Short-Term and Long-Term Outcomes After SimultaneousResection of Colorectal Malignancies and Synchronous LiverMetastases

Eduardo de Santibanes • Diego Fernandez • Carlos Vaccaro •

Guillermo Ojea Quintana • Fernando Bonadeo • Juan Pekolj •

Carlos Bonofiglio • Ernesto Molmenti

Published online: 8 June 2010

� Societe Internationale de Chirurgie 2010

Abstract

Background We evaluated the simultaneous resection of

colorectal malignancies and synchronous liver metastases.

Methods Between June 1982 and June 2006, a total of

752 patients underwent resection of colorectal hepatic

metastases. In all, 185 (25%) of them underwent simulta-

neous resection of the hepatic lesions and the correspond-

ing primary tumors.

Results The median hospital stay was 8 days (range 4–

24 days), with a median operating time of 4 h (range 2–8 h).

Altogether, 62 (33.5%) patients required intraoperative

transfusion of packed red blood cells (median 2.1 IU, range

1–5 IU), and 25 (13.5%) were given frozen fresh plasma

(median 2.1 IU, range 1–4 IU). The morbidity rate was

20.5%. There were two postoperative deaths (mortality rate

1.08%) within 30 days of the surgical intervention. Major

hepatectomy was associated with greater morbidity (37.2%

vs. 16.2%, P \ 0.01) and mortality (4.7% vs. 0%, P \ 0.05)

rates. For the overall survivals (OS) at 3 and 5 years were

60.1% (52.3–67.85%) and 36.1% (27.4-44.8%), respec-

tively. Disease-free survivals (DFS) at 3 and 5 years were

37.7% (30.2–45.3%) and 26.5% (18.7–34.3%), respectively.

Transfusion of blood products, CEA level C 200 ng/dl, and

N2 node status were found to be prognostic factors by uni-

variate analysis. CEA level C 200 ng/dl and N2 node status

achieved prognostic significance by multivariate analysis.

Conclusions The simultaneous resection of colorectal

malignancies and synchronous liver metastases is safe, avoids

an additional intervention, can be performed with low mor-

bidity and mortality, and is associated with good oncologic

outcomes. Node stage N2 and CEA level C 200 ng/dl should

be given special consideration when selecting patients.

Keywords Liver � Colorectal � Gastrointestinal �Oncology � Biliary � Critical care

Introduction

Colorectal cancer is one of the most frequent malignancies

throughout the world [1–6]. Resection of liver metastases

presenting after removal of the primary tumor can be

associated with 5-year survivals of up to 38% [7–17].

When they present synchronously (23–51% of resectable

cases [18]), however, the survival decreases to B20% [10,

19]. Except in selected cases (i.e., right colectomy, wedge

liver resection), synchronous metastases were systemati-

cally treated with two laparotomies [10, 11]. Current

studies, however, suggest that simultaneous resections can

be performed safely with comparable or even better out-

comes than staged procedures [20–31]. Furthermore,

simultaneous resections are associated with improved

patient comfort [23], massive reduction in tumor mass,

better response to chemotherapy [30], potential decreased

E. de Santibanes (&) � D. Fernandez � J. Pekolj

Hepato-pancreato-biliary and Liver Transplant Sections,

Department of General Surgery, Hospital Italiano, Buenos Aires,

Argentina

e-mail: eduardo.desantibanes@hospitalitaliano.org.ar

C. Vaccaro � G. O. Quintana � F. Bonadeo

Colorectal Section, Department of General Surgery, Hospital

Italiano, Buenos Aires, Argentina

C. Bonofiglio

Department of Anesthesia, Hospital Italiano, Buenos Aires,

Argentina

E. Molmenti

Department of General Surgery, North Shore – LIJ Health

System, Great Neck, NY, USA

123

World J Surg (2010) 34:2133–2140

DOI 10.1007/s00268-010-0654-6

risk of cancer cell dissemination [31, 32], and avoidance of

an additional surgical procedure [33].

The purpose of this study was to evaluate our 24-year

experience with simultaneous resection of synchronous

colorectal cancer and liver metastases.

Patients and Methods

From June 1982 to June 2006, a total of 2,700 patients with

colorectal malignancy and 1,375 with malignant hepatic

tumors underwent resection at the Colorectal and Hepa-

tobiliary Section of the Hospital Italiano of Buenos Aires.

Of these, 185 (13.45%) underwent simultaneous colorectal

and hepatic resection for colorectal malignancy with syn-

chronous hepatic metastases. There were 114 males and 71

females, with a median age of 63 years (range 16–

86 years). Complications were classified according to

Dindo’s scheme [33], except for transfusion of blood

products, which was not considered a complication.

