TG13: UPDATED TOKYO GUIDELINESFOR

ACUTE CHOLECYSTITIS
Jibran Mohsin
Resident, Surgical Unit I
SIMS/Services Hospital, Lahore
 Background

■ Before TG07, there were no practical guidelines through out the world primarily
targeting acute cholecystitis

■ TG07 was updated after

– total 35 meetings ofTokyo Guidelines RevisionCommittee for revision of
TGO7(TGRC)
– email exchanges with co authors abroad e.g. USA, Netherlands, UK, Germany,New
Zealand, India, Korea, China, Greece, Hong Kong, Italy, Philippines, Taiwan,
Singapore, Argentina, Australia and Malaysia
– 3 International Meetings for the Clinical Assessment and Revision ofTokyo
Guidelines
 OUTLINE

■ Terminology, Etiology and Epidemiology

■ Diagnostic Criteria
■ Severity assessment criteria/grading
■ Differential Diagnosis
■ Management
– Antimicrobial therapy
– Gallbladder drainage
– Surgical management
■ Summary
– Management bundle
– Acute Cholecystitis BundleChecklist
Terminology, Etiology and Epidemiology

■ Definition

– Acute inflammatory disease of gallbladder, often attributable to gallstones, but

many factors such as ischemia, motility disorders, direct chemical injury, infections
by microorganism, protozoon and parasites, collagen disease, and allergic reaction
are also involved
Terminology, Etiology and Epidemiology

■ Pathophysiology

– Gallstones are the cause of acute cholecystitis in majority of cases

– Involves physical obstruction at neck or in cystic duct by gallstone
– Leading to increased pressure inGB
– Determined by degree of obstruction and duration of obstruction
■ i.e. partial and short duration  biliary colic
■ Complete and long duration  Acute cholecystitis
■ If early treatment not given  severe disease and risk of complications
 Terminology, Etiology and Epidemiology

■ PathologicalClassification
STAGE FINDINGS
Edematous Cholecystitis 1st Stage 2-4 days • Interstitial fluid with dilated capillaries and lymphatics
• Edematous wall (sub serosal layer) of GB
• Intact GB tissue
Necrotizing Cholecystitis 2nd Stage 3-5 days • Edematous changes with areas of hemorrhage and scattered necrosis
(superficial, not full thickness)
• Vascular thrombosis and occlusion
Suppurative Cholecystitis 3rd Stage 7-10 days • WBC infiltration with areas of necrosis and suppuration
• Active repairing process of inflammation
• Contracted and thick wall due to fibrosis
• Intramural (not entire thickness) and pericholecystic abscesses
Chronic Cholecystitis • Repeated attacks of mild • Mucosal atrophy and fibrosis of GB wall
cholecystitis
• Chronic irritation by large gallstones
• Acute on chronic cholecystitis • Neutrophil invasion + lymphocyte/plasma cell infiltration
 Terminology, Etiology and Epidemiology

■ Special forms of acute cholecystitis

Acalculous Cholecystitis Acute cholecystitis wtihout cholecystoithiasis

Xanthogranulomatous cholecystits • Cholecystitis with xanthogranulomatous thickening of GB wall and raised GB pressure due
to stones with rupture of Rokitansky-Aschoff sinuses.
• Leakage and entry of bile into GB wall, ingested by histiocytes to form granulomas
containing foamy histiocytes
Emphysematous Cholecystitis • Air in GB wall due to gas-forming anaerobes including Clostridiumperfringens
• Often seen in diabetes and likely to progress to sepsis and gangrenous cholecystitis
Torsion of GB • INHERITED FACTORS: floating GB
• ACQURIED FACTORS: splanchoptosis, senile humpback, scoliosis, weight loss
• PHYSICAL FACTORS: sudden change in intraperitoneal pressure, sudden change of body
position, pendulum-like movement in anteflexion position, hyperperistalsis of organs near
GB, defecation, and blow to abdomen
Terminology, Etiology and Epidemiology

■ Advanced forms of and the type of complications of acute cholecystitis

Perforation of gallbladder • Due to acute cholecystitis, injury or tumors

• Most frequently due to ischemia and necrosis of GB wall

Biliary Peritonitis • Due to cholecystitis-induced GB perforation, trauma, and detached catheter during biliary
drainage and incomplete suture after biliary operation
Pericholecystitic abscess • Perforation of GB covered by surrounding tissue along with formation of abscesses around GB

Biliary fistula • Between GB and duodenum following an episode of acute cholecystitis

• Due to large stone eroding through GB wall intoduodenum
• Can also cause gallstone ileus (mechanical obstruction by stone at ileocecal valve)
Terminology, Etiology and Epidemiology

