3. Epidemiology
Manifested in 6th-7th decades of life
2-3 times common in women
Ethnicity plays important role
According to SEER incidence of GBC in US is 1-2/100,000 population 1
In Nepal2:
o3.3% primary malignancy
o1.4% incidental primary GBC
1 Rahman, R., Simoes, E. J., Schmaltz, C., Jackson, C. S., & Ibdah, J. A. (2017). Trend analysis and survival of primary gallbladder cancer in the United States: A
1973-2009 population-based study. Cancer Medicine, 6(4), 874–880.
2 Shrestha, R., Tiwari, M., Ranabhat, S. K., Aryal, G., Rauniyar, S. K., & Shrestha, H. G. (2010). Incidental gallbladder carcinoma: Value of routine histological
examination of cholecystectomy specimens. Nepal Medical College Journal: NMCJ, 12(2), 90–94
5. Etiology
Prevailing theory: chronic inflammation with subsequent cellular
proliferation
Risk factors:
o Gallstones
o Choledochal cyst
o Primary sclerosing
cholangitis (PSC)
o Anomalous
Pancreaticobiliary Junction
(APBJ)
o Old age
o Typhoid carrier/H. pylori
infection
o Females
o Gall bladder polyp (>10mm)
o GB wall calcification/
Porcelain GB
o Exposure to carcinogens
o Drugs
7. Pattern of spread
Via lymphatics
Via venous drainage
Direct invasion into liver parenchyma
At the time of diagnosis:
o 25% localized to GB
o 35% regional node involvement/ extension into adjacent liver
o 40% distant metastasis
8. Clinical Presentation
90% originate from fundus or body: produce symptoms in advanced stage
Early invasive GBC: asymptomatic or non-specific symptoms that mimics
cholelithiasis or cholecystitis
Symptomatic: RUQ pain, abdominal discomfort, nausea, vomiting, anorexia
Advanced GBC: malaise, weight loss, jaundice, abdominal mass, ascites
Palpable GB on physical examination: Courvoisier’s Sign
9. Diagnostic evaluation
Ultrasound:
Suspicious findings:
oSolitary or displaced stone, mural thickening or calcification, mass
protruding into the lumen, fixed mass in GB, loss of interface between
GB and liver, direct liver infiltration
Overall accuracy limited
Sensitivity 70-100% 1
1 Brunicardi, F., et al. (2014) Schwartz’s Principles of Surgery. 10th Edition, McGraw-Hill Education, New York
10.
11. Computed Tomography (CT) scan:
For pt. with US-detected GB lesion/ incidentally diagnosed GBC
following simple cholecystectomy
Sensitivity: 71%, specificity: 92% 1
CT findings:
oPolypoid mass protruding into the lumen/completely filling it,
focal/diffuse thickening of GB wall, mass in GB fossa with GB being
indiscernible, liver invasion, suspected nodal involvement, distant mets
oGBC complicated with simple cholecystitis: higher frequency of LN
enlargement, more-extensive wall thickness, focal irregularity in wall
thickness, less distention of GB
1 Bo, X., Chen, E., Wang, J., Nan, L., Xin, Y., Wang, C., Lu, Q., Rao, S., Pang, L., Li, M., Lu, P., Zhang, D., Liu, H., & Wang, Y. (2019). Diagnostic accuracy of
imaging modalities in differentiating xanthogranulomatous cholecystitis from gallbladder cancer. Annals of Translational Medicine, 7(22), 627.
https://doi.org/10.21037/atm.2019.11.35
12. Features of advanced disease include:
o Intrahepatic biliary dilatation
o Invasion of adjacent structures
o Lymphadenopathy
o Peritoneal carcinomatosis
o hepatic and other distant metastases
13. Magnetic Resonance Imaging (MRI):
Reliable in staging of advanced GBC
MRI + MRCP: sensitive in detection of obstructive jaundice, liver
invasion and hepatic/LN metastasis
Difficult to delineate invasion into duodenum or omental mets
Sensitivity for hepatic invasion 100%, LN invasion 92% 1
1 Schwartz, L. H., Black, J., Fong, Y., Jarnagin, W., Blumgart, L., Gruen, D., Winston, C., & Panicek, D. M. (2002). Gallbladder carcinoma: Findings at MR
imaging with MR cholangiopancreatography. Journal of Computer Assisted Tomography, 26(3), 405–410
14. Endoscopic ultrasound (EUS):
To access the depth of tumor invasion into the wall of GB
To define LN involvement in porta hepatis and peripancreatic regions
Means to obtain bile for cytologic analysis:
o73% sensitivity for diagnosis of GBC1
EUS guided FNA for FB mass
Specificity: 92%, specificity 88% 2
2 Azuma, T., Yoshikawa, T., Araida, T., & Takasaki, K. (2001). Differential diagnosis of polypoid lesions of the gallbladder by endoscopic ultrasonography. American
Journal of Surgery, 181(1), 65–70
1 Mohandas, K. M., Swaroop, V. S., Gullar, S. U., Dave, U. R., Jagannath, P., & DeSouza, L. J. (1994). Diagnosis of malignant obstructive jaundice by bile
cytology: Results improved by dilating the bile duct strictures. Gastrointestinal Endoscopy, 40(2 Pt 1), 150–154
16. Staging systems
1) Modified Nevin System (Donohue et.al. 1990, Nevin et.al. 1976)
2) Japanese Biliary Surgical Society System (Onoyama et.al. 1995)
3) AJCC/UICC TNM staging system (Beahrs and Myers 1983)
17. Tumor, Node, Metastasis (TNM) staging 1
1 Zhu AX, Pawalik TM, Kooby DA, et al. Gallbladder. In: AJCC Cancer Staging Manual, 8th ed, Amin MB (Ed), AJCC, Chicago 2017. p.303
18.
