British Journal of Surgery 1996, 83, 893-901

Review

Repeated liver resection for recurrent liver cancer

N . N E E L E M A N and R . A N D E R S S O N
Department of Surgery, Lund University Hospital, S-22185 Lund, Sweden
Correspondence to: Dr R. Andersson
~~

~~

Patients with cancer recurrence limited to the liver alone

after a first liver resection may be candidates for a repeat
resection. Some 191 second and ten third liver resections
for recurrent colorectal metastases, and 128 second and
ten third liver resections for recurrent hepatocellular
carcinoma (HCC), were evaluated after reviewing the
literature. The 5-year survival rate after second liver
resection for colorectal metastases was 26 per cent with a
median survival time of 30 months. Mortality and
morbidity rates were 1-2 and 27-4 per cent respectively.
The 5-year survival rate after second resection for HCC

was 40 per cent with a median survival time of 40 months.

The operative mortality rate was 2.3 per cent; morbidity
occurred in 13 per cent of patients with HCC. Survival
after primary colorectal resection was significantly better
for patients with metachronous metastases than for those
with synchronous disease; survival correlated with a long
interval between the first and second liver resection (in
both colorectal liver cancer and HCC). Repeated liver
resection may be performed in selected patients and yield
a similar survival to that obtained after first liver
resection.

Surgical resection has been regarded as the only

treatment that may offer potential cure of both metastatic
and primary liver cancer. However, liver resection with
radical intent is restricted to a minority of patients and,
overall, the prognosis is still poor. Only about 5 per cent
of patients presenting with colorectal liver metastases
have been considered candidates for curative surgery-?.
The resectability rate for hepatocellular carcinoma (HCC)
is not more than 20 per ~ e n t ~These
. ~ . figures reflect a
potential delay in diagnosis, and stress the importance of
a search for new diagnostic techniques, surveillance after
colorectal resection and screening for endemic HCC.
Progress in these aspects might increase the proportion of
patients for whom a curative liver resection is possible.
Advances in diagnostic measures, such as ultrasonography
and computed tomography, together with improvements
in operative techniques and perioperative care, have
encouraged a more aggressive approach, with an
increased rate of liver resection during the past two
decades2."'.
Liver resection for colorectal metastases results in a
5-year survival rate of about 25-35 per cent'-3. The 5-year
survival rate after resection for HCC may reach 30-50 per
Unfortunately, the majority of patients in both
groups will sooner or later have recurrence of disease,
usually leaving only non-curative therapy. Nevertheless, a
small number of patients with recurrence appear to have
localized potentially resectable disease confined to the
liver alone.
During the past 10 years several reports have appeared,
usually with a limited number of cases, describing patients
with liver cancer subjected to a second or even a third
liver resection. After a review of the literature, the
collected series and case reports were studied to evaluate
repeated liver resection for both colorectal liver
metastases and HCC. The focus was on long-term results,
but operative mortality and morbidity rates were also
assessed. Furthermore, features of possible prognostic
importance after resection of the primary colorectal
cancer, and after the first and second hepatectomies, were

sought. Although the patients in the present analysis were

treated in different institutions over a long period of time
and patient data in some instances were incomplete, we
feel that this review of the literature provides valuable
information on repeated liver resection.

Paper accepted 8 February 1996

0 1996 Blackwell Science Ltd

Methods and analysis

Colorectal carcinoma
Patients identified by Medline literature search who were
subjected to a repeat liver resection for colorectal liver
metastases, and for whom subsequent follow-up data were
available, were included in the protocol. Only curative or at least
intended curative resections were entered in the study; palliative
and incomplete resections were excluded. A positive resectional
margin was defined as tumour growth present within a certain
distance from the cut surface, usually 1 cm. The policy
concerning patients considered free from disease, but with
positive margins, was to include them. This is justified by their
limited number and the problem of individual identifi~ationl'-'~.
In 12 additional patients, surgery for extrahepatic disease was
performed simultaneously with, or after, the second liver
resection for colorectal m e t a s t a ~ e s ~ ~ J - "These
.
operations
included resections of lung metastases ( n = 8) and diaphragmatic
tumour extensions ( n = 3), one ileal resection, one adrenalectomy for recurrent tumour, one biopsy of a pelvic wall
recurrence followed by external radiation therapy, and one
negative exploratory laparotomy. Because of the removal of all
detectable disease at the time of the second liver resection, these
patients were included in the study. In 32 patients only the mean
survival after the second liver resection for colorectal liver cancer
was defined2*.*'.Two patients with colorectal liver disease, who
died within 1 month of pera at ion^'-'^, were also entered in the
study.
Eventually a total of 194 patients with colorectal liver cancer
were included from 24 reports"--'4, each contributing a median of
six (range one to 28) patients. Follow-up after the second liver
resection was recorded for 191 of the 194 patients and data
concerning a third liver resection were available for ten patients.
Fig. I shows age and sex distribution in 108 patients with
colorectal liver disease for whom data were available. Mean age
at primary colorectal resection in the 64 men and 44 women was
57 years; the median age was 58 (range 27-75) years. There was
no significant age difference between the sexes.

