Simultaneous versus staged liver resection of synchronous liver metastases from colorectal cancer

Article (PDF Available)inInternational Journal of Colorectal Disease 22(10):1269-76 · October 2007with41 Reads
DOI: 10.1007/s00384-007-0286-y · Source: PubMed
The surgical strategy for treatment of synchronous liver metastases from colorectal cancer remains controversial. This retrospective analysis was conducted to compare the postoperative outcome and survival of patients receiving simultaneous resection of liver metastases and primary colorectal cancer to those receiving staged resection. Between January 1988 and September 2005, 219 patients underwent liver resection for synchronous colorectal liver metastases, of whom, 40 patients received simultaneous resection of liver metastases and primary colorectal cancer, and 179 patients staged resections. Patients were identified from a prospective database, and records were retrospectively reviewed. Patient, tumor, and operative parameters were analyzed for their influence on postoperative morbidity and mortality as well as on long-term survival. Simultaneous liver resections tend to be performed for colon primaries rather than for rectal cancer (p = 0.004) and used less extensive liver resections (p < 0.001). The postoperative morbidity was comparable between both groups, whereas the mortality was significantly higher in patients with simultaneous liver resection (p = 0.012). The mortality after simultaneous liver resection (n = 4) occurred after major hepatectomies, and three of these four patients were 70 years of age or older. There was no significant difference in long-term survival after formally curative simultaneous and staged liver resection. Simultaneous liver and colorectal resection is as efficient as staged resections in the treatment of patients with colorectal cancer and synchronous liver metastases. To perform simultaneous resections safely a careful patient selection is necessary. The most important criteria to select patients for simultaneous liver resection are age of the patient and extent of liver resection.
Simultaneous Versus Staged Resection for
Synchronous Colorectal Cancer Liver Metastases
Robert CG Martin II, MD, PhD, FACS, Vedra Augenstein, MD, Nathan P Reuter, MD,
Charles R Scoggins,
MD, MBA, FACS, Kelly M McMasters, MD, PhD, FACS
BACKGROUND: The aim of this study was to compare postoperative outcomes of patients with synchronous
colorectal liver metastases treated with either simultaneous or staged colectomy and
STUDY DESIGN: From July 1997 to June 2008, a review of our 1,344-patient prospective hepato-pancreatico-
biliary database identified 230 patients treated surgically for primary adenocarcinoma of the
large bowel and synchronous hepatic metastasis. Clinicopathologic, operative, and periopera-
tive data, complications, and grade of complications (grade 1, minor, to grade 5, death) were
reviewed to evaluate selection criteria, operative methods, and perioperative outcomes. Chi-
square and proportional hazard model were used to evaluate predictors of outcomes.
RESULTS: Seventy patients underwent simultaneous resection of colon primary and liver metastasis in a
single operation; 160 patients underwent staged operations. Simultaneous resections were
similar for size (median 4 cm versus 3.7 cm) and number (median 3 cm versus 3 cm) of liver
metastases. Major liver resections (3 Couinaud segments) were similar between staged and
simultaneous (32% versus 33%, respectively), as was type of colectomy (p 0.2). Complica-
tion rates and severity were similar in both groups: 39 of 70 patients (56%) in the simultaneous
group experienced 63 complications versus 88 of 160 patients (55%) with 162 complications in
the staged group (p 0.24). Multivariate analysis identified blood transfusion as a predictor of
complication (odds ratio 2.98, p 0.001). Patients having simultaneous resection required
fewer days in the hospital (median 10 days versus 18 days, p 0.001).
CONCLUSIONS: By avoiding a second laparotomy, simultaneous colon and hepatic resection reduces overall
hospital stay, with no difference in morbidity and mortality rates or in severity of complications,
compared with staged resection. Simultaneous resection is an acceptable option in patients with
resectable synchronous colorectal metastasis. (J Am Coll Surg 2009;208:842–852. © 2009 by
the American College of Surgeons)
Synchronous liver metastasis, commonly defined as liver
metastasis occurring within 12 months of the colon pri-
mary, represents 13% to 25% of 90,000 newly diagnosed
colorectal liver metastases.
Through the expansion of
multidisciplinary care with advances in surgical training,
surgical techniques (laparoscopy and ablation), anesthetic
management, and chemotherapy, the overall survival of
these patients has significantly improved over the last 10
years when compared with historical controls.
The optimal timing for surgical resection of synchro-
nous metastasis has been debated and continues to evolve.
Referral bias, institutional bias, and patient bias still dictate
the type and timing of surgical therapy in these patients.
Some series reporting on the surgical management of syn-
chronous colorectal metastasis have recommended a staged
approach, with initial resection of the primary lesion fol-
lowed by hepatic resection 2 to 3 months later
(Table 1).
