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Important changes in 2019 guidelines
*2010 ASGE guideline: Serum bilirubin 1.8–4.0mg/dL and dilated CBD or biliru-
bin >4mg/dL singly were considered as high-risk criteria
*Biliary pancreatitis is no longer included as an intermediate-risk criterion unlike in
2010 guidelines
Q.What are the clinical situations associated with difficult CBD stone
extraction?
Ans:
Difcult CBD stones are encountered in 10–15% of ERCPs for
choledocholithiasis.
(i) Stone size>1.5cm, large number of stones (>10), barrel-shaped stones.
(ii) Stones that cannot be extracted by capturing in basket or are not amenable for
mechanical lithotripsy.
(iii) Presence of complex biliary strictures, e.g., PSC, RPC.
(iv) Hepatolithiasis, Stones in cystic duct.
(v) Presence of surgically altered upper gut anatomy (e.g., Roux-en-Y gastric
bypass and Billroth II gastro-jejunostomy).
(vi) Presence of Mirizzi syndrome.
(vii) Presence of periampullary diverticulum.
(viii) Shorter length of the distal CBD arm (≤36mm), and more acute distal CBD
angulation (≤135°).
High yield points:
• Laparoscopic cholecystectomy should be considered within a period of 2 weeks
in patients of CBD stones, who have undergone ERCP, in order to prevent vari-
ous complications viz. recurrent CBD stones, cholecystitis, biliary colic, biliary
pancreatitis, and a higher risk of conversion to open cholecystectomy, which are
more commonly seen in patients with a prolonged wait period.
• Antibiotic prophylaxis should be considered in the following group of patients:
– Patients with cholangitis
– Immune-decient patients
– Predicted incomplete drainage procedure
– Patients with coexistent PSC
• Balloon catheter preferred over wire basket for stone extraction because:
– Easy to perform
– Occlusion cholangiography can be taken
– No risk of entrapment in CBD
• Biliary endoprosthesis should be considered in case of
– Partial stone clearance
– Presence of severe acute cholangitis
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• Endoscopic Papillary Balloon Dilatation preferred over endoscopic sphincter-
otomy (ES) in:
– Presence of coagulopathy.
– Presence of peri-ampullary diverticulum.
– Surgically altered anatomy that increases the difculty in the perfor-
mance of ES.
Q.What are the approaches toward managing a case of large CBD Stone
(>15mm)?
Ans:
(i) Endoscopic Sphincterotomy followed by Endoscopic Papillary Balloon
Dilatation.
(ii) Mechanical Lithotripsy
(iii) Intraductal Shock wave Lithotripsy
• Electrohydraulic lithotripsy (EHL)
• Laser lithotripsy(LL)
(iv) Extracorporeal Shock wave Lithotripsy (ESWL)
Q.What are the diagnostic criteria used for diagnosing cholangitis?
Ans: Tokyo guidelines (TG18/TG13) diagnostic criteria for acute cholangitis:
A. Presence of systemic inammation as depicted by:
• A-1. Presence of fever (Temperature > 38 °C) and/or shaking chills.
• A-2. Laboratory values suggestive of inammatory response (WBC count
<4000, or >10,000; or, CRP ≥1 mg/dL.
B. Laboratory evidence of cholestasis
• B-1. Jaundice (Bilirubin ≥2mg/dL).
• B-2. LFT derangement (ALP > 1.5 × ULN, GGT > 1.5 × ULN,
AST>1.5×ULN, ALT>1.5×ULN).
C. Imaging
• C-1. Dilated CBD.
• C-2. Evidence of stricture, stone, stent, etc. on imaging.
Suspected diagnosis: 1 criterion from A +1 criterion from either B or C.
Denite diagnosis: 1 criterion from A, 1 criterion from B, and 1 criterion from C.
Other criteria:
Charcot’s triad: Right upper quadrant abdominal pain, jaundice, and fever.
Reynold’s pentad: Charcot’s triad with shock and altered mental status.
Q.How to assess the severity of acute cholangitis?
Ans: Severity of acute cholangitis is graded as Grade I (mild), Grade II (moderate),
and Grade III (severe) according to Tokyo guidelines 2018 (TG18/13).
Grade III acute cholangitis: At least 1 of the following criteria has to be met:
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1. CVS dysfunction: Dened as hypotension, with the need of vasopressors (either
dopamine ≥5μg/kg per min, or any dose of norepinephrine).