893

894 N. N E E L E M A N and R . A N D E R S S O N
28
24

v1

E
.a

20

G
'

16

12

n
<30

30-40

40-50

50-60

60-70

>70

Age at primary resection (years)

Fig. 1 Age and sex distribution in 108 patients who underwent
second liver resection for recurrent colorectal metastases. Age at
primary resection is shown. 0,
Men; El, women

35
m

confined to the liver alone (Table 1). In 15-33 per cent of

these patients a second liver resection was performed.
Radical reresections for recurrent disease represented
3-11 per cent of all radical liver resections performed
(Table 2). The extent of the first and second resection
was known in 131 patients, derived from 15
report~'1-15,17,19,20,24,26,28,30,31,33,34
(Table 3 ) . At the first
resection, these patients underwent 37 (25 per cent)
lobectomies, 35 (24 per cent) segmentectomies, and 76
(51 per cent) subsegmentectomies or less. At the second
resection, they underwent 42 (30 per cent) lobectomies,
39 (27 per cent) segmentectomies and 61 (43 per cent)
subsegmentectomies or less.
Nine reports defined data about morbidity after the
second resection for colorectal metastases11-15~18-2~z8.
Twenty-nine (27.4 per cent) of 106 patients had 31
postoperative complications altogether (Table 4 ) . The
most frequent complications originated from either the
biliary system (n = 7; e.g. biliary fistula n = 3, bile leakage
Table 1 Disease confined to the liver alone as a percentage of
recurrent disease and resectability rates of isolated liver disease

3oF
25

<30

30-40

40-50

50-60

60-70

>70

Age at primary resection (years)

Fig. 2 Age and sex distribution in 95 patients who underwent
second liver resection for recurrent hepatocellular carcinoma.
Men; El, women
Age at first resection is shown. 0,

Hepatocellular carcinoma
The same selection procedure was used for patients operated for
recurrent HCC. However, three palliative resections were not
excluded as the identity of the patients concerned was
uncertainj5. Eleven patients with a huge HCC, who underwent a
planned reresection or so-called two-stage
were
excluded. Three patients were recorded as operative or
postoperative death^",^^.^^.
This resulted in 128 patients with HCC, derived from 15
r e p o r t ~ l ~ Jeach
- ~ ~ ,report contributing a median of eight (range
one to 21) patients. Of the 128 patients who underwent a second
resection, ten were subjected to a third resection and also
followed up. Mean age at first liver resection for HCC in 79 men
and 16 women was 52 years; the median age was 54 (range
18-77) years (Fig. 2). Women tended to be older than men,
mean age 57 and 51 years respectively, although this difference
was not significant.
Data were collected from both groups of patients concerning
isolated liver recurrence after the first liver resection, resectability rates, the relative proportion of repeated liver resections
of the total number of curative resections, and the extent of
resection. Survival following repeated liver resection was
calculated by the Kaplan-Meier method47. The log rank test4x
was used to assess the effect of various features on survival. A P
value of less than 0.05 was considered statistically significant.