But the paradigm for surgical management of synchronous
colorectal metastasis has begun to change, with authors
reporting good results for simultaneous resection of the
colon and liver tumors.
Along with this surgical para-
digm change is also the challenge of deciding on the opti-
mal timing of chemotherapy and the effects that chemo-
therapy has on surgical and hepatic toxicity. The primary
goal of this study was to confirm that simultaneous resec-
Disclosure Information: Nothing to disclose.
Presented at the Southern Surgical Association 120th Annual Meeting, West
Palm Beach, FL, December 2008.
Received December 9, 2008; Accepted January 16, 2009.
From the Department of Surgery, Division of Surgical Oncology, University
of Louisville School of Medicine James Graham Brown Cancer Center, Lou-
isville, KY.
Correspondence address: Robert CG Martin II, MD, PhD, FACS, Division
of Surgical Oncology, University of Louisville, Norton Healthcare Pavil-
ion, 315 East Broadway, Ste 311, Louisville, KY 40202.
© 2009 by the American College of Surgeons ISSN 1072-7515/09/$36.00
Published by Elsevier Inc. doi:10.1016/j.jamcollsurg.2009.01.031
tion is similar to staged resection with regard to morbidity
and mortality.
A review of a 1,344-patient prospective hepato-pancreatico-
biliary database at the University of Louisville, Division of
Surgical Oncology, identified 230 patients who underwent
resection of a primary colorectal cancer and a synchronous
hepatic metastasis from July 1997 to June 2008. Synchro-
nous hepatic metastases were defined as those identified at
the time of diagnosis of the primary colon cancer. All colon
and hepatic resections were performed by surgeons at the
University of Louisville Department of Surgery.
The decision to perform either a staged or simultaneous
resection was determined by the treating hepatobiliary sur-
geon or in collaboration with the colon surgeon and the
hepatobiliary surgeon. Ultimately, once the oncologic de-
cision is made that surgery is indicated, the decision to
perform a synchronous resection or staged resection is
based on the complexity of the hepatectomy, complexity of
the colon or rectal resection, and the comorbidities of the
patient. The decision to perform resection or radiofre-
quency ablation was determined at the discretion of the
treating surgeon. In the patients undergoing hepatic re-
sections, anatomic segmental liver resections were performed
and classified as described by Couinaud.
resections were per formed when judged appropriate by
the attending surgeon. For patients with disease that was
believed to be unresectable because of the number, dis-
tribution, or location of the tumors, or because of pa-
tient comorbid factors, ablation was performed. Our
group has agreed and uses the recent Society of Surgical
Oncology (SSO) and the American Hepato-Pancreato-
Biliary Association (AHPBA) Consensus Conference in
that the definition of resectability is the ability to resect
and ablate all visible disease and leave enough liver be-
hind for an appropriate recovery time.
Standard pre-
operative evaluation of patients with metastatic colorec-
tal cancer included three-phase CT of the abdomen and
pelvis and chest x-ray. Earlier systemic chemotherapy of
any type and duration was allowed. Radiofrequency ab-
lation was per formed using intraoperative ultrasonogra-
phy guidance to ensure that at least a 1-cm ablation
margin was achieved around the tumors.
The technique for anesthetic management during hep-
atectomy has been previously reported.
In principle, we
use a low central venous pressure ( 5 mmHg) while main-
taining a urine output of 25mL/h and a systolic blood
pressure 90 mmHg during parenchymal transection.
Because of this desire, in patients who are undergoing syn-
chronous resection, the liver resection is usually performed
first so that volume can then be given during the colon
resection portion of the procedure. After the specimen is
Table 1. Published Results of Simultaneous Versus Staged Resection for Synchronous Colorectal Hepatic Metastasis
Author Year n Type of resection, n Morbidity, % Mortality, %
1991 36 19 simul
17 staged
1991 98 60 simul
38 staged
nr 2
1993 46 22 simul
24 staged
nr nr
1995 53 53 simul 19 0
1996 41 20 simul
21 staged
1996 1,008 115 simul
893 other
nr 7
2000 165 50 simul
115 other
nr 12
2000 97 83 simul
14 staged
58 0
2001 112 26 simul
86 staged
De Santibanes
2002 71 71 simul 21 0
2003 240 134 simul
106 staged
2007 610 135 simul
475 staged
nr, not recorded; other, staged and metachronous resections; simul, simultaneous resection.
843Vol. 208, No. 5, May 2009 Martin et al Simultaneous Colon and Hepatic Resection
removed, crystalloid is administered IV to achieve euvol-
emia. Packed red blood cells and autologous blood is usu-
ally given to maintain a hemoglobin 10 g/dL in patients
with evidence of either coronary or cerebrovascular disease.
Intraoperative blood products are not administered until
blood loss exceeds 25% of the total blood volume.
