T-tube

– Hepaticojejunostomy, Roux-en-Y

• Postoperative diagnosis
– Hepaticojejunostomy, Roux-en-Y
Cholangiocarcinoma
• May arise in the intra- or extrahepatic biliary
system
• 50-70 years old
• Risk factors: PSC, choledochal cysts, liver flukes,
oriental cholangiohepatitis, toxins, biliary
papillomatosis
• Most common
– Adenocarcinoma
– Bifurcation of right and left HD
Clinical features
• Obstructive jaundice, pruritus, RUQ pain
• Weight loss
• Fever, acholic stools
• Dark urine, hepatomegaly
• Diagnosis
– ↑ bilirubin, alk phos, AST, ALT
– ↑ CEA, CA 19-9
Classification - Bismuth
Imaging
• US - initial test
• CT scan
• MRCP
• ERCP
• PTC
• EUS
• PET CT scan
PTC - Hilar cholangiocarcinoma
MRCP - cholangiocarcinoma
Treatment
• Resectable tumors in good-risk patients
– Surgical resection
• Unresectable tumors or poor-risk patients
– Biliary drainage
• PTBD
• Endoscopic biliary stenting
Cysts of the biliary tree
• Isolated or multiple; intra-/extrahepatic or
both; congenital or acquired
• >70% abnormal pancreatobiliary junction
with a long common channel
• ↑ Cholangiocarcinoma
Classification
Type I : cystic or fusiform dilation of
extrahepatic bile duct (most common)
Type II: supraduodenal diverticulum of EHBD
Type III: intraduodenal diverticulum or cystic
dilation of intraduodenal portion
(choledochocele)
Type IVA: multiple cysts in the extra- and
intrahepatic ducts
Type IVB: multiple extrahepatic cysts
Type V: isolated or multiple cystic dilations of
IHBD
Clinical manifestations
• Pain, jaundice, abdominal mass
– 10% of patients
• Chronic intermittent abdominal pain,
intermittent jaundice, acute cholangitis
• Diagnosis
– US, CT, MRCP, EUS
• Treatment
– Type I/II : resection and hepaticoJ
– Type III : endoscopic treatment
– Type IV : resection w lobectomy
Caroli’s disease
• Multiple, segmental dilations of IHBD
• Pathogenesis
– Asso w congenital hepatic fibrosis
• Clinical features
– Cholangitis, hepatic abscess
– Portal HPN, varices, ascites
– Pruritus, abdominal pain
Diagnosis
• Lab studies: ↑ alk phosphatase, bilirubin,
leukocytosis, cholangitis
• Imaging: US, ERCP, MRCP
• Treatment
– Cholangitis : antibiotics
– Stones
• ERCP, ESWL
• Dissolution tx, ursodeoxycholic acid