Gallstone pancreatitis Journal club

1. Journal Club
Prepared by
Pranjal Rokaya
Resident
General Surgery
Moderator
As. Prof. Dr. Tanka Prasad Bohora
8th September, 2022

2. “ Knowledge is knowing that tomato is a fruit;
Wisdom is not putting it in a fruit salad”

3. Article being appraised

4. Pyramid of evidence

5. Randomised Control Trial

6. Journal Introduction
• Annals of Surgery
• Monthly peer reviewed journal of surgical science and practice.
• Started in 1885 in USA and UK.
• Impact factor in 2021 : 13.787
• 2nd highest ranked surgical journal after JAMA surgery.

7. Study design
Single center, randomised control trial.
Timing of laparoscopic cholecystectomy with intraoperative
choangiogram was compared among patients with predicted mild
gallstone pancreatitis.
Compared cholecystectomy within 24 hours of presentation to
cholecystectomy after clinical resolution.

8. Objectives of Study
To determine the feasibility of early cholecystectomy within 24 hours
of presentation regardless of symptoms or lab values for patients with
mild acute pancreatitis.
To obtain estimates of the effect of early cholecystectomy on hospital
LOS, complications, and PROs in order to determine the need for
further evaluation.

9. Setting of Study
• Conducted at Lyndon Baines Johnson General Hospital; Houstan,
Texas.
• Approximately 1300 elective and nonelective cholecystectomies
performed per year.

10. Study Population
• Patients over 18 with predicted mild gallstone pancreatitis planned to
undergo lap cholecystectomy before discharge.
• Duration: June 2016 to June 2018
• Protocol changed in August 2017, with specified 12-hour observation
period between patient enrollment and randomization, to ensure that
there was no evidence of clinical deterioration from mild to more
severe pancreatitis.

11. Gall stone pancreatitis
Clinical: Upper abdmonial pain, Nausea, Vomitting.
Absence of alcohol use disorder.
Elevated plasma lipase level above the upper limit of normal (>370 u/l).
Imaging confirmation of gall stone or sludge.

12. Predicted Mild pancreatitis
BISAP score of 0-2.
No evidence of
organ failure.
No local or systemic
complications

13. Exclusion criteria
• Patients with 2 strong or 1
very strong predictors of
choledocholithiasis.*
• Pregnancy
• Developmental delay
• Severe preexisting medical
comorbidities.
• Chronic pancreatitis.
• Native language other than
English or Spanish.

14. Study Protocol
• CONSORT guidelines were followed.
• Randomized using variable permuted blocks of 4,6 and 8 using a
computer-generated sequence.
• Prior to protocol change, eligible patients enrolled and randomised
concurrently.
• After protocol change, delayed randomization after 12 hour
observation period.

16. Block randomization
• Participants are randomized within a block.
• Sizes of blocks may vary.
• Within a block, group assignments are balanced.
• To achieve balance, some participants are not assigned randomly but
rather following a algorithm.

19. …Study Protocol
• Stratified based on intermediate (having only moderate predictors vs
high risk (having 1 strong predictor) for choledocholithiasis.
• Not blinded: Patients and healthcare providers.
• Blinded: Post-operative PRO assessors and data analysts.
• Intervention: Laparoscopic cholecystectomy with IOC within 24 hours of
presentation regardless of laboratory or clinical symptom resolution.
• Control: Lap cholecystectomy once the patient had resolution of abdominal
pain and down-trending lab values.

20. Study Outcomes
• Primary: Total 30-day length of Stay (LOS) in hours.
• Secondary
ERCP rates
Complications (unplanned transfusions, SSI, pneumonia, bile duct injury, retained stone at 30d, and
bowel injury.)
Clavien-Dingo grading of complications.
Readmissions within 30 days.
Exacerbation of pancreatitis.
Conversion to open cholecystectomy

21. Clavien- Dingo classification
Grade
1. Any deviation from normal postoperative course w/o need for pharmacological treatment or surgical,
endoscopic and radiological interventions.
Accepted therapeutic regimens: Antiemetics, antipyeretics, analgesics, electrolytes and fluid therapy.
2. Require pharmacological treatment with drugs other than accepted for grade . Blood transfusion,
antibiotics and TPN included.
3. Requiring surgical, endoscopic or radiological intervention.
3a. Intervention under regional/local anesthesia
3b. Intervetnion under general anesthesia
4. Life threatening complication requiring intensive care.
4a. Single organ dysfunction
4b. Multi organ dysfunction
5. Patient demise