Outflow control of the hepatic veins before parenchymal
division was nearly always obtained in lobectomy or ex-
tended resections. The liver parenchyma was divided using
Kelly clamps to crush liver tissue and expose bile ducts and
blood vessels, which were clipped, tied, or stapled, or uti-
lized a hemostatic assist device. Intermittent inflow vascu-
lar occlusion (the Pringle maneuver)
was used and ap-
plied for 5- to 10- minute intervals, released briefly, and
reapplied as necessary. Pringle time was recorded as the
total cumulative Pringle time applied during parenchymal
Postoperative complications and length of hospital stay
were recorded and then graded using our standard classifi-
cation scale of complications which has been reported pre-
For patients with more than one complication,
comparison of in-hospital and 90-day postoperative com-
plications were evaluated by assigning the complication
with the highest severity level for each patient. Complica-
tions were defined by published criteria.
Earlier cardiac
history was defined as a history of angina, previous coro-
nary artery disease defined by cardiac catheterization, pre-
vious myocardial infarction, cardiac valve dysfunction re-
quiring medication, or a history of congestive heart failure
or tachyarrhythmia. Earlier pulmonary disease history was
defined as abnormal pulmonary function tests, history of
asthma requiring daily meter-dosed inhalers, or tobacco
use greater than a 25-pack of year history. All patients were
reviewed and classified using a preoperative Clinical Risk
Score prognostic scoring system defined for colorectal me-
This five-point preoperative clinical score evalu-
ates patients by five factors: disease-free interval of less than
12 months, CEA 200 ng/ml, lymph-node positive pri-
mary, more than one hepatic lesion, and hepatic lesion 5
cm in size.
Chi-square, Student’s t-test, and Mann-Whitney U
test for nominal, continuous, and ordinal variables were
used to evaluate the association of independent variables
to surgical complications. Proportional hazards analysis
was per formed on all variables found significant by uni-
variate analysis. Relative risk (RR) with 95% confidence
intervals was calculated as a measure of association. Dif-
ferences of p 0.05 were considered significant. Statis-
tical analysis was performed using JMP software ( JMP;
SAS Institute Inc).
A total of 230 patients were treated for synchronous colo-
rectal hepatic metastasis. There was an even distribution of
women (staged resection, 43% versus simultaneous resec-
tion, 46%) and men (staged, 57% versus simultaneous,
54%), with a median age of 61 years (range 23 to 85 years)
for staged and 58 years (range 27 to 78 years) for simulta-
neous. All other earlier medical history and comorbidites
were similar for both the staged and simultaneous groups
(Table 2). The primary colorectal adenocarcinoma was lo-
cated within the right colon (staged, 33% versus simulta-
neous, 45%), left colon (staged, 34% versus simultaneous,
Table 2. Patient Demographics
(n 160)
(n 70) p Value
Race, %
Caucasian 80 86
African American 8 8 ns
Gender, %
Female 43 46 0.7
Male 57 54
Age, y 61 58 0.06
Cardiac history, %
Yes 86 87 0.8
No 14 13
Pulmonary history, %
Yes 5 3 0.4
No 95 97
Diabetes, %
Yes 10 18 0.2
No 90 82
Alcohol history, %
Yes 9 15 0.2
No 91 85
Tobacco use
Yes, % 42 47 0.6
No, % 72 72 0.9
Mean pack years: yes, n 42 47 0.6
Earlier hepatic disease, %
Yes 0 0 ns
No 100 100
Hypertension, %
Yes 33 34 ns
No 67 66
Earlier thrombotic event, %
Yes 4 6 ns
No 96 94
Earlier abdominal surgery, %
Yes 13 15 0.6
No 87 85
844 Martin et al Simultaneous Colon and Hepatic Resection J Am Coll Surg
23%), or rectum (staged, 23% versus simultaneous, 30%).
The majority of patients presented with rectal bleeding or
anemia. A small minority presented with obstruction
(n 15, 7%) or perforation (n 3, 1%).
Seventy patients underwent simultaneous resection of a
colorectal primary and hepatic metastasis. These patients
were compared with 160 patients who underwent staged
resection. The extent of hepatic disease was similar, with
staged patients found to have similar numbers of hepatic
metastases (p 0.6) and metastases (p 0.1) when com-
pared with patients undergoing simultaneous resection
(Table 3). Overall, the patients subjected to a staged resec-
tion were at similar risk as the simultaneous group in terms
of longterm prognosis as defined by the metastatic colorec-
tal risk score (Table 3).