Results
Colorectal carcinoma
Some 33-48 per cent of patients with recurrence after a
first liver resection for colorectal metastases had disease

Recurrence in
liver only
(%)

Resectability
rate
(%)
33
29
21
26
15
26

Reference

Year

Colorectal metastases
Lind et ~ 1 . ~ '
Nordlinger et al. 24
Hohenberger et aL2'
Stone et al. I'
Butler et
Bozzetti et al. li

1992
1987
1990
1990
1986
1992

42
41
48

HCC
Kanematsu et aL3*
Suenaga et al. 45
Capussotti et
Ikeda et ~ 1 . ~

1988
1994
1994
~ 1993

82
89
72
91

33

12
24
23
22

HCC, hepatocellular carcinoma

Table 2 Curative repeated liver resection as a percentage of the
total number of curative procedures
Reference

Year

(%I

Colorectal metastases
Lind et aL3'
Nordlinger et aLZ4
Butler et al.32
Bozzetti et aLI5
Tomas-de la Vega et al. 22
Lange et al. 33
Griffith et al. l 7
Fowler et al. l 4

1992
1989
1986
1992
1984
1989
1990
1993

9
7
3
7
10
11
8
10
8.1

1993
1988
1986
1994
1993
1989
1993

12
4
9
13
10
14
14

Overall
HCC
Matsuda et
Kanematsu et ~ 1 . ~ ~
Nagasue et ~ 1 . ~ ~
Suenaga et al.45
Ikeda et al.42
Lange et al. 33
Zhou et aL4'
Overall

11.8

HCC, hepatocellular carcinoma

0 1996 Blackwell Science Ltd, British Journal of Surgery 1996, 83, 893-901

R E P E A T E D LIVER R E S E C T I O N F O R R E C U R R E N T LIVER CANCER

Table 3 First and second liver resections in 131 patients with
colorectal metastases and 121 patients with hepatocellular
carcinoma according to the extent of resection

Colorectal
metastases
Extent of resection

HCC

First
Second First
Second
resection resection resection resection

Lobar resection
37 (25)
Left lobectomy
12
Extended left lobectomy 2
Right lobectomy
20
Ext. right lobectomy
3
Segmental resection
35 (24)
4
Trisegmentectomy
Bisegmentectomy
25 *
Unisegmentectomy
4t
2.
Unknown
76 (51)
Subsegmental resection
Total
148

42 (30)
11
0
28

41 (33)
15

0
21
5
31 (25)

39 (27)
11
11.t
130
4
61 (43)
142

3
i3n
9
6
52 (42)
124

0
4

n
30 (24)
0
14**
11
5
87 (71)
123

Values in parentheses are percentages. *Including 15 left lateral

segmentectomies (11, 111); tincluding two left lateral
segmentectomies (11, 111); $including two resections of the
quadrate lobe (IV); including one resection of the quadrate
lobe (IV) and two resections of the caudate lobe (I); Yincluding
eight left lateral segmentectomies (11, 111); **including 11 left
lateral segmentectomies (11,111). HCC, hepatocellular carcinoma
Table 4 Postoperative complications and morbidity in 35 of 152

patients who underwent second resection for either recurrent

colorectal fiver metastases or hepatocellular carcinoma
No. of complications
after second resection
Colorectal
metastases
Biliary system
Biliary fistula
Bile leak
Biliary tract stenosis
Intra-abdominal abscess
Subphrenic abscess
Subhepatic abscess
Not specified
Respiratory complication
Pleural effusion
Not specified
Wound infection
Haemorrhage
Ascites
Liver failure
Thrombophlebitis
Congestive heart failure
Bacteraemia
Bacterial peritonitis
Unknown
Total
Morbidity rate

7
3
3
1
6
4
1
1
7
4
3
3
2
1
2
1
1
1

HCC
1
1

1
1

1
3

31

29 of 106 (27.4)

6 of 46 (13)

Values in parentheses are percentages. HCC, hepatocellular

carcinoma
n = 3 ) or the respiratory system ( n = 7 ; e.g. pleural
effusion n = 4). Another major complication was intraabdominal abscess formation (n = 7; e.g. subphrenic
abscess n = 4). Reoperation was required in four patients:

895

Table 5 Extent of use and type of adjuvant therapy after second

liver resection for colorectal metastases
Reference

No. of
Year patients Type of adjuvant therapy

Griffith et aZ.
Bozzetti et aZ.

