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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_585_Библиотеки_им_академика_М_И_Перельмана.pdf
Digital Surgical Diagnosis
andTreatment ofGallbladder Cancer
YingbinLiu, HaibinLiang, JianmingWang, YanLiu,
andChihuaFang
15
15.1 Introduction
Gallbladder cancer refers to a malignant epithelial tumor
arising in the gallbladder (the fundus, body and neck of
the gallbladder, and the cystic duct), with an overall 5-year
survival rate of only 5% (Hueman et al. 2009; Hundal
and Shaffer 2014). In China, the incidence of gallbladder
cancer accounts for 0.4% to 3.8% of biliary tract disease,
ranking sixth among gastrointestinal cancer. In recent
years, the incidence of gallbladder cancer has increased.
Like most malignant tumors, gallbladder cancer has hidden early symptoms and nonspecic clinical presentations.
However, gallbladder cancer has an aggressive biological nature. Gallbladder cancer may invade several important neighboring organs and adjacent blood vessels due
to its anatomical location and strong ability to invade and
metastasize. Most patients with gallbladder cancer have
advanced cancer when they are diagnosed, and are often
associated with liver invasion, lymph node metastasis, distal bile duct invasion, invasion and distant metastasis of the
head of the pancreas. Surgical treatment of these patients
usually requires R0 resection of multiple organs, which is
difcult and risky. This chapter focuses on the application
of three-dimensional visualization technology in the treatment of gallbladder cancer combined with hepatectomy
and pancreaticoduodenectomy.
Invasion and metastasis of gallbladder cancer mainly
include the following ve aspects.
Y. Liu · H. Liang
Xinhua Hospital, School of Medicine, Shanghai Jiaotong
University, Shanghai, China
J. Wang · Y. Liu
Tongji Hospital Afliated to Tongji Medical College, Huazhong
University of Science and Technology, Wuhan, China
C. Fang (
Zhujiang Hospital, Southern Medical University,
Guangzhou, China
*)
15.1.1 Invasion oftheLiver andIntrahepatic
Metastasis
The close anatomical relationship between the liver and gallbladder makes the liver the most common organ of direct
invasion and metastasis of gallbladder carcinoma. The
venous plexus, located in the serous layer of the gallbladder,
communicates with the portal vein and the extrahepatic bile
duct plexus. The blood dissemination of gallbladder carcinoma can enter the hepatic vein along the gallbladder vein or
the venous plexus around the gallbladder wall or into the
liver via the choledochal venous plexus. Also, the gallbladder venous plexus can ow directly through the liver bed into
the portal vein. Due to the above characteristics of cholecystic venous reux, liver invasion, or metastasis of gallbladder
carcinoma is usually characterized by localized liver metastasis and less metastasis of the whole liver (Mekeel and
Hemming 2007, b). Generally, there are two ways: rst,
direct local invasion. Because the gallbladder wall lacks the
mucosal muscle layer and the gallbladder bed of the liver has
no serous membrane, if the gallbladder cancer cell invades
the mucosal layer, it can easily break through the lamina propria of the gallbladder and invade the subserous layer, thus
directly inltrating the liver. Therefore, for T1b gallbladder
carcinoma, the resection of gallbladder lesions should
include at least the liver tissue above 2cm around the gallbladder bed; second, localized intrahepatic metastasis. In the
loose connective tissue between the gallbladder and the liver,
several venules ow directly back into the gallbladder bed or
merge into the liver after converging into one to two branches,
and further into the portal vein. These veins could supply the
S4b and S5 of the liver. Thus, gallbladder cancer can be
metastasized to the above segments of the liver by blood
ow. If gallbladder carcinoma has invaded the liver tissue
above the gallbladder bed, and then into the hepatic vein,
portal vein, or hepatic bile duct branch in the right liver, right
hemi-hepatectomy, or right trisectionectomy is necessary for
R0 radical treatment.