Preoperative Staging

Routine preoperative evaluation included a complete

physical examination, chest radiography, carcinoembry-

onic antigen (CEA) (obtained at our laboratory in 79 of the

185 patients) and cancer antibody (CA) 19-9 levels,

colonoscopy, abdominal ultrasonography (US), and com-

puted tomography (CT) scans of the chest, abdomen, and

pelvis. Positron emission tomography was not part of our

protocol due to lack of medical insurance coverage.

Patient Selection

A total of 492 patients with colorectal cancer and synchro-

nous liver metastases were evaluated. Simultaneous liver

and colorectal resection was undertaken in 185 cases

(37.6%). Simultaneous liver and colorectal resection was not

undertaken in patients with performance status American

Society of Anesthesiologists (ASA) IV; emergency resection

in the setting of obstruction, perforation, or hemorrhage [28];

tumors whose colorectal origin could not be clearly estab-

lished; extrahepatic metastases; failure to achieve negative

intraoperative colorectal (R0) and hepatic (R0) resection

margins; or inability to retain a postresection liver volume of

at least 35% of the total liver volume [34]. Size and number

of liver metastases were not considered exclusionary factors.

All of the resections were performed by surgical teams that

had experience with both procedures.

Preoperative Care

Mechanical bowel preparation was with 90 ml of an oral

phosphate solution. Antibiotic prophylaxis consisted of

750 mg oral ciprofloxacin and 1 g intravenous ornidazole

administered less than 1 h prior to surgery.

Surgical Technique

Prior to 1999, we used inhalational anesthetic agents. In

1999, we adopted total intravenous anesthesia (TIVA).

Central venous pressure (CVP) was kept at \5 cm H2O,

and vasopressors were added whenever necessary to avoid

hypotension.

The abdomen was entered through a midline incision

and its contents explored thoroughly. Colorectal resection

was undertaken prior to liver resection. An R0 colorectal

resection was achieved in those cases where all criteria

were verified. Prior to continuing with the liver resection,

all surgical instruments and drapes were removed and

replaced with clean sterile ones.

The falciform ligament was divided to allow for US

evaluation of the liver. The midline incision was extended

transversely for metastases located in Couinaud’s segments

VI or VII. Major hepatectomy was defined as resection of

at least three segments [35]. Liver transection was carried

out with a cavitation ultrasonic aspirator (CUSA; Valley,

Boulder, CO, USA) and/or by means of Kelly clamp tissue

crushing. Argon beam coagulation was used for hemosta-

sis. We applied the Pringle maneuver only in cases where

bleeding was encountered during the parenchymal tran-

section despite CVP \ 5 cm H2O. We did not use pre-

conditioning. An initial occlusion period of 20 min was

followed (if necessary) by a rest period of 5 min and a

second occlusion period of 15 min. In cases of multiple

metastases with no involvement of large vessels, we per-

formed wedge resection with margins of at least 1 cm. At

the end of the procedure, we placed one to three suction

drains that were removed 3–5 days later in the absence of

bile leaks. Postoperative recovery was in the intensive care

unit (ICU).

Follow-up

Routine postoperative follow-up was every 4 months and

included a complete physical examination, US or CT, liver

function tests, complete blood count, and assays for elec-

trolytes, blood urea nitrogen (BUN), creatinine, and CEA

as well as the prothrombin time (PT) and partial throm-

boplastin time (PTT). Median follow-up was 35 months

(range 12–128 months). All patients received chemother-

apy according to the following guidelines for stage IV

tumors: prior to 1996, 5-fluorouracil (5FU) and leucovorin

[36]; from 1996 to 2003, FOLFIRI [folinic acid (leucovo-

rin)/5FU/irinotecan] [37, 38]; and since 2003, FOLFOX

[folinic acid (leucovorin)/5FU/oxaliplatin] and FOLFIRI

[39–41].

2134 World J Surg (2010) 34:2133–2140

123

Statistical Analysis

Continuous data were expressed as the median and range.

Overall and disease-free survival rates were calculated with

the Kaplan–Meier method and expressed as median values

with 95% confidence intervals (95% CI). Survival curves

were compared using the log-rank test. Results were con-

sidered to be statistically significant at P B 0.05.

Results

Technical Aspects

Tables 1 and 2 detail the colorectal and hepatic resections

performed. The median number of metastases was 2 (range

1–15). In all, 82 patients had only one metastasis (44.3%),

46 had two (24.9%), 28 had three (15.1%), 11 had four

(5.9%), 10 had five (5.4%), 3 had six (1.6%), and one each

(0.5%) had 7, 9, 10, 14, and 15. Liver resection margins

were C1 cm in 169 cases, 1–9 mm in 5 cases, and\1 mm

(considered to be positive) in the remaining 11 cases

(P = NS).