■ Incidence
– Around 10 % of general population have gallstones

– 20-40 % of asymptomatic gallstone have risk for developing some type of S/S. (1-3
% annually)

– 1-2 % asymptomatic and 1-3 % mild symptomatic gallstones annually present with
severe symptoms or complications (acute cholecystitis/cholangitis/ pancreatitis and
severe jaundice)
Terminology, Etiology and Epidemiology

■ Incidence
– Acute cholecystitis – most frequent complication of cholelithiasis (3.8 - 12 %)

– 6.0 % cases are of severe (accompanying organ dysfunction- Grade III) acute
cholecystitis

– 0.2 – 1.0 % cases of ERCP develop acute cholystitis

Terminology, Etiology and Epidemiology

■ Etiology
– 90-95 % gallstones
– 3.7 – 14 % acalculous cholecysytitis

■ Mechanism
– Gallstone  Cystic duct obstruction  bile stasis  activation of inflammatory
mediators and mucosal injuries
Terminology, Etiology and Epidemiology

■ Risk Factors
– “4Fs” ( forties, female, fat, fair) and “5Fs” ( 4Fs + fecund or fertile) associated with
lithogenesis in GB but no established association with acute cholecystitis except obesity

– Drugs: Hormone replacement therapy (2X), thiazides?, Hepatic artery chemotherapy,

statins (protective)

– AIDS (AIDS cholangiopathy and acute acalculous cholecystitis)

– Parenteral Nutrition, thermal burn, infection, surgery, trauma, long term ICU stay
Terminology, Etiology and Epidemiology

■ Prognosis
Mortality rate
Grade I 0.6 %
Grade II 0%
Grade III 21.4 %
overall 1.7 %
Terminology, Etiology and Epidemiology
 Diagnostic Criteria

■ Murphy’s (1903) sign shows high specificity( 79 – 96 %), however the sensitivity has
been reported low ( 50-65 %), thus not applicable in making a diagnosis of acute
cholecystitis due to low sensitivity

TG13 Diagnostic criteria for acute cholecystitis

A. Local signs of inflammation etc. 1. Murphy’s sign
2. RUQ mass/pain/tenderness Sensitivity (91 %)
B. Systemic signs of inflammation etc. 1. Fever Specificity (97%)
2. Elevated CRP
3. Elevated WBC count
C. Imaging findings Characteristic of acute cholecystitis IMAGING:
USG
SUSPECTED DIAGNOSIS: one item in A + one item in B CT
DEFINITE DIAGNOSIS: one item in A + one item in B +C Tc-HIDA scans
 Diagnostic Criteria
■ Most typical clinical sign of acute cholecystitis is abdominal pain ( RHC or epigastric) -72-93 %
■ Followed in frequency by nausea and vomiting
■ Fever >38OC only in 30 % cases
■ Muscular defense (guarding) in 50 % cases
■ Palpable tumors, rebound tenderness, stiffness (rigidity) are rare
Diagnostic Criteria
 Diagnostic Criteria

■ No specific blood tests for making a diagnosis of acute cholecystitis

– General inflammatory findings (> 10,000 mm3/dLTLC, > 3 mg/dL CPR level)
– Mild increase of serum enzymes in hepatobiliary system
– Raised bilirubin (up to 4 mg/dL) even in absence of complications
 Diagnostic Criteria

■ Ultrasonography should be performed at the initial consultation for all cases for which
acute cholecystitis is suspected (satisfactory diagnostic capability even if done by ER
physicians)

■ Ultrasonography shows 50-88 % sensitivity and 80-88 % specificity

■ Diagnostic if all of following are present

– Thickening of GB wall (5mm or more)
– Pericholecystic fluid
– Direct tenderness when probe is pushed against GB (ultrasonographic Murphy’s sign
– superior to ordinary Murphy’s sign in that it is possible to press GB accurately i.e 90
% sensitivity and specificity)
 Diagnostic Criteria

■ Others
– GB enlargement, GB stones(13 % cases), debris echo and gas imaging
– sonolucent(hypoechoic) layer, referred to as a low-echo zone (8 % sensitivity, 71 %
specificity)
– Low-echoic area with an irregular multiple structure (62 % sensitivity, 100 %
specificity)
 Diagnostic Criteria

