Gall bladder cancer

• Mc biliary neoplasm
• aggressive nature (propensity toward nodal metastases, direct hepatic
invasion, and seeding of peritoneal surfaces).
• usually diagnosed at an advanced stage
• overall median survival of less than 6 months.
• 22 per 100,000 in women in Delhi, India.
• processes promoting chronic gallbladder irritation and inflammation are also risk
factors: history of biliary disease, Mirizzi syndrome, age, female gender, obesity, high
carbohydrate diet, ethanol abuse, and tobacco abuse (all of which are associated
with calculous biliary disease) have been associ- ated with a higher risk of gallbladder
cancer.14–17 Moreover, 69% to 86% of patients with gallbladder cancer have a
personal history of gallstone disease.
• The presence of an abnormal pancreaticobiliary duct junction, thought to promote
chronic biliary inflammation, has been associ- ated with both choledochal cyst
disease and gallbladder cancer.19 The incidence of gallbladder cancer in the so-
called porcelain gallbladder, presumably resulting from chronic inflammation and
calcification of the gallbladder wall, was once estimated to be as high as 61%;
however, more contemporary analyses suggest that the correct figure is more likely
between 7% and 25%
• The infundibulum of the gallblad- der lies adjacent to the right portal pedicle
within the porta hepatis; as a result, tumors arising in the infun- dibulum
commonly invade the right portal pedicle and require a right trisectionectomy
for complete surgical extirpation.

• The thin gallbladder wall is composed of an inner mucosa, a thin lamina propria,
and a single muscularis layer (unlike the two muscle layers that line most hollow
viscera). The serosa of the gallbladder is typically opened during a standard
cholecystectomy, with the avascular subserosal layer being used as the surgical
plane of dis- section; the ability of mucosally based tumors to microscopi- cally
invade across the serosa explains the high prevalence of positive resection
margins after standard cholecystectomy for gallbladder cancer.
• The pattern of lymphatic flow appears to be directed initially toward the
cystic and perichole- dochal lymph nodes, then to the posterior pancreatico-
duodenal, periportal, and common hepatic artery nodes within the
hepatoduodenal ligament, and eventually to the celiac, aortocaval, and
superior mesenteric artery nodes.22 There appears to be no ascending
lymphatic drainage into the hilum of the liver. For this reason, meticulous
lymphadenectomy within the hepatoduodenal ligament is a critical
component of surgical strategy in the management of gallbladder cancer.
Unfortunately, the potential for direct drainage from the pericholedochal
nodes into the aortocaval nodes explains the difficulty of completely
encompassing the extent of lymphatic involve- ment after surgical resection.
• 60% of gallbladder cancers arise in the fundus, with 30% arising from
the body and 10% from the neck

• it is unlikely that most gallbladder cancers arise from precursor

adenomata.
• categorized as infiltrative, nodular, combined nodular-infiltrative,
papillary, and combined papillary-infiltrative. Infiltrative tumors,
which are the most common variety, initially appear as indurated
areas of gallbladder wall thickening that spread into the subserosal
plane, which is typically violated during routine cholecystectomy.
Nodular tumors invade into adjacent pericholecystic structures early,
but unlike infiltrative cancers, induce sharply defined borders that can
facilitate curative resection. Papillary tumors tend to grow in a
polypoid fashion, often filling into the lumen of the gallbladder with
minimal wall invasion; as such, this variety
• of tumors tends to be associated with more favorable prognoses.
• Microscopically, adenocarcinoma is the most common histologic
subtype seen with gallbladder malignancies. Other histologic subtypes
that have been reported include adenosquamous carcinoma, oat cell
carcinoma, sarcoma, carcinoid, lymphoma, and melanoma.
• Review of the literature suggests that only 10% of cases are confined
to the gallbladder wall at the time of diagnosis; 59% exhibit direct
invasion into hepatic parenchyma, 45% demonstrate lymph node
metastases, and 20% present with distant extrahepatic metastases.
• The most common site of extraabdominal spread is the lungs,
although pulmonary metastases are rare in the absence of extensive
intraperitoneal disease.
• gallbladder carcinoma develops via distinct pathways, either occurring
de novo with predominant p53 alteration with low percentage of K-
ras mutation, or via adenoma-carcinoma sequence in the absence of
p53, K-ras, or adenomatous polyposis coli (APC) gene mutations
• Mutations identified thus far include BRAF mutations in 7 of 21 (33%)
resected specimens, and interestingly K-ras and BRAF mutations were
not identified in the same specimens.
• complaints that mimic those of benign biliary colic. Symptoms of
persistent pain, weight loss, anorexia, jaundice, and a palpable right
upper quadrant mass are typically indicative of advanced disease that
is not amenable to surgical resection. A review of the Memorial Sloan
Kettering Cancer Center (MSKCC) experience highlighted the
observation that 95% of patients presenting with jaundice were
ultimately noted to harbor unresectable disease
• In the presence of appropriate symptomatology, carcino- embryonic antigen (CEA) elevations greater
than 4 ng/ mL have been shown to predict gallbladder cancer with 50% sensitivity and 93%
specificity.29 Similarly, elevations of carbohydrate antigen (CA) 19-9 greater than 20 U/ mL are 79.4%
sensitive and 79.2% specific.

