mainly focused in the controversies of surgical management of gall bladder cancer

1. Management of Gall bladder cancer
Dr. Romil Jain
Department of Surgical Gastroenterology and Liver transplant
Sir Ganga Ram Hospital
New Delhi

2. Headings
• Diagnosis of carcinoma gall bladder
• Jaundice as a presenting sign.
• Techniques of standard radical
cholecystectomy and related controversies
• Neoadjuvant and adjuvant treatment
• Summary

3. Diagnosis of carcinoma gall bladder
 Clinical scenarios –
• Preoperatively
• Intraoperatively - at the time of surgical exploration for
abdominal symptoms attributable to another disease
process
• Postoperatively- examination of the gallbladder specimen
typically removed for cholecystectomy due to cholelithiasis.

4.  Risk factors
• Gall stone disease: present in 70 to 90% of the
patients. However overall incidence in GB cancer in
gall stone patients is 0.3 to 3%. Risk increases with
size >3cm and longer duration
• Porcelain GB: intramural calcification of wall, risk
reported to be upto 50%, modern series reported less
than 10% (Khan et al 1.1%). More risk with the
selective or incomplete calcification. (Stephen &
Berger)
• Gall bladder polyp : age >60, size>1 cm (> 0.8 cm in
PSC), associated gall stones have increased risk.

5. • Chronic inflammatory states
Chronic infection with salmonella and helicobacter
Primary sclerosing cholangitis
APBDJ
Drugs : Isoniazide, OC pills, methyl dopa
Obesity
Occupational – oil, paper, textile and shoe industry
workers
.

6. Pre operative suspicion
 Patients with right upper abdominal pain, and particularly
those with jaundice or signs of duodenal obstruction
 More typically have locally advanced disease that may
be identified preoperatively.
 Patients with early gallbladder cancer are often
asymptomatic, or may have nonspecific symptoms that
mimic, or are due to cholelithiasis or cholecystitis. So
malignancy not typically suspected preoperatively.

7. Incidental detection
 Found in 0.3 to 3.0 percent in patients undergoing
laparoscopic cholecystectomy.
 Duffy A et al. Gallbladder cancer (GBC): 10-year experience at Memorial
Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol 2008
 Cavallaro A et al. Incidental gallbladder cancer during laparoscopic
cholecystectomy: managing an unexpected finding. World J Gastroenterol
2012
• At surgical exploration (open or laparoscopic)
• Commonly in final histopathology report.

8. Intraoperative incidental detection
• Two possibilities:
• an obvious GB mass seen or
• mass seen on cut open specimen.
• Rule out distant metastasis
• Talk to patients relatives
• Conversion to open
• Cholecystectomy and frozen section tumor ? cystic duct
margin?
• Look for celiac lymph nodes and inter aortocaval nodes
• Inform anesthetist
• Radical cholecystectomy with liver non anatomical
(wedge) or anatomical resection with lymphdenectomy

9. Incidental detection on pathology
 What will be the approach?
• Managed by an expert in hepatobiliary surgery
 History and physical examination
 Preoperative symptoms and signs
 Preoperative imaging
 Reassess histopathology by an expert - T stage, N stage, cystic
duct margin?
 Talk to surgeon –bile spillage? retrieval bag? Any doubtful
lesion? location?
 Patient’s performance status and comorbidity
 Restaging- CT scan (chest, abdomen and pelvis) + MRI / PET
CT scan
 Staging laparoscopy – around 20% yield
 Interaortocaval lymph node sampling: 18% yield.

12. Preoperative imaging
• When surgery is being considered, preoperative imaging
is important to identify patients with absolute
contraindications to resection.
• Imaging is less sensitive for peritoneal disease, present
in a significant number of patients and requires
diagnostic staging laparoscopy.
• However, there are no definitive guidelines for imaging
prior to surgery.