Right hemicolectomy was more common in the simul-
taneous group, although there were more left hemicolecto-
mies in the staged group (Table 3). Simultaneous resection
was associated with a significantly greater number of he-
patic ablations and hepatic wedge resections ( Table 3), with
the staged group having a greater number of segmental
resections, which accounted for the greatest difference in
surgical procedures between the two groups. There were
similar proportions of major hepatic resections ( 3 seg-
ments) performed for both groups. The tendency to per-
form major liver resections as simultaneous procedures was
not significantly influenced by the location of the primar y
colon cancer. There was similarity in the simultaneous ma-
jor hepatic resection patients who required right or left
colectomy.There was also similarity among patients requir-
ing rectal resection, and major hepatic resections were per-
formed equally in both groups.
Overall operative duration for the staged group was a
median of 235 minutes (range 70 to 400 minutes), which
was longer than for the simultaneous group, whose opera-
tions lasted a median of 180 minutes (range 80 to 420
minutes, Tables 46). The median operative blood loss for
the simultaneous group was 300 mL (range 20 to 1,500
mL), compared with the staged group, which had a median
blood loss of 350 mL (range 100 to 1,500 mL) for colec-
tomy and hepatectomy (p 0.9). In the 70 patients who
underwent a simultaneous resection, 35 (50%) patients
received blood transfusion during their hospitalization. In
the 160 patients who underwent a staged resection, 72
(45%) patients received a blood transfusion during one of
their hospitalizations. The length of hospital stay was also
significantly shorter for the simultaneous resections than
for the combined hospitalizations of the staged colorectal
and hepatic resections (Table 7). Even when patients with
major liver resections (lobectomy or more) were consid-
Table 3. Extent of Disease and Resection Performed in
Patients with Resectable Synchronous Hepatic Metastasis
(n 160)
(n 70)
Liver lesions, n, median
(range) 3 (1–8) 3 (1–16) ns
Size of lesions, cm,
median (range) 4 (0.8–13.0) 3.7 (0.3–8.8) ns
CEA, ng/ml, median
(range) 14.7 (0.8–1,300) 34.5 (1.3–597) 0.6
Primary resection, %
Right colectomy 33 45
Left colectomy 34 23
Low anterior resection 15 23 ns
resection 8 7
Total colectomy 10 10
Node-positive colon, %
Yes 63 68 0.5
No 37 32
Location of lesions,
segment, %*
Earlier chemotherapy, %
5-FU 54 43
Oxaliplatin 30 34
Irinotecan 17 2 0.001
Other 39 43
No 30 48
Duration of
mo, n (median) 3 (0–12) 0 (0–13) 0.01
Metastatic colorectal risk
score, %
2 22 16 0.83
Liver ablation/resection*
Ablation 46 57
Wedge 15 36 0.2
Segmental 29 18
Lobe 40 47
*P ercentages are greater than 100% because some patients presented with bilobar
disease and underwent multiple types of liver ablation or resection techniques.
845Vol. 208, No. 5, May 2009 Martin et al Simultaneous Colon and Hepatic Resection
ered, operative time, blood loss, and length of stay were
significantly longer for the staged resections.
Complications after all surgical procedures occurred in
127 of 230 (55%) patients. In the simultaneous group, 39
(55%) patients sustained 63 complications. In the staged
group, 88 (55%) different patients experienced 162 com-
plications for both hospitalizations. When the types of
complications were evaluated, the difference in the overall
complication rates between the simultaneous and the
staged groups primarily occurred from the need for a sec-
ond laparotomy in the staged group (Table 4). When the
specific laparotomy complications were evaluated, there
was an increase in the number in staged patients (Table 4).
When the hepatectomy (hepatic fluid or abscess) and co-
lonic complications (pelvic abscess or anastamotic leak)
were evaluated, there was no difference in procedure-
specific complications. The overall complication rate for
simultaneous resection (56%) was similar for staged resec-
tions (55%; p 0.9). This was true even when the analysis
was restricted to the 97 patients who underwent major liver
resection (lobectomy or greater), with the overall compli-
cations of simultaneous resections (17 of 33, 50%) being
significantly less than for staged resections (38 of 64, 60%;
p 0.04; Table 7).
When the complications were graded by severity, the
relative distribution of mild complications (grades 1 and
2), moderate complications (grades 3 and 4), and periop-
erative mortality (grade 5) was found to be similar between
the groups, with a greater risk of grade 2 complications in
the staged patients and risk of grade 3 in the simultaneous
patients (Table 5). There was a greater incidence of mild
complications (grades 1 and 2) in the staged group (68%)
when compared with the simultaneous group (53%). An
increased proportion of complications were severe (grades
3 and 4) in the simultaneous group (45%) compared with
the staged group (32%). There was no significant differ-
ence in operative mortality rates (simultaneous, 1 [2%]
versus staged, 3 [2%]). When only the most severe compli-
cation was considered for each patient, the relative propor-
tion of mild (grades 1 and 2) and severe (grades 3 and 4)
complications was not found to be different in the staged or
simultaneous groups (Table 6).
