Journal club presentation on "Incidental Gallbladder Cancer after Cholecystectomy"

1. Dr. A. K. M. Lutful Haque
MS (general surgery) part-III student
Surgery Unit IV DMCH

2. Title
Systematic review of management of incidental
gallbladder cancer after cholecystectomy

3. Authors
• K. Søreide Clinical Surgery Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK; Department of
Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, and Department of Clinical Medicine, University of
Bergen, Bergen, Norway.
• R. V. GuestClinical Surgery Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh , UK
• E. M. Harrison Clinical Surgery Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK
• T. J. Kendall Division of Pathology, Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK
• O. J. Garden Clinical Surgery Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK
• S. J. Wigmore Clinical Surgery Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK

4. Correspondence to
Professor K. Søreide,
Department of Gastrointestinal Surgery, Stavanger University Hospital,
PO Box 8100, N-4068 Stavanger, Norway
(e-mail: ksoreide@mac.com)

5. Source
• British Journal of Surgery
Volume 106; Issue 1;Page no 32-45
• Paper accepted on 1 October 2018
• Published on January 2019

6. Abstract
• Background:
• Gallbladder cancer is rare.
• Incidental gallbladder cancer after cholecystectomy are increasing.
• The aim - to review the available data for current best practice for optimal
management of incidental gallbladder cancer.
• Methods:
• A systematic PubMed search of the English literature to May 2018 was
conducted.

7. Abstract(continued)
• Results:
• The search identified 12 systematic reviews and meta-analyses, several
consensus reports, multi-institutional series and national audits.
• Incidence is 0⋅25–0⋅89%
• Most patients were staged with pT2 (half) or pT1 (one-third) cancers.
• Patients with T1a or less survival rate up to 100% after cholecystectomy alone
• For T1b or above cancer reresection is recommended.
• The type, extent and timing of reresection remain controversial.
• Perforation at initial surgery has a higher risk of disease dissemination.

8. Abstract(continued)
• PET may detect residual disease.
• The incidence of port-site metastases is - 10%.
• Routine resection of port sites has no effect on survival.
• Adjuvant chemotherapy is poorly recommended.
• Conclusion:
• Management of incidental gallbladder cancer continues to evolve, with more
refined suggestions for subgroups at risk and a selective approach to
reresection.

9. Introduction
• Gallbladder cancer has a dismal prognosis
• One-third presents with distant metastasis
• Early gallbladder cancers discovered incidentally at histopathological
examination.
• 0⋅25–0⋅89% of specimens demonstrated a incidental GB cancer
• In endemic regions incidence is higher (up to 2%) and presents much
younger (at 40 years)

10. Introduction(continued)
• Incidental gallbladder cancers have a more favourable prognosis.
• The role, timing and extent of further surgery, and the impact on
outcome, remain controversial.
• The aim - to explore currently available data for management of
incidental gallbladder cancer after cholecystectomy

11. Methods
• A PubMed search was undertaken of the English literature up to May
2018 using the search words
‘gallbladder cancer’ and ‘incidental’ and ‘surgery’, ‘laparoscopy’, ‘pathology’,
‘staging’, ‘CT/MRI/PET’ with ‘consensus’, ‘guideline’, ‘meta-analysis’, ‘systematic
review’ alone or in combination.
• The main focus of the systematic search was to identify consensus
reports, guidelines, systematic reviews and meta-analyses
• Published in the most recent 5 years (1 January 2013 to 30 May
2018).

12. Methods(continued)
• The literatures predominantly retrospective
• Data obtained from larger multicentre or collaborative work
• Small, retrospective or single-institution series were excluded
• Each included study was searched for additional references

13. Results
• Thus the identified studies included were
• 12 systematic reviews with or without meta-analysis,
• 7 consensus reports and guidelines,
• 15 multi-institutional series, and
• 7 national series/audits or registries.

14. Results - Pathology and staging for incidental
gallbladder cancer
• There is debate around routine pathological examination of all
gallbladders
• Routine histopathological investigation detects more incidental
gallbladder cancers
• Correct pathological staging for planning of further management.

17. Results - Pathology and staging for incidental
gallbladder cancer (continued)
• Tis or pT1a have a very low risk of recurrence
• pT1b is considered to require further surgery.
• For pT2 cancers, the location in the gallbladder is important
• The presence of pN+ is considered an adverse prognostic factor
• The cystic duct margin should be reported as part of the resection
margin

18. Results - Intraoperative events at primary
surgery
• Intraoperative perforation of the gallbladder bears a higher risk of
local recurrence
• This does not change if a bag is used for retrieval.
• Perforation or bile spillage associated with peritoneal carcinomatosis
• Type of surgery has no influence on outcome.

19. Results - T category at presentation
• The most frequent stage at presentation was pT2, followed by pT3
and pT1.
• Incidental gallbladder cancers found on HPE alone is - T1 two-thirds.

