1. Management of Acute Cholecystitis in Cancer Patients –a Comparative Effectiveness Approach
Thejus T. Jayakrishnan, MBBS; Ryan T. Groeschl, MD; Ben George, MD;
James P. Thomas, MD, PhD; Sam Pappas, MD; T. Clark Gamblin, MD, MS;
Kiran K. Turaga, MD, MPH
Department of Surgery

2. Disclosures
I have no relevant financial relationship with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial service(s) discussed in this CME activity.
I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.

3. Cholecystitis in General Population
Commonest etiology – Gallstones
10-15% Gallstone prevalence in the US
1-4% Symptomatic/year1
1Sanders, 2007

4. Rx Options Surgically fit Cholecystectomy Cholecystostomy/
Surgically unfit
Cholecystostomy/
Conservative medical treatment
Coagulopathy
Neutropenic
-Definitive
-Recurrence 10-40%

5. Cholecystitis in Cancer
2. Endoscopy:
Biliary stenting
3. Int. Radiology:
TACE
1. Surgery:
Gastrectomy
4. Drugs: Somatostatins
Immunosuppression
Cancer Cachexia
Increased risk in cancer patients
(Relative Risk 1.38)1
1Thomsen, 2008

6. Management Challenges
Increased risk of complications
Neutropenia-immunosuppression
Advanced age & malnutrition
Cholecystectomy vs. no Cholecystectomy
Interruption of cancer therapy
The risks of recurrence in a limited life span
Impact on overall prognosis of the patients
Surgical complications - adhesions, thrombocytopenia
Metastases

7. Hypothesis
A prognostic model for the management of acute cholecystitis in cancer patients can be developed incorporating patient specific risk factors to yield the optimal survival

8. Methods
Step 1: Generate the base-case scenario – literature review(PubMed) Step 2: Formulate new algorithm Step 3: Decision analyses of new algorithm vs. conventional strategies

9. Comprehensive search to obtain base-case estimates
Methods
Comprehensive search to obtain base-case estimates
Preliminary search: Literature related to cholecystitis in cancer patients
Second search: Risk factors for cholecystitis in cancer patients Therapy related, Cancer related and Host factors
Third search: Current management strategies for cholecystitis in the general population

10. New Algorithm: Initial Management
Low Risk
Cholecystectomy
Re-evaluate surgical risk
Start NPO, Analgesics, Antibiotics
Low Risk
Cholecystectomy
Reassess for surgical risk PC
High Risk
Continue with cholecystostomy
Decision analyses
High Risk
8 Hours
24 Hours
48 hours
72 hours
PC – Percutaneous Cholecystostomy

11. Decision Tree: Strategies
Cx - Cholecystectomy
PC – Percutaneous Cholecystostomy
TreeAge PRO 2012

12. Decision Tree: New Algorithm
Cx - Cholecystectomy
PC – Percutaneous Cholecystostomy

13. Decision Tree: Follow-up

14. Probabilities Variable Probability Ranges High risk for surgery
Morbidity
Cholecystectomy
0.50
0.10 to 0.60
Percutaneous cholecystostomy
0.10
0.05 to 0.30
Medical management
0.3
0.10 to 0.40
Mortality
0.15
0.05 to 0.50
0.03
0.01 to 0.10
0.05
Low risk for surgery
0.04
0.01
0.005 to 0.05
0.02
0.005
0.001 to 0.01
Percutaneous cholecystostomy
0.001
to 0.005
0.002

15. Assumptions Variable Probability Ranges
Reduction in survival due to recurrent cholecystitis
0.05
0.02 to 0.20
Reduction in survival due to interruption to cancer therapy
0.1
0.05 to 0.50

16. Reference Case
60 year-old patient with advanced cancer with an expected survival of 12 months presenting with acute cholecystitis

17. Risk Factors for Recurrent Cholecystitis
Category
Risk Factors
Level of evidence 1
Therapy Related Factors
Surgery
Gastrectomy
Level I
Endoscopic procedures
ERCP, Stenting
Chemotherapy
Somatostatin
Myelosuppressive drugs
Tyrosine Kinase inhibitors: Sunitinib, Sorafenib
Level II
Level IV
Cancer Related Factors
General Health
Prolonged fasting
Total Parenteral Nutrition
Weight loss
Low Immunity
Metastasis
Melanoma
Renal Cell Carcinoma
Host Factors
Gallstones
Shared risks with cancer
Obesity
Smoking
Estrogen Therapy
1CEBM Levels of Evidence

18. Results: Estimated Survival
For an estimated survival of 12 months:
Low surgical risk patients
New Algorithm 11.9 months vs. CT 11.8months vs. PC 11.8months vs. DC 11.9months
High surgical risk patients
New Algorithm 11.6 months vs. DC 9.9 months vs. PC 11.4 months and CT 11 months
PC – Percutaneous cholecystostomy
Cx - Cholecystectomy

19. Two-Way Sensitivity Analyses of Probability of Recurrence and Expected Survival
Low
Moderate
High

20. Discussion PC associated with resolution of acute symptoms
% successful clinical resolution
90% resolution in hours
Length of stay: PC alone > Early cholecystectomy
Early cholecystectomy decrease overall hospital length of stay and hospital cost

21. Limitations The absence of high quality base-case data
Hospice or palliative care not incorporated
Assumption of constant rates (eg: recurrence)
Quality of life and cost-effectiveness not studied

22. Conclusions
A prognostic model based on the premise of “early aggression” and “delayed thoughtfulness” in the management of cholecystitis in patients with advanced malignancies is feasible

23. Acknowledgement Dr Kiran K. Turaga (Mentor), Dr T. Clark Gamblin
Faculty at the Department of Surgery - MCW

24. THANK YOU