19.
20. Management
Resection remains the only potential for cure
oSimple cholecystectomy
oRadical (Extended) cholecystectomy
oBile duct resection
oHepatic resection
oLymph node dissection
oLaparoscopic port site resection
21. Radical Cholecystectomy
En bloc removal of gall bladder with a rim of at least 2 cm adjacent
gall bladder bed
Formal central liver resection (segments IVb and V) may be
appropriate depending upon the location of tumor (fundus, body,
neck)
Laparoscopic vs open surgery?
oWullstein, C., Woeste, G., Barkhausen, S., Gross, E., & Hopt, U. T. (2002). Do
complications related to laparoscopic cholecystectomy influence the
prognosis of gallbladder cancer? Surgical Endoscopy, 16(5), 828–832
oMatthews, J. B. (2010). Planned laparoscopic approach for early-stage
gallbladder cancer: The glass is one-third full. Archives of Surgery (Chicago,
Ill.: 1960), 145(2), 133
24. In some cased it involves resection of
o Entire liver lobe (hepatic lobectomy)
o Suprapancreatic segment of extrahepatic
bile duct (bile duct resection)
o Regional LN dissection in an En bloc
fashion.
Main difference between this procedure
and original radical cholecystectomy
described by Glenn et.al compromise
the extent of regional
lymphadenectomy and presence or
absence of bile duct resection.
Fig. Extended" radical cholecystectomy for gallbladder
cancer. The dashed line indicates the scope of wedge
resection. The double-headed arrows indicate lines of
division of the extrahepatic bile duct. The pale blue area
indicates the extent of regional lymph node dissection
25. Bile duct resection
Tumor extending into CBD or negative cystic duct margin (via frozen
section) can’t be achieved: extrahepatic bile duct resection should be
performed
Reconstruction with Roux-en-Y hepaticojejunostomy
Some recommends routine excision of extrahepatic bile duct as a mean of
achieving more complete lymphadenectomy
When ducts compromised during skeletonization of porta hepatis:
resection and reconstruction is warranted
27. Inter aortocaval LN sampling
Interaortocaval (16b1) LN involvement in GBC: sign of advanced
disease with a dismal prognosis equivalent to that of distant
metastasis
CT indicator (size >10 mm and heterogeneous internal architecture) of
16b1 LN
oBut positive predictive value is less
That’s why detection of 16b1 LNs, intraoperative biopsy and frozen
section analysis of these nodes have been proposed 1
1 Noji, T., Kondo, S., Hirano, S. et al. CT evaluation of paraaortic lymph node metastasis in patients with biliary cancer. J Gastroenterol 40, 739–743 (2005)
28. Lymph node dissection
Indicated whether or not bile duct resection is performed if GBC >T1a
LN mets found in 35-80% with tumors invading perimuscular connective tissues(≥T2) 1
More reliable predictors of poor outcome after surgery
o 5-yr survival: 57% without vs 12% with LN metastases2
Involves removal of all LN in porta hepatis and along hepaticoduodenal ligaments
including those of cystic duct, CBD, hepatic artery and portal vein
1 Pilgrim, C. H. C., Usatoff, V., & Evans, P. (2009). Consideration of anatomical structures relevant to the surgical strategy for managing gallbladder
carcinoma. European Journal of Surgical Oncology: The Journal of the European Society of Surgical Oncology and the British Association of Surgical
Oncology, 35(11), 1131–1136.