Short-Term Outcomes

The median hospital length stay was 8 days (range 4–

24 days). In all, 82 (44.3%) patients required admission to

the intensive care unit (ICU), with a median length of stay

of 40 h (range 12–200 h) and a median mechanical venti-

lation period of 9 h (range 3–164 h). The median surgical

time was 4 h (range 2–8 h). A total of 36, (19.45%) hep-

atectomies required a Pringle maneuver. There was no

association between the Pringle maneuver and anastomotic

leaks. Altogether, 60 (32.4%) patients required intraoper-

ative transfusion of packed red blood cells (median 2.1 IU,

range 1–5 IU), and 23 (12.4%) were given fresh frozen

plasma (median 2.1 IU, range 1–4 IU). Overall morbidity

was 20.5% (38/185 patients).

There were 38 complications as follows: pleural effusion

(11), wound infections (7), bleeding (5), intraabdominal

abscess (4), postoperative ileus (4), hepatic dysfunction (3),

abdominal wall dehiscense (2), anastomotic leak (1), and

atelectasis (1) (Dindo’s classification of complications)

(Table 3). All were successfully treated medically or by

percutaneous drainage except for the sole anastomotic leak

(STROC IIIb), which required a diverting ileostomy and

drainage of a pelvic collection.

Major hepatectomy was associated with higher mor-

bidity (37.2% vs. 16.2%, P \ 0.01) and mortality (4.7% vs.

0%, P \ 0.05) rates. There were two (1.08%) postoperative

deaths (STROC V) due to liver failure and sepsis within

30 days of surgery. Both patients were [65 years of age

(69 and 75 years) and had undergone major hepatic

resection: right hepatectomy with right colectomy and right

trisectionectomy with low anterior resection, respectively.

Among patients undergoing major hepatectomy, those

Table 1 Colorectal resections performed simultaneously with the

liver procedures

Colorectal resection No.

Right colectomy 41

Left colectomy 23

High anterior resection 37

Low anterior resection 38

Very low anterior resection 21

Sigmoid colectomy 7

Total colectomy 7

Subtotal colectomy 3

Transverse colectomy 3

Abdominoperineal resection 5

Total 185

Table 2 Liver resections performed simultaneously with colorectal

procedures

Type No.

Wedge resections 114

Minor resections 29

Left lateral sectionectomy 12

S VI ? S VII 8

S V ? S VIII 5

S IVb ? S V 3

Major resections 42

Right hepatectomy 18

Right hepatectomy ? S 1 4

Left hepatectomy 11

Left hepatectomy ? wedge 5

Total 185

The terminology is that of the Committee of the International Hepato-

Pancreato-Biliary Association [70]

S liver segment

Table 3 STROC stratification

of 38 complicationsSTROC stratification No.

I 0

II 28

IIIa 4

IIIb 3

IVa 1

IVb 0

V 2

World J Surg (2010) 34:2133–2140 2135

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aged C 65 years had a significant higher mortality rate

(16.7% vs. 0%, P = 0.02).

Long-Term Outcomes

Tumor recurrence was observed in 64% of cases (119/185

patients). Recurrences were detected (on occasions at more

than one site) in: liver (n = 98), lung (n = 43), peritoneum

(n = 16), abdominal wall (n = 3), bone (n = 4), and

adrenal gland (n = 1). There was no association between

site of recurrence and location of the primary tumor within

the colon and rectum. The 3- and 5-year overall survival

rates were 60.1% and 36.1%, respectively. The corre-

sponding disease-free survivals were 37.8% and 27.9%,

respectively.

Colorectal tumors were staged according to the TNM

classification. There were 4 T1, 15 T2, 148 T3, and 18 T4

cases. N staging showed 62 N0, 80 N1, and 43 N2 cases. T

stage was not prognostic. Overall survival (OS) and dis-

ease-free survival (DFS) were inversely correlated with the

N stage (Table 4).

The median weight of the hepatic resection specimens

was 356 g (range 3–1800 g), with a median metastasis

diameter of 4.5 cm (range 1–28 cm). Size did not correlate

with prognosis.

The median number of liver metastases was 2.29 (range

1–15). Statistical analysis (not shown) revealed that one or

two versus three or more liver metastases showed a sig-

nificant inverse correlation with DFS but had no effect on

OS (Table 5).

Resection margins and CA 19-9 levels had no effect on

either OS or DFS. The median preoperative CEA value was

23 ng/ml (range 0.2–550.0 ng/ml). The CEA level was

correlated with the outcome (Table 6).

Transfusion of packed red blood cells and fresh frozen

plasma showed an inverse correlation with both OS and

DFS (Table 7). Transfusion of blood products, CEA level,

and N2 node status were found to be prognostic by uni-

variate analysis (Table 8). On multivariate analysis, only

the CEA level and N2 node status reached significance

(Table 9).

