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Acute Cholecystitis and

The Timing of Surgery:
When is it time to heal with steel?

Vincent C. Schooler, MD
Resident Grand Rounds
June 6, 2003
Clinical Cases
Case 1
• 80 yo female

• 3 days of N/V/RUQ pain

• PMH: Cholelithiasis, DM, CHF, HTN

• WBC 17 (6% bands); Tbili 9, ALP 197, AST
699, ALT 650, Amylase 103, Lipase 19
• Abd CT ⇒ Cholelithiasis with pericholecystic
fluid and gallbladder distention
• HIDA Scan ⇒ Cystic duct obstruction
Clinical Cases
Case 2
• 48 yo male

• progressive RUQ pain for 2 weeks

• PMH: DM, HTN, Obesity

• WBC 6.8, Tbili 0.8, ALP 88, AST 34, ALT
66
• Abd U/S: Cholelithiasis in neck of
gallbladder, negative Murphy’s sign, No
CBD dilatation
Clinical Questions
• What is the optimal time for surgery in these
patients?

• What is the evidence that supports a
laparoscopic approach to patients with acute
cholecystitis?

• What evidence-based clinical factors exist to
predict a successful laparoscopic surgical
outcome?
Statistics

• About 3 million adults in the U.S. have
gallstones

• Elderly, diabetics, obese patients, debilitated
patients ⇒ increased incidence of gallstones

• 90% of acute cholecystitis cases due to
gallstones
Background
• Aging is the most significant factor ⇒
higher incidence of acute cholecystitis1

• Acute Cholecystitis is the initial
presentation of symptomatic gallstones
in 15% - 20% of patients3
Acute Cholecystitis

• RUQ Pain
• Fever
• Leukocytosis

• Severe persistent pain
• +/- Jaundice
• Positive Murphy’s Sign
Acute Cholecystitis3

• Persistent cystic duct obstruction
• Pain lasts > 4 hours
• Usually fatty food ingestion ≥ 1 hr before pain
∀ ≠ Biliary Colic
3= Cleveland Clinic Journal of Med
Acute Cholecystitis

• Distention and inflammation of the
gallbladder
• Obstruction of cystic duct ⇒ Chemical
irritants in the bile
• Lysolecithin
• Prostaglandins
UptoDate 2003
Acute Cholecystitis2

• Thickened gallbladder wall or edema
• Pericholecystic Fluid
• Sonographic Murphy’s Sign
Acute Cholecystitis
Acute Cholecystitis

• Early stages ⇒ Edema and hyperemia
• Later stages ⇒ Adhesions, fibrosis, and necrosis

• Triangle of Calot visible in early stages
Courtesy of Netter
Management of Acute
Cholecystitis
• Supportive care with IVFs, bowel rest, & Abx

• Almost half of patients have positive bile
cultures

• E. Coli is most common organism

• Antibiotic choice: Ampicillin + Aminoglycoside
or 3rd generation cephalosporin
Management cont.

• No evidence exists showing a definite
benefit with use of antibiotics

• NSAIDs may improve course of acute
cholecystitis6

• SURGERY is the only definitive treatment
Management cont.

• 1st open cholecystectomy: 1886 by Justus Ohage
• 1st half of 20th Century: Supportive care ⇒ delayed
open cholecystectomy

• In 1970’s – mid-1980’s: Open cholecystectomy
early in the treatment course

• “Golden 72 hours” Rule
• Studies in early 1980’s ⇒ early surgery was better
than delayed surgery (using standard open
approach)14

• Laparoscopic surgery developed in late 1980’s

• Complications from LC dependent on laparoscopic
skill of surgeon (major bleeding, wound infection,
bile leak, and biliary injury)

• Was the benefit of early surgery by the open
approach true laparoscopically??
Timing of Surgery

• Early surgery = Within 72 hours of
admission or onset of symptoms

• Delayed surgery = Supportive care
only followed by discharge and
readmission in 6-12 weeks for surgery
Timing of Surgery

• Based on patient’s overall risk of surgery
• American Society of Anesthesiologists (ASA)
Scale7 is a guide for decisions on surgery
Laparoscopic vs. Open Cholecystectomy
Kiviluoto et al.8
• 63 pts. randomized to LC vs. OC; > 60 y.o. = 59% vs. 48%
• 1º endpt = hosp. mortality and morbidity, length of hosp. stay
• 16% of LC group needed conversion to open
• No deaths in either group; Hosp. stay average of 2 days shorter in LC
group (p=0.0063) Lancet 1998.
8

50 42
40
30
Rate (%) Morbidity
20
10 3
0
Lap Chole Open Chole p=0.0048
Timing of Surgery
Chandler et al.10
Objective: Compare the safety and efficacy of
early vs. delayed laparoscopic cholecystectomy
for treatment of acute cholecystitis
Study Design:
• RCT of 43 pts.
• Early = LC within 72 hours of admission
• Delayed = LC after symptom resolution or after
5 days of treatment
• IVFs, Piperacillin, bowel rest
• Delayed group also given indomethacin