2 Birnbaum, D. J., Viganò, L., Russolillo, N., Langella, S., Ferrero, A., & Capussotti, L. (2015). Lymph node metastases in patients undergoing surgery for a
gallbladder cancer. Extension of the lymph node dissection and prognostic value of the lymph node ratio. Annals of Surgical Oncology, 22(3), 811–818
31. Lymph node dissection cont.
At least 6 LNs should be removed for proper staging 1
Number of metastatic LN and LN ratio are more prognostic than
location of metastatic LN
1 Zhu AX, Pawlik TM, Kooby DA. et al. Gallbladder. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), Springer 2017. p.303
32. Hepatic resection
Either margin-negative resection with at least 2cm non-anatomic wedge resection of GB fossa OR
anatomic wedge resection of segment IVb and V 1
Tumors of fundus and body of GB: far from the inflow structures of liver
Various resection margins proposed: ranging from 1-5 cm 2
No data to showing benefit for anatomic resection of segments IVb and V with localized diseases 3
Anatomic resection: reduces risk of bleeding and bile leakage 4
1 Blumgart LH. Surgery of the Liver, Biliary Tract and Pancreas, 4th edition, Saunders, Philadelphia 2007
2 Endo, I., Shimada, H., Takimoto, A., Fujii, Y., Miura, Y., Sugita, M., Morioka, D., Masunari, H., Tanaka, K., Sekido, H., & Togo, S. (2004). Microscopic liver metastasis: Prognostic factor
for patients with pT2 gallbladder carcinoma. World Journal of Surgery, 28(7), 692–696
3 Sicklick, J. K., & Choti, M. A. (2005). Controversies in the surgical management of cholangiocarcinoma and gallbladder cancer. Seminars in Oncology, 32(6 Suppl 9), S112-117
4 Scheingraber, S., Justinger, C., Stremovskaia, T., Weinrich, M., Igna, D., & Schilling, M. K. (2007). The standardized surgical approach improves outcome of gallbladder
cancer. World Journal of Surgical Oncology, 5, 55
33. Hepatic resection cont.
Veins from GB drain into middle hepatic vein via cholecysto-hepatic
veins 1
Direct lymphatic drainage into liver has also been demonstrated 1
More aggressive surgery like extended right hepatectomy for tumor
infiltration into segments IV, V and VII
1 Misra, M. C., & Guleria, S. (2006). Management of cancer gallbladder found as a surprise on a resected gallbladder specimen. Journal of Surgical Oncology, 93(8), 690–698
34. Conclusion: Tumor biology and stage, rather than extent of resection, predict
outcome after resection for gallbladder cancer. Major hepatic resections,
including major hepatectomy and CBD excision, are appropriate when
necessary to clear disease but are not mandatory in all cases.
35. Laparoscopic port site resection
Laparoscopic manipulation doesn’t diminish the survival of patients with
incidentally found GBC 1
Some recommend port site excision at the time of reexploration after lap
cholecystectomy 2
Radical resection doesn’t require resection of previous port sites 3
Tumor found in previous port site is a marker for disseminated peritoneal
disease
Thus removal of port site will not be curative 4
1 Maker, A. V., Butte, J. M., Oxenberg, J., Kuk, D., Gonen, M., Fong, Y., Dematteo, R. P., D’Angelica, M. I., Allen, P. J., & Jarnagin, W. R. (2012). Is port site resection necessary in the surgical
management of gallbladder cancer? Annals of Surgical Oncology, 19(2), 409–417
2 Giuliante, F., Ardito, F., Vellone, M., Clemente, G., & Nuzzo, G. (2006). Port-sites excision for gallbladder cancer incidentally found after laparoscopic cholecystectomy. American Journal of
Surgery, 191(1), 114–116
3 Maker, A. V., Butte, J. M., Oxenberg, J., Kuk, D., Gonen, M., Fong, Y., Dematteo, R. P., D’Angelica, M. I., Allen, P. J., & Jarnagin, W. R. (2012). Is port site resection necessary in the surgical management of
gallbladder cancer? Annals of Surgical Oncology, 19(2), 409–417
4 Berger-Richardson, D., Chesney, T. R., Englesakis, M., Govindarajan, A., Cleary, S. P., & Swallow, C. J. (2017). Trends in port-site metastasis after laparoscopic resection of incidental gallbladder cancer: A
systematic review. Surgery, 161(3), 618–62
36.
37. Surgery for Gall bladder cancer
Accurate staging of the disease
Proper patient selection & surgical planning
Identifying patient who would or would not benefit from surgery
oDetect metastatic disease (US, CT, MRI, PET)
oLocoregionally advanced disease (resectability?/need for downstaging)
Avoiding non-therapeutic laparotomy
oStaging laparoscopy
oAdvanced extended laparoscopic staging
38. Unresectable disease
Absolute contraindication to resection:
Liver mets
Peritoneal mets
Malignant ascites
Tumor involvement of paraaortic, paracaval, SMA and/or Celiac artery LN
Extensive involvement of hepaticoduodenal ligament by tumor either directly or through LN
involvement
Encasement or occlusion of major vessels (common hepatic artery or main portal vein) by tumor