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021
C. Fang, W. Y. Lau (eds.), Biliary Tract Surgery, https://doi.org/10.1007/978-981-33-6769-2_15
337
338
Y. Liu et al.
15.1.2 Lymph Node andNerve Metastasis
Lymph node metastasis is common in advanced gallbladder
carcinoma because of the abundant distribution of lymphatic
vessels in the subserous layer of the gallbladder. The tumornode- metastasis (TNM) staging classication, published
jointly by the American Joint Committee on Cancer (AJCC)
and Union for International Cancer Control (UICC), is the
most widely used in the staging of gallbladder cancer (Edge
and Compton 2010; Fred etal. 2010). The lymph nodes associated with the metastasis of gallbladder carcinoma are
divided into two stations: the lymph nodes associated with
the hepatoduodenal ligament, cystic, common bile duct,
hepatic artery, and portal vein are N1; the retroportal (caudad), posterosuperior pancreaticoduodenal, posteroinferior
pancreaticoduodenal, anterior common hepatic, posterior
common hepatic, right celiac, and superior mesenteric lymph
nodes are N2. For lamina propria gallbladder cancer (TNM
stage T1a of AJCC gallbladder cancer), the 5-year survival
rate after simple cholecystectomy ranges between 85% and
100% (Yamaguchi and Tsuneyoshi 1992; Shirai etal. 1992),
and no further hepatectomy or reoperation is needed. For
tumors that have invaded the muscular layer of the gallbladder wall (TNM stage T1b of AJCC gallbladder cancer),
lymph node dissection is required because the tumors have
invaded the muscular layer, and lymph node metastasis can
coincide. The lymph node metastasis of T1b gallbladder cancer rst involves the triangular lymph nodes of the gallbladder and the lymph nodes distributed along the common bile
duct. The lymph node metastasis rate is 15.7%, and the lymphatic vessel inltration rate is 18% (Goetze and Paolucci
2012). In addition to the above-mentioned early gallbladder
cancer, 62.5%–73.0% of the patients with metastasis of gallbladder cancer have lymph nodes metastasis (Kim et al.
2010). The lymphatic reux of the gallbladder rst ows
away from the liver along with the paracentral lymph nodes
(group 12b), and then to the lymph nodes adjacent to the
abdominal aorta (group 16) by conuence with the lymph
nodes of the posterior portal vein (group 12p) and the superior posterior pancreatic head (group 13a). It has been conrmed that group 13a lymph node is the boundary point
between the rst station lymph node and the second station
lymph node of gallbladder carcinoma. Therefore, group 13a
lymph node biopsy was performed routinely during the operation, and the results are negative. The lymph nodes of the
hepatoduodenal ligament (group 12) and hepatic artery
(group 8) are dissected. Lymph node biopsy is positive in
group 13a. Lymph nodes are dissected, including hepatoduodenal ligament (group 12), hepatic artery (group 8), peripancreatic head (group 13), and celiac trunk (group 9). During
surgical treatment, skeletonization of the hepatoduodenal
ligament is necessary to remove the involved lymph nodes
thoroughly. Pancreatoduodenectomy is necessary if the
lymph nodes around the lower common bile duct or peripan-
creatoduodenal lymph nodes have been metastasized. The
lymph nodes in group 16 are the dividing points for distant
metastasis of lymph nodes in gallbladder cancer, and patients
with positive lymph nodes in this group are treated with
extended radical surgery. The median survival time is not
signicantly prolonged. Therefore, group 16 positive lymph
nodes are regarded as distant metastasis (M1 stage) and do
not signify a requirement for radical treatment. Surgical
treatment is not recommended. Nerve invasion is associated
with lymph node metastasis and direct inltration of bile
ducts. Since the retrohepatic plexus mainly innervates the
bile duct and portal vein, when the extrahepatic bile duct is
invaded, perineural invasion can be detected in 96% of cases
at the same time. The perineural invasion of gallbladder carcinoma tends to invade the lower part of the bile duct. In
order to achieve R0 radical treatment, pancreaticoduodenectomy is necessary (Chen 2011).
15.1.3 Intraductal Spread ofGallbladder
Carcinoma
Gallbladder carcinoma can directly invade the intrahepatic
bile duct through the gallbladder bed. Due to its anatomical
location, it mainly involves the right hepatic duct and its
branches. It often requires combined hepatectomy of S4b
and S5 or right hemi-hepatectomy. Gallbladder cancer can
also directly invade the extrahepatic bile duct. According to
the location of invasion, it can be divided into hilar inltration and cystic duct conuence inltration. The former
symptoms are similar to those of hilar cholangiocarcinoma,
while the latter is similar to those of middle and lower segment cholangiocarcinoma; however, the progress of the
disease is faster than that of cholangiocarcinoma.
Hepatectomy combined with extrahepatic bile duct resection should be performed; in addition, combined pancreaticoduodenectomy is necessary for patients with lower bile
duct invasion.