10
Amer Surg 2000
Chandler et al.
• Inclusion: RUQ pain, WBC ≥ 10K, temp >38ºC, U/S evidence
• Exclusion: Hx. of PUD, GB perforation, unclear diagnosis

Conclusions:
• No statistically significant decrease in the complication rate in the
delayed group
Limitations: Small study group, average age < 40 years old

Early vs. Delayed LC
40
35
30
25
Complication
% 20 Conversion
15 Gangrenous
10
5
0
Early Delayed
Eldar et al.11

Objective: Determine the optimal timing of laparoscopic
cholecystectomy for acute cholecystitis and to evaluate
preop. and operative factors associated with conversion
from LC to OC

Study Design:
• 137 patients treated for acute cholecystitis
• Prospective, non-randomized trial
• 7 patients excluded due to choledocholithiasis
• LC done on all patients as soon as diagnosis established
• Cephazolin given preop to all patients

11
World J Surg 1997
Eldar et al.
Results:

• 28% conversion rate overall (37/130 total patients)

• Mean age 50 in LC group vs. 60 in converted group

• Patients with lap chole >96 hours after symptom onset ⇒
higher conversion rate (47% vs. 23%, p=0.022)

• Complication rate: 8.5% in LC vs. 27% in converted group
Eldar et al.

Conversion Complication

Odds Odds
Ratio Ratio (* =
NS)
Acute 630.8
gangrenous WBC > 13K 13.7
cholecystitis Bili. >0.8mg/dl 9.1
Nonpalpable 111.2
gallbladder Gender 8.9*
WBC > 13K 15.25 Large bile 8.5
Hx. of biliary 12.4 stones
disease
Age > 65 10.5
Eldar et al.

Conclusions:
• 3/5 independent factors associated with conversion from
LC can be determined preoperatively (WBC, age, hx of
biliary disease)

• 2/4 independent factors associated with complications
from LC can be determined preoperatively (WBC, Serum
bili)

Limitations: Validation of these factors needed using RCT,
small study
Timing of Surgery

Lai et al.12
Objective: Define the optimum
management between early and
delayed laparoscopic
cholecystectomy

Study Design:
• Average age in each group of 56
years old
• Early group = LC within 24
hrs of randomization
• Delayed group = LC in 6-8
wks
12
Brit J Surg 1998
Timing of Surgery

Lai et al.
Results:
• No major bile duct injuries in either group
• 21% (early) vs. 24% (delayed) conversion rate
• No statistically significant difference in conversion rate, postop. pain or
complications
• 16% of delayed group had a recurrence and failed conservative Rx
Conclusions:
• Early LC better than delayed LC due to lower conversion rate and
potentially lower risk of complications
Limitations: Selection bias (exclusion of patients with sxs > 1 week)
Timing of Surgery

Lo et al.13
Objective: Compare early with
delayed laparoscopic chole.
(LC) for acute cholecystitis

Study design:
• Early = LC within 72 hrs of
admission
• Delayed = LC 8-12 weeks
after resolution of acute
attack
13
Annals Surg 1998
Lo et al.
Inclusion: RUQ tenderness, T > 37.5ºC, WBC > 10K, U/S
evidence
• 44% of patients in trial had symptoms for ≥ 3 days
• Median age of 60 years old

Results:
• 16% of patients in delayed group failed conservative Rx.⇒
urgent LC

Comparison of Outcomes for Laparoscopic Cholecystectomy
29
30 23
20
Rate (%) 11 13 Conversion
10 Complication
0
Early Delayed
Timing of Surgery

Lo et al.
Conclusions:
• Lower hosp. stay and recuperation period in early vs.
delayed group (5 days vs. 7 days)
• Key factor that is controllable in the timing of surgery
involves delay from admission to surgery
• Delayed group ⇒ more fibrotic adhesions on gallbladder ⇒
increased conversion rate and morbidity
• Optimal timing of LC is within 72 hours of admission

Limitations: Low number of obese patients, unclear how
many diabetics in trial
Timing of Surgery

Koo et al.4
Objective: Review the results of laparoscopic
cholecystectomy (LC) in patients with acute
cholecystitis with attention to cost and clinical outcome
Study Design:
• Retrospective review of 60 patients who had LC for
acute cholecystitis
Exclusion: Patients with histopathologic evidence of acute
cholecystitis due to pancreatitis or carcinomatosis and
patients without definite signs and symptoms of acute
cholecystitis
4
Arch Surg 1996
Timing of Surgery
Koo et al.
• 3 groups based on timing of surgery

• Group 1: LC within 72 hours of onset of symptoms

• Group 2: LC between 4th and 7th day of symptom onset

• Group 3: LC after 7 days of symptoms

Results:

40 32 28
30 Conversion
Rate (%) 20 13
10
0
Group 1 Group 2 Group 3
Timing of Surgery