39. Unresectable disease cont.
Relative contraindication to resection:
Pre-operative jaundice in fundus based GBC
Perihilar-type GBC arising from infundibulum or cystic duct
40. Identifies metastatic disease or other findings that contraindicate
tumor resection 1
Recommended prior to laparotomy for all suspected or proven GBC
>pT1b 2
Use of two ports avoid missing detectable lesions
Staging laparoscopy
1 Shih, S. P., Schulick, R. D., Cameron, J. L., Lillemoe, K. D., Pitt, H. A., Choti, M. A., Campbell, K. A., Yeo, C. J., & Talamini, M. A. (2007). Gallbladder cancer: The role of
laparoscopy and radical resection. Annals of Surgery, 245(6), 893–901
2 Agarwal, A. K., Kalayarasan, R., Javed, A., Gupta, N., & Nag, H. H. (2013). The role of staging laparoscopy in primary gall bladder cancer--an analysis of 409 patients: A
prospective study to evaluate the role of staging laparoscopy in the management of gallbladder cancer. Annals of Surgery, 258(2), 318–323
41. Staging laparoscopy cont.
A prospective study of primary GBC
patients between May 2006 and
December 2011: Of the 409 primary GBC
patients who underwent SL, 95 had
disseminated disease [(surface liver
metastasis (n = 29) and peritoneal
deposits (n = 66)]. The overall yield of SL
was 23.2% (95/409)
42. Staging laparoscopy cont.
Discussion: Disseminated disease is relatively uncommon in patients with IGBC and
SL provides a very low yield. However, patients with poorly differentiated, T3 or
positive-margin gallbladder tumors are at high risk for Disseminated Disease and
targeting these patients may increase the yield of SL
43. Resectable disease
Early T stage disease: tumors confined to the wall of GB (ie,
stage 0, I or II; Tis, T1 or T2)
Tumors extending beyond the mucosa (ie, T1a): better
outcomes with more radical surgery 1
1 Sternby Eilard, M., Lundgren, L., Cahlin, C., Strandell, A., Svanberg, T., & Sandström, P. (2017). Surgical treatment for gallbladder cancer—A systematic literature
review. Scandinavian Journal of Gastroenterology, 52(5), 505–514
44. T1a:
oTumors limited to lamina propria
oCystic duct margin negative
oSimple cholecystectomy alone is adequate 1
oCure rate: 73-100% 1
oRe-resection for T1a tumors doesn’t appear to provide an
overall survival benefit 2
1 Wakai, T., Shirai, Y., Yokoyama, N., Nagakura, S., Watanabe, H., & Hatakeyama, K. (2001). Early gallbladder carcinoma does not warrant radical resection. The British Journal of
Surgery, 88(5), 675–678
2 You, D. D., Lee, H. G., Paik, K. Y., Heo, J. S., Choi, S. H., & Choi, D. W. (2008). What is an adequate extent of resection for T1 gallbladder cancers? Annals of Surgery, 247(5), 835–
838
45. T1b:
Tumor invades muscular layer
Optimal approach is controversial, Pt benefit from more radical approach
Higher incidence of LN metastases compared to T1a (15% vs 2.5%) 1
High loco-regional recurrence 50-60%
High rates of liver involvement 0-13%
Median survival advantage >3 yrs: extended vs simple cholecystectomy 2
o 9.85 vs 6.42 years
1 de Aretxabala, X. A., Roa, I. S., Burgos, L. A., Araya, J. C., Villaseca, M. A., & Silva, J. A. (1997). Curative resection in potentially resectable tumours of the gallbladder. The
European Journal of Surgery = Acta Chirurgica, 163(6), 419–426
2 Abramson, M. A., Pandharipande, P., Ruan, D., Gold, J. S., & Whang, E. E. (2009). Radical resection for T1b gallbladder cancer: A decision analysis. HPB: The Official Journal
of the International Hepato Pancreato Biliary Association, 11(8), 656–663
46. Method: Retrospective cohort study from the National Cancer Data Base
(2004-2012) with non-metastatic T1b GBC
Conclusion: <50% of the patients with a T1b GBC primary tumor undergo
the recommended surgical treatment. Given that 15% of these patients
have nodal metastasis and in light of the previously described benefits of
adjuvant therapy for node positive GBC, failure to perform RC-RL risks
incomplete staging and thus undertreatment for patients with T1b GBC.