Table 5. Severity of All Complications Occurring in 127 Pa-
1, %
2, %
3, %
4, %
5, %
(n 39) 63 17 36 45 0 2
(n 88) 162 15 53 30 2 2
Table 6. Most Severe Complication for Each Patient
Most severe grade
(n 88), %
(n 39), % p Value
Grades 1 and 2 25 16 0.1
Grades 3 and 4 21 19 0.5
Grade 5 2 2 ns
Table 7. Outcomes and Complications after Staged or
Simultaneous Resection Involving Major Liver Resections
( Lobectomy/ Segments)
(n 64)
(n 33)
Operative time, min
(range) 268 (195–793) 202 (203–445) 0.06
Total blood loss, mL
(range) 750 (250–1,500) 450 (100–1,500) 0.01
Length of stay, d
(range) 18 (7–54) 12 (5–31) 0.001
Total complications, n 68 35 ns
Total patients with
complications, n (%) 38 (60) 17 (50) 0.6
Total patients with
grade 3 or 4
complications, n (%) 18 (28) 5 (15) 0.24
Mortality, n (%) 1 (4) 0 (0) ns
Table 4. Outcomes and Complications after Staged or Si-
multaneous Resection
(n 160)
(n 70)
Complications, n (%)
Yes 88 (55) 39 (56) ns
No 72 (45) 31 (45)
complications, n
Wound infection 8 6
Ileus 10 9 0.001
Pulmonary 16 2
Cardiac 11 2
Pelvic abscess 2 2 ns
Hepatic fluid/
abscess 9 6 ns
Hepatic failure 8 1 ns
Operative time, min
(range) 235 (70–400) 180 (80–420)
Total blood loss, mL
(range) 350 (100–1,500) 300 (20–1,500) 0.9
Units of blood, n
(range) 2 (1–10) 2 (1–10)
Length of stay, d
(range) 18 (6–54) 10 (5–63) 0.001
846 Martin et al Simultaneous Colon and Hepatic Resection J Am Coll Surg
The patient population was then analyzed for factors
predictive of any complication after surgical resection. Uni-
variate analysis did not demonstrate a significant difference
in complications when age, gender, preoperative cardiac
history, diabetes, preoperative pulmonary disease, albumin
at the time of colectomy or hepatectomy, hemoglobin at
the time of colectomy or hepatectomy, preoperative to-
bacco use, hypertension, type of chemotherapy, duration of
chemotherapy, blood loss at the time of colectomy, duration of
colectomy, type of colectomy, or Pringle time were examined
(Table 8). F actors found to be significant on both univariate
and logistic regression were extent of hepatic resection or
ablation and blood loss at liver resection (Table 8). The
trend toward an increased rate of complications stems from
the greater number of patients who underwent both he-
patic ablations and minor resections simultaneously, dem-
onstrating a greater disease burden treated in these patients,
in both the staged and simultaneous groups. There was an
increase in complications for patients who underwent ab-
lation, potentially related to the increased amount of he-
patic parenchyma that was ablated in combination with a
colectomy, but volume of ablation was not recorded in this
study so this trend is unproved at this time.
Approximately 23% to 51% of the 157,000 new colorectal
cancer patients will present with synchronous colorectal
cancer and liver metastasis.
Validation and optimization
of established treatment criteria and oncologic guidelines
are imperative to improved progress in patient survival,
morbidity, mortality, and hospital stay.
Optimal manage-
ment of patients with synchronous colorectal hepatic me-
tastasis remains a multifactorial treatment strategy, based
on symptoms, location and extent of disease, and the pa-
tient’s per formance status and underlying comorbidities.
The data presented here demonstrate that simultaneous
major hepatic resection ablation with colectomy is safe,
with less overall morbidity, shorter overall hospital stay, and
similar mortality. Additional benefits are the avoidance of a
potential delay in surgical therapy for the metastatic disease
and a reduction in the risk that these metastases could
spread if untreated.
There are several methods for the optimal treatment of
metastatic colorectal cancer that are currently in practice.
All demonstrate the efficacy of combination surgical resec-
tion or ablation with chemotherapy and the addition of
radiation therapy for rectal primaries. Traditional surgical
training has mandated removal of the primary tumor in
management of synchronous metastatic colorectal cancer
to avoid obstruction or bleeding. But with the advent of
colonic stents and with the significant primary tumor re-
sponse rates, this approach is dramatically changing. The
optimal timing of therapy (ie, chemotherapy first, liver
first, colon first, or combined resection) is less about the
diagnosis of metastatic colorectal cancer and more about
the extent of disease, risk of disease, and patients’ perfor-
mance status.
Recent reports have demonstrated the benefits of the
perioperative or neoadjuvant chemotherapy approach.