Discussion

More than a decade ago, Hughes et al. [13] recommended

simultaneous resections in patients with single metastases

who could physiologically tolerate simple removal of the

liver lesion in the setting of an uncomplicated colorectal

resection with minimal blood loss and contamination.

Since then, more extensive hepatic resections have been

attempted [20, 27]. However, despite thorough preopera-

tive workups with US, CT, magnetic resonance imaging

(MRI), and 18F-fluorodeoxyglucose positron emission

tomography (FDG-PET) [42–47], widespread metastases

are encountered in approximately 30% of patients at the

time of surgery. The 64% recurrence rate in our series, with

most lesions located in the liver, suggests the presence of

microscopic residual disease undetectable at the time of

surgery. This finding also supports the use of adjuvant

therapies during both the pre- and postoperative periods

and could serve as a criticism for the absence of PET

scanning in our protocol.

Although no randomized trials have been published so

far, recent series on simultaneous resections reported

similar or improved short-term and equivalent long-term

outcomes [8, 20, 23, 26–28, 42–51]. Accordingly, the

Standards Practice Task Force, the American Society of

Colon and Rectal Surgeons [52], and a recent systematic

review [49] listed simultaneous colorectal and liver resec-

tions among recommended guidelines with levels of evi-

dence III, grade C II or III, and grade C, respectively.

Martin et al. [20] reported that simultaneous resections

had fewer complications (49% vs. 67%, P \ 0.01), shorter

median hospital stays (10 vs. 18 days, P \ 0.01), and

similar mortality rates (2.2% vs. 2.8%, P = NS) when

compared to staged procedures. Moreover, when compar-

ing patients who underwent major liver resections (lobec-

tomy or more), those with simultaneous surgeries had a

lower morbidity rate (60% vs. 70%, P = 0.03), shorter

operating times, decreased hospital stays, and a twofold

decrease in laparotomy complications. Capussotti et al. [53,

54] and Martin et al. [20] reported that the combined

morbidity was greater after staged procedures than after

Table 4 N stage (TNM classification) and long-term outcome

N stage 3-Year DFS 5-Year DFS 3-Year OS 5-Year OS

N0 (n = 64) 38.7% (25.3–52.1) 30.3% (16.8–43.8) 56.8% (43.1–70.5) 41.6% (26.4–56.8)

N1 (n = 79) 44.9% (33.1–56.6) 33.8% (21.4–46.1) 65.9% (54.4–77.4) 41.5% (27.8–55.2)

N2 (n = 42) 17.8% (5.2–30.3) 9.2% (0–23.9)* 50.4% (34.4–66.4) 11.9% (12.0–24.5)*

Results are the mean and 95% CI

DFS disease-free survival, OS overall survival

* P \ 0.05

2136 World J Surg (2010) 34:2133–2140

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simultaneous resections, with no difference in mortality.

Martin et al. [20] reported no difference in severe

morbidities.

Weber et al. [27], despite performing major resections in

more than half of their patients (56% vs. 31%, P = 0.01),

found no difference in median hospital stay (17 vs.

16 days), morbidity (23% vs. 32%), or mortality (0% vs.

0%) rates. In their series, there was no difference in long-

term OS or DSF among both groups (94%, 45%, and 21%

at 1, 3, and 5 years after simultaneous resections, and 92%,

45%, and 22% after delayed resections, respectively).

Chua et al. [28] compared 64 patients with concurrent

resections to 32 patients with staged resections. Both

groups had comparable primary tumors, liver metastases,

and treatment types (colectomies and hepatectomies).

There were no perioperative deaths or differences in mor-

bidity rates (53% and 41%, respectively; P = 0.8); and the

median hospital stay was significantly shorter after con-

current resections (10 and 17 days, respectively;

P \ 0.001).

Our data compare favorably with the above series. We

encountered low morbidity and mortality rates (21.08%

and 1.08%, respectively) and a shorter hospital stay

(median 8 days), even with 24% major liver procedures

and 31% low anterior resections. Our OS (60.1% and

36.1% at 3 and 5 years, respectively) and DFS (37.8% and

27.9% at 3 and 5 years, respectively), even in the absence

of PET-CT and neoadjuvant therapy, were similar to those

of recent series. Although there are differing views with

respect to the effect of increased venous pressure on

intestinal anastomoses, we did not encounter any deleteri-

ous effect from the Pringle maneuver in the setting of

Table 5 Number of metastases and survival

No. of metastases 3-Year DFS 5-Year DFS 3-Year OS 5-Year OS

1–2 (n = 155) 41.3% (31.9–50.7) 31.5% (21.8–41.1) 63.9% (454.7–73.1) 36.2% (25.9–46.4)

C3 (n = 30) 26.7% (14.4–39.1) 14.4% (1.7–27.1)* 50.5% (36.5–64.5) 37.1% (20.3–53.9)