13. • USG
• Doubtful features are, mural thickening or calcification, a mass
protruding into the lumen, a fixed mass in the GB.
• Endoscopic USG: more accurate but data are conflicting.
• Compared with transabdominal US, EUS more often correctly
predicted the histologic diagnosis (97 versus 76 percent)

14. EUS is a useful to assess
• the depth of tumor invasion into the GB wall and
• for defining lymph node involvement
• bile for cytologic analysis, sensitivity of 73 percent for the
diagnosis of GBC.
• EUS guided FNA
• Sadamoto Y,Kubo H, Harada N, et al. Preoperative diagnosis and staging of gallbladder
carcinoma by EUS. Gastrointest Endosc 2003; 58:536.
• Mohandas KM, Swaroop VS, Gullar SU, et al. Diagnosis of malignant obstructive jaundice by bile
cytology: results improved by dilating the bile duct strictures. Gastrointest Endosc 1994; 40:150.

15. • On CT, GBC can appear as
• a polypoid mass protruding into the lumen or completely
filling it, a focal or diffuse thickening of the gallbladder
wall, or a mass in the gallbladder fossa; liver invasion,
suspected nodal involvement, or distant metastases.
• Difficult to differentiate inflammation with malignancy
• Pilgrim CH, Groeschl RT, Pappas SG, Gamblin TC. An often overlooked diagnosis:
imaging features of gallbladder cancer. J Am Coll Surg 2013
• Liang JL, Chen MC, Huang HY, et al. Gallbladder carcinoma manifesting as acute
cholecystitis: clinical and computed tomographic features. Surgery 2009

16. Yoshimitsu k, Honda H et al. CT evaluation according toTNM staging in operated patients GB cancer. Am J
Roentgenol 2002

17. Loading…
• Dynamic MRI and MR cholangiopancreatography (MRCP)
can help to differentiate benign from malignant gallbladder
lesions in equivocal cases.
• MRI is particularly useful for visualizing invasion into the
hepatoduodenal ligament, portal vein encasement, and lymph
node involvement
• Yoshimitsu K, et al. J Magn Reson Imaging 1997
• Schwartz LH, Black J, Fong Y,et al.. J Comput Assist Tomogr 2002
• Jung SE, Lee JM, Lee K, et al.. Eur Radiol 2005

18. Kim JH, Tim KH et al.preoperative evaluation of GB cancer by MRCP , MRI and contrast
MRI. J Magn Rason Imaging 2002, 16;676-69

19. PET scan
• Most GB cancers are PET avid
• Help differentiate between benign and malignant tumors
and diagnose extrahepatic spread (Petrowsky et al., 2006).
• Limited in differentiating between inflammatory states and
malignancy (Corvera et al, 2008)
• More accurate in diagnosing metastatic disease than CT
scan.
• PET/CT had a sensitivity of 100% compared to 25% with
CT alone (P < .001), and PET alone changed surgical
management in 17% of cases (Petrowsky et al, 2006).
• Petrowsky H, et al: Impact of integrated positron emission tomography and

20. Radiological approach
• The usual first test for gallbladder symptoms is ultrasound
• Duplex ultrasound adds information in terms of local
vasculature involvement
• When GBC is proven or suspected preoperatively, imaging
with CT or MRI should provide adequate data on local extent
of tumor and assess for metastases.
• PET can be a valuable adjunct in searching for metastatic
disease when CT or MRI provides an equivocal information.
• Invasive cholangiography indicated only when a therapeutic
intervention, such as stenting, is anticipated.

21. Preoperative pathologic
diagnosis
 Preoperative histologic diagnosis is unnecessary with disease
that is amenable to resection
 Tendency to seed the peritoneum, biopsy tracts, and surgical
wounds
 Significant false-negative rates in smaller lesions.
 For a patient with unresectable or metastatic disease, a
percutaneous
 biopsy is indicated.
 Bile cytology has been proposed as a way of making the
diagnosis, sensitivity reported 75%, but a deliberate attempt to
make the diagnosis this way is unwarranted.

22. Diagnostic staging laparoscopy
• Diagnostic staging laparoscopy frequently identifies metastatic
disease or other findings that contraindicate tumor resection
that may not be apparent on preoperative imaging
studies. (30% and 20% after primary non curative
cholecystectomy)
• Butte JM, Gönen M, Allen PJ, et al. The role of laparoscopic staging in patients
with incidental gallbladder cancer. HPB (Oxford) 2011; 13:463.
• Gaujoux S, Allen PJ. Role of staging laparoscopy in peripancreatic and
hepatobiliary malignancy. World J Gastrointest Surg 2010; 2:283.