1990
1992

16 (67)
3 (44)

Vaillant et aL* 1993

1993
Fowler et uZ.~
~ ~
Fong el ~ 1 . 1994

6 (43)
2 (38)
1 (40)
1

Overall

Systemic chemotherapy
Hepatic artery and systemic
chemotherapy
Intraperitoneal chemotherapy
Radiation therapy
Immunotherapy
Cryotherapy

29 (45)

Values in parentheses are percentage of patients receiving

adjuvant therapy
thoracocentesis was needed in two patients with right
pleural effusion; the other two had a subhepatic or a
subphrenic abscess requiring surgical drainage. Two
patients died within 1 month of the second liver resection
and were regarded as postoperative deaths. The causes
were myocardial infarction occurring on the fourth day
after right trisegmentectomy, and tonsillar herniation
due to an undetected cerebral metasta~is~.Another
(possibly third) patient was reported to be succumbing
because of acute bilateral nosocomial pneumonia in spite
of aggressive treatment, although the underlying type of
cancer was not specified23.After excluding this last report,
the estimated operative mortality rate was 1.2 per cent
(two of 163 patients).
Five report^'^,'^,'^^",^^ mentioned the use of adjuvant
therapy after the second resection for colorectal
metastases (Table 5). Twenty-nine (45 per cent) of 65
patients received some form of adjuvant therapy, systemic
chemotherapy accounting for more than 50 per cent of
the cases. Treatment for recurrence after the second
hepatic resection is evidently rare enough to be left
unmentioned except in a few
In 48 of 111 patients (43 per cent), resection of the
primary colorectal cancer and the hepatic metastases took
place at the same operative intervention. These
metastases were considered synchronous. In 63 patients
(57 per cent), metachronous metastases were removed
after a median delay of 13 months after the colorectal
resection. The median interval between the first and
second liver resection for colorectal metastases was 12
months; there was no difference between synchronous and
metachronous disease. The median interval between the
second and third liver resection (data obtained from seven
patients) was 14 months.
Altogether the ten patients subjected to a third liver
resection because of colorectal liver metastases achieved a
median survival afterwards of 27 months. A total of 191
second liver resections resulted in a median survival of 30
months; the corresponding 1-,3- and 5-year survival rates
after the second resection were 87, 40 and 26 per cent
respectively (Fig. 3). Median survival after the first liver
resection was 50 months (data obtained from 146
patients) and respective 1-, 3- and 5-year survival rates
were 98, 68 and 39 per cent. Median survival after the
primary colorectal resection was 68 months (data from
111 patients) and 3-, 5- and 10-year survival rates were 77,
57 and 20 per cent respectively. The 12 patients subjected
to additional metastatic surgery beyond the second liver
resection achieved a median survival of 34 months.

0 1996 Blackwell Science Ltd, British Journal of Surgery 1996,83, 893-901

896 N . N E E L E M A N and R . A N D E R S S O N
Table 6 summarizes potential predictors of outcome for
patients with colorectal cancer during the course of their
disease. Sex and age did not prove prognostically
important, and increasing age did not negatively influence
survival. Patients above the age of 60 years tended to
show a better survival than younger patients, both after
the primary colorectal resection ( P = 047) and after the
first liver resection (P = 0.08), although these differences
did not reach statistical significance. This tendency was,
however, not demonstrable when comparing patients
above versus below 65 years of age.
Survival after the primary colorectal resection was not
apparently influenced by the site or Dukes stage of the
primary cancer. The appearance in time of the liver
metastases did not prove to be of prognostic importance

after the first or second liver resection, but it affected

survival after the primary colorectal resection, which was
shorter in patients with synchronous metastases ( P = 0.04).
This is also true for the interval between the
hepatectomies. Patients with colorectal disease and an
interval longer than 1 year did significantly better than
those with a shorter interval, both after primary colorectal
resection (P = 0.004) and after first hepatic resection
( P < 0.001). However, survival after second resection was
not apparently influenced by the preceding time interval
between liver resections. A comparison between patients
100

5
m
.-

80

5,

*al 60

.I

7 40

q
E

20

I
400

I
800

I
I
I
I
I
I
1200 1600 2000 2400 2800 3200
Length of survival (days)

Fig. 3 Survival after second liver resection for recurrent

colorectal liver metastases

600

1200

1800

2400

3000

Length of survival (days)

Fig. 4 Survival after first liver resection according to the total

fewer than four; 0,
four or
number of colorectal metastases (0,
more) resected at first and second liver resection ( P = 0.10,
Kaplan-Meier test)

Table 6 Features possibly affecting survival after the primary colorectal procedure and after first and second liver resection for colorectal
metastases
~

After primary
procedure

After first
liver resection

P*

No.

P*

No.