Results are the mean and 95% CI

* P \ 0.05

Table 6 CEA level and survival

CEA level 3-Year DFS 5-Year DFS 3-Year OS 5-Year OS

(\200 ng/ml) (n = 14) 68.8% (43.2–94.3) 68.8% (43.2–94.3) 92.3% (77.8–100) 82.1% (59.1–100)

(C200 ng/ml) (n = 65) 21.1% (10.7–31.5)* 16.5% (6.5–26.5)* 53.3% (40.6–66.1)* 19.4 (7.7–31.1)*

Results are the mean and 95% CI

CEA carcinoembryonic antigen

* P \ 0.05

Table 7 Transfusion of blood products and survival

Transfusion 3-Year DFS 5-Year DFS 3-Year OS 5-Year OS

No (n = 123) 40.2% (30.7–49.6) 30.1% (20.4–39.8) 65.7% (56.4–74.9) 39.4% (28.2–50.7)

Yes (n = 62) 29.9% (17.5–42) 17.7% (3.9–31.4)* 50.1% (36.7–63.3) 25.6% (11.5–39.6)*

Results are the mean and 95% CI

* P \ 0.05

Table 8 Prognostic factors for disease-free survival

Factor Univariate analysis Multivariate analysis

Score P Score P

CEA C 200 4.9 (1.7–13.7)* 0.002 4.7 (1.7–13.2)* 0.003

N2 node status 1.8 (1.2–2.7)* 0.004 1.7 (0.9–3.1)* 0.05

Transfusion 1.4 (0.9–2.1)* 0.05 1.3 (0.7–2.2) 0.38

Results are the mean and 95% CI

* P \ 0.05

Table 9 Prognostic factors for overall survival

Factor Univariate analysis Multivariate analysis

Score P Score P

CEA C 200 10.1 (2.4–42.3)* 0.001 9.5 (2.3–40.0)* 0.002

N2 node status 1.9 (1.2–2.9)* 0.006 1.9 (1.0–3.6)* 0.04

Transfusion 1.5 (1.0–2.3)* 0.04 0.9 (0.5–1.6) 0.7

Results are the mean and 95% CI

* P \ 0.05

World J Surg (2010) 34:2133–2140 2137

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CVP \ 5 cm H2O [18, 20, 53, 55, 56]. Our length of

mechanical ventilation and ICU stay have diminished since

the establishment of a postanesthesia recovery room that

allows stabilization of patients prior to their transfer to the

surgical ward.

Several variables have been proposed as predictors of

outcome after metachronous liver resection [11, 14, 16,

56–61]. Advanced tumor stage [62] and CEA serum levels

[200 ng/ml are invariably associated with extensive pri-

mary colorectal disease and represent poor prognostic

factors [7]. Patients with one or two liver metastases had a

similar prognosis, and those with three or more lesions had

decreased 5-year survival (13% vs. 28%, respectively,

P \ 0.0001) [60]. The extent of liver involvement was also

related to outcome by Doci et al. [63], who observed that

patients with \25% liver involvement had a better 5-year

survival than those with 25–50% involvement (40% and

19%, respectively; P = 0.005). Similar results were

reported by Ekberg et al. [61], who reported no 5-year

survivors among those with [50% liver involvement.

Several studies have demonstrated the importance of the

surgical resection margin as an independent predictor of

outcome. Patients with positive margins were reported to

have a median survival time (14.2 months) similar to that

of selected untreated patients [62, 63]. However, extended

resections showed no increased survival when compared to

resections with 1- to 2-cm free margins. In our series, we

observed that even margins \1 cm have no deleterious

effect on survival. This observation could be explained (at

least in part) by the small number of patients with margins

\1 mm or by the fact that the cavitation and aspiration

effect of the CUSA could potentially decrease the margin

available for pathology examination.

Based on 1,001 consecutive cases, Fong et al. [7] pro-

posed a risk score based on five clinical criteria: nodal

status of the primary tumor; disease-free interval

\12 months; more than one lesion; preoperative CEA level

[200 ng/ml; and size of the largest lesion [5 cm. Each

criterion was assigned one point. The 5-year actuarial

survival for patients with 0 points was 60%. No patients

with 5 points survived 5 years. Nordlinger et al. [14], after

evaluating 1,568 cases, proposed a classification similar to

Fong’s but with age ([60 years) and margin positivity as

additional variables. In our series, N2 node stage and CEA

level C200 ng/dl had a negative impact on long-term

survival in cases of simultaneous resection.

The time frame of our series straddles the introduction

of multislice helical CT scans as well as improvements in

staging and the development of effective systemic che-

motherapy to down-stage hepatic metastases [48, 64–70].

