This document summarizes the management of gallbladder carcinoma and associated controversies. It discusses presentations of gallbladder cancer, diagnosis and staging techniques including imaging and tumor markers. It covers staging systems from AJCC and NCCN as well as management guidelines. Controversies discussed include the extent of liver and lymph node resection, the role of laparoscopy versus open surgery, PET-CT, CBD excision, neoadjuvant therapy, and HPD. Issues related to incidental gallbladder cancer are also summarized, including timing and extent of reoperation after index cholecystectomy. The role of adjuvant therapy is discussed.

1. Management of Carcinoma Gall Bladder and
Controversies
Presenter- Dr. Vikram Singh Sodha
M.Ch Gastrosurgery resident
KGMU, Lucknow
Moderator- Dr. Sandeep Verma Sir

2. Presentations of gall bladder cancer
• Incidental finding at surgery
• Incidental finding at histopathology
• Mass on imaging
• Jaundice
National Comprehensive Cancer Network (NCCN 2021)

3. Presentations of gall bladder cancer
• Obvious
• Suspected
• Unsuspected
• Incidental
• Missed
VK Kapoor et al. 1996

9. Diagnosis and staging
• USG abdomen- First line investigation with routine lab investigations
• CT chest, abdomen and pelvis is recommended (NCCN)
• PET CT- Not routinely recommended (NCCN)
• Tumor markers- CEA and CA 19-9

10. Imaging
• USG abdomen-
CEUS- is more accurate (84% vs. 65%) to differentiate between benign and
malignant GB lesions (Kong et al. 2018).

11. Computed Tomography (CT)
• CT chest, abdomen and pelvis- modality of choice for staging
• Poor sensitivity to detect peritoneal or omental metastases
• Poor for evaluation of duodenum, colon and biliary tract
National Comprehensive Cancer Network (NCCN 2021)

13. Positron Emission Tomography (PET)
• PET CT- changed management of GBC
Incidental GBC- 13%
Preoperative diagnosis of GBC- 31% (Leung et al. 2014).
• False negative-
Small (<0.5 cm) size peritoneal disease
Mucinous adenocarcinoma
Uncontrolled diabetes
• False positive-
Done too early (within 4 weeks) (incidental GBC patients)
Inflammatory lesions

14. • Indications of PET
Locally advanced GBC before a major operation
Patients with incidental GBC who are delayed for reoperation (>4 weeks)
• PET lesions- need to be confirmed by tissue diagnosis before curative
intent treatment is denied.

15. Tumor Markers
• CEA and CA 19.9- not recommended for the diagnosis
• Baseline CA 19.9-
Predicts the burden of disease
Predicts prognosis
Used to monitor response to neoadjuvant therapy (Agrawal et al. 2018).

16. American Joint Committee on Cancer (AJCC) (8th edition)
• T2 has been sub classified as
T2a- tumor on the peritoneal side
T2b- tumor on the hepatic side
• N stage has been changed from location-based to number-based
N1: 1–3 positive LNs
N2: 4 or more positive LNs

18. NCCN
• Stage I- early GBC
• Stage II- early or advanced- debatable
• Stage III- locally advanced
• Stage IV A- locally advanced (Resectable, unresectable)
• Stage IV B- Metastatic
• Agarwal et al (2013)- T2 as early GBC
• Higuchi et al (2014)- Early GBC- limited to the mucosa or muscularis
propria (T1) regardless of LN metastasis.

19. EUS
• Endoscopic US-
Diagnosis of early GBC
Evaluate the depth of invasion
Select cases for laparoscopic extended cholecystectomy
Celiac plexus neurolysis (CPN)
Aorto-caval LN FNAC
• CEEUS- Evaluate the microvasculature and real-time perfusion
Leem et al. 2018

20. Tissue Diagnosis
• Tissue diagnosis is not required (if there is a radiological suspicion of
malignancy and lesion is resectable)

21. Staging Laparoscopy
• Non-therapeutic laparotomy was avoided in 23% (Agarwal et al. 2013).
• The yield of SL was 17% but it increased to 53% (high-risk GBC patients)
(Davidson et al. 2019)
• The yield of SL in incidental GBC- 4% (2/46) (MSKCC New York, USA) (Butte et
al. 2011).

22. • SL is recommended in high-risk patients with incidental GBC
Bile spill during the index cholecystectomy
Delayed presentation
Advanced T stage
Poor differentiation

23. Management as per NCCN guidelines

33. Controversies

34. Extent of liver resection
• Segment IV B & V versus Wedge

39. Extent of lymphadenectomy
• Periduodenal and peripancreatic LNs- matter of great controversy.
• Western centers consider these as distant LNs (do not advocate resection in
the presence of involvement of these LNs)
• Japanese considered these as regional lymph nodes.
• Frequency of LN involvement increases with T stage
T1a- <5%
T1b- 5–10%
T2- 40–60%
T3, T4- 80–90%

40. • Adequate lymphadenectomy- minimum of 6 LNs should be excised
• Superior retro pancreatic LN (13a) is the transition between N1 and N2
LNs (Kelly et al. 2014).
• 5 year survival- Patients with positive 13a LNs was similar to N1 disease
(40% and 33%, respectively) (Chaudhary et al. 2019).
• Extensive retroperitoneal LN dissection between the origins of CA and
IMA is not recommended.

42. Japan Society of Biliary Surgery (JSBS)

47. Laparoscopic versus Open surgery
• Indications of Laparoscopic EC
Preoperatively diagnosed early GBC (i.e., T1/T2)
No liver infiltration
No CBD involvement
• EUS is strongly recommended for selection of cases for laparoscopic
• Laparoscopic resection- is still in the early phase of adoption curve (Han
et al. 2019a).