21. Results - Timing of re-resection
• Early contact with a hepatobiliary centre should be made
• Time interval to reresection: 1 - 11 months (median 2–3months)
• Inferior outcomes within the first 4weeks and after 8weeks
• 4–8-week window had the best outcome.

22. Results - Timing of re-resection(continued)
• If perforation occurred a period of observation may be allowed
• Time is not the determinant of outcome.
• Biology is the most essential factor for progression of disease.

23. Results - Preoperative restaging before
resection
• Chest and abdominal CT
• PET–CT
• high sensitivity for disseminated disease
• before reresection in any T1b cancer and above
• for ruling out local residual disease
• Staging laparoscopy

25. Results - Type and extent of reresection
• T1a
• survival rate 100%,
• < 2% risk of pN+ disease on reresection;
• simple cholecystectomy is curative
• T1b
• extended resection with lymphadenectomy
• 10% will have pN+ status.
• Extended surgery doesn’t confers a survival benefit in T1b cancers.

26. Results - Type and extent of
reresection(continued)
• Liver involvement or node metastasis is related to poor survival
• No improved survival after either excision of common bile ducts
(CBDs) or multiple organ resections.

27. Results - Open and laparoscopic surgery
• Type of surgical access (laparoscopic, converted or open) bears no
negative influence on survival.
• No clear adverse outcomes from laparoscopic resections compared
with open operations
• Laparoscopic access route is increasingly entertained and promoted.
• Laparoscopic access associated with a reduced lymph node yield.

28. Results - Effect of radical and extensive
reresection on outcome
• Unresectable advanced disease at reoperation 23% -50%.
• Peritoneal and port-site metastasis.
• The extraction site is at significantly higher risk
• The risk of port-site metastasis is associated with
• increased T category and
• presence of poor histopathological features.

29. Results - Effect of radical and extensive
reresection on outcome
• No survival benefit from routine port-site excision
• Port-site excision in documented intraoperative perforation of the
specimen.
• If CBD not involved there is no benefit for extrahepatic bile duct
resection
• ‘Radical cholecystectomy’ morbidity is higher.

30. Results - Role of tumour markers
• CEA and CA 19-9
• raised vale - low and non-specific value
• within the normal range - good prognosis.
• CA 242 and thymidine kinase
• promising or better and require further validation.

31. Results - Outcome prediction and prognostic
score
• Higher T category and the presence of lymph node metastasis - poor
survival.
• The Gallbladder Cancer Predictive Risk (GBPR) -- locoregional or
disseminated disease
• The GBPR score is an independent factor for overall and recurrence-
free survival.

33. Results - Adjuvant chemotherapy
• The concept of neoadjuvant therapy is not possible
• Any T2 disease and above with N1 disease—adjuvant thrapy
• Reresected cancers received adjuvant radiotherapy – better survival.
• There are no randomized trials for radiotherapy as adjuvant therapy.

34. Results - Adjuvant chemotherapy(continued)
• Gemcitabine is the drug of choice.
• Since 2010, cisplatin and gemcitabine have been the preferred
combination
• Better survival for capecitabine after radical surgery of biliary tract
cancer.

37. Discussion
• Biology is the determinant of survival.
• Defining the biology from improved clinical, imaging and biomarker
• The role and timing of imaging in directing surgery or sparing patients
• The role of adjuvant therapy needs to be investigated in better detail
• Improved data quality from prospective observational cohorts,
imaging studies, oncogenomic profiling studies and novel
therapeutics.

38. Limitations
• The literatures predominantly retrospective
• Lack of high-quality data.
• Incidental diagnosis – true incidental post operative

39. References
• Lau CSM, Zywot A, Mahendraraj K, Chamberlain RS. Gallbladder carcinoma in the United
States: a population based clinical outcomes study involving 22 343 patients from the
surveillance, epidemiology, and end result database (1973–2013). HPB Surg 2017; 2017:
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• Choi KS, Choi SB, Park P, Kim WB, Choi SY. Clinical characteristics of incidental or
unsuspected gallbladder cancers diagnosed during or after cholecystectomy: a systematic
review and meta-analysis. World J Gastroenterol 2015; 21: 1315–1323.
• Jamal K, Ratansingham K, Siddique M, Nehra D. Routine histological analysis of a
macroscopically normal gallbladder – a review of the literature. Int J Surg 2014; 12: 958–
962.
• Ghidini M, Tomasello G, Botticelli A, Barni S, Zabbialini G, Seghezzi S et al. Adjuvant
chemotherapy for resected biliary tract cancers: a systematic review and meta-analysis.
HPB (Oxford) 2017; 19: 741–748.
• Goetze TO, Paolucci V. Benefits of reoperation of T2 and more advanced incidental
gallbladder carcinoma: analysis of the German Registry. Ann Surg 2008; 247: 104–108.

40. References
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• Zhang W, Hong HJ, Chen YL. Establishment of a gallbladder cancer-specific survival model
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• Stein A, Arnold D, Bridgewater J, Goldstein D, Jensen LH, Klümpen HJ et al. Adjuvant
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