One-stage ultrasonographically guided

hepatectomy for multiple bilobar

colorectal metastases: A feasible and
effective alternative to the 2-stage
approach
Guido Torzilli, MD, PhD, Fabio Procopio, MD, Florin Botea, MD, Matteo Marconi, MD,
Daniele Del Fabbro, Matteo Donadon, MD, Angela Palmisano, MD, Antonino Spinelli, MD,
and Marco Montorsi, MD, Milan, Italy

Background. Two-stage hepatectomy with or without portal vein embolization allows treatment of
multiple bilobar metastases, thereby expanding operative indications for these patients. Two operations
are needed, however, and some patients are not able to complete the treatment strategy because of disease
progression. Using experience gained from our policy of ultrasonographically guided resection, we
explored the safety and effectiveness of 1-stage operative procedures in patients otherwise recommended for
the 2-stage approach.
Methods. A total of 29 patients with multiple ($4) bilobar colorectal liver metastases (CLM) were selected from 100 consecutive patients submitted to surgical resection. The total number of preoperative
CLM was 163 (median, 5; range, 2--20). The operative strategy was based on tumor-vessel relationships
at intraoperative ultrasonography (IOUS) and on findings at color Doppler IOUS.
Results. There was no in-hospital mortality. Tumor removal was feasible with 1-stage operative
procedures in all but 3 patients who underwent laparotomy. The overall morbidity rate was 23%
(6/26); none of the patients required reoperation. Major morbidity occurred in 1 patient (4%). Blood
transfusions were administered in 4 patients (15%). After a mean follow-up of 17 months (median, 14;
range, 6--54), 3 patients had died from systemic recurrence, 12 patients were alive without disease, and
11 were alive with disease. No local recurrences were observed at the resection margin.
Conclusion. IOUS-guided resection based on strict criteria allows a 1-stage operative treatment in selected
patients with multiple bilobar CLM. This strategy decreases the need for a two-stage hepatectomy, thereby
avoiding the disadvantages of a 2-stage approach. (Surgery 2009;146:60-71.)
From the Third Department of General Surgery, University of Milan, IRCCS Istituto Clinico Humanitas,
Rozzano, Milan, Italy

OPERATIVE TREATMENT OF COLORECTAL LIVER METASTASES

(CLM) remains the gold standard therapy, limited
only by its technical feasibility.1 The key to the procedures success is leaving enough remnant liver to ensure patient survival. In cases of multiple and bilobar
Supported in part by a research grant from the Cesare Banno`
Foundation for Cancer Research.
Accepted for publication February 13, 2009.
Reprint requests: Guido Torzilli, MD, PhD, Associate Professor
of Surgery, Chief, Liver Surgery Unit, Third Department of Surgery, University of Milan, IRCCS Istituto Clinico Humanitas, Via
Manzoni 56, 20089 Rozzano, Milan, Italy. E-mail: guido.torzilli@
unimi.it.
0039-6060/$ - see front matter
2009 Mosby, Inc. All rights reserved.
doi:10.1016/j.surg.2009.02.017

60 SURGERY

CLM, the most commonly used operative approach

is a 2-stage hepatectomy.2 This multistep strategy
uses limited resections and major hepatectomies
with or without preresection portal vein embolization (PVE).2,3 This method also allows extending
operative indications to those patients previously
judged to be unresectable, because the metastatic
disease would demand the removal of too much
liver parenchyma for the resection to be curative.
This approach, however, has some drawbacks. Two
operations are needed, each of which is associated
with mortality and morbidity. In addition, some
patients do not complete this treatment approach
because of tumor progression during the interval
between the 2 surgical procedures or after PVE.
A possible alternative, however, does exist. We
have shown, both for primary and metastatic liver

Torzilli et al 61

Surgery
Volume 146, Number 1

DL

DL

CLM

DL
CLM

G A
B
P

CLM
G A
B
P

HV

E
DL

CLM
G A
B
P

CLM

DL
HV

Fig 1. Operative strategy based on intra-operative ultrasonography tumor type, appearance, and relation between
colorectal liver metastases (CLM) and major hepatic vessels: (A) <0.5 cm distance between the CLM and the Glissonian
pedicle (G); (B) <0.5 cm distance between the CLM and the hepatic vein (HV); (C) contact <1/3 circumference
between the CLM and G; (D) contact >1/3 circumference between the CLM and G; (E) contact between the CLM
and HV. The dotted line shows the dissection line (DL). A, Artery; B, bile duct; P, portal branch.