22. Patient reported outcomes (PR0)
• Assessed by short term change in functional health status between admission and
postoperative assessment at 1 month using Gastrointestinal Quality of Life Index (GIQLI).
• GIQLI includes 36 questionnares
Symptoms
Emotions
Physical dysfunction
Social dysfuntion
Effect of medical treatment

23. Results

24. Baseline patient characteristics

26. Procedural characteristics

27. Outcomes
Negative binomial regression for length of stay and number of procedures

28. Complications after Control Versus Early Cholecystectomy

29. One month outcomes, Early versus Control operation

30. Discussion
1st RCT that compared the timing of Lap Chole before 24 hours of
admission to later within the same admission.
Demonstrated early Lap chole is feasible and decreased 30-day hospital
LOS. (16 hours vs 43 hours, p<0.03)
Early cholecystectomy also decreased index hospital LOS and the need
for ERCP. ( 15% vs 29% ERCP, p<0.038)
Similar improvement in quality of life after surgery in both groups.

31. …Discussion
72% probability that early cholecystectomy led to increased
complications, majority being minor (Clavien Dingo grade 1 or 2).
Difficulty in predicting severity of pancreatitis potential barrier to
early cholecystectomy.

32. Limitations of study
Results may not be generalizable to other hospitals.
Didn’t incorporate lap CBD exploration.
The inability to accurately predict the severity of acute pancreatitis
soon after admission may limit implementation.

33. Conclusion of study
In patients with predicted mild gall stone pancreatitis,
cholecystectomy within 24 hours of admission significantly reduced
rates of ERCPs, time to surgery and 30 day LOS.
However, increased the risk of minor complications.
Limitations of current predictive models for acute pancreatitis at
admission warrants further investigation.

34. Critical Appraisal

35. 1. Did trial address a clearly focused issue?
• Authors were explicit and clear on inclusion criteria.
• Participants, Intervention, comparison group and outcomes were
clearly defined.

36. 2. Was the assignment of patients randomised?
• Permuted block randomization was used.
• Allocation sequences were concealed from researchers and patients.

37. 3. Were all of the patients who entered the trial properly
accounted for at the conclusion?
 2 patients assigned to the intervention group developed severe pancreatitis;
thus not receiving the intervention.
Reasons were clearly stated for drop out of patients.
All patients randomised were analysed in same groups regardless.(Intention to
treat analysis).

38. 4. Were patients, health workers and study personnel
‘blind’ to treatment?
Didn’t use any form of blinding in patients and HCP.
All outcome measures were objective.

39. 5. Were the groups similar at the start of trial?
Patients across groups were similar in characteristics such as age, sex,
BMI, race, and ASA classification.
 Findings on USG, BISAP scores, and admission lab values were also
similar except lipase which was higher in the control group.

40. 6. Aside from the experimental intervention, were the
groups treated equally?
• All participants were recruited using same means in both the groups.
• Both the groups underwent same operative procedure, difference
only being the timing of the operation.
• Since there was no blinding, couldn’t be 100% certain whether
participants were treated equally.

41. 7. How large was the treatment effect?
Primary and secondary outcomes were measured objectively.
Equal number of participants in both groups responded on 1 month
followup.
Sample size was relatively small, research was a only a single centre
study .

42. 8. How precise and accurate was the estimate of
treatment effect?
• Primary outcome: Total 30 day LOS (50 vs 77 hours) used 95% CI with
IRR 0.68 (0.65-0.71).
• Study correlated increased rate of ERCP with delayed
cholecystectomy: contradiction with natural course of the disease?
• IOC performed in 91% in early vs 83% in control group.

43. 9. Were all clinically important outcomes considered?
Included most common clinical outcomes relevant to both patient
and health care providers.
Tool used for PRO assessment was reliable and externally validated.
Doesn’t specify some postoperative complications (DVT, atelectasis.

44. 10. Are the benefits worth the harm and costs?
• Weighing in additional LOS of 22 hours vs increase in complications.
• Protocol change due to failure of predictive models.
• No similar RCT was performed with similar timing ( one RCT
compared surgery within 48 hours to surgery after resolution but
stopped midway.

45. 11. Can results be applied to our context?
Research finished 4 years ago, guidelines still favor cholecystectomy in index
admission without specifying timing.
Performed in setting with 24 hour availability of lap cholecystectomy facility.
Performed in low socioeconomic population comparable to ours.
Average BMI of patients enrolled was much higher compared to mean BMI of
our population.
Performed in a medically insured population.

46. References
1. Mueck KM, Wei S, Pedroza C, Bernardi K, Jackson ML, Liang MK, et al.
Gallstone Pancreatitis. Annals of Surgery. 2019 Sep;270(3):519–27.

47. •Thanks