~~

After second
liver resection

P*

No.
~~

Sex
M
F
Age (years)
5 60
> 60
I 65
> 65 years
Site of primary tumour
Colon
Rectum
Dukes stage
B
C
Timing of first metastases
Synchronous
Metachronous
Interval between first and second
live resection (years)
<1
31
Total number of nodes resected
1-3
>3
Adjuvant therapy after second
resection
Yes
No

42
59

43
58
82
19

I
I

;; I

:: }
:: 1
:; 1

0.26
0.07
0.40
0.34

44
64

:: 1.

;; 1
;; 1

0.18

44
29

0.04

63
48

0.004
0.24

I
1

;; I
44
24

0.40
0.08

0.44

:: 1
:: I
;; 1

0.39

1
:: 1
2: 1

0.00007

44
24

0.49
0.43

0.10

ji:

0.49
0.23
0.25
0.33

0.09
0.48

0.14
0.13

0.37

*Log rank test

0 1996 Blackwell Science Ltd, British Journal of Surgery 1996,83, 893-901

REPEATED LIVER RESECTION FOR RECURRENT LIVER CANCER

897

with a total of three or fewer and four or more

metastases, removed at the two liver resections, demonstrated that a limited cumulated number of metastases
tended to correlate with a longer survival after the first
liver resection, although this did not reach statistical
significance ( P = 0.10; Fig. 4 ) . The use of adjuvant therapy
did not seem to improve the results of the second liver
resection for colorectal metastases.

resection3. No postoperative chemotherapy was given to

four patients in a comparative study4. Non-surgical
treatment for recurrence of HCC after second liver
resection was known to be applied in nine of 13 patients
(five had chemotherapy, four percutaneous ethanol
injection and three transcatheter arterial emboli~ a t i o n ) ,A
~ ~number
.
of patients with recurrence received
lipiodoli~ation~~.
In patients with HCC the median intervals between first
and second, and between second and third, liver resection
Hepatocellular carcinoma
were 19 and 15 months respectively. Median survival
times after first (data obtained from 124 patients), second
The majority of the 128 patients with HCC had
from 128 patients) and third liver resection (data
concomitant liver disease. In three Asian s t ~ d i e s ~ ~ ~ ~ (data
,
from ten patients) were 77, 40 and 29 months respectively.
reporting on a total of 43 patients, the presence of
Three-, 5- and 10-year survival rates after first liver
underlying cirrhosis varied between 89 and 100 per cent.
resection were 82, 64 and 30 per cent respectively, and the
HCC was associated with
In three European
respective 1-, 3- and 5-year survival rates after second
chronic hepatic disease in 57 per cent (ten patients with
resection for HCC were 82, 56 and 40 per cent (Fig. 5 ) . If
cirrhosis, two with chronic hepatitis and one with
the first surgical intervention is considered as the onset of
haemochromatosis). Except for one patient with Child
disease in both colorectal carcinoma and HCC, the latter
grade C hepatic dysfunction, who was alive without
no other
disease 6 months after second liver rese~tion~,
patient was identified as having poor liver reserve at the
time of second liver resection. Another seven patients
without concomitant liver disease were identified?
three of them died with liver tumour 85, 27 and 11
months after second resection. One patient was alive with
disease at 47 months and the final three patients were
tumour free at 54, 28 and 2 months.
Recurrence of HCC limited to the liver alone after a
first liver resection varied between 72 and 91 per cent and
was followed by a repeat resection with curative intent in
12-24 per cent (Table 1). These repeated resections
correspond to 4-14 per cent of all curative liver resections
1
I
I
1
I
I
I
performed (Table 2). Data on the extent of resection were
0
1000 2000 3000 4000 5000 6000 7000
recorded from 121 patient~16.33-37.39-43.45.46 (Table 3). Some
Length of survival (days)
41 (33 per cent) lobar, 31 (25 per cent) segmental, and 52
(42 per cent) subsegmental resections were performed at
Fig. 6 Survival after primary resection for colorectal cancer
the first intervention. Six (5 per cent) lobar, 30 (24 per
(-)
and after the first resection for hepatocellular
cent) segmental, and 87 (71 per cent) subsegmental
carcinoma (HCC) (---). HCC is associated with significantly
resections were performed at the second liver resection.
better survival (P = 0.03, Kaplan-Meier test)
The calculated morbidity rate after the second resection
for HCC was 13 per cent (Table 4 ) . Three patients died
within 1 month after the operation, one because of
Table 7 Features possibly affecting survival after first and second
liver resection for hepatocellular carcinoma
bleeding from oesophageal varices secondary to cirrhosis
and one from septic complications. The cause of death in
After first
After second
the third is not known. The resulting operative mortality
liver resection liver resection
rate was 2.3 per cent (three of 128 patients).
The use of postoperative adjuvant therapy after the
No.
P*
No.
P*
second resection of HCC was rarely mentioned. One
Sex
study reported that 17 patients were routinely given
M
adjuvant chemotherapy for 3 days after second liver
F
Age (years)