2. CNS dysfunction: Dened by altered consciousness.
3. Respiratory dysfunction: Dened as PaO2/FiO2 ratio <300.
4. Kidney dysfunction: Dened by presence of oliguria, or creatinine >2.0 mg/dL.
5. Liver dysfunction: Dened as an INR >1.5.
6. Hematological dysfunction: Dened by platelet count of <100,000/mm
3
.
Grade II (moderate) acute cholangitis
Presence of at least two of the following criteria is mandatory:
1. Total leukocyte count (>12,000/mm
3
, or, <4000/mm
3
)
2. Presence of high-grade fever (dened by temperature of ≥39°C)
3. ≥75 years old
4. Serum bilirubin ≥5mg/dL
5. Serum albumin <0.73×ULN
Grade I (mild) acute cholangitis
Patients with cholangitis who does not fulll the criteria for Grade II or III chol-
angitis are said to have Grade I (mild) acute cholangitis.
Q.How to Manage a Case of Choledocholithiasis with Cholangitis?
Ans:
Grade I
(Mild)
Antibiotics
and general
supportive care
Finish course
of antibiotics
Biliary
drainage
Treatment
for etiology
if still needed
(endoscopic treatment,
percutaneous treatment,
or surgery)
Early
drainage
Antibiotics
and general
supportive care
Urgent biliary drainage
Organ support
Antibiotics
*
*
*
Grade II
(Moderate)
Grade III
(Severe)
Adapted from ASGE guidelines
*Blood culture should be sent before starting antibiotics.
During biliary drainage, bile samples should be taken and sent for culture and
sensitivity testing.
†Principles of treatment for acute cholangitis:
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• Antibiotics
• Biliary drainage
• Treatment of the underlying cause
Patients with CBD stones presenting as mild or moderate cholangitis, CBD
clearance should be considered during initial biliary drainage procedure, if possible.
Q.Which antibiotics are commonly used to treat biliary infection? Which
antibiotics have good biliary penetration?
Good penetration efciency
(ABSCR>1)
Low penetration
efciency
(ABSCR<1)
Piperacillin/Tazobactum (4.8) Ceftriaxone (0.75)
Tigecycline (>10) Cefotaxime (0.23)
Amoxicillin/clavulanate (1.1) Meropenem (0.38)
Ciprooxacin (>5) Ceftazidime (0.18)
Ampicillin/sulbactam (2.4) Vancomycin (0.41)
Cefepime (2.04) Amikacin (0.54)
Levooxacin (1.6) Gentamicin (0.3)
Penicillin G (>5)
Imipenem (1.01)
ABSCR Antibiotics Bile/Serum Concentration Ratio
Further Reading
Manes G, et al. Endoscopic management of common bile duct stones: European Society of
Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2019;51(05):472–91.
Dumonceau JM, et al. Endoscopic biliary stenting: indications, choice of stents, and results:
European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline—Updated
October 2017. Endoscopy. 2018;50(9):910–30.
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© The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2022
V. Singh, A. Roy (eds.), Clinical Rounds in Hepatology,
https://doi.org/10.1007/978-981-16-8448-7_21
P. Debnath
Department of Gastroenterology, TNMC and BYL Nair Charitable Hospital, Mumbai, India
A. Roy · V. Singh (
*)
Department of Hepatology, Post Graduate Institute of Medical Education and Research,
Chandigarh, Punjab, India
21
Approach toBiliary Obstruction
andEvaluation ofBiliary Stricture
PrasantaDebnath, AkashRoy, andVirendraSingh
A previously healthy 39-year-old female patient presented with right-sided abdomi-
nal pain and jaundice with associated pruritus, clay-colored stools, and fatigue for
14 days. No history of fever, anorexia, weight loss, nausea, vomiting. She had his-
tory of cholecystectomy 1 year back. She denied any previous episodes of jaundice
or weight loss. On admission, physical examination revealed scleral icterus. She
was afebrile. The abdomen was soft, non-tender, and liver and spleen were not
palpable.
Investigations
Parameter
Values Parameter
Values
Hemoglobin 11.2 INR 1.4
Platelet count 298 HBsAg NR
Total leukocyte count 7000 Anti-HCV NR
Total bilirubin (Direct) 10.8 (7.0) AMA/pANCA Neg
AST 98 S Na/K 137/4.3
ALT 48 Urea 32
ALP 566 Creatinine 0.8
Albumin 3.9 CA 19-9 12
USG Abdomen: Liver 16cm, enlarged, bilateral central and peripheral IHBRD,
dilated CHD with distal CBD being normal. Pancreas and spleen: normal.