15.1.4 Invasion ofAdjacent Organs
Most of the cystic duct, as well as the body and fundus of the
gallbladder, are free margins, adjacent to organs and tissues,
including distal stomach, duodenal bulb, and its descending
part, transverse colon liver curvature, etc. Tumors growing
on the free edge of the gallbladder can invade directly into
the stomach, duodenum, transverse colon, omentum, and
abdominal wall after breaking through the serosa layer of the
gallbladder. The invaded stomach, duodenum, and colon
must be removed simultaneously during the operation. If the
tumor originates from the body of the gallbladder in the liver,
the tumor can directly invade the liver parenchyma in the
gallbladder fossa, which is often accompanied by the inva-
15 Digital Surgical Diagnosis andTreatment ofGallbladder Cancer
339
sion of the right branch of the portal vein. For the evident
invasion of the right portal vein, cholecystectomy combined
with right hemi-hepatectomy is required to achieve R0 radical resection. Late-stage tumors can lead to the formation of
tumor thrombus in the portal vein and its intrahepatic
branches; the prognosis is very poor.
15.1.5 Peritoneal Dissemination andDistant
Metastasis
Most of the gallbladder is freely exposed to the peritoneal cavity, except for the part of the gallbladder bed which is attached
to the liver. Therefore, when the gallbladder tumor breaks
through the serous layer, the tumor cells may fall off into the
peritoneal cavity and form the peritoneal implant metastasis.
The conventional planting and spreading sites are peritoneum,
omentum, mesentery, and pelvic oor. Advanced gallbladder
cancer can metastasize to organs such as lung, bone, brain,
supraclavicular lymph nodes through lymphatic and venous
reux. Patients with advanced gallbladder cancer who have
extensive celiac implantation or distant organ tissue metastasis
have lost the chance of radical operation and can only undergo
palliative treatment, with a very poor prognosis.
More than 80% of gallbladder patients are diagnosed as
intermediate and advanced, thus losing the chance of surgical treatment. At present, the therapeutic effect of gemcitabine, cisplatin, capecitabine, uorouracil (5-FU)-based
chemotherapy, radiotherapy, as well as new targeted therapeutic drugs such as erlotinib, bevacizumab, and programmed death receptor 1 (PD-1) antibody, on gallbladder
cancer is not noticeable, and there are no effective drugs to
improve the survival rate of advanced gallbladder cancer.
Despite unsatisfactory outcomes, radical surgery remains the
only possible cure for gallbladder cancer. Therefore,
expanded radical cholecystectomy is still a signicant choice
for surgeons. Hepatopancreatoduodenectomy (HPD) is a
challenging procedure with high perioperative mortality and
postoperative complications; however, it can improve the
prognosis of advanced gallbladder cancer.
15.2 Clinical Stages
15.2.1 TNM Staging forGallbladder Cancer
The tumor-node-metastasis (TNM) staging published by the
American Joint Committee on Cancer (AJCC) (Table15.1)
(Amin etal. 2017) is the most widely used in various staging
methods for gallbladder cancer. The staging system provides
a unied standard for the clinical-pathological diagnosis of
gallbladder cancer. It comprehensively assesses clinicopathological factors such as depth of local invasion of gallbladder
cancer, the extent of invasion of adjacent organs, involve-
Table 15.1 AJCC stage groupings and TNM denitions (8th ed.,
2017)
TNM staging Tumor (T) Node (N) Metastasis (M)
0 Tis N0 M0
I T1 N0 M0
IIA T2a N0 M0
IIB T2b N0 M0
IIIA T3 N0 M0
IIIB T1–3 N1 M0
I VA T4 N0–1 M0
IVB Any T N2 M0
Any T Any N M1
T: primary tumor; Tx: primary tumor cannot be assessed; T0: no evidence of primary tumor; Tis: carcinoma in situ; T1: tumor invades the
lamina propria or muscular layer; T1a: tumor invades the lamina propria;
T1b: tumor invades the muscle layer; T2: tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the
serosa (visceral peritoneum). Or tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver; T2a:
tumor invades the perimuscular connective tissue on the peritoneal side,
without involvement of the serosa (visceral peritoneum); T2b: tumor
invades the perimuscular connective tissue on the hepatic side, with no
extension into the liver; T3: tumor perforates the serosa and/or directly
invades the liver, and/or extrahepatic adjacent organ or tissue structure,
such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts; T4: tumor invades main portal vein or hepatic artery or
invades two or more extrahepatic organs or structures; N-regional lymph
nodes; Nx: regional lymph nodes cannot be assessed; N0: no regional
lymph node metastasis; N1: metastases to one to three regional lymph
nodes; N2: metastases to four or more regional lymph nodes; M-distant
metastasis; M0: no distant metastasis. M1: distant metastasis
ment of portal vein and hepatic artery lymph nodes, and distant metastasis. It is helpful to evaluate the resectability, the
choice of treatment, and the prognosis of gallbladder
carcinoma.