-5 100

I50
> 50
2 6.5

> 6.5
Interval between first and
second liver resection (years)

60

2 1
>i

6 20
0

91

<2

1000

2000
3000
4000
Length of survival (days)

5000

Fig. 5 Survival after second liver resection for recurrent

hepatocellular carcinoma

6000

>2
Maximal node size at
second resection (mm)
< 40
> 40
*Log rank test

0 1996 Blackwell Science Ltd, British Journal ofsurgely 1996, 83, 893-901

43
15

0.36

898 N . N E E L E M A N

and R . A N P E R S S O N

second hepatectomy. Patients with colorectal liver cancer

in the older age groups demonstrated a survival similar to
that of younger patients. Patients above the age of 60
years tended to do better than younger patients, both
after the primary colorectal resection (P = 0.07) and after
the first liver resection for metastases (P = 0.08). A similar
beneficial effect on survival after a first liver resection for
colorectal metastases, favouring patients older than 60
years, has been reported p r e v i o ~ s l y ~These
~.
results may
be attributed to the use of stricter selection criteria for
older patients. In the elderly, factors other than age, such
as performance status, co-existent heart disease, dementia,
diabetes, are considered when evaluating surgical risks
Discussion
and benefitss6. It may therefore be expected that resectColorectal carcinoma
ability rates are lower in the elderly, rendering morbidity,
mortality and survival rates after liver resection
Recurrence after a first liver resection for colorectal
comparable to those of younger patient^'^^^^^'.
metastases occurs in the majority of patients. The 2-year
The present review suggests that the primary site of the
recurrence rate has been estimated as 50-70 per cent6,49%s.
cancer, whether colon or rectum, has no prognostic
Approximately one-third of patients will have recurrence
importance~2~51~sx.
Concerning stage of the primary
isolated to the liver alone~2~51~s2;
in the present study this
tumour, opinions differ about whether patients with
varied between 33 and 48 per cent. Metastatic disease
metastases from Dukes C colorectal carcinoma do
confined to the liver was resected in 15-33 per cent of
better24,5or n ~ t ~after
~ liver
, ~ resection
~ , ~ than
~
those with
instances, in comparison to a previously reported rate of
metastases from Dukes B tumours. The present review
24 per cent. Thus, a second liver resection for colorectal
does not demonstrate a significant decrease in survival in
metastases could only be performed in a minority of
patients with Dukes C carcinoma.
patients with recurrence after a first hepatectomy.
The influence of synchronous versus metachronous
Morbidity and mortality rates of 27.4 per cent and 1.2 per
metastases on survival after liver resection has been
cent respectively were identified, levels similar to those
discussed. Several studies have failed to show any
observed after a first liver resection.. Similar rates were
difference in s ~ r v i v a l ~ ~ while
, ~ ~ ~others
,
have found
recently published in two multicentre reports of large
metastases to be associated with a less
,
numbers of reresections for colorectal m e t a s t a s e ~ ~ ~ ~ ~synchronous
favourable outcome58,61.In a review, Ballantyne and Q u i d
which confirms that reresection may be performed in
estimated the 5-year survival rate after resection for
selected patients in reasonable safety.
Comparing survival after a single hepatic resection with
metachronous lesions to be somewhat better (31 per cent)
survival after a second hepatic resection may reveal if
than that after resection for synchronous disease (27 per
reresection is worthwhile. A 5-year survival rate of 26 per
cent). In the present study, patients with metachronous
cent after a second resection for colorectal metastases
metastases did no better after either the first or the
compares well with the 25-35 per cent reported in
second hepatic resection, but survival after the primary
patients with only one liver resection-?. Also the aforecolorectal resection was considerably improved compared
mentioned two recent multi-institutional studies provide
with that for patients with synchronous metastases.
similar data on s ~ r v i v a 1 ~Survival
~ . ~ ~ . after first resection is
Patients with a disease-free interval exceeding 1 year
improved by a subsequent second resection. Patients with
after the colorectal resection have been said to have a
colorectal liver metastases and repeated liver resection in
significantly improved survival after liver resection,
the present review had a 5-year survival rate after first
compared with patients with an interval of less than 1
liver resection of 39 per cent.
years9. It has been proposed that a long interval may
In ten patients the median interval before and the
indicate a biologically less aggressive tumour60. The
median survival after the third liver resection (14 and 27
interval between first and second liver resection has also
months respectively) were similar to those noted at 191
been studied. An interval exceeding 1 year correlated with
second resections (12 and 30 months respectively).
significantly better survival after primary colorectal
Nordlinger et d S 3
also reported on 12 patients who
resection and after first liver resection. A longer interval
underwent a third liver resection for colorectal metastases
tended to correlate with increased survival after second
with a mean interval before the third liver resection of
liver resection, although this was not statistically
15.2 months and a mean survival of 1 2 5 months. As no
significant. Recently, a multi-institutional study failed to
effective alternative treatment seems available, and since
demonstrate a significant difference in survival after
resection can be performed with reasonable operative
repeated liver resection between patients with a diseasemorbidity and mortality rates (with a demonstrable effect
free interval after the first liver resection of less than 1
on survival which in the present study approached survival
year and those with a disease-free interval of more than 1
obtained after a second resection), a third liver resection
year. It may be that subclinical disease is present in a
seems justified in selected patients. Surgery should be
number of patients after the first liver resection, who
considered when feasible, but the actual benefit in survival
would therefore benefit from repeated liver resection
terms remains unclear. A prospective, randomized study
after a short interval.
would be needed for a proper assessment.
It has been suggested that a limited number of
To improve results it is necessary to identify prognostic
metastases at the first liver resection correlates with a
factors. Apart from synchronous or metachronous
better prognosissl~ss~sy.
In the present study, the total
dissemination and the time interval between liver
number of metastases resected at the two liver resections
resections, none of the other factors studied proved
tended to influence outcome after first liver resection, but
statistically significant. No feature predicted survival after
not significantly. Others have reported that the number of
appears to have a significantly better prognosis (P = 0.03;
Fig. 6).
Several factors were analysed for their possible effect
on outcome (Table 7). Sex, age and maximal tumour
size at second liver resection were not of prognostic
importance. Similar to colorectal metastases, for HCC
a longer interval between liver resections was related
to an improved survival after first resection (P=0.001),
although this did not affect survival after second
resection.

