Incidental CAGB, Carcinoma Gallbladder, Tumor markers, AJCC TNM 8th edition, Oncologic outcomes, Completion extended cholecystectomy, Adjuvant chemotherapy

1. APPROACH AND MANAGEMENT
OF INCIDENTAL CARCINOMA
GALLBLADDER
Moderator: Dr Narendra Pandit
Presenter: Dr Anand Ujjwal Singh

2. Sequence of flow
• Definition IGBC (Incidental gallbladder carcinoma)
• Importance and epidemiological trends
• HPE assessment
• AJCC TNM staging 8th ed.
• Intraoperative events of Primary (Index) surgery
• Staging evaluation: Imaging and Laparoscopy
• Factors a/w poor oncologic outcome
• Surgery : stage wise
• Residual disease (RD)
• Tumor markers
• Adjuvant Chemotherapy

3. INCIDENTAL GALLBLADDER CARCINOMA (IGBC)
• IGBC is diagnosed on pathologic assessment following
cholecystectomy for presumed benign disease
Leonid Cherkassky et al. Surg Oncol Clin N Am 28 (2019)

4. IMPORTANCE?
• Laparoscopic cholecystectomy (LC) most frequently performed general
surgery procedure
• routine histopathological investigation
• IGBC  more favourable prognosis than cancers presenting with symptoms
• role, timing and extent of further surgery and the impact on outcome,
remain controversial
Sorcide K et al. Systematic review of management of incidental gallbladder
cancer after cholecystectomy, British Journal of Surgery 2019

5. Epidemiological trend
• incidence of gallbladder cancer has increased in the past two decades
 increase in cholecystectomy rates.
• in recent series from Western countries 0⋅25–0⋅89 % of specimens
demonstrated a gallbladder cancer as an incidental, unexpected
finding
Lundgren L et al. Are incidental gallbladder cancers missed
with a selective approach of gallbladder histology at
cholecystectomy? World J Surg 2018

8. HISTOPATHOLOGICAL ASSESSMENT
• routine rather than selective histopathological investigation detects
more IGBC
• Essential to establish correct pathological stage  for planning
further management
Lundgren L et al. Are incidental gallbladder cancers missed
with a selective approach of gallbladder histology at
cholecystectomy? World J Surg 2018

9. • Pathological examination is important for appropriate staging and
further management
• essential to establish the correct pathological stage for planning of
further management
Sorcide K et al. Systematic review of management of incidental gallbladder
cancer after cholecystectomy, British Journal of Surgery 2019

10. What to look for specifically in HPE report?
• pT and node status
• Grade
• Lymphovascular and perineural invasion
• Cystic duct margin status
• Intraoperative Bile spillage  peritoneal carcinomatosis

11. Table : Importance of determining Stage on prognosis and outcome as shown
by difference in estimated 5 year survival in various stages
Sorcide K et al. Systematic review of management of incidental gallbladder
cancer after cholecystectomy, British Journal of Surgery 2019

12. What can be done in our setup?
• Case burden
• Coordination with pathologist
• Resurgery at earliest  as early as 10 days to upto 3 months in
delayed presentation

13. AJCC TNM Staging (8th Edition)
AJCC CANCER STAGING MANUAL, 8TH EDITION

14. Sorcide K et al. Systematic review of management of incidental gallbladder
cancer after cholecystectomy, British Journal of Surgery 2019

15. Fig: T1 showing the tumor invading the lamina propria or muscle layer of the gallbladder
AJCC Cancer Staging Manual, 8th edition

16. Fig. 2: T2 showing the tumor invading perimuscular connective tissue of the gallbladder
with no extension of the tumor beyond serosa or into the liver
AJCC Cancer Staging Manual, 8th edition

17. Intraoperative events at primary surgery
Sorcide K et al. Systematic review of management of incidental gallbladder
cancer after cholecystectomy, British Journal of Surgery 2019

18. • intraoperative perforation of the gallbladder bears a higher risk of
local recurrence
• Perforation or bile spillage may be associated with an almost
universal risk of peritoneal carcinomatosis and a poor prognosis
Isambert M et al. Incidentally-discovered gallbladder cancer: when,
why and which reoperation? J Visc Surg 2011
Tian YH et al.Surgical treatment of incidental gallbladder cancer
discovered during or following laparoscopic
cholecystectomy. World J Surg 2015

19. Sorcide K et al. Systematic review of management of incidental gallbladder
cancer after cholecystectomy, British Journal of Surgery 2019
Staging Evaluation : Imaging

20. • Frequent metastasis to the liver, lungs, intraabdominal lymph nodes,
and peritoneum
• Aim  spare nontherapeutic laparotomy and resection
Leonid Cherkassky et al. Surg Oncol Clin N Am 28 (2019)

21. Contrast-enhanced computed tomography (CT) scan of the chest,
abdomen and pelvis:
• evaluate for locally unresectable and/or metastatic disease
• Nonregional local nodal or visceral metastatic disease
MRI liver protocol or a multiphase CT study:
• assess for proper hepatic artery or main portal vein involvement 
locally advanced disease  preclude resection
Leonid Cherkassky et al. Surg Oncol Clin N Am 28 (2019)

