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Abstract
Background: Although radical cholecystectomy is the standard of care for gallbladder cancers that invade
perimuscular connective tissue or perforate visceral peritoneum, the role of extended right hepatectomy in
achieving negative resection margins is not clear.
Methods: Clinicopathologic, perioperative, and long-term outcome data were reviewed from patients who
underwent hepatic resection for gallbladder cancer.
Results: From 1995 to 2005, 22 consecutive patients underwent hepatic resection for gallbladder cancer,
and 11 underwent extended hepatectomy. Negative resection margins were achieved in all patients. There
were no significant differences in postoperative morbidity, mortality, and long-term survival after extended
and minor hepatectomy. T3 tumors negatively predicted overall and recurrence-free survival.
Comments: Extended hepatectomy achieves negative resection margins for patients with gallbladder
cancer and is associated with acceptable morbidity and long-term survival. 2007 Excerpta Medica Inc.
All rights reserved.
Keywords: Extended liver resection; Gallbladder cancer; Radical cholecystectomy
base of the cystic plate and thus may not be sufficient for
tumors that lie near the gallbladder neck, in Hartmanns
pouch, or that extend into the triangle of Calot [1]. The role
of extended hepatectomy, where the plane of transection is
well to the left of the cystic plate, in decreasing local or
regional recurrence and prolonging long-term outcome is
not well defined. The objective of this study was to report
our experience with hepatic resection for gallbladder cancer,
with a focus on the safety and long-term outcomes of
extended hepatectomy, for patients suspected to have disease near the cystic plate.
Methods
After obtaining approval from the Institutional Review
Board at Duke University Medical Center, patients who
underwent hepatic resection for gallbladder cancer from
August 1995 to December 2005 were identified from a
prospective hepatectomy database. After 2001, patients who
were discovered to have gallbladder cancer due to an incidental finding on pathologic specimen examination after
simple cholecystectomy or on preoperative diagnostic imaging were evaluated for extended right hepatectomy as the
procedure of choice for definitive surgical resection. We
typically performed an extended hepatectomy in the following circumstances: (1) when the cystic duct margin of the
0002-9610/07/$ see front matter 2007 Excerpta Medica Inc. All rights reserved.
doi:10.1016/j.amjsurg.2007.02.013
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S.K. Reddy et al. / The American Journal of Surgery 194 (2007) 355361
previous cholecystectomy specimen was positive or unknown, (2) after open cholecystectomy or when the initial
operative indication was acute cholecystitis because we
anticipated that the triangle of Calot would be obliterated by
scar tissue, (3) when node-positive disease was evident
before hepatic resection (either in the initial cholecystectomy specimen or detected on preoperative imaging), (4) for
patients presenting with preoperative jaundice because of
biliary obstruction, and/or (5) for large-mass lesions detected on preoperative imaging (usually computed axial
tomography [CAT]). Patients without any of these criteria
were offered minor hepatic resection (segment 4B/5 hepatectomy). Patients 75 years old and those with extensive
medical comorbidity were not offered extended hepatectomy. Portal vein embolization (PVE) was used when the
estimated volume of the future liver remnant was 25% of
the native liver volume or in cases of severe steatosis (as
detected by CAT scan).
A retrospective review of patient demographics, tumor
characteristics, surgical treatment, length of hospital stay, postoperative course, use of adjuvant chemotherapy or radiotherapy, and long-term outcomes was completed. Operative mortality included any death attributed to liver resection (as
determined by the operative surgeon) and all death within 30
days of partial hepatectomy. Deaths were ascertained by clinic
or hospital records, the Social Security Death Index, and the
Institutional Review Board Tumor Registry. Overall survival
reflected deaths from any cause. The last date of any clinical
correspondence was used to determine length of recurrencefree survival after hepatectomy.