15.2.2 Surgical Strategy
Radical surgery is the only possible cure for primary gallbladder cancer (Yu etal. 2004; Lee etal. 2009). The choice
of specic surgical methods should be based on the TNM
staging of gallbladder carcinoma (Miyano etal. 2000). The
main points of standardized operation include hepatectomy
scope, lymph node dissection range, extrahepatic bile duct
management, management of gallbladder carcinoma, and
application of laparoscopic surgery.
15.2.2.1 Range ofHepatectomy
According to the approach of tumor invading the liver, the
range of hepatectomy includes wedge resection of the liver
(2cm from the gallbladder bed), hepatic S4b+S5 resection,
right hemi-hepatectomy, or right triple hepatectomy.
Tis/T1a Stage
Gallbladder carcinoma invading the lamina propria of the
gallbladder mucosa.
340
Y. Liu et al.
This stage is mostly occult gallbladder cancer and typically diagnosed after cholecystectomy. In those with Tis/T1a
stage, no rupture or bile leakage would occur if the gallbladder is completely resected. If the gallbladder is taken out in
the specimen bag, the 5-year survival rate can potentially
reach 100% (Zhu etal. 2010) with no need for liver resection
or second operation to remove the Trocar sinus (Hundal and
Shaffer 2014).
T1b Stage
Gallbladder carcinoma invading the muscle layer of
gallbladder.
Since there is no serosal layer in the gallbladder, after
breaking through the mucosal layer, tumor cells can easily
recirculate into the liver through the gallbladder vein at an
early stage, inltrating into the liver parenchyma, resulting
in micrometastasis of the liver bed. The liver metastasis distance of the T1b tumor is no more than 16mm (Isambert
etal. 2011); therefore, radical resection can be achieved by
wedge-shaped hepatectomy 2cm above the gallbladder bed.
Stage T2
Gallbladder carcinoma invading the perimuscular connective
tissue, with no extension beyond the serous layer or into the
liver.
The reported 5-year survival rate for patients with stage
T2 gallbladder carcinoma treated with simple cholecystectomy was 20–40% (Miller and Jarnagin 2008). Mayo etal.
reported a threefold increase in median survival among
patients with this stage who received radical resection compared with simple cholecystectomy (Mayo etal. 2010). Tsuji
etal. (2004) injected indocyanine green dye into the intramuscular artery of the gallbladder. It was found that the average range of staining in the middle hepatic lobe was 2–5cm
away from the gallbladder bed, and at least one direction of
the staining range was more than 4 cm in each patient.
Therefore, wedge resection alone in stage T2 cannot achieve
R0 resection, and resection of segments IVb and V should be
performed at the least.
Stage T3
Gallbladder carcinoma breaks through the serous layer of the
gallbladder and/or directly invades the liver and/or invades
an adjacent organ or tissue outside the liver. The main routes
of gallbladder invasion into the hepatic parenchyma include:
invade the liver. R0 resection can be achieved after S4b+S5
resection of the liver (Mekeel and Hemming 2007). For
patients with liver bed involvement >2cm, tumors located in
the neck of gallbladder, invasion of gallbladder triangle, or
lymph node metastasis of hepatoduodenal ligament (T3N1), it
is suggested that right hemi-hepatectomy or right triple hepatectomy is necessary when cancer cells metastasize along the
lymphatic duct or Glisson system to the entire right liver.
Stage T4
Gallbladder carcinoma invades the main portal vein or
hepatic artery, or more than two extrahepatic organs or tissues. For stage IVB (T4N2M0 and T4N0-2M1) gallbladder
cancer, surgery is not recommended because of distant
metastasis (Mekeel and Hemming 2007). For patients with
stage IVa (T4N0–1M0), selective extended radical cholecystectomy for gallbladder cancer can be performed according
to the patient’s condition (Kondo etal. 2002).