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Q.What Is the most probable diagnosis based on the given vignette?
Ans: Extrahepatic obstructive jaundice due to post-cholecystectomy biliary stricture.
Q.How do you differentiate between benign and malignant biliary stricture
clinically?
Ans:
Benign vs. Malignant:
Clinical and laboratory clues:
Favors benign etiology Favors malignant etiology
Young patient without any weight loss Unintentional weight loss +
Poor general well being
Cholangitis more frequent Cholangitis less frequent
H/O PSC(primary sclerosing cholangitis) or
decompensation in known PSC patient
H/O gall stone disease Long stricture >1cm
Higher IgG4 level(In suspected
Immunoglobulin G4 disease)
Asymmetrical stricture
? Normal CA 19-9 ? Raised CA 19-9
H/O cholecystectomy or hepatobiliary
surgery
Presence of anomalous pancreatobiliary junction
H/O Trauma H/O choledochal cyst
Stable weight Short course without antecedent illness
Fluctuation in laboratory parameters Progressive disease without uctuation
Additional points:
• In postoperative setting (cholecystectomy/hepatobiliary surgery), an acute pre-
sentation indicates iatrogenic bile duct injury/biliary stricture.
• Presentation during an episode of acute pancreatitis may indicate stone-related
biliary obstruction.
• A gradual presentation evolving in <3 months generally indicates an inamma-
tory process, which is likely to improve in due course.
• However, symptom duration >3 months after an insult/injury generally indicates
a more brotic stricture, which is less likely to improve with time and may
require more aggressive therapy (endoscopic/surgical).
• Malignancy should be suspected when there is an occult/delayed presentation
and no risk factors are identied.
• Waxing waning clinical picture or laboratory abnormalities generally suggest a
benign stricture, whereas a progressive disease course is indicative of an under-
lying malignant etiology.
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Laboratory features:
• Elevated ALP (alkaline phosphatase)with normal transaminase or serum biliru-
bin is suggestive of intra- or extrahepatic bile duct obstruction.
• Elevated aminotransferases with ALP and/or bilirubin indicate simultaneous
presence of hepatitis, or an acute presentation of CBD obstruction.
• Complete CBD obstruction + healthy liver, i.e., without any hepatocellular
injury, serum bilirubin usually remains below 20mg/dL.
• Bilirubin >20mg/dL indicates associated hepatocellular injury, in the presence/
absence of biliary obstruction.
• Long-standing obstruction with jaundice may lead to fat maldigestion and mal-
absorption, as well as deciency of fat-soluble vitamins, including vitamin K,
leading to elevated PT/INR.
Q.What are the cholangiographic features of malignancy?
Cholangiographic features of malignancy:
1. Progressive focal stricturing over time
2. Abrupt shelf-like borders
3. Length of stricture >14mm
4. Presence of IHBR(intrahepatic biliary radicle) dilation
5. Intraductal polypoid or nodular mass on cholangiogram
In the setting of PSC with dominant stricture:
1. Length of stricture >1cm
2. Location: at bifurcation of CHD
3. Irregular margins on cholangiogram
Q.What are the common causes of Benign Biliary Stricture? (Table21.1)
Table 21.1 Differential diagnosis of benign biliary stricture
Common Less common
Primary sclerosing cholangitis
Chronic pancreatitis
Post-cholecystectomy stricture
Bilioenteric anastomosis
Inammatory strictures
IgG4 cholangiopathy
Post-liver transplantation
Bile-duct ischemia
Vasculitis: SLE- and ANCA-associated
Radiation therapy
Portal cavernoma cholangiopathy
Tuberculosis
Post-sphincterotomy
Trauma
Mirizzi syndrome
Parasitic infection
AIDS cholangiopathy
Post-radiofrequency ablation
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Q.How do you differentiate between the Intra- and Extrahepatic Causes for
Cholestasis? (Table21.2)
Q.State Courvoisiers Law
Ans: Ludwig Courvoisier stated, “with obstruction of the common duct by a stone,
dilatation is rare. The organ is usually well shrunken. With obstruction from other
kinds, on the contrary, distension is the rule. Shrinking occurs in only one-twelfth
of cases.”
No mention of malignancy, nor regarding the site of the biliary obstruction was
made in the original statement.
Q.Mention the Exceptions to Courvoisiers Law
• Double impaction of calculi, one obstructing the cystic duct and the other occlud-
ing the distal CBD.The CBD stone causes biliary obstruction and a stone in the
cystic duct leads to mucocele or empyema of gall bladder, leading to palpable GB.