• Radiographic findings on ultrasonography include the presence of a polypoid gallbladder mass (seen
in 27% of gallbladder cancer cases) or an invasive gallbladder-based lesion (seen in 50% of cases);
other sonographic findings consistent with gallbladder cancer include discontinuous gallbladder
mucosa, echogenic mucosa, or submucosal echolucency.31 Computed tomographic (CT) findings
seen in patients with gallbladder cancer include a mass filling the gallblad- der lumen in 42% of
cases, a polypoid mass in 26%, a mass in the region of the gallbladder fossa without a distinctly
recognizable gallbladder in 26%, and diffuse wall thickening in 6% (Fig. 112.1).32 Magnetic
resonance imaging (MRI) and magnetic resonance cholangiopan- creatography (MRCP) are especially
accurate means of identifying small hepatic metastases and involvement of the common bile duct.
• Despite the high frequency of nodal involvement, definitive preoperative
identification of lymph node metastases is challenging. Enlarged benign
inflammatory lymph nodes are commonly encountered at the time of
laparotomy. Although the CT finding of ringlike or het- erogeneous
enhancement of a more than 10-mm large lymph node has been found
to identify lymph node metastases with 89% accuracy, only 38% of nodal
metastases are preoperatively identified by CT.33 Endoscopic ultra-
sonography may be useful for assessing peripancreatic and periportal
adenopathy. Fluorodeoxyglucose positron emission tomography (PET) is
useful for identifying distant metastases that may contraindicate surgical
intervention, but PET efficacy for nodal metastases is limited.
• The striking ability of disseminated gallbladder cancer cells to implant
within needle tracts limits the utility of percutaneous core biopsy for
diagnosis. Percutaneous fine-needle aspiration appears to have a
lower incidence of needle tract seeding while providing satisfactory
diag- nostic accuracy, and it can be used in cases of surgically
unresectable disease in which a definitive tissue diagnosis may direct
nonoperative therapy.35 Cytologic analysis of bile samples collected
either percutaneously or endoscopi- cally is not often helpful for
diagnosing gallbladder cancer, with suboptimal sensitivities of
approximately 50%
• This emphasizes the importance of thorough lymph- adenectomy. To
reiterate, the cystic duct, common bile duct, hepatic artery, and
periportal lymph nodes are considered N1 disease in the 7th edition
of AJCC staging manual, whereas the paraaortic, paracaval, superior
mesenteric artery, and celiac lymph nodes are N2 nodes.

• 8 th edition changed to number based rather than location based.

• Standard lymphadenectomy for regional clearance is thus limited to
the hepatoduodenal ligament. If N2 disease is suspected, most
surgeons will sample nodes in the N2 distribution for staging purposes
but will not completely clear these nodal basins in the interest of
sparing the patient added morbidity. Imaging plays a critical role
when considering surgical re-resection after incidentally found
gallbladder cancer, or when planning surgery for suspected
gallbladder cancer. Most authors advocate for some combination of
CT, MRI, and PET
management
• The likelihood of N1 disease is low for patients with T1a tumors, and,
for this reason, simple cholecystectomy should be curative.41–43 A
notable exception to this is the situation in which the cystic duct
margin remains positive, in which case re-resection to negative
margins is imperative. On occasion, this may necessitate common bile
duct excision with reestablishment of biliary-enteric continuity.
Additional debate surrounds the management of T1b disease, with
studies suggesting that T1b disease can present with lymph node
metastases in up to 20% of patients and many authors advocating for
radical resection
• the so-called radical or extended cholecystectomy. This consists of
cholecystectomy with en bloc resection of a rim of segments IVB and
V and lymphadenectomy of the cystic, pericholedochal, periportal,
and posterior pancreaticoduodenal lymph nodes residing in the
hepatoduodenal ligament and local aortocaval lymph nodes
• The subserosal plane of dissection used in the standard cholecystectomy is
likely to violate T2 tumors; indeed, patients with T2 tumors resected by simple
cholecystectomy have a 40% to 50% likelihood of margin positivity.37,41
Furthermore, approximately one-half of patients with T2 tumors harbor nodal
metastases. For these reasons, extended cholecystectomy with portal
lymphadenectomy is the procedure of choice for patients with stage II disease.