22. CT-MRI vs. PET scan
• PET doesnot necessarily confirm suspicious CT findings
• PET is helpful in confirming distant nodal disease suggested by CT
• PET has decreased utility in the case of the incidental diagnosis:
tumors are commonly diagnosed at earlier stages
Postoperative gallbladder bed is PET-avid from postoperative
inflammation
Leonid Cherkassky et al. Surg Oncol Clin N Am 28 (2019)

23. Staging evaluation: Laparoscopy
• Peritoneal metastasis  commonly detected by laparoscopy and for
which imaging has low sensitivity
• Selective Laparoscopy can be performed in:
Positive margin at initial cholecystectomy
Poorly differentiated tumor
T3 disease
Imaging shows residual disease
Leonid Cherkassky et al. Surg Oncol Clin N Am 28 (2019)

24. FACTORS ASSOCIATED WITH POOR
ONCOLOGIC OUTCOMES:
• Advanced T stage
• Node positive status
• Histologic grade of differentiation
• Lymphovascular invasion
• Total Lymphnode count more than 6
• CBD involvement
• Jaundice
• Port site, biopsy tract and peritoneal seeding
Leonid Cherkassky et al. Surg Oncol Clin N Am 28 (2019)

25. Way forward?
• Reresection is the standard approach to managing incidental
gallbladder carcinoma
• curative-intent extended cholecystectomy
• increasing rates of detection at earlier stages of disease
• Timing of reresection should be as early as possible
Leonid Cherkassky et al. Surg Oncol Clin N Am 28 (2019)

26. Clinical scenarios
Gallbladder cancer after cholecystectomy (depth of penetration of
gallbladder wall and surgical margins)

27. Gallbladder cancer after cholecystectomy
T1a lesion:
• penetrates lamina propria, does not invade muscle layer
• Cholecystectomy
• < 3% likelihood of nodal disease

28. T1b lesion:
• Penetrating the muscularis, not the deeper connective tissues or
serosa
• Cholecystectomy (if margins are clear)

29. T1b lesion (with perineural, lymphatic or vascular invasion):
• Completion Extended cholecystectomy (directed at obtaining R0
resection including draining lymph node basins)

30. Removal of lymphnode basins:
• Pericholedochal
• Periportal
• Hepatoduodenal
• Right celiac
• Posterior pancreaticoduodenal

31. Fig: Topographical distribution of the regional
lymph nodes of the gallbladder
Shirai Y et al. Regional lymphadenectomy for gallbladder
cancer: Rational extent, technical details, and patient
outcomes. World J Gastroenterol. 2012

32. • Roux en Y reconstruction :
Resection of the cystic duct margin to involved mucosa sometimes
may require resection of CBD
• 2 cm of apparently normal hepatic parenchyma from GB fossa is
resected  local extension into hepatic parenchyma

33. Port site resection?
• No role
• Morbidity >> Survival benefit
• Alternative: Visceral peritoneal biopsy to exclude peritoneal/
metastatis disease

34. Bile duct resection?
• Not done unless
 Positive cystic duct margin
 Densely involved nodes in Hepatoduodenal ligament

35. T2 lesion:
• Extension beyond Muscularis, not beyond serosa
• Radical cholecystectomy
• Any residual disease after operative intervention predicts poor outcome
> 40% have LN metastasis
Upto 25% have positive margins
After standard cholecystectomy

36. • type of surgical access (laparoscopic, converted or open) bears no
negative influence on survival
Goetze TO et al. Surg Endosc 2013

37. Residual Disease (RD):
• justification for reresection  goal of removing RD and achieving R0
margin status
• RD found at the time of curative-intent resection or on pathologic
assessment  marker of poor prognosis
• clinical equivalent of regional and metastatic disease
Leonid Cherkassky et al. Surg Oncol Clin N Am 28 (2019)

38. • 5 yrs survival: 60-80% (no RD)  25-40% (with RD) ; Better survival
outcome than Nonincidental GBC
• Relatively good prognosis  early management with multimodality
therapy

39. Role of tumor markers:
• currently no good biomarkers for gallbladder cancer
• Proposed:
• CEA
• CA 19-9
• CA 242
• Thymidine kinase

40. Tabe: Gallbladder Cancer Predictive Risk (GBPR)
Sorcide K et al. Systematic review of management of incidental gallbladder

41. Adjuvant Chemotherapy
• cisplatin and gemcitabine have been the preferred combination
• no difference in recurrence-free survival between GEMOX
(gemcitabine–oxaliplatin) and observation alone in biliary tract
cancers
• randomized BILCAP trial  better survival for capecitabine after
radical surgery of biliary tract cancer
• ongoing European trial (ACTICCA-1130) compares cisplatin–
gemcitabine combination with observation alone after radical surgery
Sorcide K et al. Systematic review of management of incidental gallbladder
cancer after cholecystectomy, British Journal of Surgery 2019

42. Conclusion
• Important to followup the HPE reports
• Intraoperative events of primary surgery is to be documented
• Evaluation and staging is of utmost importance
• Reresection is the standard approach to managing incidental gallbladder
carcinoma
• Residual disease also has a good prognosis if detected and managed early
• Adjuvant chemotherapy is a work in progess and has improved survival outcome

43. thankyou