There are multiple reports demonstrating the benefits of
chemotherapy before resection of the liver metastasis to
downstage a patient’s disease to a resectable point or to
better assess the overall tumor biology
and determine if
surgical resection will be beneficial.
But duration of che-
motherapy is of utmost importance, and it should be used
only to assess if there is a response, not to maximize treat-
ment response, because of the deleterious effects of long-
term chemotherapy use.
In addition, neoadjuvant chemotherapy may treat mi-
croscopic disease immediately, allow for additional disease
to declare itself, and assess the effectiveness of the treatment
Some also believe that chemotherapy should be
given in metastatic colorectal cancer before resection of
even the primary lesion. It has been reported that resection
of the primary lesion gives minimal palliative benefit and in
turn, can increase mortality, morbidity, and delay in bene-
ficial chemotherapy.
In the last decade we have achieved significant advance-
ments in hepatobiliary surgical training (far greater num-
ber of surgeons), hepatobiliary techniques (laparoscopic
resections and hepatic ablation technology), anesthetic
management, and overall critical care, which has made he-
patic resection safer and increased overall quality of life.
Recent data have demonstrated that even major liver resec-
tions are now done with minimal morbidity and mortality.
Intuitively, it appears that reco very from one major operation
(open or laparoscopic) is faster than from two. Multiple stud-
ies show that performing a simultaneous colectomy and hep-
atectomy results in similar mortality and morbidity rates, but
shorter hospital stays than for staged operations.
In addi-
tion, the two groups have similar operative times, intraopera-
tive blood loss, and complications.
Additional factors such as risk of undergoing general
anesthesia twice and interruption of chemotherapy need to
be taken into consideration when deciding whether to do a
staged versus simultaneous operation. Resistance to change
and to new methods of treatment is not a new phenome-
non in medicine. The most current data about simulta-
neous colon and liver resections are still evolving. Many
patients present to small centers where they are able to get
only a part of their therapy and they may not be referred to
another center until they have already had a resection or
847Vol. 208, No. 5, May 2009 Martin et al Simultaneous Colon and Hepatic Resection
chemotherapy. General practitioners, surgeons, and on-
cologists need to have the understanding and the confi-
dence that these data are the guides to optimal treatment of
metastatic colorectal cancer at this time.
It takes a huge
amount of coordination to treat a patient with metastatic
colorectal cancer, and guidelines for treatment are essential
for optimal outcomes for these patients.
In the past, several studies advocating simultaneous re-
sections indicated that major hepatectomies should be
done separately from colorectal resections.
The data
showed an increased mortality with an anatomic lobec-
tomy during a combined procedure.
Our data showed
no difference in mortality, morbidity, and severity of com-
plications between the staged and simultaneous resection
groups, even with major liver resections (Table 7). The
major differences in our data when compared with data
from Reddy and coworkers
are the very tight interval of
this analysis (10 years versus 21 years for Reddy and col-
leagues’ work), in which there have been significant ad-
vances in operative and anesthetic techniques, and our lack
of effect from neoadjuvant chemotherapy on hepatic resec-
tion. We analyzed the severity of complications with major
and minor liver resections and similar colorectal procedures
and found no statistical difference between the results from
the two groups. Only extent of blood loss was a significant
factor of complication (odds ratio 2.98, p 0.001) in
these two groups.
The limitations of this study are that it is a retrospective
review of our prospective database and demonstrates the
surgical bias and training of the three lead authors (RCGM,
CRS, and KMM). This has led to the equal distribution of
surgical management, staged versus simultaneous, but is
also confirmator y of the surgical outcomes.
In conclusion, simultaneous resection of the colon pri-
mary lesion and hepatic metastasis is safe, acceptable, and
supported by our and multiple other studies. The role of
chemotherapy remains in place and the optimal timing of
therapy should be based on multiple factors including the
patient’s extent of disease, comorbidities, body habitus,
Table 8. Evaluation of Factors Predictive of All Complica-
tions after Surgical Procedures
Factor Complication Univariate Multivariate
Age, y, median
Yes 60 0.6 ns
No 61
Gender, %
Male 50 0.3 ns
Female 44
Cardiac history, %
Yes 39 0.4 ns
No 48
Pulmonary history, %
Yes 67 0.2 ns
No 46
Past alcohol history, %
Yes 49 0.01 ns
No 21
Past abdominal surgery, %
Yes 56 0.06 ns
No 41
Any preoperative
chemotherapy, %
Yes 60 0.1 ns
No 40
Type of chemotherapy, %
5-FU 44 0.06
Irinotecan 9 0.08 ns
Oxaliplation 29 0.5
Other 37 0.6
Duration of
mo, median
Staged 3 0.5 ns
Simultaneous 0
Type of colectomy, %
Right 33 0.1 ns
Left 20
Low anterior resection 12
resection 8
Extent hepatic resection,
Lobe 62 0.03 1.4 (1.0–1.9)
Lobe 38
Blood loss, median, mL 250 0.001 2.98 (1.5–3.2)
Timing of resection, %
Simultaneous 56 0.3 ns
Staged 55
Table 8. Continued
Factor Complication Univariate Multivariate
Type of liver resection/
ablation, %
Ablation 44 0.02 ns
Left lateral segment 9
Left lobectomy 8
Right lobectomy 19
Right posterior
segment 4
Wedge resections 15
Lobe 34
848 Martin et al Simultaneous Colon and Hepatic Resection J Am Coll Surg
and the experience of the operating surgeon(s) to provide
the best care. At initial diagnosis, metastatic colorectal can-
cer is best treated with a team approach including one or
more surgeons (based on surgical specialty), medical on-
cologists, and radiation oncologist if needed. Such practice
will allow for patients to have their cancer treated more
quickly and efficiently and get more out of hospital time,
but without increased risks.