23.  A large prospective study of 409 patients undergoing
staging laparoscopy for gallbladder cancer, 23 percent
of patients had disseminated disease.
 Agarwal AK et al. Ann Surg 2013
 Laparoscopic ultrasound should be employed as
adjunctive imaging.
 Shoup M, Fong Y. Surgical indications and extent of resection in gallbladder
cancer. Surg Oncol Clin N Am 2002

24. Contraindications to resection
 Absolute contraindications to surgery for gallbladder cancer
• include liver metastasis, peritoneal metastases,
• involvement of N2 nodes,
• malignant ascites,
• extensive involvement of the hepatoduodenal ligament, and
• encasement or occlusion of major vessels.
 Surgery should only be considered to palliate specific
problems.

25. • Direct involvement of colon, duodenum, or liver does
not represent an absolute contraindication.
• There is no role for a palliative radical surgery, for the
purpose of debulking.
• Although not proven, debulking simple cholecystectomy
is recommended by some to prevent future episodes of
cholecystitis in patients with locally unresectable
disease.

26. General approach
 An open rather than laparoscopic procedure is generally
recommended, although some data suggest the feasibility of a
planned laparoscopic approach for an early-stage (T1a)
gallbladder cancer.
 Reddy YP et al.. Eur J Surg Oncol 2000
 Cho JY, Han HS, Yoon YS, et al. Laparoscopic approach for suspected early-stage
gallbladder carcinoma. Arch Surg 2010
 However, preoperative staging is not entirely reliable at
identifying patients with T1a disease, and improperly staged
tumors are at risk for inadequate resection and subsequent

27. • An open approach is more often chosen to minimize the risk
for bile spillage.
• Open surgery is usually performed through a right subcostal
incision.
• Frozen section to evaluate the margins of the specimen.
Comment on cystic duct margin is important.
• A negative margins to be obtained.

28. • If the cystic duct stump is negative, only regional lymph
node dissection is performed (except T1a tumors).
• And if it is positive, extrahepatic bile duct resection is also
undertaken.
• For incidentally detected cancer, the surgical
management is similar to primary resection of gallbladder
cancer.

29. Specific considerations
T1a tumor- it means its involving lamina
propria
• Cystic duct margin negative
• Cure rates following simple cholecystectomy range
from 73 to 100 percent in case series.
• Suzuki K, Kimura T, Ogawa H.
• Surg Endosc 2000; 14:712. Yildirim E, Celen O, Gulben K, Berberoglu U. The
surgical management of incidental gallbladder carcinoma. Eur J Surg Oncol 2005;
31:45.

30. • Re resection for T1a tumors does not appear to
provide an overall survival benefit.
• Coburn NG, Cleary SP, Tan JC, Law CH. Surgery for gallbladder
cancer: a populationbased analysis. J Am Coll Surg 2008; 207:371
• .
• You DD, Lee HG, Paik KY, et al. What is an adequate extent of resection for
T1 gallbladder cancers? Ann Surg 2008; 247:835.

31. T1b tumor- involving muscular layer
• The optimal approach to T1b disease is more controversial.
• Initial reports have showed no significant difference in
overall survival.
• But presently re resection was supported because,
1.
2.
3.
4.
Higher incidence of lymph nodes mets (15 vs 2.5%)
High loco regional recurrence 50 to 60%
High rates of liver involvement 0 to 13%
Increased median survival (9.5 Vs 6.4 years)
Abramson MA, et al. Radical resection for T1b gallbladder cancer:
a decision analysis. HPB 2009
Pawlik TM et al. J Gastrointest Surg 2007

32. T2 tumor- involvement of peri muscular connective tissue.
• Extended cholecystectomy is indicated.
• As high chances of residual disease 40 to 76%
• High chances of liver (10%) and lymph nodal involvement
(30% to 60%)
• High rates of local recurrence after simple cholecystectomy.
Shimada H, Endo I, Togo S, et al. The role of lymph node dissection in the treatment of
gallbladder carcinoma. Cancer 1997
Kapoor VK. Incidental gallbladder cancer. Am J Gastroenterol 2001