Statistical analyses were performed using the Stats Di-
Table 1
Tumor characteristics, treatments, and outcomes
Stage
Liver resection
BDE
Previous chol
Pathology
Grade
Adjuvant therapy
Status (mo)
T3N1
T3N1
T3N1
T3N1
T3N0
T3N0
T3N0
T3N0
T3N0
T3N0
T3N0
T3N0
T2N1
T2N1
T2N0
T2N0
T2N0
T2N0
T2N0
T2N0
T2N0
T1N0
N
Y
Y
Y
N
N
Y
N
Y
Y
N
Y
Y
Y
Y
N
N
N
Y
Y
N
N
N
Y
Y
Y
N
Y
Y
N
Y
N
Y
Y
Y
Y
Y
Y
Y
N
Y
Y
Y
N
Adenoca
Adenoca
Adenoca
Adenoca
Adenoca
Adenoca
Adenoca
Squamous
Adenoca
Adenoca
Adenoca
Adenoca
Adenoca
Adenoca
Adenoca
Adenoca
Adenoca
Papillary
Adenoca
Papillary
Adenoca
Papillary
Poor
Well
Poor
NA
Poor
Poor
Poor
Poor
Well
Moderate
Moderate
Poor
Moderate
Well
Moderate
Well
Well
Moderate
Well
Moderate
Well
Well
Y
Y
Y
N
N
Y
Y
Y
Y
N
N
N
Y
Y
Y
Y
Y
N
N
N
Y
N
DOD (11)
NED (27)
DOD (4)
NED (24)
DOD (5)
DOD (10)
DOD (52)
NED (48)
DOD (62)
DOD (24)
POD (1)
NED (30)
NED (52)
NED (67)
DOD (62)
DOC (45)
NED (107)
NED (37)
NED (26)
AWD (14)
NED (18)
NED (12)
Note: Numeric data in status column refers to number of months from partial hepatectomy to date of death, disease recurrence, or last date of follow-up
for patients who had NED. Adjuvant therapy refers to either chemotherapy or external beam radiation therapy.
Adenoca adenocarcinoma; AWD alive with disease; BDE bile duct excision; chol cholecystectomy; DOC dead of other causes; DOD dead
of disease; NED no evidence of disease; POD postoperative death.
S.K. Reddy et al. / The American Journal of Surgery 194 (2007) 355361
Severe
Reoperation Mortality
complication
1
0
5
0
0
0
0
357
Fig. 1. Overall and recurrence-free survival after hepatic resection for all
22 patients with gallbladder cancer.
(59%) of patients received adjuvant chemotherapy or radiotherapy. Administration of adjuvant therapy did not
affect overall or recurrence-free survival. Table 3 lists
stages and treatments for 5-year survivors after partial
hepatectomy. All but 1 of these patients were treated with
adjuvant therapy.
Comments
Extended hepatectomy may provide long-term oncologic
survival in selected patients with gallbladder cancer by
ensuring a negative margin of resection, which many investigators have shown is a key positive predictor of long-term
survival [1,4,8 10]. Because radical cholecystectomy is often associated with a minimal margin at the base of the
cystic plate (because of the relatively thin liver parenchyma
interposed between the gallbladder and the main right or
sectoral bile ducts), extended hepatic resection may be necessary to achieve negative margins, particularly for large
cancers located in the infidibulum or in Hartmanns pouch
or that extend into the triangle of Calot. This point is
especially important for patients who (1) present for definitive surgical resection after previous simple cholecystectomy for acute cholecystitis, (2) who underwent previous
open cholecystectomy, (3) who have a positive cystic duct
margin after simple cholecystectomy, (4) who have known
node-positive disease, and/or (5) who present with preoperative jaundice caused by biliary obstruction. In these patients, the triangle of Calot is often obliterated by tumor or
scar, thus making it difficult to distinguish cancer from
benign inflammatory tissue. Extended hepatic resection may
be especially useful in these patients as a sure method to
achieve an oncologically negative resection margin by staying outside the plane of previous surgery. Other groups have
also recognized the potential of extended resection in patients with gallbladder cancer. Kondo et al [11] stated that
extended right hepatectomy was necessary for curative resection in cases of hepatic hilum gallbladder carcinomas.