A retrospective study by Hiroaki Shimizu et al. (2007)
showed that the resection rate was 65.8% on 79 cases of stage
T4 patients with gallbladder carcinoma and the 5-year survival rate in the postoperative follow-up was 13.7% and zero
for the unoperated group, respectively. The 5-year survival
rate of the operated group was signicantly higher than that
of the unoperated group. It is suggested that for T4N0–1M0
patients with gallbladder cancer, extended radical resection
combined with selective organ resection according to the
patient’s condition, may still reach R0 resection, which can
improve the prognosis of the patients. The range of hepatectomy is right hemi-hepatectomy or right trisectionectomy.
15.2.2.2 Lymph Node Dissection Range
According to the route of lymph node metastasis, the lymphatic
reux of gallbladder rst returns in the hepatic direction along
with the para-common bile duct lymph nodes (group 12b), and
then to the para-abdominal aortic lymph nodes (group 16) after
the conuence with the lymph nodes of the posterior portal
vein (group 12p) and the posterior superior pancreatic head
(group 13a). It has been conrmed that the lymph nodes in
group 13a are the demarcation points of the rst and second
lymph nodes for lymphatic metastasis of gallbladder cancer,
while those in group 16 are the demarcation points for distant
lymph node metastasis of gallbladder cancer. The results of
groups 13A and 16 of intraoperative lymph node biopsy are of
great signicance in guiding lymph node dissection.
• Direct inltration to the liver parenchyma near the adjacent gallbladder bed.
• Invasion of S4b and S5 through the gallbladder vein.
• Transference to the liver through the lymph nodes of the
hepatoduodenal ligament via the porta hepatis along with
the lymphatic duct and Glisson system.
In stage T3NO, for gallbladder carcinoma with liver bed
involvement <2cm, there are only the rst two pathways to
Stage Tis/T1a
Only cholecystectomy is needed for gallbladder cancer
in this stage, with a 5-year survival rate of 100%.
Therefore, regional lymph node dissection is not necessary (Yu etal. 2004).
Stage T1b
It was found that lymph node metastasis of T1b gallbladder
cancer rst involved triangular lymph nodes of gallbladder
15 Digital Surgical Diagnosis andTreatment ofGallbladder Cancer
341
and lymph nodes distributed along the common bile duct.
The lymph node metastasis rate was 15.7%, and the lymphatic vessel inltration rate was 18% (Goetze and Paolucci
2012). Therefore, hepatoduodenal ligament (group 12)
lymph nodes and common hepatic artery (group 8) lymph
nodes should be dissected. Routine intraoperative lymph
node biopsy of the upper and posterior pancreatic head
(group 13a), abdominal trunk (group 9), mesenteric root
(group 14), and abdominal aorta (group 16) revealed that
lymph node metastasis of the upper and posterior pancreatic
head (group 13a) was still possible in stage T1b gallbladder
cancer (Isambert et al. 2011), suggesting that lymph node
metastasis in the second station might occur.
Therefore, in order to achieve R0 resection and improve
the prognosis, it is suggested that routine 13a lymph node
biopsy should be performed, and if the result is negative;
hepatoduodenal ligament (group 12) and hepatic artery
(group 8) lymph node dissection is recommended. If the
biopsy of group 13a lymph node is positive, enlarged lymph
node dissection should be performed [including hepatoduodenal ligament (group 12), hepatic artery (group 8), peripancreatic head (group 13), and periceliac trunk (group 9)].
Stage T2
The lymph node metastasis rate in the T2-stage gallbladder
carcinoma is as high as 46%. The 5-year survival rate is 50%
and 10%, respectively (P<0.05), showing a signicant difference; therefore, lymph node dissection is required (Goetze
and Paolucci 2012). Regarding stage T1b, the rate of lymph
node metastasis in stage T2 is signicantly higher than that
in stage T1b. Therefore, it is still recommended to decide
whether to perform extended lymph node dissection according to the results of 13a lymph nodes in this stage. The
extended lymph node dissection included lymphatic node
groups 8, 9, 12, and 13.