• 5-year survival rates are 70% to 90% for patients with stage II disease treated
with extended cholecystectomy, as compared with 20% to 40% after simple
cholecystectomy alone (with no 5-year survivors among those with positive
margins)
• Occasionally, tumors localized to the infundibulum of the gallbladder
can present unique surgical challenges because extensive tumor
within the region of the adjacent right portal pedicle may necessitate
removal of the right hemiliver, in addition to resection of segment
IVA; this is undertaken in the form of an extended right hepatectomy
or right trisectionectomy.
• Unfortunately, no long-term survival has been observed among
patients with stage IV disease. Involvement of N2 nodes outside of
the hepatoduodenal ligament and distant metastases are indicative of
more aggressive tumor biology than that seen in bulky tumors
extending into the hepatic parenchyma or in those with nodal disease
confined to the hepatoduodenal ligament.
• In a more recent series, 66% of those presenting after incidental discovery were
eligible for reexploration, and, of those, 17% had no evidence of residual
disease.47 Ultimately, 62% of those reexplored underwent R0 or curative
resections, but this represents only 41% of those presenting following incidental
disease discovery.47 Still more discouraging, evidence suggests that the presence
of residual disease identified on liver resection following cholecystectomy with
incidentally discovered gallbladder cancer confers similar survival to patients with
stage IV disease. This makes the case for prudent preoperative investigation prior
to index operations and likely reflects the invariable violation of the subserosal
plane during laparoscopic cholecystectomy that can result in inadvertent
peritoneal seeding. This also underscores the importance of staging laparoscopy,
which remains an effective means of identifying patients with unresectable
gallbladder cancer.
Operative staratergy
• The operative strategy begins with exploratory lapa- roscopy. If no
evidence of peritoneal or unsuspected hepatic spread is noted, the
surgeons proceed with open deliberate abdominal exploration
through a bilateral subcostal or right transverse incision with a vertical
exten- sion to the xiphoid process. If no evidence of technically
unresectable disease, distant disease, or N2 nodal metastases is
identified, the lymphadenectomy is begun by mobilizing the duodenal
sweep with an extensive Kocher maneuver.
• The retroduodenal lymphatic tissue is harvested with care taken to
include aortocaval and superior mesenteric nodes. The portal
lymphatic tissue may be skeletonized off of the extrahepatic biliary
system, but in cases of prior hilar dissection, tumor extension into the
bile duct, or extreme obesity, comprehensive portal
lymphadenectomy may require excision of the extrahepatic bile ducts.
In this scenario the supraduodenal bile duct is divided and elevated,
and its surrounding lymphatic tissue is swept off of the underlying
portal vein and hepatic artery as dis- section proceeds toward the
hepatic hilus.
• At the hilus, the hilar plate is lowered by incising Glisson capsule along
the base of segment IVB. A determination is made at this point
regarding the extent of hepatic resection that will be necessary for
complete tumor extirpa- tion. For patients with extensive invasion into
the porta hepatis, an extended right hemihepatectomy or right
• trisectionectomy may be necessary. If the bile duct has been divided, a
right hemihepatectomy or trisectionectomy will require division of the
left hepatic duct; if the bile duct has been divided and resection of
segments IVB and V is sufficient for tumor clearance, the common
hepatic duct is typically divided below the confluence of the right and
left hepatic ducts.
• In the absence of significant tumor extension into the porta hepatis,
resection of segments IVB and V is per- formed. Prior to hepatectomy,
care is taken to maintain a low central venous pressure, and the
patient is placed into a moderate Trendelenburg position to minimize
the risk of air embolism. Inflow control to segment IVB can be
obtained by dissection in the region of the umbilical fissure, where
the vessels to IVB can be identified and ligated to minimize
intraoperative hemorrhage
• Control of the segment V vessels is usually achieved after paren-
chymal transection has commenced; care must be exercised to avoid
inadvertent injury to the adjacent right anterior sectoral branches or
to the segment VIII vessels. Impor- tantly, the middle hepatic vein
draining segments IVB and V runs between segments IVA and VIII and
enters the portion of liver to be resected; care must be taken to avoid
injury to this vessel, which is divided during paren- chymal
transection.
• Inflow and outflow control and accurate segmental resection are
facilitated by the use of intraoperative ultrasonography, which can
identify the anatomy and course of the relevant vessels. In cases in
which extrahepatic biliary resection has been performed, a retrocolic
Roux-en-Y hepaticojejunostomy is constructed to reestablish biliary-
enteric continuity. Finally, for patients who have previously undergone
laparoscopic cholecystec- tomy, the surrounding skin and fascia of the
laparoscopic port sites can be excised and submitted for pathologic
analysis for staging, based upon surgeon preference.
• ADJUVANT THERAPY
• In MSKCC data, among those patients undergoing curative resection, a
median survival of 26 months and a 5-year actuarial survival of 38%
were observed. Factors predictive of poor survival were advanced T
stage and N stage.48 Gallbladder cancer is unfortunately highly
resistant to chemotherapy, and its proclivity toward diffuse peritoneal
spread limits the applicability of radiation therapy.