Koo et al.
Conclusions:
• Group 1 (LC within 72 hrs of sxs) had lower conversion rate,
shorter & less costly operations, and shorter convalescent rates
• More severe inflammation in gallbladders from groups 2 and 3
• NS relation: WBC, LFTs, or U/S findings and conversion rate
• Patients presenting within 72 hrs. from symptom onset ⇒ LC
• Patients presenting after 72 hrs. from sxs. onset ⇒ consider
elective LC in 6-8 weeks
Limitations: Selection bias, No description of patient
demographics of each group
Clinical Predictive Factors
Schafer et al.15
Objective: Define preop. criteria to predict both the
surgical strategy for managing acute cholecystitis and
the severity of inflammation
Study Design:
• 236 patients with acute cholecystitis had LC or OC within
48 hours of admission
• Non-randomized decision for LC vs. OC

• Resected gallbladders classified into 3 subgroups
• Type I (Mucosal inflammation); Type II (Phlegmonous
inflammation); Type III (Gangrenous or necrotizing inflammation)
Inclusion: RUQ tenderness, fever, leukocytosis, elevated
CRP levels, U/S findings
15
Amer J Surg 2001
Schafer et al.
Preoperative Findings
140 132
90 127
80 120
70
100
60
ASA (I,II)
50 80
%
40 ASA
30 (III,IV) 60
20 37 Mean Age
40 (p<0.001)

10
0 20 Mean WBC
LC Conv OC (p<0.05)

0 Mean
LC Conv OC CRP(mg/ L)
(p<0.001)
Schafer et al.

40
35
30
25 Gangrenous
(TypeIII)
%2
0
1
5 Postop
Com plication
1
0
5
0
LC Conv OC
Schafer et al.
Type I Type II Type III
(n=109) (n=63) (n=64)
Mean Age 54.7 63.3 66.8
Preop Sxs 2.2 3.2 3.6
Duration
(days)
Mean 11.5 12.9 14.1
WBC(X109/L)

Mean CRP 42.1 91.0 146.4
(mg/L)
Conversion 10 43 49
Rate (%)
Complication 14 24 40
Schafer et al.
Conclusions:
• CRP levels, duration of symptoms, WBC count
determined to be preoperative parameters that
predict the severity of inflammation

• 5 independent parameters that determine the type of
surgical approach (CRP levels, WBC count, ASA class,
duration of symptoms, and age)

• Increased CRP levels associated with advanced
inflammation of gallbladder
Schafer et al.
• As severity of inflammation increased ⇒ complication
rate increased
• CRP levels > 100 mg/L related to local tissue necrosis

• Defined a set of preoperative conditions that may help
determine the safest method of surgery
Limitations:
• Elevation of CRP levels may be also due to bacterial
infection (Trial did not evaluate for it)
• Selection bias

• Validation of markers needed with RCT

• Timing of Surgery not evaluated
Clinical Predictive Factors

Rattner et al.16
Objective: Determine which preoperative data correlates
with successful completion of a laparoscopic
cholecystectomy in patients with acute cholecystitis
Study Design:
• 20 of 281 pts. with acute cholecystitis had LC between
1990-92 at Mass General Hospital
Inclusion: Fever, leukocytosis, RUQ tenderness,
intraoperative findings of severe acute inflammation,
pathologic evidence of AC
Exclusion: Intraoperative findings of AC but no clinical
signs, lab signs, or pathologic evidence of AC
16
Annals Surg 1993
Rattner et al.

Results:
• Degree of leukocystosis, ALP elevation, and
APACHE II scores were significantly associated
with failure of laparoscopic surgery

• Interval from admission to surgery: 0.6 days
(successful group) vs. 5 days (failure group)

• Failure of LC related to gangrenous changes in
gallbladder
Rattner et al.

Conclusions:
• Surgery within 48 hrs of admission ⇒ successful LC

• Optimal timing of surgery is as soon as possible after
diagnosis of acute cholecystitis

Limitations: Retrospective, small study, recall bias
(authors of study reviewed their own surgical cases),
laparoscopic expertise unknown
Clinical Cases Follow-up

Case 1:
• 48 hrs after admission: LC ⇒ converted to open chole
due to adhesions in RUQ and necrosis of her
gallbladder
• Diagnosis: Acute obstructive cholecystitis
• Uneventful recovery
Case 2:
• 4 days after admission: LC ⇒ converted to open chole
due to necrosis of the gallbladder and cystic duct
junction
• Diagnosis: Acute Necrotizing Cholecystitis
• Uneventful recovery
Conclusions

• LC compared with OC has decreased pain and disability without
an increase in morbidity or mortality
• LC is more cost-effective
• Outcome of LC influenced by expertise of surgeon
• ASA scale useful but difficult to classify all patients
• Percutaneous cholecystostomy useful alternative in ASA IV, V
patients BUT 50% still require surgery15
• Conversion from laparoscopic to open cholecystectomy should
not be viewed as a complication
• Conversion must occur if anatomy is obscured or excessive
bleeding occurs18
Conclusions

• Most significant clinical factor for successful
LC is the duration of symptoms

• Increased chance of gangrene of the
gallbladder after 72 hrs

• Elderly, diabetics, obese patients, and
debilitated patients can safely undergo
laparoscopic cholecystectomy for acute
cholecystitis
Conclusions
• Should be performed within 72 hrs of admission

• If > 72 hours since admission, then evidence
supports attempted lap chole with a low threshold
for conversion to an open procedure

• More data needed to determine role of CRP levels
in preoperative management of patients with
acute cholecystitis