52. Role of PET CT
• Not routinely recommended (NCCN)
• PET CT- changed management of GBC
Incidental GBC- 13%
Preoperative diagnosis of GBC- 31% (Leung et al. 2014).
• Indications of PET
Locally advanced GBC before a major operation
Patients with incidental GBC who are delayed for reoperation (>4 weeks)

58. CBD Excision ? Routine ? Selective
• Routine CBD excision is not recommended
CBD involvement in GBC:
1. Direct infiltration from GBC neck.
2. LNs in the hepatoduodenal ligament
3. Intraductal spread from a papillary tumor in the GB.
4. Micro-vessel invasion (MVI) of CBD wall (Igami et al. 2015).

59. Selective excision of the CBD
• Direct involvement of the CBD (GB neck & cystic duct tumor)
• Bulky lymph nodal involvement in HDL making lymphadenectomy difficult
• LNs adherent to the CBD
• Cystic duct margin positive on frozen section analysis
• Associated choledochal cyst
• Papillary tumors (high propensity for intraductal embolic spread)

63. Role of Neo-adjuvant therapy
• It is not standard of care for GBC
• NCCN recommended Neoadjuvant therapy in resectable GBC with SOJ and
locally advanced GBC

64. The role of Neoadjuvant Chemotherapy or Chemo radiotherapy for
Advanced Gallbladder Cancer – A Systematic Review
Hakeem Abdul R et al
European Journal of Surgical Oncology 2018

70. Systemic Chemotherapy Combined with Resection for Locally
Advanced Gallbladder Carcinoma: Surgical and Survival Outcomes
John M. Creasy
Journal of the American College of Surgeons

74. Hepato-Pancreato-Duodenectomy (HPD)
• Direct infiltration of duodenum and pancreas
• Intrapancreatic extension of involvement of the CBD
• Involvement of HDL in a GBC neck tumor.
• Large periduodenal/peripancreatic LNs densely adherent to or even
infiltrating duodenum/pancreas

75. Indications for PD in GBC
• Involvement of duodenum/pancreas
• Extensive bulky densely adherent retro duodenal/retro pancreatic
lymph nodes
• Biliary involvement (in a papillary tumor) in the intrapancreatic part.
• Synchronous GBC and pancreatic/periampullary cancer.

76. The key issues in the management of incidental GBC are
1. Is a reoperation required or is follow-up alone sufficient (after the index
simple cholecystectomy)?
2. Which patients should undergo reoperation?
3. What investigative workup is required before reoperation?
4. When should the reoperation be performed?
5. What should be the extent of reoperation?

77. • Incidence of residual disease
• T1b-20%
• T2- 24%
• T3- 72% (Gil et al. 2019)

78. Is a reoperation required or is follow-up alone sufficient (after the
index simple cholecystectomy)?
• T1a- observation
• T1b- Completion extended cholecystectomy (NCCN)
• T1b- No uptake on PET. The authors recommended observation (TMH)
• T2 and above- Completion extended cholecystectomy (NCCN)

81. Timing of Reoperation
• Ideal time to Re-operate in incidental GBC ???
• As early as posible ??
• 4 – 8 weeks after index operation ??

84. • Chinese report of 80 incidental
GBCs—patients who were
reoperated within 2 weeks (n =
37) had better (median 86
months) survival than those who
were operated between 2 weeks
and 1 month (n = 26, median 26
months) and those who were
operated after 1 month (n = 17,
median 27 months) (Du et al.
2018).

85. Extent of Reoperation
• T1b ? Observation ? Reresection
• In a meta-analysis (22 articles, 2578 patients with T1 GBC) SC and EC
showed comparable survival patterns in both T1a and T1b (Lee et al.
2018).
• German Registry (883 cases of incidental GBC) reresection improved
survival in T1b from 34% to 75% and reresection was recommended
(Goetze and Paolucci 2014).
• EC provided survival benefit over SC in patients with tumor >1 cm
(Wang et al. 2019).

92. What investigative workup is required before reoperation?
• PET-CT:
Incidental GBC who are delayed for reoperation (>4 weeks)
Advanced T stage
Lymph Node positive
Bile spillage
• SL is recommended in high-risk patients with incidental GBC
Bile spill during the index cholecystectomy
Delayed presentation
Advanced T stage
Poor differentiation

93. Port-Site Excision
• PSE is not recommended (AHPBA consensus (Aloia et al. 2015), NCCN
guidelines (Benson et al. 2019a) and Brazilian consensus (ISG-HPB- Cancer et
al. 2020).

96. Adjuvant Therapy
Indications for use of adjuvant therapy in incidental GBC:
• T2 or more
• Node positive, margin positive, poor histological features
• Patients who had bile spill during the index cholecystectomy
• Who had papillary tumor should also receive adjuvant chemotherapy,
irrespective of the T or N status.

97. Adjuvant Therapy
• T2 or beyond
• Node-positive
• Margin positive (R1 resection status)
• Gross residual disease (R2 resection status)
• Poor histological features

101. • ACTICCA (randomized multinational phase III trial)- Adjuvant
gemcitabine versus capecitabine versus observation alone after
curative-intent resection in BTC (Stein et al. 2015).
• Superiority of gemcitabine + cisplatin over gemcitabine alone was
proved in a Japanese multicenter study (Okusaka et al. 2010).
• There is no established second-line chemotherapy for GBC but
FOLFOX has been suggested (Javle et al. 2019).

102. Thank You