33. • 5 year survival is 24 to 40 % without re resection , may
approaches up to 80 to 100% after resection
• Toyonaga T, Chijiiwa K, Nakano K, et al. Completion radical surgery after
cholecystectomy for accidentally undiagnosed gallbladder carcinoma. World J Surg 2003;
27:266
• Survival in patients with T2 lesions is related to the number of
lymph nodes removed.
• Downing SR, Cadogan KA, Ortega G, et al. Early-stage gallbladder cancer in the
Surveillance, Epidemiology, and End Results database: effect of extended surgical
resection. Arch Surg 2011
• One report suggests that for gallbladder cancer to be considered
node negative, at least six lymph nodes should have been
removed.
• Ito H, Ito K, D'Angelica M, et al. Accurate staging for gallbladder cancer: implications for
surgical therapy and pathological assessment. Ann Surg 2011;

34. Resectable T3, T4 and node positive cancer.
• In the past, surgeons were reluctant to operate on patients
with locally advanced (T3/4) disease because of an
overall poor prognosis.
• Cubertafond P, Mathonnet M, Gainant A, Launois B. Radical surgery for gallbladder cancer.
Results of the French Surgical Association Survey. Hepatogastroenterology 1999
• Support for radical surgery with reports indicating long term
survival in patients with T3 and T4 tumors, 15 to 63 percent
and 7 to 25 percent of patients, respectively.
• Kayahara M, Nagakawa T. Recent trends of gallbladder cancer in Japan: an analysis of 4,770 patients.
Cancer 2007; 110:572.

35.  Some advocate even more extensive resection
involving hepatectomy, pancreaticoduodenectomy,
colectomy, and even nephrectomy for potentially
resectable disease.
 A median survival time of 17 months.
 Dixon E, Vollmer CM Jr, Sahajpal A, et al. Ann Surg 2005;
 But morbidity and mortality rates are high (48 to 54,
and 15 to 18 percent, respectively).
 In general, patients with lymph node metastases
outside the hepatoduodenal ligament should not
undergo resection.

36.  Results with radical lymphadenectomy are less favorable
with N2 disease.
 Tashiro S, Konno T, Mochinaga M, et al. Treatment of carcinoma of the gallbladder in
Japan. Jpn J Surg 1982;
 If preoperative FNA confirms involvement of N2 nodes,
surgery should be performed only for palliation of specific
problems.
 In a series of 104 patients treated at Memorial Sloan-
Kettering over a 12-year period, major hepatectomy,
resection of adjacent organs other than the liver, and
common bile duct excision increased perioperative
morbidity and were not associated with better survival.
 D'Angelica M, Dalal KM, DeMatteo RP, et al. Analysis of the extent of resection for

37. Managing an incidental gallbladder cancer found on pathology
 Timing of re resection
 A retrospective analysis from the US Extrahepatic Biliary
Malignancy Consortium (JAMA Surg,2017)
 Those who underwent reoperations between four and
eight weeks from the date of the original cholecystectomy
had better overall survival.
 Due to reduced inflammation and full appreciation of
subclinical diseases (compared with reoperating <4
weeks) but does not allow too much time for disease
dissemination.
 Ethun CG, Postlewait LM, Le N, et al. Association of Optimal Time Interval to

38.  Managing an incidental GBC found intraoperatively
 The surgeon should maintain a high index of suspicion in
patients with risk factors.
 If an obviously malignant lesion is encountered, it is best not to
sample the lesion laparoscopically to reduce the hazard of
seeding.
 The procedure should be converted to an open resection, if
resection will be undertaken.

39.  Options include the following:
• Completing the cholecystectomy and obtaining a frozen
section, if positive, do extended cholecystectomy.
• For surgeons unfamiliar with complex hepatobiliary
surgery, closing the patient with or without simple
cholecystectomy and referral to a high-volume center.

40. • Fong et al from MSKCC found no difference in long term
complications and survival.
• Fong Y,Jarnagin W, Blumgart LH. Gallbladder cancer: comparison of patients presenting initially
for definitive operation with those presenting after prior noncurative intervention. Annals of
surgery. 2000 Oct 1;232(4):557-69..