■ Findings on contrast enhanced CT characteristic of acute cholecystitis

– GB distension (41 %)
– Pericholecystic fat stranding/density (52 %)
– GB wall thickening (59 %)
– Subserosal edema (31 %)
– Mucosal enhancement
– Transient focal enhancement of liver adjacent to gallbladder due to increased venous flow in cholecystic
vein draining directly into liver parenchyma
( during arterial phase of dynamic CT, disappears during portal and equilibrium phase)
– Pericholecystic fluid collection (31 %)
– Pericholecystic abscess
– Gas collection within GB
– High- attenuation GB bile (24 %)
 Diagnostic Criteria

■ Tc-HIDA scan
– GB normally visualized within 30 min if cystic duct is patent i.e. no cholecystitis

– Failure of GB to fill within 60 min after administration of tracer  obstructed cystic duct

– 80-90 % sensitivity for acute cholecystitis

– False positive largely explained by cystic duct obstruction induced by chronic inflammation and some
cases normal GB don’t fill due to SOD

– “Rim sign” = blush of increased pericholecystic radioactivity (30 % cases)

– Significantly higher specificity and accuracy than US

 Diagnostic Criteria

US versus Tc-HIDA scan

■ Gold standard is Tc-HIDA scan
■ BUT initial investigation of choice isUS
– Immediate availability
– Easy access
– Lack of interference by elevated serum bilirubin levels (cholestasis interferes with
biliary excretion of agents used for scintigraphy)
– Absence of ionizing radiation
– Information regarding presence of stone
Severity assessment criteria/grading
 Differential Diagnosis

■ Gastric and Duodenal ulcer

■ Hepatitis
■ Pancreatitis
■ GB cancer
■ Hepatic abscess
■ Fitz-Hugh-Curtis syndrome
■ Right lower lobar pneumonia
■ Angina pectoris/MI
■ UTI
Flowchart for management

1st LineT/M

1st LineT/M
 Management

■ Initial medical treatment while considering for surgery and ER drainage

– Nill By Mouth
– IV hydration and electrolytes correction
– Antimicrobial
– Analgesic
– Respiratory and hemodynamic monitoring

■ Appropriate organ support in severe acute cholecystitis

– Artificial respiration, intubation and vasopressors
– along with ER drainage/cholecystectomy
 Management

■ Analgesics should be initiated in early stage as it doesn’t affect positive rate of

sonographic Murphy’s sign

■ NSAID (diclofenac 75 mg IM) administration is effective for impacted stones attack for
PREVENTING acute cholecystitis
■ NSAID also effective for improvement of GB function in chronic cholecystitis
■ NOT effective to improve the course of cholecystitis after its acute onset
 Antimicrobial therapy

■ PrimaryGoal
– To limit both systemic septic response and local inflammation
– To prevent SSI (superficial, deep, organ space)
– To prevent intrahepatic abscess formation

■ Early and non-severe cases  Prophylactic

■ Others with SIRS  therapeutic
Antimicrobial therapy
 Antimicrobial therapy

■ Bile cultures should be obtained at the beginning of any procedure performed. GB bile
should be sent for culture in all cases of acute cholecystitis expecting those with grade
I severity

■ TG13 suggest cultures of bile and tissue when perforation, emphysematous changes,
or necrosis of GB are noted during cholecystectomy

■ Blood cultures are not routinely recommended for grade I community-acquired acute
cholecystitis
 Antimicrobial therapy

■ Factors influencing the selection of antimicrobial agents for acute cholecystitis

– Targeted organisms
– Pharmacokinetics
– Pharmacodynamics
– Local Antibiogram (local epidemiology and susceptibilitydata)
– H/O antimicrobial usage (< 6 months, increased risk of resistance)
– Renal and hepatic function (Dosage adjustment)
– H/O of allergies and other adverse events
 Antimicrobial therapy

■ Initiated as soon as diagnosis of acute cholecystitis is suspected

– For case in septic shock, within 1 h of recognition
– For other cases, as long as 4 h may be spent obtaining definitive diagnostic studies
prior to beginning antimicrobial therapy
– Should definitely be started before any procedure (endoscopic or operative)

■ Anaerobic therapy is appropriate if biliary-enteric anastomosis is present

Velosef (Cephradine) Tanzo/Tazocin (Piperacillin/tazobactam)
Oxidil (Ceftriaxone) Teinam (Imipenem/cilstatin)
Zinacef (Cefuroxime) Meronem (Meropenem)

Antimicrobial therapy
 Antimicrobial therapy

■ Historically, biliary penetration of agents has been considered in selection of

antimicrobial agents

■ However, there is considerable lab and clinical evidence that as obstruction occurs,
secretion of antimicrobial agents into bile stops. (need RCT to determine clinical
relevance and significance of biliary penetration in treating acute cholecystitis)
Antimicrobial therapy
 Antimicrobial therapy