47. T2:
Invades the peri muscular connective tissue on the peritoneal side, without
involvement of serosa
Extended cholecystectomy is indicated 1
High chance of residual disease 40-76%
High chance of liver 2 (10%) and LN 3 (30-60%) involvement
High rates of local recurrence after simple cholecystectomy
1 Wright, B. E., Lee, C. C., Iddings, D. M., Kavanagh, M., & Bilchik, A. J. (2007). Management of T2 gallbladder cancer: Are practice patterns consistent with national
recommendations? American Journal of Surgery, 194(6), 820–825; discussion 825-826
3 Shimada, H., Endo, I., Togo, S., Nakano, A., Izumi, T., & Nakagawara, G. (1997). The role of lymph node dissection in the treatment of gallbladder carcinoma. Cancer, 79(5), 892–
899. https://doi.org/10.1002/(sici)1097-0142(19970301)79:5<892::aid-cncr4>3.0.co;2-e
2 Pawlik, T. M., Gleisner, A. L., Vigano, L., Kooby, D. A., Bauer, T. W., Frilling, A., Adams, R. B., Staley, C. A., Trindade, E. N., Schulick, R. D., Choti, M. A., & Capussotti, L. (2007). Incidence of finding
residual disease for incidental gallbladder carcinoma: Implications for re-resection. Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract, 11(11),
1478–1486; discussion 1486-1487
48. Subdivided depending on the invasion site into:
o T2a (peritoneal)
o T2b (hepatic)
T2b has worse prognosis
Extended cholecystectomy should be mandated in pt with T2b (hepatic)
but not T2a (peritoneal) disease 1
This approach, however is not universally accepted
o Standard of care: extended cholecystectomy for all resectable T2 disease 2
1 Lee, W., Jeong, C.-Y., Jang, J. Y., Kim, Y. H., Roh, Y. H., Kim, K. W., Kang, S. H., Yoon, M. H., Seo, H. I., Yun, S. P., Park, J.-I., Jung, B.-H., Shin, D. H., Choi, Y. I., Moon, H. H., Chu, C. W., Ryu, J. H.,
Yang, K., Park, Y. M., & Hong, S.-C. (2017). Do hepatic-sided tumors require more extensive resection than peritoneal-sided tumors in patients with T2 gallbladder cancer? Results of a
retrospective multicenter study. Surgery, 162(3)
2 Kwon, W., Kim, H., Han, Y., Hwang, Y. J., Kim, S. G., Kwon, H. J., Vinuela, E., Járufe, N., Roa, J. C., Han, I. W., Heo, J. S., Choi, S.-H., Choi, D. W., Ahn, K. S., Kang, K. J., Lee, W., Jeong, C.-Y., Hong,
S.-C., Troncoso, A. T., … Jang, J.-Y. (2020). Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: An international multicentre study. The British Journal of
Surgery, 107(10), 1334–1343
49. Survival in patient with T2 lesion is related to the number of LN
removed 1
5 yr survival is 24-40% without resection and may approach to 80-100
after re-resection 2
1 Downing, S. R., Cadogan, K.-A., Ortega, G., Oyetunji, T. A., Siram, S. M., Chang, D. C., Ahuja, N., Leffall, L. D., & Frederick, W. A. I. (2011). Early-stage gallbladder cancer in the
Surveillance, Epidemiology, and End Results database: Effect of extended surgical resection. Archives of Surgery (Chicago, Ill.: 1960), 146(6), 734–738
2 Toyonaga, T., Chijiiwa, K., Nakano, K., Noshiro, H., Yamaguchi, K., Sada, M., Terasaka, R., Konomi, K., Nishikata, F., & Tanaka, M. (2003). Completion radical surgery after
cholecystectomy for accidentally undiagnosed gallbladder carcinoma. World Journal of Surgery, 27(3), 266–271
50. Locally advanced and node positive disease
In past because of overall poor prognosis: surgeons were reluctant to
perform surgery 1
Support for radical surgery with reports indicating long term survival
in pt with T3 and T4 tumors, 15 to 63% and 7 to 25% of pt
respectively 2
1 Cubertafond, P., Mathonnet, M., Gainant, A., & Launois, B. (1999). Radical surgery for gallbladder cancer. Results of the french surgical association survey. Hepato-
Gastroenterology, 46(27), 1567–1571
2 Kayahara, M., & Nagakawa, T. (2007). Recent trends of gallbladder cancer in Japan: An analysis of 4,770 patients. Cancer, 110(3), 572–580
51. Some groups advocate even more extensive resection:
oHepatectomy, pancreaticoduodenectomy, colectomy and nephrectomy
Medial survival of 17mths, 2% mortality rate 1
But morbidity and mortality rates are high (48 to 54% and 15 to 18%
respectively)
Study of 79 major hepatectomies had longer survival 32 mths as
compared to 10 mths for major hepatectomies +
pancreaticoduodenectomy 2
1 Dixon, E., Vollmer, C. M., Sahajpal, A., Cattral, M., Grant, D., Doig, C., Hemming, A., Taylor, B., Langer, B., Greig, P., & Gallinger, S. (2005). An aggressive surgical approach leads
to improved survival in patients with gallbladder cancer: A 12-year study at a North American Center. Annals of Surgery, 241(3), 385–394
2 Mizuno, T., Ebata, T., Yokoyama, Y., Igami, T., Yamaguchi, J., Onoe, S., Watanabe, N., Ando, M., & Nagino, M. (2019). Major hepatectomy with or without pancreatoduodenectomy
for advanced gallbladder cancer. The British Journal of Surgery, 106(5), 626–635
52. T3:
Tumor invades through serosa
Extended cholecystectomy en bloc with involved adjacent organ