This could explain the widespread disease found in 30% of

patients at laparotomy. We currently recommend neoad-

juvant chemotherapy in patients with unfavorable

prognostic factors such as advanced colorectal tumors,

more that three metastases, tumors in intimate proximity to

major hepatic vessels (in order to preserve liver paren-

chyma), CEA C 200 ng/dl, or radiologic evidence of

enlarged lymph nodes in the hepatic pedicle or the mes-

entery of the colon/rectum.

In patients C65 years of age who require resections of

[65% of the total liver volume, we perform the liver

resection first in an attempt to decrease morbidity and

mortality. In those [65 years, and in the absence of the

unfavorable prognostic factors mentioned above, we pro-

ceed with simultaneous resection.

Conclusions

The simultaneous resection of a colorectal malignancy and

synchronous liver metastases is a safe, efficient approach

that avoids additional major surgical intervention. It can be

performed with low morbidity and mortality and is asso-

ciated with good oncologic outcomes. Node stage N2 and

CEA level C 200 ng/dl should be given special consider-

ation when selecting patients.

References

1. Geoghegan JG, Scheele J (1999) Treatment of colorectal liver

metastases. Br J Surg 86:158–169

2. NHS Center for Reviews and Dissemination (1997) Effective

health care: the management of colorectal cancer, vol 3, no. 6.

University of York, York

3. NH Executive (1997) Guidance on commissioning cancer ser-

vices: improving outcomes in colorectal cancer: the research

evidence. Department of Health, London

4. Jemal A, Tiwari RC, Murray T (2004) Cancer statistics, 2004.

CA Cancer J Clin 54:8–29

5. Liu LX, Zhang WH, Jiang HC (2003) Current treatment for liver

metastases from colorectal cancer. World J Gastroenterol 9:193–

200

6. Saito H (2000) Screening for colorectal cancer. Dis Colon Rec-

tum 43(Suppl):S78–S84

7. Fong Y, Cohen AM, Fortner JG et al (1997) Liver resection for

colorectal metastases. J Clin Oncol 15:938–946

8. Nadig DE, Wade TP, Fairchild RB et al (1997) Major hepatic

resection: indication and results in a national hospital system

from 1998 to 1992. Arch Surg 132:115–119

9. Nordlinger B, Jaeck D, Guiget (1992) Multicentric retrospective

study by the French Surgical Association. In: Nordlinger B, Jaeck

D et al (eds) Treatment of hepatic metastases of colorectal cancer.

Springer-Verlag, Paris, pp 129–146

10. Scheele J, Stangl R, Altendorf-Hofmann A et al (1991) Indicators

of prognosis after hepatic resection for colorectal secondaries.

Surgery 110:13–29

11. Doci R, Gennari L, Bignami P et al (1991) One hundred patients

with hepatic metastases from colorectal cancer treated by resec-

tion: analysis of prognosis determinants. Br J Surg 78:797–801

12. Schlag P, Hohenberger P, Herfath C (1990) Resection of liver

metastases in colorectal cancer: competitive analysis of treatment

2138 World J Surg (2010) 34:2133–2140

123

results in synchronous versus metachronous metastases. Eur

J Surg Oncol 16:360–365

13. Hughes KS, Simon R, Songhorabodi S et al (1988) Resection of

the liver for colorectal metastases: a multi-institutional study of

indication for resection. Surgery 103:278–288

14. Nordlinger B, Guiguet M, Vaillant JC et al (1996) Surgical

resection of colorectal carcinoma metastases to the liver: a

prognostic scoring system to improve case selection, based on

1568 patients—Association Francaise de Chirurgie. Cancer

77:1254–1262

15. Elias D, Cavalcanti A, Sabourn JC et al (1998) Results of 136

curative hepatectomies with a safety margin of less than 10 mm

for colorectal metastases. J Surg Oncol 69:88–93

16. Fong Y, Fortner J, Sun RL et al (1999) Clinical score for pre-

dicting recurrence after hepatic resection for metastatic colorectal

cancer: analysis of 1001 consecutive cases. Ann Surg 230:309–

321

17. Minagawa M, Makuuki M, Torsilli G et al (2000) Extension of

the frontiers of surgical indications in the treatment of liver

metastases from colorectal cancer: long term results. Ann Surg

231:487–499

18. Minagawa M, Yamamoto, Miwa S et al (2006) Selection criteria

for simultaneous resection in patients with synchronous liver

metastasis. Arch Surg 141:1006–1012

19. Lambert LA, Colacchio TA, Barth RJ (2000) Interval hepatic

resection of colorectal metastases improves patient selection.

Arch Surg 135:473–480

20. Martin R, Paty P, Fong Y et al (2003) Simultaneous liver and

colorectal resections are safe for synchronous colorectal liver

metastases. J Am Coll Surg 197:233–242

21. Lyass S, Zamir G, Matot I et al (2001) Combined colon and

hepatic resection for synchronous colorectal liver metastases.