0 1996 Blackwell Science Ltd, British Journal ofsurgery 1996, 83, 893-901

REPEATED LIVER RESECTION FOR RECURRENT LIVER CANCER

metastases resected at second resection does not significantly influence long-term survival, although a higher
number of nodes (more than three) results in a higher
mortality rate during the first year after operatiod4.
The use of adjuvant therapy after second liver resection
did not result in improved survival. However, some
studies on adjuvant chemotherapy after a first liver
resection have appeared and further investigations are
needed62z63.
Also, for patients with irresectable metastases,
attempts have been made to prolong survival and
maintain quality of life, mainly by regional chemot h e r a ~ y ~Transplantation
~,~~.
would be a treatment option
for disease restricted to the liver. Such a patient, excluded
from analysis, underwent
an orthotopic liver
transplantation 25 months after the first (palliative) liver
resection, but died shortly after the operationI2. Although
the spectrum of diseases treated by liver transplantation
has broadened in recent years, there is a growing
reluctance about regarding malignant disease as an
indication because of the high risk of tumour recurrence66,
which may be particularly high in patients with cancer of
colorectal origin. However, it should be stated that
possibly one-third of patients with recurrent disease after
a first liver resection may have disease limited to the
l i ~ e r ' , ~ , These
~ ~ , ~ ~patients,
.
usually characterized by
adequate liver function but poor prognosis, may be
candidates for future liver transplantation.
Factors reported predictive for outcome after first liver
resection for colorectal metastases include free resectional
margin, unilateral or bilateral disease, and presence or
absence of regional lymph node metastases and
extrahepatic d i ~ e a s e ~In, ~the
. present review, 12 patients
were identified who had removal of localized extrahepatic
disease in addition to a second resection for colorectal
metastases. The median survival in these patients was 34
months, which is 4 months longer than that for the total
series of patients.