Conclusion: Tumor biology and stage, rather than extent of resection, predict
outcome after resection for gallbladder cancer. Major hepatic resections, including
major hepatectomy and CBD excision, are appropriate when necessary to clear
disease but are not mandatory in all cases
53. T4:
Invades main portal vein, hepatic artery and adjacent extrahepatic
organs
Generally locally unresectable
Curative resection in selected patient with stage IVa disease (T4, N0-
1,M0)
54. Node positive:
Tumor involvement of locoregional LN: 5-yr survival rate - 28-60%
with radical resection 1
Radical lymphadenectomy results are less favorable of nodal disease
beyond hepatoduodenal ligament, posterosuperior
pancreaticoduodenal area and along common hepatic artery 1
FNA +ve tumors: surgery done for palliation of specific problems
1 Chijiiwa, K., Noshiro, H., Nakano, K., Okido, M., Sugitani, A., Yamaguchi, K., & Tanaka, M. (2000). Role of surgery for gallbladder carcinoma with special reference to lymph
node metastasis and stage using western and Japanese classification systems. World Journal of Surgery, 24(10), 1271–1276; discussion 1277
55. Managing incidental GBC found on pathology
Incidental GC: 0.25-1.5% of pt undergoing lap chole 1
Should undergo staging evaluation with imaging modalities
Management depends upon the disease extent (T stage)
If the T stage of resected, incidental GBC is T1b, T2 or T3: surgical
reeploration and re-resection
1 Duffy, A., Capanu, M., Abou-Alfa, G. K., Huitzil, D., Jarnagin, W., Fong, Y., D’Angelica, M., Dematteo, R. P., Blumgart, L. H., & O’Reilly, E. M. (2008). Gallbladder cancer (Gbc): 10-
year experience at memorial sloan-kettering cancer centre(Mskcc). Journal of Surgical Oncology, 98(7), 485–489
56. Optimal timing of re-resection:
Reoperations between 4th-8th week from original cholecystectomy
had better overall survival 1
o4 weeks: 23.7 mths, 8 weeks: 26.6 mths
Due to reduced inflammation and full appreciation of subclinical
disease (compared with reoperating <4 week) but does not allow too
much time for disease dissemination
1 Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C. G.,
Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., … Maithel, S. K. (2017). Association of optimal time interval to re-resection for incidental gallbladder cancer with overall
survival: A multi-institution analysis from the us extrahepatic biliary malignancy consortium. JAMA Surgery, 152(2), 143–149
57.
58. Managing incidental GBC intraoperatively
Surgeon should maintain high index of suspicion in pt with risk factors
If obvious malignant lesion encountered: best not to sample the
lesion laparoscopically to reduce the hazard of seeding
Procedure should be converted to open resection, of resection will be
undertaken
Completing the cholecystectomy and obtain frozen section, if
positive: extended cholecystectomy
59. To compare patients with gallbladder cancer presenting for therapy
with and without prior operation elsewhere to determine if an initial
noncurative procedure alters outcome
Mortality, complication, and long-term survival were the same
60. The scoring model to predict IGBC includes age, female gender, previous
cholecystitis, and either jaundice or acute cholecystitis
The scoring system was applied to three risk-groups, based on the risk of having
IGBC, eg. the high-risk group (>8 points) included 7878 patients, with 154
observed and 148 expected IGBC cases.
61. Bile spillage
Association with incomplete resection and systemic recurrence
When GB cancer is suspected during LC conversion to open surgery for
preventing bile spillage and achieving curative resection should be
considered
62. Laparoscopic radical surgery
Traditionally, Laparoscopic surgery not routinely recommended in
non-incidental setting
Recent studies suggest equivalent outcomes between laparoscopic
and open approaches
Robotic-assisted procedures have also been described and are carried
out
63.
64. Adjuvant therapy
Despite conflicting data, limited level I data
Currently, Gemcitabine-based regimens, often combining with platinum agent:
common choice for treating GBC
Gemcitabine shown to improve median overall survival (9.5 months) 1
Japanese multi-institutional trial: randomized resection f/b adjuvant mitomycin
and 5-FU vs resection alone2
o 5-yr survival 20.3% vs 11.6%
1 Sharma, A., Dwary, A. D., Mohanti, B. K., Deo, S. V., Pal, S., Sreenivas, V., Raina, V., Shukla, N. K., Thulkar, S., Garg, P., & Chaudhary, S. P. (2010). Best supportive care compared with
chemotherapy for unresectable gall bladder cancer: A randomized controlled study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 28(30), 4581–4586
2 Takada, T., Amano, H., Yasuda, H., Nimura, Y., Matsushiro, T., Kato, H., Nagakawa, T., Nakayama, T., & Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract.