Author Contributions
Study conception and design: Martin
Acquisition of data: Martin, Augenstein, Reuter
Analysis and interpretation of data: Martin, Augenstein, Scog-
gins, McMasters
Drafting of manuscript: Martin, Augenstein, Scoggins,
Critical revision: Martin, Reuter, Scoggins, McMasters
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DR C WRIGHT PINSON (Nashville, TN): This paper retrospec-
tively looked at 70 patients who underwent simultaneous resection
versus 160 patients who underwent staged resections. And I’m going
to suggest that the retrospective approach does leave us open to some
selection bias; there was an application here of the surgeon’s judg-
ment. I submit that there is no difference in outcomes when that
surgeon’s judgment is applied. It’s not the same as saying that if you
take all comers there is no difference. I think we need to conclude
that simultaneous resection is acceptable when in the surgeon’s judg-
ment the extent of the disease, the level of comorbidities, and the
technical conduct of the operation are all favorable. That’s somewhat
different than the conclusion stated.
Second, I would like to ask a question about the median length of
stay. Both 10 days for the liver resection and 18 days for the com-
bined operation on a staged approach seem a little long to me, and I’d
like to you comment on those lengths of stays.
Third, what order do you do the simultaneous operation in and
how do you decide? Because you found that the only prediction of
complication, or the only two predictions of complications were the
lobectomy as a more major operation, and blood loss. I wonder if that
has influenced the order that you do the operation. Would you do the
liver resection first now?
My final question has to do with looking at the number of lesions
removed; I noticed that in some cases they were up to 16. So I would
like to hear about your indications for resection of liver metastases,
and can you tell us about the median and longterm survival figures
for these groups of patients?
DR BRYAN M CLARY (Durham, NC): In brief summary, this
group provides yet another in a growing list of reports that detail the
surgical outcomes of patients with synchronous hepatic metastasis.
As Dr Martin pointed out, he is no stranger to this topic, having
authored what I think is one of the seminal papers in the field.
In the experience reported today, he and his colleagues compared
the outcomes of 150 patients undergoing staged resections with 70
patients who did not. This is a contemporary experience spanning 11
years, and it is important to emphasize that the colorectal resection of
all staged patients was performed at Louisville. This fact represents, I
think, the strength of this report and is in contrast to many reports on
the topic originating from tertiary hepatic experiences where the
primary tumor resection was not necessarily performed in the same
I will not restate your results as I would rather listen to you ex-
pound on the implications of your findings. Ultimately your experi-
ence complements the existing literature that suggests we can per-
form simultaneous resections in selected patients with a degree of
morbidity comparable to those performed in a staged manner.
I don’t know that your comments on patients requiring major
hepatectomy are biased, as you know, and partially pointed out in
your introductory comments, is to be very selective in those patients,
although I think we would also agree from our experience authored
by Reddy that in patients requiring minor hepatectomy it is likely
The simultaneous approach appears to have advantages with re-
spect to patient convenience and possible cost-associated measures
including length of stay, operative time, et cetera. I think it would be
a mistake, though, to simply leave it as that, as there are broader
implications of your findings.
Aside from what systemic therapy should be given to patients, the
appropriate timing of the modes of therapy, I think, is fundamental
as the most important question in these patients. If in fact a simul-
taneous approach is equivalent in morbidity and offers other advan-
tages, it clearly necessitates even more an integrated approach with
medical oncologists, hepatic surgeons, and colorectal surgeons. For
the rectal cancer patient population you would also include the ra-
diation oncologist.