Patients who can tolerate oral feeding may be treated with oral therapy.
 Antimicrobial therapy

Use of Antibiotic irrigation

■ Irrigation of surgical fields with antimicrobial agents
■ Clearly effective in reduction of wound infection
■ May be effective as effective as use of systemic antimicrobial agents

■ Combined use of systemic and topical antimicrobial agents may have additive effects
(especially if different agents are used)
 GB Drainage

Drainage (PTGBD)
Percutaneous Trans hepaticGB
GB Drainage

Aspiration (PTGBA)

Naso(-biliary) GB drainage (ENGBD)

Endoscopic
transpapillary
GB stenting (EGBS)

Naso(-biliary) GB drainage
Endoscopic Ultrasound (EUS)-guided
GB stenting
 GB Drainage

■ Percutaneous transhepatic GB drainage (PTGBD)

– Recommended essential Standard GB drainage method for surgically unfit patients
with acute cholecystitis

– Safe alternative to one-shot definitive treatment in form of early cholecystectomy in

surgically high risk populations e.g. mortality rate in elderly or critically ill patients
up to 19 %

– Low complication rate 0-13 % with procedure related mortality 0.36 %

 GB Drainage

■ Grade II  only when patient does not respond to conservativetreatment

■ Grade III  recommended with intensive care

■ PREDICTOR FOR FAILURE OF CONSERVATIVETREATMENT:

ATADMISSION AT 24-h and 48-h follow-up

• Age > 70 years • WBC >15000 cell/µl

• Diabetes • Elevated temperature
• Tachycardia • Age > 70 years
• DistendedGB
GB Drainage

Under fluoroscopy
(Seldinger technique)
6- to 10-Fr pigtail
catheter
GB Drainage
 GB Drainage

INDICATION:
end-stage liver disease (in whom
percutaneous approach is difficult to
perform)
GB Drainage
GB Drainage
GB Drainage
GB Drainage
 Surgical Management
Grade I (mild) EARLY laparoscopic Cholecystectomy
Grade II (moderate) MOST CASES EARLY laparoscopic or open cholecystectomy
(within 72 hr after onset of acute cholecystitis) in
experienced centers
“difficult gallbladder” ( severe local continues medical treatment or drainage (PTGBD
inflammation i.e. >72 h from onset, WBC or surgical cholecystostomy) preferable
count >18,000 and palpable tender mass in
RUQ) DELAYED cholecystectomy
Serious local complications(biliary EMERGENCY open or laparoscopic depending on
peritonitis, pericholecystic abscess, liver experience (along with general supportive care)
abscess, GB torsion or emphysematous/
gangrenous/ purulent cholecystitis
Grade III (severe) DELAYED cholecystectomy (2-3 months later after
improvement of patient’s general condition) when
indicated
 Surgical Management

OPTIMAL APPROACH
■ Until 1st half of 1990’s --. Open cholecystectomy was the standard technique of acute
cholecystitis
■ Open cholecystectomy with mini-incision is able to produce as good results as those
obtained by laparoscopic procedure although superiority of laparoscopic procedure is
now well established
■ TG13 recommends laparoscopic cholecystectomy over open cholecystectomy

■ However, the 1st priority is ALWAYS patient safety

 Surgical Management

OPTIMALTIMING
■ Preferable to perform cholecystectomy soon after admission, particularly when less
than 72 hours have been passed since the onset of symptoms

■ Definition of early surgery  within 72-96 h from onset of symptoms (NOT time of
diagnosis or admission)
■ Definition of elective (DELAYED) surgery  6 weeks or more after onset
 Surgical Management

OPTIMALTIME FOR CONVERSION FROM LAPAROSCOPICTO OPEN

CHOLECYSTECTOMY
■ Surgeons should NEVER hesitate to convert to open surgery to prevent injuries when
they experience difficulties in performing laparoscopic cholecystectomy i.e. low
threshold
 Surgical Management

■ Optimal time for cholecystectomy following PTGBD

– Often performed after several days/2 weeks
– BUT remains controversial due to lack of any strong evidence(no RCT)

■ Optimal time for cholecystectomy following endoscopic stone extraction of bile duct
in patients with cholecysto-choledocholithiasis in acute cholecystitis
– No definitive conclusions could be made due to insufficient evidence
 Management bundle

■ Bundle = collection of mandatory items or procedures to be performed in clinical

practiceOR
■ Group of therapies for a disease that, when implemented together, may result in
better outcomes than if implemented individually
Management bundle
Management bundle
Management bundle
Acute Cholecystitis BundleChecklist
Available at surgicalpresentations