• Pancreatic stone obstructing the ampulla.
• Recurrent pyogenic cholangitis.
• Periampullary malignancy in post-cholecystectomy patient.
• Mirizzi syndrome.
Q.How to investigate a case of indeterminate biliary stricture?
Ans: Indeterminate biliary stricture is dened as biliary stricture, which remains
undiagnosed when basic workup including transabdominal imaging (USG/CT/
MRI) and ERCP with routine cytological brushing are non-diagnostic.
Table 21.2 Points of differentiation of intra- and extrahepatic cholestasis
Points
Intra-
hepatic
Extra-hepatic
Pruritus More
severe
Less severe
Cholangitis
−
+
Pain abdomen + ++
Decompensated liver disease ++ + (in cases with secondary
biliary cirrhosis)
H/O surgery/endoscopic intervention
−
++
H/O recent CAM/antibiotic use
+/− −
Prodrome with anorexia, nausea, vomiting
+/− −
H/O travel, sexual contact, blood transfusion, or
intravenous drug use
+/− −
Presence of an abdominal lump
−
+
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• Incidence: 20% of biliary strictures are labelled as indeterminate.
• 25% of stricture operated as malignant turns out to be benign.
Diagnosis:
Tools for investigation
ERCP
• Tissue sampling (Brush cytology)
• Intraductal forceps biopsy
• Intraductal transmucosal (trans-papillary) ERCP-FNA
• Cholangioscopy with forceps biopsy
EUS: FNA, IDUS
CT
MRI
PET scan
Brush cytology: Overall brush cytology are cheap and readily available but
given the potential pauci-cellular nature of tumors and difculties in tissue targeting
and acquisition are overall poorly sensitive. Shown to have a sensitivity of 30–60%
and specicity of 60–90%. Results are usually classied as positive, negative, or
suggestive of atypical cells. Atypical cells are common result in biliary brush cytol-
ogy, especially in primary sclerosing cholangitis and may lead to need for
resampling.
Bonus point:
ABBS Score (Atypical Biliary Brushing Score): Score ≥4 associated with
malignancy (Witt etal., Diag Cyto, 2012).
Variables Score
Age ≥ 60
+1
Endoscopic impression malignant +2
Procedure indication: pancreatic mass +1
Stricture in CHD +2
Stricture in distal CBD +1
Presence of PSC +2
CA-19-9 >300U/mL +1
Both brush cytology and intraductal biopsy have comparable diagnostic specic-
ity with limited sensitivity (Sensitivity 45% and 48%, respectively). The combina-
tion of both lead to modest increase in sensitivity (59%) (Navaneethan et al.,
GIE, 2015).
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Q.Mention novel sampling and processing techniques in the evaluation of
Indeterminate Biliary Stricture
Smash protocol: Crushing of serial forceps biopsy samples between slides fol-
lowed by xation, staining (Papanicolaou), and on-site evaluation. Sensitivity 76%,
specicity 100% (Wright AJG, 2011).
Advanced analytical methods:
(a) Fluorescent In-situ Hybridization (FISH)
(b) Digital Image Analysis
(c) Flow cytometry
(d) Next Generation Sequencing (genomic alterations—KRAS, TP53, CDKN2A,
SMAD) 4) Biliseq (28 genes)
(e) Extracellular vesicles
FISH:
• Detect polysomic cells before other tests.
• Meta-analysis: FISH in PSC sensitivity: 68%, specicity: 70% (Navaneethan
etal., GIE, 2014)
• Combined triple assessment (standard brush cytology, intraductal biopsy, FISH):
sensitivity: 82%, specicity 100%. (Nanda etal., Ther Adv Gastro, 2015)
Q.What are the Advanced Imaging Tools for the Evaluation of Indeterminate
Biliary Stricture?
1. EUS
Features suggestive of malignancy:
• Presence of hypoechoic mass.
• Bile duct wall thickness>3mm.
Sensitivity 79%; specicity: 79%; PPV: 73%; NPV: 80% (Lee et al.,
AJG, 2004).
• EUS better than triphasic CT and MRI for tumor detection.
• EUS identies 100% of distal & 83% hilar tumors (Mohamadnejad et al.,
GIE, 2011).
• EUS FNA for diagnosis of CCA: sensitivity 73% (distal better than hilar; 81%
vs. 59%).
• With percutaneous as well as EUS guided FNA the risk of tumor seeding of
needle track increases, thus making potentially transplant ineligible.
2. Intra-ductal Ultrasound (IDUS)
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