(2002). Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary
carcinoma. Cancer, 95(8), 1685–1695
65. Most recently, Phase II trial: combination of Gemcitabine,
Capecitabine and radiation therapy in pt with extrahepatic biliary
tract and GBC showed promising results 1
1 Ben-Josef, E., Guthrie, K. A., El-Khoueiry, A. B., Corless, C. L., Zalupski, M. M., Lowy, A. M., Thomas, C. R., Alberts, S. R., Dawson, L. A., Micetich, K. C., Thomas, M. B., Siegel, A. B., & Blanke, C.
D. (2015). Swog s0809: A phase ii intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and
gallbladder carcinoma. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 33(24), 2617–2622
66. Neoadjuvant therapy
Provide opportunity to determine biologically aggressive tumors who
may not benefit from extensive operation
Small case series suggest: Gemcitabine-Platinum based combinations
have some role 1
Recent study from MD Anderson Cancer Center: retrospective review
of their GBC resected with wide 1-cm negative margin and received
either neoadjuvant or adjuvant therapy: 5-yr survival 50.6%
1 Sirohi, B., Rastogi, S., Singh, A., Sheth, V., Dawood, S., Talole, S., Ramadwar, M., Kulkarni, S., & Shrikhande, S. V. (2015). Use of gemcitabine-platinum in Indian patients with
advanced gall bladder cancer. Future Oncology (London, England), 11(8), 1191–1200
67. Adjuvant therapy showed not improvement in survival, and
neoadjuvant treatment had only served to significantly delay time to
operation
68. Palliative procedures
Palliation for jaundice, upper abdominal pain and symptoms of biliary
obstruction
Methods:
• Simple cholecystectomy
• Endoscopic or percutaneous biliary drainage
• Endoscopic stenting or intestinal bypass
• Biliary bypass:
• Patient who can tolerate surgery
• Recurrent obstruction
• Segment II cholangiojejunostomy and staying away from the hepatoduodenal
ligament, the most common site of disease progression, successfully palliated the
majority of patients 1
1 Kapoor, V. K., Pradeep, R., Haribhakti, S. P., Singh, V., Sikora, S. S., Saxena, R., & Kaushik, S. P. (1996). Intrahepatic segment III cholangiojejunostomy in advanced carcinoma of the
gallbladder. The British Journal of Surgery, 83(12), 1709–1711
69. Prognosis
5 year survival of all pt with GB cancer: <5%
Median survival of 6 mths
T1 treated with cholecystectomy: 85%-100%, 5 year survival
T2 treated with extended cholecystectomy vs cholecystectomy: >70% vs 25%-
40%
Advanced disease with resectable GB: 5 year survival of 20%
Median survival of pt with distant mets: 1-3mths
70. Prognosis cont..
Non-specific symptoms and advanced stage of disease at
presentation: poor outcomes
o5-yr survival rate: 5-12%
Recurrence after resection : commonly Liver or celiac/retro pancreatic
nodes
Prognosis for recurrent disease: poor
Death commonly d/t biliary sepsis or liver failure
71. Reference
Schwartz’s Principle of surgery, 10th edition
Bailey short practice of surgery, 27th edition
Sabiston textbook of surgery, 20th edition
https://www.uptodate.com/contents/gallbladder-cancer-epidemiology-risk-
factors-clinical-features-and-
diagnosis?search=gallbladder%20cancer&source=search_result&selectedTitle=1~
71&usage_type=default&display_rank=1#H17
Internet sources
-uncommon but highly fatal
-advanced stage at diagnosis, late presentation
predominantly occurring in elderly
Highest incidence in women in northern India and Pakistan and south America: Chile, Bolivia, Ecuador, Highest mortality rate in Chile d/t GBC
Reason: higher incidence of cholelithiasis and salmonella infection: risk factor
Gall stones: >80% /95% with GBC has cholelithiasis and GBC is approx. 7 times more common in pt with gall stones, doesn’t depend upon the type of stone
20 yr risk of cancer development is <0.5%
Larger stones >3cm: 10 fold increased risk of cancer; symptomatic>asymptomatic
Calcified porcelain GB: >20% incidence of GBC
Choledochal cyst: increased risk anywhere in biliary tree but highest in GB
Carcinogens: azotoluene, nitrosamines
Drugs: Isoniazid, methyldopa, OCPs
- Better outcome with papillary histologic subtype which includes <10%
Lymphatics present in subserosal layer only
Lymphatic flow from Gb first to cystic duct node (Calot’s) then peri choledochal and hilar nodes and finally peripancreatic, duodenal, periportal, celiac and SMA nodes
Veins drain directly into adjacent liver, usually segments IVb and V
Diagnosed pre-operatively(suspicion if RUQ pain, jaundice and signs of duodenal obstruction), intraoperatively (obvious GB mass, focal thickening) and post-operatively
Advanced: direct invasion to biliary tree and hepatoduodenal ligament
Courvoisier sign :in a patient with painless jaundice and an enlarged gallbladder (or right upper quadrant mass), the cause is unlikely to be gallstones and therefore presumes the cause to be an obstructing pancreatic or biliary neoplasm until proven otherwise.