41. Gall bladder cancer with jaundice
• Suggests porta hepatis involvement.
• Reported as advanced disease with dismal
prognosis.
• Many western authors consider jaundice as a
contraindication.

42. Loading…
• In 240 patients at MSKCC who presented with gallbladder
cancer, 82 (34%) were jaundiced and were more likely to have
advanced stage disease
• Only six underwent resection with curative intent, and only four
had an R0 resection.
• The median disease-specific survival of patients with jaundice
was 6 months, significantly worse than those without jaundice
(16-month disease-specific survival; P < .0001).
• None from the jaundiced group survived 2 years.
• Hawkins WG, Dematto RP, Jarnagin WR et al. jaundice predicts advanced disease and mortality in
patients with gall bladder cancer. Ann Surg Oncol; 2004;11:310- 15.

43. • Study by Agrawal et al, suggested that biliray obstruction is
not a sign of inoperability.
• In their study, total 51 patients with jaundice
• Total 27% underwent resection.
• Median survival - 26 months.
• 7 patients survive more then 2 years.
• They suggested that on the basis of jaundice only, patients
should not be deferred for resection.
• Agarwal AK, Mandal S, Singh S, Bhojwani R, Sakhuja P,Uppal R. Biliary obstruction in gall bladder
cancer is not sine qua non of inoperability. Annals of surgical oncology. 2007

44. • A retrospective study by Varma and colleagues (2009)
reported that although jaundice was associated with a higher
stage at presentation, it did not preclude resection.
• Total 120 patients 89 (54%) had jaundice.
• Half of those patients 44 patients who presented with
jaundice underwent R0 resections.
• Varma V,Gupta S, Soin AS, Nundy S. Does the presence of jaundice and/or a lump in a patient with
gall bladder cancer mean that the lesion is not resectable?. Digestive surgery. 2009

45. Bile spillage
 Bile spillage is likely to be an association with an
incomplete resection and systemic recurrences.
 Am Surg 2011 Clinical implication of bile spillage in patients undergoing
laparoscopic cholecystectomy for gallbladder cancer. Lee JM al.

46. Surgical techniques
 Staging laparosocpy
 Inter aortocaval lymph node sampling
 Frozen section
 Extent of lymph nodal resection
 Bile duct excision
 Hepatic resection
 Port site excision
 Hepatopancreatoduodenectomy
Laparoscopic radical surgery role

47. Inter aorto caval lymph node
sampling
• Interaortocaval (16b1) lymph node (LN) involvement in
gallbladder cancer (GBC) is a sign of advanced disease with
a dismal prognosis equivalent to that of distant metastasis
• Kaneoka Y,Yamaguchi A, Isogai M, Harada T, Suzuki M. (2003) World J Surg 27:260–265.
• Kondo S, Nimura Y, Hayakawa N, Kamiya J, Nagino M, Uesaka K. (2000). Br J Surg
87:418–422.

48. • CT indicator - (size >10 mm and heterogeneous internal
architecture) of the 16b1 LN. But positive predictive value is
less.
• And that is why detection of 16b1 LNs, intraoperative biopsy
and frozen-section analysis of these nodes have been
proposed
• Noji T, Kondo S, Hirano S, Tanaka E, Ambo Y,Kawarada Y et al. (2005) CT
evaluation of para-aortic lymph node metastasis in patients with biliary cancer. J
Gastroenterol

49. • Patients with aortocaval lymh node positive had a
high preoperative CA19-9 , CEA and jaundice.
• Agarwal AK, Kalayarasan R, Javed A, Sakhuja P.. HPB: The Official Journal of the
International Hepato Pancreato Biliary Association. 2014;16

50. Frozen
section
• Although single most important factor to decide about further
treatment, there is paucity of literature regarding role of
frozen section.
• Aoki et al did study on 990 lap cholecystectomy and found that
sensitivity 64% and specificity 100%.
• Low sensitivity was due to inability to find pTis and T1
lesion.
• Aoki T, Tsuchida A, Kasuya K, et al. Is frozen section effective for diagnosis of
unsuspected gallbladder cancer during laparoscopic cholecystectomy? Surg Endosc
2002;16(1):197-200