I have a few questions. One of the criticisms of performing simul-
taneous hepatic resections is that early recurrences are theoretically
more likely; these patients have not been selected by time and/or
850 Martin et al Simultaneous Colon and Hepatic Resection J Am Coll Surg
    • "A meta-analysis of 2,880 patients with SCRLM who were followed up for at least 36 months reported that simultaneous resection is as safe as delayed resection as long as patients were less than 70 years old and without severe coexisting disease [39]. Similarly, in the study of Thelen et al. [40], patients with the simultaneous approach had far higher mortality than staged, which was associated with age >70 years and major hepatectomy. Furthermore, a time test approach has been suggested by some authors favoring the staged strategy to evaluate the biological behavior of the metastatic disease, to treat potentially occult disease, and to avoid liver resection in patients with rapidly progressing disease [41]. "
    [Show abstract] [Hide abstract] ABSTRACT: Ideally, tumors that might cause morbidity and mortality should be treated, preferably early, with proven, convincing, and effective therapy to prevent tumor progression or recurrence, while maintaining a favorable risk-benefit profile for the individual patient. For patients with colorectal cancer (CRC), this diagnostic, prognostic, and therapeutic precision is currently impossible. Despite significant improvements in diagnostic procedures, a sizable number of patients with CRC have liver metastases either at presentation or will subsequently develop it. And in many parts of the world, most cancer-related deaths are still due to metastases that are resistant to conventional therapy. Metastases to the liver occur in more than 50% of patients with CRC and represent the major determinant of outcome following curative treatment of the primary tumor. Liver resection offers the best chance of cure for metastases confined to the liver. However, due to a paucity of randomized controlled trials, its timing is controversial and a hotly debated topic. This article reviews some of the main controversies surrounding the surgical management of colorectal cancer liver metastases (CRLM). Electronic supplementary material The online version of this article (doi:10.1186/s12957-014-0420-6) contains supplementary material, which is available to authorized users.
    Full-text · Article · Dec 2015
    • "The subgroup analysis showed that the baseline imbalance of preoperative chemotherapy did not interfere with the postoperative morbidity (Details inFigure S8). However, only 6 studies [6,8,9,19,22,23] reported both preoperative chemotherapy and long-term survival after operations. Because of lacking of essential data, we were unable to correct the baseline imbalance of preoperative chemotherapy for long-term survival. "
    [Show abstract] [Hide abstract] ABSTRACT: The optimal timing of resection for synchronous colorectal liver metastases is still controversial. Retrospective cohort studies always had baseline imbalances in comparing simultaneous resection with staged strategy. Significantly more patients with mild conditions received simultaneous resections. Previous published meta-analyses based on these studies did not correct these biases, resulting in low reliability. Our meta-analysis was conducted to compensate for this deficiency and find candidates for each surgical strategy.
    Full-text · Article · Aug 2014
    • "Although some preliminary studies have reported their experience dealing with laparoscopic or open simultaneously resection for CLM, our subgroup analysis hits 3 studies comparing both surgical approaches. Pooled outcome demonstrates laparoscopic hepatectomy and colectomy synchronously did not increase morbidity and overall survival which was accordance with reported researches [42,45]. Proper patient selection for laparoscopic and open hepatectomy for CLM remains a major topic the surgeons focus on. "
    [Show abstract] [Hide abstract] ABSTRACT: To compare short-term and long-term results of colorectal patients undergoing laparoscopic and open hepatectomy. Moreover, outcomes of laparoscopic versus open procedures for simultaneous primary colorectal tumor and liver metastasis resection were compared. A systematic search was conducted in the PubMed and EmBase databases (until Oct. 22. 2013) with no limits. Bibliographic citation management software (EndNote X6) was used for extracted literature management. Quality assessment was performed according to a modification of the Newcastle-Ottawa Scale. The data were analyzed using Review Manager (Version 5.1), and sensitivity analysis was performed by sequentially omitting each study. Finally, 14 studies, including a total of 975 CLM (colorectal liver metastasis) patients, compared laparoscopic with open hepatectomy. 3 studies of them, including a total of 107 CLM patients, compared laparoscopic with open procedures for synchronous hepatectomy and colectomy. Laparoscopic hepatectomy was associated with a significantly less blood loss, shorter hospitalization time, and less operative transfusion rate. In addition, lower hospital morbidity rate (OR = 0.57, 95%CI:0.42-0.78, P = 0.0005) and better R0 resection (OR = 2.44, 95%CI:1.21-4.94, P = 0.01) were observed in laparoscopic hepatectomy. For long-term outcomes, there were no significant differences between two surgical procedures on recurrence and overall survival. In comparison of synchronous hepatectomy and colectomy, laparoscopic procedure displayed shorter hospitalization (MD = -3.40, 95%CI:-4.37-2.44, P<0.00001) than open procedure. Other outcomes, including surgical time, estimated blood loss, hospital morbidity, and overall survival did not differ significantly in the comparison. Laparoscopic hepatectomy with or without synchronous colectomy are acceptable for selective CLM patients. We suggest standard inclusion criteria of CLM patients be formulated.
    Full-text · Article · Jan 2014
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