Furthermore, Shiari et al [12] demonstrated that the extent
of hepatic microscopic angiolymphatic portal tract invasion
correlates with gross tumor depth. Therefore, a greater resection may be needed for thicker tumors to achieve microscopically negative margins. However, despite recent decreases in the incidence of complications after liver
resection, several large studies have noted extended hepatectomy to be a predictor of postoperative morbidity and
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S.K. Reddy et al. / The American Journal of Surgery 194 (2007) 355361
Fig. 2. Overall and recurrence-free survival by extent of resection for patients who underwent previous laparoscopic cholecystectomy.
mortality [13-15]. Given this setting, we evaluated our series of hepatic resection for gallbladder cancer where extended hepatectomy was performed in patients suspected to
have disease near the cystic plate.
The lack of differences in postoperative mortality and
median length of hospital stay between major and minor
hepatectomy suggests that extensive hepatic resection can
be done safely in patients with gallbladder cancer (Table 2).
None of the patients who underwent major hepatectomy
experienced postoperative mortality or required reoperation.
Although this absence of postoperative mortality rate is
likely due to small patient numbers, several other studies
have reported low (10% to 30%) mortality rates (Table 4).
Extended hepatectomy was associated with a higher frequency of severe postoperative complications than with
minor resections in our study (45% vs 27%); however, small
patient numbers precluded an adequate analysis of significance. Our morbidity rate is consistent with that found in
other studies (Table 4). Common bile duct excision was
associated with postoperative morbidity (67% vs 10%), a
finding confirmed by others [3].
In this small series, extended hepatectomy achieved a
negative resection margin in those patients with high likelihood of disease and/or inflammation near the cystic plate.
Long-term survival after major hepatectomy in these selected patients was similar to those patients not likely to
have cancer or inflammation near the cystic plate and who
consequently underwent minor hepatectomy (Fig. 2). Extended hepatectomy is also associated with good long-term
outcomes in patients with advanced primary (T3) and nodal
disease. Five of eleven (45%) patients who underwent major
resection were NED at last follow-up, and two of seven
5-year survivors underwent extended right hepatectomy
S.K. Reddy et al. / The American Journal of Surgery 194 (2007) 355361
359
Table 3
Tumor characteristics and treatment of 5-year survivors after partial hepatectomy*
Stage
Liver resection
BDE
Adjuvant therapy
Status
T2N0
T2N0
T3N0
T2N0
T3N0
T2N1
T2N1
4B/5 wedge
4B/5 bisegmentectomy
Extended right hepatectomy
4B/5 wedge
4B/5 bisegmentectomy
4B/5 wedge
Extended right hepatectomy
N
N
N
Y
Y
Y
Y
122
76
71
62
62
68
67
Y
N
Y
Y
Y
Y
Y
NED
NED
NED
DOD
DOD
NED
NED
Table 4
Review of series with 10 extended hepatic resections for gallbladder cancer
Study
Year
Mortality
(%)
Morbidity
(%)
Survival
Ogura et al [16]
1991 302
Matsumoto et al [18]
1992
Bloechle et al [8]
18
48
10
10
20
1995
10
10
30
Bartlett et al [3]
Tsukada et al [4]
Fong et al [5]
1996
1996
2000
12
18
42
0
0
10
42
34
Endo et al [17]
2001
10
Kondo et al [2]
2002
40
30
Kondo et al [11]
2002
56
19
Kondo et al [6]
2003
51
20
Nagino et al [19]
2006
61
18
This study
2006
11
3-y survivors: 2
67
45
3-y survivors: 7
5-y survivors: 4
14% 3- and 5-y survivors
18% 3- and 5-y survivors
3-y survivors: 10
5-y survivors: 5
3-y survivors: 3
Comments
Note. Data specified are for lobectomy or extended hepatectomy only. Mortality and morbidity refer to postoperative events, and survival refers to
long-term outcome.
BDE bile duct excision; ERH extended right hepatectomy; PVE portal vein embolization.
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S.K. Reddy et al. / The American Journal of Surgery 194 (2007) 355361
S.K. Reddy et al. / The American Journal of Surgery 194 (2007) 355361
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