51. • Another study, in consecutive 1793 lap cholecystectomy,
frozen done in suspicious lesion.
• Sensitivity was 90% and specificity was 100%
• Kwon AH, Imamura A, Kitade H, Kamiyama Y.Unsuspected gallbladder cancer diagnosed during
or after laparoscopic cholecystectomy. Journal of surgical oncology. 2008 Mar 1;97(3):241-5

52. Extent of lymph
nodal excision
• The lymphatic drainage of the gallbladder is via several pathways
and does not always follow a predictable drainage pattern.
• In some cases, lymph nodes associated with gallbladder cancer
can first be seen posterior to the pancreas or portal vein.
• Shirai Y,Yoshida K, Tsukada K, et al.. Br J Surg 1992; 79:659.
• Uesaka K, Yasui K, Morimoto T, et al. J Am Coll Surg 1996; 183:345.
• Ito M, Mishima Y,Sato T.. Surg Radiol Anat 1991; 13:89.

54. • LN involvement seen in 35 to 80 % with ≥T2.
• LN dissection is still indicated for >T1a even when lymph node
involvement is not obvious intraoperatively.
• LN involvement is one of the best predictors of a poor outcome
after surgery (five year survival of 57% without vs 12 % with
LN metastases)

55. • D1 lymphadenectomy removes N1 lymph nodes (cystic artery,
hepatic artery, portal vein, and common bile duct)
• D2 removes additional N2 lymph nodes (periaortic, celiac
artery, superior mesenteric artery, and inferior vena cava nodes)
• Optimal extent of lymphdenectomy controversial.
• N2 lymph nodal removal is not associated with increased
survival, but it provides accurate staging.

56. • The latest edition of the American Joint Committee on Cancer
staging manual requires that at least 3 lymph nodes be removed
for proper staging of gallbladder cancer.
• American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton
CC, et al (Eds),Springer, New York 2010. p.211.
• Other experts(MSKCC) advocate removal of more (at least 6)
lymph nodes.
• Ito H, Ito K, D'Angelica M, et al. Accurate staging for gallbladder cancer: implications
for surgical therapy and pathological assessment. Ann Surg 2011; 254:320.

57.  Because an extended lymphadenectomy allows for better
prognostic stratification of patients, it is suggested to
perform a D2 rather than a D1 lymphadenectomy for
gallbladder cancer when it can be performed without
substantially increasing postoperative complications.

58. Bile duct excision
• When the tumor extends into the common bile duct, or
frozen section analysis of the cystic duct margin is positive,
extrahepatic bile duct resection should be performed.
• Jayaraman S, Jarnagin WR. Management of gallbladder cancer. Gastroenterol Clin
North Am 2010; 39:331.
• Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet
Oncol 2003; 4:167
• Reconstruction with Roux en Y hepaticojejunosotmy.

59. • In a study by Pawlik et al, 42 percent of patients had residual
disease in the common bile duct when the cystic duct stump had
a positive margin on frozen section.
• Pawlik TM, Gleisner AL, Vigano L, et al. Incidence of finding residual disease for incidental
gallbladder carcinoma: implications for reresection. J Gastrointest Surg 2007; 11:1478.
• Some have advocated routine resection of the extrahepatic bile
ducts, regardless of the result of the cystic duct stump frozen
section, as a means to achieving a more complete
lymphadenectomy
• Shimizu Y,Ohtsuka M, Ito H, et al. Should the extrahepatic bile duct be resected for locally advanced
gallbladder cancer? Surgery 2004; 136:1012.

60. • However, several retrospective series have not shown a
survival benefit for this approach in the management of
gallbladder cancer
• Shih SP, Schulick RD, Cameron JL, et al. Gallbladder cancer: the role of laparoscopy and
radical resection. Ann Surg 2007; 245:893.
• Further supporting this view, a retrospective study found that
common duct resection does not necessarily yield a greater
lymph node count.
• Pawlik TM, Gleisner AL, Vigano L, et al. J Gastrointest Surg 2007; 11:1478.

61. Hepatic resection
 The basic principle is achieving a negative surgical margin, while
preserving the maximal amount of liver parenchyma.
 The rational of resection includes:
 Resection of liver invaded or likely to be invaded
directly by the tumor.
 To remove micro-metastasis in segment 4b + 5 as a
result of direct venous drainage of gallbladder through
cystic vein to these segments,
 To resect en bloc Glisson’s sheath because of potential
invasion of hepatoduodenal ligament.