Stage T3
The study found that the lymph node metastasis rate of stage
T3 gallbladder cancer was 54% around the common bile
duct and 38% around the gallbladder duct (Goetze and
Paolucci 2012). The 5-year survival rate of the patients with
negative lymph node examination was as high as 80%, while
that of the patients with positive lymph node examination
was only 34% (Shirai et al. 2012). Therefore, expanded
lymph node dissection was recommended. In patients with
positive group 16 lymph nodes, although extended radical
surgery was performed, the survival period was not signicantly prolonged (Nishio etal. 2007). Therefore, in order to
obtain R0 resection, routine intraoperative lymph node
biopsy is recommended: enlarged lymph node dissection
was performed on those with negative group 16 lymph
nodes; positive group 16 lymph nodes were considered as
distant metastasis, which lacks a signicant benet from
radical surgery. So, radical surgery was not recommended.
Stage T4
Intraoperative lymph node biopsy of group 16 for patients
with stage T4 cholecystectomy was performed. If the result
was positive and considered as distant metastasis (M1), it
cannot be treated by surgery (Yu etal. 2004; Shimizu etal.
2007); if the result was negative and had no distant metasta-
sis, extended radical cholecystectomy is still expected to
achieve R0 resection and improve the prognosis, so enlarged
lymph node dissection can be performed according to the
patient’s condition (Shimizu etal. 2007).
15.2.2.3 Extrahepatic Bile Duct Management
The management should be based on intraoperative biopsy
results of the incised margin of the cholecystic duct; if it is
positive, extrahepatic cholecystectomy, ranging from the
upper back of the pancreatic head to the rst hilum of the
liver, and bile duct jejunum Roux-en-Y anastomosis should
be performed.
Stage Tis/T1a
Cholecystectomy alone can achieve R0 resection without
extrahepatic bile duct resection (Yu etal. 2004).
Stage T1b
Routine extrahepatic cholangiotomy for patients with gallbladder cancer in this stage produces no signicant improvement in the prognosis of patients but increases the incidence of
postoperative complications. Therefore, it is not recommended
that routine extrahepatic cholangiotomy be performed.
Extrahepatic cholangiotomy is decided according to the results
of the cystic duct margin. There is no need to resect extrahepatic bile duct in the case of negative biopsy of the cystic duct
incision margin but combined extrahepatic bile duct resection
is necessary for positive biopsy.
Stage T2
The study shows (Goetze and Paolucci 2012) that the 5-year
survival rate of patients with gallbladder cancer after extrahepatic cholangiectomy is 100%, while the survival rate of
the patients without the extrahepatic cholangiectomy was
only 60%, showing a signicant difference. Therefore, it is
recommended to remove the extrahepatic bile duct. A multicenter retrospective study found that there was no signicant
difference in the 5-year survival rate between patients who
underwent extrahepatic bile duct resection and those who did
not (72% vs. 81%, P=0.1450). Routine prophylactic resection of extrahepatic bile duct did not improve the prognosis
of patients, but it increased the risk of bile leakage, bile duct
stenosis, and reux cholangitis (Shimizu et al. 2004).
Therefore, based on the results of large sample studies, routine extrahepatic bile duct resection is not recommended,
and the decision to perform an extrahepatic cholecystectomy
should be made according to the biopsy results of the cholecystectomy margin.
342
Y. Liu et al.
Stage T3
Studies have shown that there is no signicant difference in
the 5-year survival rate between extrahepatic bile duct resection and non-extrahepatic bile duct resection when the cystic
duct is not invaded at this stage (62% vs. 46%, P=0.4107);
however, routine extrahepatic bile duct resection does
increase the risk of surgical trauma and postoperative complications (Shirai et al. 2012). NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines) suggest that the
presence of lymph node metastasis and R0 resection are
independent factors affecting the prognosis of patients in this
stage. The 5-year survival rates for patients with stage T3
gallbladder who received resection of the extrahepatic bile
duct, and for those who did not were 33% and 49%, respectively, with no statistical difference from those with no resection (Network NCC 2014). Therefore, based on the results of
extensive sample studies, routine extrahepatic bile duct
resection is not recommended for patients with gallbladder
cancer at this stage, and intraoperative biopsy of cystic duct
incision margin is recommended.
Stage T4
For gallbladder carcinoma without distant metastasis
(T4N0–1M0), extended radical cholecystectomy is expected
to achieve R0 resection and improve prognosis. Combined
extrahepatic bile duct resection can be performed according
to the patient’s condition (Shimizu etal. 2007).
Based on the above ndings, a radical surgical procedure
for gallbladder cancer based on TNM staging was summarized (Table15.2).