Hepatocellular carcinoma
Recurrence of HCC occurs in 43-57 per cent of patients
within 2 years of first tumour r e m ~ v a l ~ . ~a~rate
. ~ ' , lower
than that for colorectal metastases. Disease confined to
the liver alone is present in a higher percentage in HCC,
in the present study varying between 72 and 91 per cent,
which is similar to other report^^,'^,^',^^. Resectability
varies between 12 and 24 per cent, from which it follows
that only a few patients are selected for a second surgical
intervention. After second resection complications occur
in 13 per cent of patients and reoperation is rare, which
compares well with morbidity rates observed after first
r e s e ~ t i o n ~This,
~ , ~ ~together
.
with a mortality rate of 2.3
per cent, suggests that second and even third resections of
the liver are well tolerated in selected patients.
The value of a repeated liver resection for HCC can be
expressed a5 prolonged survival. A 5-year survival rate of
30-50 per cent after a single liver r e ~ e c t i o n ~ .is~ -similar
'~
to 40 per cent after a second resection. In these patients
the 5-year survival rate after the first of the two resections
was calculated as 63 per cent in the present study.
Partially responsible for this result are the ten patients
who received an additional third Iiver resection. The
disease-free interval before and survival after third
resection were shorter than before and after second
resection.
Identification of factors influencing survival may be
useful. Neither sex nor age affected survival. Recent

899

reports suggest that the results of liver resection for HCC

in the elderly are satisfactory and not necessarily worse
than those in younger patients with otherwise similar
clinical feat~reP-~O.
A longer interval between hepatectomies predicts an improved total survival ( P = O.OOl),
but it does not seem to influence survival after the second
resection for HCC. Similar findings have been noted in
patients with colorectal liver cancer.
The size of the HCC influences the extent of
hepatectomy which, in turn, probably affects operative
mortality. It is generally believed also to affect long-term
prognosis'0, although the present study could not support
this with respect to second liver resection. Other factors,
such as presence of cirrhosis, vascular invasion, satellite
nodes, absence of capsule formation and tumour growth
at the resectional margin, have been reported to be
associated with a less favourable outcome after first liver
resection for HCC'OZ~~.
It may be that the same factors
also affect prognosis after second resection, but this
requires further study.
Efforts are frequently made to decrease the risk of
recurrence and so potentially to improve the outcome for
patients with irresectable HCC. Surgical resection
combined with chemotherapy may result in longer
disease-free survival, but this needs further evaluation by
randomized trials and long-term follow-up71.The same is
true for more recently introduced therapeutic modalities,
such as transcatheter arterial chemoembolization,
percutaneous ethanol injection and cryosurgery, which
may be applied when surgical intervention is no longer
considered fea~ible~.~'.
Such a situation probably occurred
for a patient34, excluded from the present analysis, who
underwent an unsuccessful liver transplantation after a
trisegmentectomy and three subsequent wedge resections.
Transplantation as a potential therapy for HCC still
carries the risk of early tumour recurrence, despite
excluding patients with extrahepatic malignancy. In
general, the indications for liver transplantation are
moving away from malignant, in favour of benign,
disease66.At the same time, however, it is recognized that
carefully selected patients with HCC (small and
uninodular or binodular tumours, cirrhosis, poor liver
reserve) benefit more from liver replacement than from
liver resection, leaving a definite but incompletely defined
role for liver transplantation in the treatment of HCC72,73.
In conclusion, repeated liver resection may be performed
without major risk in a selected group of patients with
recurrence of colorectal liver metastases or HCC. This
offers a hope of long-term survival. To improve the results
of resectional therapy for liver cancer, more effort should
be made to ensure early detection and careful follow-up.
Selection criteria for resectional operations on the liver
require further definition.

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Announcement
National Confidential Enquiry into Counselling for Genetic Disorders.
Medullary thyroid carcinomalmultiple endocrine neoplasia type 2 audit,
1990-1991
This report to the Department of Health has now been published. Copies are available,
free of charge, from the following address:
Royal College of Physicians of London, Genetic Enquiry Centre, St Marys Hospital,
Hathersage Road, Manchester M13 OJH, UK. Tel: 0161 276 626216317.

0 1996 Blackwell Science Ltd, British Journal of Surgery 1996, 83, 893-901

901