- Many patients with an incidental GBC are found retrospectively to have had suspicious US finding
recommendation is consistent with consensus-based guidelines from the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO)
Potential resectability is a key factor
Elevated liver enzymes: bile duct obstruction
Tumor markers: not diagnostically useful, preoperative elevation then serial assay needed after surgery to r/o recurrence or persistence of disease
- Bile spillage, excessive tissue handling, port site metastasis/abdominal wall implantation, intent to undergo definitive surgery
the first-echelon nodes (cystic duct and pericholedochal node groups)
the second-echelon nodes (posterosuperior pancreaticoduodenal, retroportal, right celiac, and hepatic artery node groups)
- Risk of routine extrahepatic bile duct resection: complications of hepaticojejunostomy like: bile leak, anastomotic stricture and CBD resection doesn’t yield greater LN count
- Patients with aortocaval lymh node positive had a high preoperative CA19-9, CEA and jaundice.
Study performed by Itaru Endo in 2002 of 20 patients: Microscopic metastases were detected in the resected livers from 5 of 20 patients. There were more metastatic lesions within 1 cm of the gallbladder bed than were located 1 to 2 cm away from it.
Anatomic resection: Overall hospital mortality was 9% and procedure related mortality was 4%
The pattern of drainage of the gallbladder veins may provide support for anatomic IVb/V resection over nonanatomic resection
Prevent micrometastasis
2: Giuliante and co had found incidental ca in 17% of cases of routine lap chole and this recommended for port site excision
3: Maker and co: From 1992 to 2009, 113 patients with incidental GBC and Port site disease was seen only in patients with T2 or T3 tumors (19%) thus recommended against resection of port site as it is a case of disseminated peritoneal disease
4: Based on data extracted from 27 papers the incidence of port-site metastasis in incidental gallbladder cancer has decreased from 18.6% prior to 2000 to 10.3%
Involvement of SMA/Celiac artery LN: Such involvement is considered distant rather than locoregional metastatic disease and therefore incurable
Direct involvement of the colon, duodenum, or liver does not represent an absolute contraindication. Given that the majority of patients with gallbladder cancer who present with preoperative jaundice will have disseminated disease, such patients should undergo multidisciplinary evaluation before surgery is offered
- Liver surface disease or peritoneal deposits
- Conclusions: In the present series with an overall resectability rate of 58.4%, SL identified 94.1% of the Detectable Lesion (DL)s and thereby obviated a nontherapeutic laparotomy in 55.9% of patients with unresectable disease and 23.2% of overall GBC patients. It had a higher yield in locally advanced tumors than in early-stage tumors; however, the accuracy in detecting unresectable disease and a DL were similar.
IGBC: incidental GBC
Early stage disease: potentially resectable with curative intent
Randomized trials comparing simple cholecystectomy with radical surgery for gallbladder cancer have not been performed; all available studies are retrospective reports.
- 2: Dong and co.: 290 pt. A retrospective analysis was conducted on 52 patients with pathologic stage T1 (27 [52%] with T1a and 25 [48%] with T1b), Twenty-one of the 52 study subjects (40.3%) underwent simple cholecystectomy. No peritoneal dissemination occurred regardless of the surgical method (laparoscopy or open surgery)
- Abramson created a Makrov model to estimate and compare life expectancy associated with management strategies of T1b tumor patients
Failure to perform extended cholecystectomy risks incomplete staging and thus undertreatment (omission of adjuvant chemotherapy) of those with T1b gallbladder cancer
RC-RL: radical chole- radical lymphadenectomy
- Lee and co: 192 pt with T2 disease, median f/u of 30 mths, Among hepatic-sided T2 patients, the 5-year overall survival was greater in patients who underwent radical cholecystectomy including lymph node dissection with liver resection than in patients who underwent lymph node dissection without liver resection (80.3% vs 30.0%,
- Kayahara analyzed 4,774 patients with gallbladder cancer were analyzed between 1988 and 1997 based on data from the Biliary Tract Cancer Registration Committee of the Japanese Society of Biliary Surgery
Extensive resection for patients with higher T stage but potentially resectable disease
Higher morbidity and mortality with hepatectomy + pancreaticoduodenectomy
- Not associated with improved survival
-this approach is most commonly futile given the frequent coexistence of metastatic disease. N2 or M1 diseases are distant metastasis and not curable
locoregional lymph nodes (cystic duct, common bile duct, hepatic artery, or portal, and portal vein)
- For inexperienced surgeon closing the incisions with or without simple cholecystectomy and referral to a more experienced surgeon or center is appropriate
- Data registered in the nationwide Swedish Registry for Gallstone Surgery (GallRiks) was analyzed
- provides relief of symptoms with minimal perioperative morbidity and mortality