62.  In extended cholecystectomy -removal of at least a 2 cm
margin of liver adjacent the gallbladder bed.
 Veins from the gallbladder drain mostly into the middle hepatic
vein provide support for anatomic IVb/V resection over
nonanatomic resection, but no randomised data available to
support the fact.
 Also anatomic approach reduces the risk for bleeding or bile
leakage.
 Scheingraber S, Justinger C, Stremovskaia T, et al. The standardized surgical approach
improves outcome of gallbladder cancer. World J Surg Oncol 2007


63.  At present either non anatomical or anatomical resection can
be done.
 The standard resection is an anatomic resection of segments
IVb and V, but it is possible to do a smaller wedge resection
for early-stage cancers with no radiographic disease in the
liver.
 Blumgart’s Surgery of liver, biliary tract and pancreas 6th
edition

64. • Right extended hemihepatectomy should be performed, if
possible, for tumors of the body or neck that involve the
right portal triad or with inflammation distinction between
tumor and scar is obscured .
• Bartlett DL. Gallbladder cancer. Semin Surg Oncol 2000

65. • Horiguchi et al. compared these two methods of Gb bed
resection and segment 4b and 5 resection
• They analyzed 85 patients with pT2N0 GBC with a median
follow-up of 85 months:
• No difference in 5-year survival rate (p = 0.53) and disease
free survival rate (p = 0.23). No difference in incidence of
recurrence in two groups (p = 0.39).
• Horiguchi A, Miyakawa S, Ishihara S, et al.. J Hepatobiliary Pancreat Sci
2013
• Araida et al. conducted a questionnaire-based retrospective study
of 4243 cases of GBC reporated same.
Araida T, Higuchi R, Hamano M, et al. J Hepatobiliary Pancreat Surg 2009;16(2):204-15.

66. • K.reddy et al did a study on extended hepatectomy.
– Portal vein embolization.
• estimated volume of the future liver remnant - 25%.
– 22 curative hepatic resection - 11 extended hepatectomy - 4 of 11
preoperative PVE
– 3-year overall and recurrence-free survival - 72% and 68%.
Reddy SK, et al. Extended hepatic resection for gallbladder cancer. The American Journal of
Surgery. 2007

67. Port site
excision• After laproscopic manipulation, port site recurrences have been
described.
• Maker AV,Butte JM, Oxenberg J, et al. Is port site resection necessary in the surgical
management of gallbladder cancer? Ann Surg Oncol 2012; 19:409.
• Nowadays radical resection does not require resection of
the previous laparoscopy port sites.

68. • If tumor is found in the port sites, is a marker for peritoneal
spread and removal of the port sites will not be curative.
• Port site resection is not associated with overall survival or
recurrence-free survival.
• Yamaguchi K, Chijiiwa K, Ichimiya H, et al. Gallbladder carcinoma in the era of
laparoscopic cholecystectomy. Arch Surg 1996; 131:981.
• Giuliante F,Ardito F, Vellone M, et al. Portsites excision for gallbladder cancer
incidentally found after laparoscopic cholecystectomy. Am J Surg 2006;
191:114.18.

69. Hepatopancretoduodenecto
my
• The philosophy of achieving of R‘0’ resection
• In advanced GBC with adjacent organ removal including
hepatopancreaticoduodenectomy (HPD).
• Reasons –
• First is the direct invasion of pancreas or duodenum
• Second to facilitate excision of densely adherent
peripancreatic lymph nodes.
• Former indication is usually considered worth HPD as survival
is likely to be more after R‘0’ resection is achieved.

70. • The second indication (lymphadenectomy) is not well accepted
as lymph nodes in itself is a poor prognostic feature and high
postoperative morbidity and mortality.
• Sakamoto Y,Nara S, Kishi Y,et al. Surgery 2013
• Lim CS, Jang JY, Lee SE, et al. Reappraisal of hepatopancreatoduodenectomy as a treatment
modality for bile duct and gallbladder cancer. J Gastrointest Surg 2012;
• Araida T,Yoshikawa T,Azuma T, et al.. J Hepatobiliary Pancreat Surg 2004

71. Laparosocpic radical
surgery
• Traditionally, laparoscopic surgery has not been routinely
recommended in the non incidental setting.
• Recent studies suggesting equivalent outcomes between
laparoscopic and open approaches.
• Robotic-assisted procedures have also been described and are
carried out.