J Surg Oncol 78:17–21

22. Vogt P, Raab R, Ringe B et al (1991) Resection of synchronous

liver metastases from colorectal cancer. World J Surg 15:62–67

23. Weber JC, Bachellier P, Oussoultzoglou E et al (2003) Simul-

taneous resection of colorectal primary tumour and synchronous

liver metastases. Br J Surg 90:956–962

24. Doko M, Zovak M, Ledinsky M et al (2000) Safety of simulta-

neous resections of colorectal cancer and liver metastases. Coll

Antropol 24:381–390

25. Tanaka K, Shimada H, Matsuo K et al (2004) Outcome after

simultaneous colorectal and hepatic resection for colorectal

cancer with synchronous metastases. Surgery 136:650–659

26. Fujita S, Akasu T, Moriya Y (2000) Resection of synchronous

liver metastases from colorectal cancer. Jpn J Clin Oncol 30:7–11

27. De Santibanes E, Bonadeo F, Pekolj J et al (2002) Simultaneous

colorectal and hepatic resection for colorectal cancer: post-

operative and long-term outcomes. J Am Coll Surg 195:196–202

28. Chua HK, Sondenaa K, Tsiotos GG et al (2004) Concurrent vs.

staged colectomy and hepatectomy for primary colorectal cancer

with synchronous hepatic metastases. Dis Colon Rectum

47:1310–1316

29. Cady B, Stone MD (1991) The role of surgical resection of liver

metastases in colorectal carcinoma. Semin Oncol 18:399–406

30. Espi A, Arenas J, Garcia-Granero E et al (1996) Relationship of

curative surgery on natural killer cell activity in colorectal cancer.

Dis Colon Rectum 39:429–434

31. Topal B, Aerts JL, Roskams T et al (2005) Cancer cell dissem-

ination during curative surgery for colorectal liver metastases.

Eur J Surg Oncol 31:506–511

32. Raa ST, Oosterling SJ, van der Kaaij NP et al (2005) Surgery

promotes implantation of disseminated tumor cells, but does not

increase growth of tumor cell clusters. J Surg Oncol 92:124–129

33. Dindo D, Demartines N, Clavien PA (2004) Classification of

surgical complications: a new proposal with evaluation in a

cohort of 6336 patients and results of a survey. Ann Surg

240:205–213

34. Adam R (2007) Colorectal cancer with synchronous liver

metastases. Br J Surg 94:129–131

35. Strasberg SM (1997) Terminology of liver anatomy and liver

resections: coming to grips with hepatic Babel. J Am Coll Surg

184:413–434

36. Moertel CG (1994) Chemotherapy for colorectal cancer. N Engl

J Med 330:1136–1142

37. Douillard JY, Cunningham D, Roth AD et al (2000) Irinotecan

combined with fluorouracil compared with fluorouracil alone as

first-line treatment for metastatic colorectal cancer: a multicentre

randomised trial. Lancet 355:1041–1047

38. Rougier P, Van Cutsem E, Bajetta E et al (1998) Randomised

trial of irinotecan versus fluorouracil by continuous infusion after

fluorouracil failure in patients with metastatic colorectal cancer.

Lancet 352:1407–1412

39. Rothenberg ML, Oza AM, Bigelow RH et al (2003) Superiority

of oxaliplatin and fluorouracil-leucovorin compared with either

therapy alone in patients with progressive colorectal cancer after

irinotecan and fluorouracil-leucovorin: interim results of a phase

III trial. J Clin Oncol 21:2059–2069

40. De Gramont A, Figer A, Seymour M et al (2000) Leucovorin and

fluorouracil with or without oxaliplatin as first-line treatment in

advanced colorectal cancer. J Clin Oncol 18:2938–2947

41. Giacchetti S, Perpoint B, Zidani R et al (2000) Phase III multi-

center randomized trial of oxaliplatin added to chronomodulated

fluorouracil-leucovorin as first-line treatment of metastatic colo-

rectal cancer. J Clin Oncol 18:136–147

42. Glove C, Douse P, Kane F et al (2002) Accuracy of investigations

for asymptomatic colorectal liver metastases. Dis Colon Rectum

45:476–484

43. Hueber RH, Park KC, Sheph JF et al (2000) A meta-analysis of the

literature for whole-body FDG PET. J Nucl Med 41:1177–1189

44. Vall C, Andia E, Sanchez A et al (2001) Hepatic metastases from

colorectal cancer: preoperative detection and assessment of

respectability with helical CT. Radiology 218:55–60

45. Kinkel K, Lu Y, Both M et al (2002) Detection of hepatic

metastasis from cancer of the gastrointestinal tract by using

noninvasive imaging methods (US, CT, MR imaging, PET): a

meta-analysis. Radiology 224:748–756

46. Fong Y, Saldinger P, Akhurst T et al (1999) Utility of 18F-FDG

positron emission tomography scanning on selection of patients

for resection of hepatic colorectal metastases. Am J Surg

178:282–287

47. John TG, Garden OJ (1993) Needle tract seeding of primary and

secondary liver carcinoma after percutaneous liver biopsy. HPB

Surg 6:199–203

48. Fernandez FG, Drebin JA, Linehan DC et al (2004) Five-year

survival after resection of hepatic metastases from colorectal

cancer in patients screened by positron emission tomography with

F-18 fluorodeoxyglucose (FDG-PET). Ann Surg 240:438–450

49. Hillingso JG, Wille-Jorgensen P (2009) Staged or simultaneous

resection of synchronous liver metastases from colorectal cancer:

a systematic review. Colorectal Dis 11:3–10

50. Jaeck D, Bachellier P, Weber JC et al (1996) Surgical treatment

of synchronuos hepatic metastases of colorectal cancer: simul-

taneous or delayed resection. Ann Chir 50:507–512

51. Foster JH, Berman MM (1997) Long-term survival; colon and

rectum metastases. In: Solid liver tumor. Saunders, Philadelphia,

pp 221–225

52. Otchy D, Hyman NH, Simmang C et al (2004) Practice param-

eters for colon cancer. Dis Colon Rectum 47:1269–1284

53. Capussotti L, Ferrero A, Vigano L et al (2007) Major liver

resections synchronous with colorectal surgery. Ann Surg Oncol

14:195–201

World J Surg (2010) 34:2133–2140 2139

123

54. Capussotti L, Vigano L, Ferrero A et al (2007) Timing of

resection of liver metastases synchronous to colorectal tumor:

proposal for prognosis-based decisional model. Ann Surg Oncol

14:1143–1150

55. Elias D, Detroz B, Lasser P et al (1995) Is simultaneous

hepatectomy and intestinal anastomosis safe? Am J Surg

169:254–260

56. Jenkins LT, Millikan KW, Bines SD et al (1997) Hepatic resec-

tion for metastatic colorectal cancer. Am Surg 63:605–610

57. Iwatsuki S, Dvorchik I, Madariaga JR et al (1999) Hepatic

resection for metastatic colorectal adenocarcinoma: a proposal of

a prognostic scoring system. J Am Coll Surg 189:291–299

58. Yamamoto J, Shimada K, Kosuge T et al (1999) Factors influ-

encing survival of patients undergoing hepatectomy for colorectal

metastases. Br J Surg 86:332–337

59. Yasui K, Hirai T, Kato T et al (1997) A new macroscopic clas-

sification predicts prognosis for patient with liver metastases from

colorectal cancer. Ann Surg 226:582–586

60. Taylor M, Forster J, Langer B et al (1997) A study of prognostic

factor for hepatic resection for colorectal metastases. Am J Surg

173:467–471

61. Ekberg H, Tranberg KG, Andersson R et al (1987) Pattern of

recurrence in liver resection for colorectal secondaries. World

J Surg 11:541

62. Scheele J, Stangl R, Altendorf-Hofmann A (1990) Hepatic

metastases from colorectal carcinoma: impact of surgical resec-

tion on the natural history. Br J Surg 77:1241–1246

63. Doci R, Bignami P, Gennari L (1996) Liver metastasis: clinico-

pathological prognostic factors in metastasis from colorectal

cancer. Ann Ital Chir 67:761–765

64. Thelen A, Jonas S, Benckert C et al (2007) Simultaneous versus

staged liver resection of synchronous liver metastases from

colorectal cancer. Int J Colorectal Dis 22:1269–1276

65. Mentha G, Arnaud AD, Sylvain T et al (2008) ‘Liver first’

approach in the treatment of colorectal cancer with synchronous

liver metastases. Dig Surg 25:430–435

66. Allen P, Kemeny N, Jarnagi W et al (2003) Importance of

response to neoadjuvant chemotherapy in patients undergoing

resection of synchronous colorectal liver metastases. J Gastroin-

test Surg 7:109–117

67. Mentha G, Majno PE, Andres A et al (2006) Neoadjuvant che-

motherapy and resection of advanced synchronous liver metas-

tases before treatment of the colorectal primary. Br J Surg

93:872–878

68. Benoist S, Nordlinger B (2007) Neoadjuvant treatment before

resection of liver metastases. Eur J Surg Oncol 33(Suppl 2):535–541

69. Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative

chemotherapy with FOLFOX4 and surgery versus surgery alone

for resectable liver metastases from colorectal cancer (EORTC

Intergroup trial 40983): a randomised controlled trial. Lancet

371:1007–1016

70. Strasberg SM, Belghiti J, Clavien PA et al (2000) The Brisbane

2000 terminology of liver anatomy and resections. HPB (Oxford)

2:333–339

2140 World J Surg (2010) 34:2133–2140

123

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