15.3 Evaluation ofGallbladder Cancer
by 3D Visualization
The formulation of surgical strategies for gallbladder cancer
depends on accurate preoperative imaging and disease
assessment. The assessment of gallbladder cancer includes T
stage assessment, lymph node metastasis assessment, and
resectability assessment, to select appropriate treatment
methods. The application value of digital 3D reconstruction
technology based on CT and MRI images in preoperative
evaluation of gallbladder cancer mainly includes three
aspects: (1) individualized evaluation of the 3D anatomical
structure of hepatic vessels and its variation characteristics;
(2) systematic evaluation of lesion inltration and its stereogeometric relationship with vascular structure; (3) enabling
the surgeon to perform more accurate surgical planning and
judge the resectability of the tumor.
15.3.1 T Staging Assessment
The depth of local invasion of gallbladder cancer is the basis
for determining the surgical approach. Preoperative clinical
Table 15.2 Radical surgery for gallbladder cancer based on TNM
staging (Jhamb etal. 2015)
TNM staging for
gallbladder cancer Radical surgical approach
Tis or T1a Simple cholecystectomy
T1b
Biopsies of lymph nodes
in group 13A were
negative
Biopsies of lymph nodes
in group 13A were
positive
T2
Biopsies of lymph nodes
in group 13A were
negative
Biopsies of lymph nodes
in group 13A were
positive
T3
Biopsies of lymph nodes
in group 16 were positive
Hepatic invasion <2cm,
and biopsies of lymph
nodes in group 13A were
negative
Hepatic invasion >2cm,
and biopsies of lymph
nodes in group 16 were
negative
Invading the adjacent
organs of the liver
T4
Biopsies of lymph nodes
in group 16 were positive
Biopsies of lymph nodes
in group 16 were
negative
Radical cholecystectomy: complete
resection of gallbladder and liver wedge (at
least 2cm from the gallbladder
bed)+lymph node dissection of hepatic
duodenal ligament (group 8, group 12)
Excision of the gallbladder and en bloc
wedge resection (at least 2cm from the
gallbladder bed)+enlarged lymph node
dissection (groups 8, 9, 12, and 13)
Excision of the gallbladder and hepatic
segments 4 and 5 en bloc + dissection of
the hepatoduodenal ligament–lymph nodes
Excision of the gallbladder and hepatic
segments 4 and 5 en bloc + enlarged lymph
node dissection
Palliative care rather than surgical
treatment is recommended
Excision of the gallbladder and hepatic
segments 4 and 5 en bloc + enlarged lymph
node dissection
Excision of the gallbladder and right
hemi-hepatectomy or tri-sectionectomy en
bloc + enlarged lymph node dissection
Excision of the gallbladder and right
hemi-hepatectomy or tri-sectionectomy en
bloc + enlarged lymph node dissection +
combined resection of the involved organs
Palliative care, rather than surgical
treatment is recommended
Extended radical cholecystectomy
combined with resection and reconstruction
of the involved vessels and/or excision of
the extrahepatic organs
T staging of three-dimensional visualization relies mainly on
Multidetector Computerised Tomography (MDCT) and
MRI. Most stages T1 and T2 are occult gallbladder carcinoma. Because preoperative imaging staging is difcult,
conrmation mainly depends on intraoperative rapid frozen
sections and postoperative pathological examination. The
clinical staging of T3 and T4 can be conrmed by preoperative imaging.
15.3.1.1 Stage T2
MDCT
It showed diffuse thickening and uneven enhancement of
gallbladder wall, obvious thickening, and enhancement of
inner layer, weak enhancement of outer layer (double layer
mode), a clear boundary from organs surrounding the gallbladder, suggesting that the tumor did not break through
the serous layer (Kim etal. 2008; Yoshimitsu etal. 2002).
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MRI
The boundary between tumor and the serosal layer is clear;
the line between the tumor bulge and the serous low signal is
evident in T2 reversed-phase; a thickened gallbladder wall is
strengthened in the portal phase; subserosal delayed enhancement suggests invasion of the subserosal layer in the delayed
phase (Kim etal. 2014; Yoshimitsu etal. 2012).
15.3.1.2 Stage T3
MDCT
The serosal layer of the gallbladder shows nodules of tumors,
suggesting that the tumor has broken through the serosal layer;
the fat layer between the tumor and the adjacent organ disappears, resulting in the invasion of the liver (liver involvement
≤2cm) or an adjacent organ (such as the stomach, the duode-
num, the colon, the pancreas, the large omentum, and the extrahepatic bile duct) (Kim etal. 2008; Yoshimitsu etal. 2002).