74. Adjuvant therapy
• Despite conflicting data, limited level I data.
• Currently, gemcitabine-based regimens, often combined with a
platinum agent, have become the most common choice for
treating gallbladder cancer
• Gemcitabine shown to improve median overall survival (9.5
months).
• Sharma A, Dwary AD, Mohanti BK, et al. Best supportive care compared with chemotherapy for
unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol 2010;28:4581–6.

75. • Japanese multi-institutional trial, randomized resection
followed by adjuvant mitomycin and 5-FU vs resection
alone.
• The study showed 5-year survivals of 20.3% vs 11.6% in
favor of adjuvant therapy in patients with gallbladder cancer.
• Takada T,Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for
gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in
patients with resected pancreaticobiliary carcinoma. Cancer 2002;95:1685–95

76. • Most recently, a phase II trial combining gemcitabine,
capecitabine, and radiation therapy in patients with
extrahepatic biliary tract and gallbladder cancers showed
promising results.
• Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al. SWOG S0809: a phase II intergroup trial of
adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in
extrahepatic cholangiocarcinoma

77. Neoadjuvant therapy
• Neoadjuvant chemotherapy is thought to provide an
opportunity to be determine, biologically aggressive tumors
who, arguably, may not benefit from extensive operations.
• Small case series suggested gemcitabine-platinum based
combinations have some role.
• Sirohi B, Rastogi S, Singh A, et al. Use of gemcitabine-platinum in Indian patients
with advanced gall bladder cancer. Future Oncol 2015
• Kato A, Shimizu et al. Surgical resection after downsizing
chemotherapy for initially unresectable locally advanced biliary tract
cancer: a retrospective single-center study. Ann Surg Oncol 2013.

78. • In a recent study from the MD Anderson Cancer Center, a
retrospective review of their gallbladder cancers resected
with wide 1-cm negative margins and received either
neoadjuvant or adjuvant therapy. 5 year survival was 50.6%.
• Adjuvant therapy showed no improvement in survival, and
neoadjuvant treatment had only served to significantly delay
time to operation in their study.
• Glazer ES, Liu P,Abdalla EK, et al. Neither neoadjuvant nor adjuvant therapy
increases survival after biliary tract cancer resection with wide negative margins. J
Gastrointest Surg 2012;16:1666–71.

79. Palliative procedures
 Pallation 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 –in patients who can tolerate surgery is biliary bypass, but
many patients fail these procedures with recurrent obstruction.
 In one study, intrahepatic segment III cholangiojejunostomy and staying
away from the hepatoduodenal ligament, the most common site of disease
progression, successfully palliated the majority of patients.
 Kapoor VK, Pradeep R, Haribhakti SP, et al. Intrahepatic segment III cholangiojejunostomy in advanced carcinoma of the
gallbladder. Br J Surg 1996

80. Summary
• Surgery is the only curative option.
• High index of clinical suspicion should be kept in mind.
• 0.2% to 3% of all lap cholecystectomy specimen shows GB
cancer.
• Pre op imaging – CT dual phase angio- assessment of hepatic
reserve.
• All patients should undergo staging laparoscopy, aorto caval
lymph node sampling and cystic duct margin frozen.

81. • Jaundice indicates advanced disease but not precluding
resection.
• Radical cholecystectomy – liver bed excision with
lymphdenectomy with or without bile duct excision is the
treatment of choice.
• N1 group of lymph node removal, N2 to stage the disease
unresectable.
• AJCC 3, MSKCC 6 lymph node removal.
• Bile duct excision frozen positive/ ischemia/ trauma

82. • T1a tumor bile spillage or cystic duct margin?
• T1b and further completion cholecystectomy
• No clear cut role of neoadjuvant therapy.
• Adjuvant therapy advised in node positive, T2 tumors, R1
margin, poor differentiation.

83. Thank
you