MRI
Tumor nodules or irregular serosal layers can be seen in the
serosa layer. T1 reversed phase: the destruction of the low
signal layer (the fat layer between the gallbladder and adjacent organs) in the outer gallbladder indicates an invasion of
the liver or an adjacent organ (Kim etal. 2014; Yoshimitsu
etal. 2012).
15.3.1.3 Stage T4
MDCT and MRI suggest that the tumor invades ≥2 adjacent
organs of gallbladder or liver (>2cm); the tumor also invades
portal vein or hepatic artery trunk (Kim etal. 2008, 2014;
Yoshimitsu etal. 2002, 2012) (Figs.15.1 and 15.2).
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Fig. 15.1 Abdominal CT image (T staging). (a) Arterial phase; (b) Portal venous phase; (c) equilibrium phase
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Fig. 15.2 Reconstructed 3D images of the gallbladder (T staging). (a) Arterial phase; (b) Portal venous phase; (c) Image fusion
15.3.2 Assessment ofLymph Node Metastasis
The assessment of lymph node metastasis in gallbladder cancer is an important basis for the development of surgical
plans and decision-making. The lymphatic reux of gallbladder rst returns to the para-choledochal lymph nodes
15.3.3 Resectability Assessment
15.3.3.1 General Assessment
Surgical tolerance should be assessed preoperatively based
on the patient’s age, weight, vital organ function, and
complications.
(group 12b) away from the liver and then ows to the paraabdominal aortic lymph nodes (group 16) after the conuence with the posterior portal vein (group 12p) and the
posterior superior pancreatic head (group 13a). It has been
conrmed that the lymph nodes in group 13A are the demarcation points of the rst and second lymph nodes for lymphatic metastasis of gallbladder cancer, while those in group
16 are the demarcation points for distant lymph node metastasis of gallbladder cancer. Therefore, preoperative imaging
examinations should focus on the evaluation of lymph nodes
in Groups 13a and 16.
Ultrasonography can well show lymph nodes in the hilar
region, peripancreatic head, and retroperitoneum, but it is not
ideal for lymph nodes in the root of the mesentery. CT and
MRI can clearly show lymph nodes in all regions. At present,
judging lymph node metastasis from imaging is usually
based on the following conditions: the shortest diameter of
lymph nodes (>5 mm), enhancement, fusion lobulation or
burr, and internal necrosis of lymph nodes (Isambert etal.
2011) (Figs.15.3 and 15.4).
15.3.3.2 Liver Function Assessment
If combined hepatectomy is to be performed, the liver function should have a full assessment preoperatively. (1) ICG
R15<15%; (2) Child-Pugh score: Class A patients should be
selected, Child class B patients should perform hepatectomy
with caution, and Child class C patients are not suitable for
any surgical liver resection; (3) Measurement of functional
liver volume: the functional volume of the reserved liver
must be no less than the essential functional liver volume.
Future liver remnant (FLR) of patients with jaundice should
be larger than 40%, and that of patients without jaundice
should be larger than 30%, which is the prerequisite for safe
hepatectomy. The conditions for radical resection of gallbladder cancer include: (A) The lesions and regional metastatic lymph nodes of the gallbladder and adjacent organs
can be removed; (B) The residual liver function can be compensated, and the integrity of vascular structure can be preserved or reconstructed; and (C) The patients can tolerate the
surgical trauma.
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Fig. 15.3 Abdominal CT image (T staging). (a) Arterial phase; (b) portal venous phase; (c) equilibrium phase
15.3.3.3 Virtual Surgery Assessment
Preoperative understanding of the location and spatial adjacency of tumors is of great signicance for surgical resection. 3D visualization technology based on 3D models can
more intuitively display the variation of the vascular structure of the hepatobiliary system and show the adjacent
relationship between tumors and blood vessels. On this basis,
surgeons can perform virtual hepatectomy, calculate the
residual liver volume, and improve the safety and success
rate of surgical resection.
3D Visualization ofTumor andHepatic Artery System
Clarifying the classication and variation of the hepatic
artery is of great signicance for preventing hepatic artery
injury and guiding hepatic artery resection and reconstruction (Figs.15.5 and 15.6).
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Fig. 15.4 Reconstructed 3D images of the lymph node (N staging). (a) Arterial phase; (b) portal venous phase; (c) image fusion
Fig. 15.5 (a-b) CT imaging of hepatic artery system (arterial phase)