neoplasms, that a well-defined policy of ultrasonically guided hepatectomy allows us to carry out
radical operations safely and without major removal of liver parenchyma in the vast majority of
patients, even when the tumors have complex
presentations such as multiplicity and vascular
invasion.4-7 Using information gleaned from this
experience, we explored the feasibility, safety,
and effectiveness of a 1-stage operative procedure
in a prospective cohort of patients who otherwise
would have undergone the 2-stage approach.
METHODS
Terminology. The terminology for liver anatomy
and resections used in this study is based on the
Brisbane classification.8 Hepatic resections are
considered major when at least 3 adjacent segments
are removed. The hepatic vein (HV) at the caval
confluence, the so-called hepatocaval confluence,
was defined as the last 4 cm of the HV before its
confluence into the inferior vena cava (IVC). Postoperative death was analyzed at 30 days and 90 days
after operation. Any adverse event that required
additional operative treatment or any invasive
corrective procedure was considered a major
postoperative morbidity. Liver failure was considered mild when the total serum bilirubin concentration ranged from 2 to 5 mg/dL for >3 days
postoperatively, medium when it ranged from 5 to

10 mg/dL for >3 days postoperatively, and severe

when it exceeded 10 mg/dL for >3 days postoperatively.9 Local tumor recurrence was defined as
recurrence at the cut-edge (true local recurrence),
and was analyzed after a minimum follow-up of
6 months.
Eligibility criteria. Inclusion criteria for the
current study were as follows: (1) patients presenting with resectable CLM; (2) 4 or more lesions;
(3) bilobar involvement of the liver; (4) contact or
close adjacency (<0.5 cm) of at least 1 CLM with a
major intrahepatic vascular structures (first- or
second-order portal branches and/or HV at caval
confluence). A criterion for nonresectability was
the presence of bilateral tumor involvement of the
first-order portal branches for $1/3 vessel circumference, even with minimal bile duct dilation at
any imaging modality.
Pre-operative work-up. Preoperative imaging
work-up consisted of abdominal transcutaneous
ultrasonography (US), computed tomography
(CT), or magnetic resonance imaging (MRI), and
chest spiral CT for every patient. From 2004,
18-fluoro-2-deoxy-glucose positron emission tomography (18F FDG-PET) imaging was also included.
Patients were selected for 1-stage resection based
on technical feasibility, regardless of size or number
of metastases, after a multidisciplinary meeting
with our medical oncologists. Technical feasibility

62 Torzilli et al

Surgery
July 2009

Fig 2. The inferior right hepatic vein (IRHV) as it appears at intraoperative ultrasonography. The main feature is that it runs behind the main right (RPV) and
right sectional (P5-8 and P6-7) portal branches. IVC, Inferior vena cava.

Fig 3. eFlow mode shows the hepatopetal flow (arrows)

in the sectional (P5-8 and P6-7) portal branches (red in
P5-8: blood flow toward the probe; blue in P6-7: blood
flow opposite to the probe) once the right hepatic vein
(RHV) is clamped by finger compression (no color inside
the vessel).

was established if residual liver volume (RLV) with

optimal blood inflow and outflow and biliary
drainage was expected to be sufficient. RLV was
considered sufficient if it represented 40% of the
whole liver volume in the case of normal (or
even steatotic) liver, if it represented $50% of
the whole liver volume in the presence of cirrhotic
liver, or if the total serum bilirubin level ranged
between 1 and 1.5 mg/dL. In the event of diseased
liver parenchyma and a total serum bilirubin
level ranging between 1.5 and 2 mg/dL, tumorectomy alone was considered acceptable. In addition, hepatic resection was contraindicated if
serum bilirubin level was $2 mg/dL. Using CT
or MRI, surgeons calculated the liver volume by
adding together the liver areas determined for
each slice.
Operative technique. A J-shaped laparotomy was
usually performed. For those patients with tumor(s) close to the hepatocaval confluence or in
the paracaval portion of segment 1, a J-shaped
thoracoabdominal incision was carried out. Intraoperative ultrasonography (IOUS) was performed
using an Aloka SDD 5500 and, more recently, an
Aloka Alpha 10 (Aloka, Tokyo, Japan), both
equipped with the standard 2--6 MHz convex
probe, 5--10 MHz T-shaped, and the 5--10 MHz
microconvex probe. The staging was completed

with contrast-enhanced intraoperative ultrasonography (CEIOUS); the contrast agent consisted of

4.8 mL of microbubbles filled with sulfur hexafluoride (SonoVue; Bracco Imaging, Italy), which
was injected intravenously.10,11
At this point, based on the IOUS criteria for
tumor--vessel relations reported previously,4,5 the
operative strategy was defined. In particular, vessels were spared if IOUS showed the following:
(1) the portal branch or HV was separated by a
thin layer of liver parenchyma (detectable by
IOUS even if < 5 mm) from a CLM (Fig 1, A
and B); or (2) the portal branch was in contact
with a CLM without vessel wall discontinuation,
with contact < 1/3 of the vessel diameter, and
without proximal bile duct dilation (Fig 1, C). In
all the other conditions (Type C), Vessel resection
was carried out (Fig 1, D and E), In particular, in a
condition similar to type B (Fig 1, C), but between
a CLM and an HV, the vessel was considered invaded and therefore resected (Type Cb) (Fig 1, E).
To determine the extent of resection, parenchyma fed by the portal branch that is to be
resected must be considered.4 In the case of resecting an HV, the extension of the resection to the
whole liver parenchyma drained theoretically by
that vein was considered only in the absence of
at least one of these conditions:

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Torzilli et al 63

Fig 4. Arrows in the image on the left are showing flow directions toward the inferior vena cava (IVC) in the right hepatic vein (RHV) and middle hepatic vein (MHV), using the eFlow mode. On the right, after finger compression is applied to the caval confluence of the RHV, flow direction in the RHV indicated by the arrows is reversed (red), while it
remains hepatofugal (blue) as shown by the arrows in the MHV. Furthermore, color flow in the portal branches to segment 8 ventral (P8v) and 8 dorsal (P8d) remains hepatopetal (red and blue, respectively).

d
d

IOUS showing accessory HVs (Fig 2);

Color Doppler IOUS, with or without eFlow mode
(Aloka, Tokyo, Japan), showing hepatopetal blood
flow in the feeding portal branch once the HV to be
resected was clamped, if not already occluded by the
tumor5 (Fig 3);
Color Doppler IOUS, with or without eFlow mode,
showing reversal of blood flow into the HV to be
resected once it was clamped or compressed, if not
already occluded by the tumor (Fig 4);
eFlow mode IOUS directly detecting collateral circulation and showing the HV to be resected connecting
with the one adjacent to it (Fig 5).

HVs were encircled and clamped when they were

to be resected at their caval confluence. In contrast,
these HVs were compressed only by IOUS-guided
finger compression when the plan was to divide the
vessel away from its caval confluence.
Once the operative strategy was defined, both
hemilivers were mobilized, usually by dividing the
right and left triangular and coronary ligaments.
Mobilization together with the J-shaped incision
(and, in selected patients, according to the aforementioned criteria, the J-shaped thoracoabdominal approach) allowed the liver to be retracted to
the right or the left. This method enabled the
surgeon to approach lesions located in the posterosuperior and paracaval segments.
The areas for resection were demarcated (Fig 6, A)
on the surface of the liver by using an electrocautery

device under IOUS control. The flat tip of the device

was positioned between the probe and the liver surface, which resulted in a shadow visible on IOUS.
Another method to draw the resection area on the
liver surface with the aid of IOUS was to use the fingertips. With the thin tip of the electrocautery device positioned between the probe and the liver
surface, the surgeon used a fingertip to push on
the opposite side, thus making the livers profile visible on IOUS. As a result, spatial relationships
between the fingertip, the shadow of the
electrocautery device, and the tumor edge could
be estimated precisely and the resection area
marked on both liver surfaces (Fig 7).
The parenchymal transection was performed
using intermittent clamping by the Pringle maneuver12 using Pean forceps, the crush-clamping
method, and bipolar electrocautery for vessel coagulation. Vessels thicker than 2 mm were ligated
with 2-0 or 3-0 sutures. Ultrasonographic guidance
was used to direct the dissection plane, which appeared as an echogenic line due to the entrapment
of air bubbles and clots between the cut surfaces
(Fig 8). Once thick vessels were exposed on the
dissection plane, the so-called hooking technique
was used to avoid erroneous vessel ligation.13
This technique involves encircling the vessel with
a suture that is visible on IOUS as an echogenic
spot with a posterior shadow. Ultrasonographic
guidance enables the stitch to be hooked to the

64 Torzilli et al

Surgery
July 2009

Fig 5. From the left to the right, arrows show intraoperative ultrasonography detection (with the eFlow) of a collateral
vessel connecting the middle hepatic vein (MHV) and the right hepatic vein (RHV).

Fig 6. (A) The resection areas (arrows and asterisks) on various aspects of the liver surface defined with an electrocautery
device under intraoperative ultrasonography guidance to completely remove the 49 CLM. (B) From left to right,
the cuts (arrows and asterisks) on the various aspects of the liver surface obtained at the end of the resections that
were carried out to remove the 49 CLM.

exposed vessel; the vessel can then gently be pulled

up, which causes it to stretch slightly, outlining the
traction point on IOUS.
To improve guidance along the proper trajectory of the dissection plane, the surgeons fingertips were positioned at the posterior aspect of the
resection area. Once resection was accomplished,
the specimen and the liver cut surface were

examined with IOUS to be sure of complete

nodule removal. The specimen was studied with
the water bath technique, which consists of realtime control to assure that the targeted nodule was
entirely present within the specimen removed
from the liver (Fig 9). In addition, the cut surface
of the liver was refilled with saline to avoid the
artifacts generated by the residual air bubbles

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Torzilli et al 65

Fig 8. The dissection plane (arrows) is visible at intraoperative ultrasonography and is passing just adjacent to
the portal branch to segment 5 and 8 (P5-8) along a systematic extended right posterior sectionectomy (SERPS)
procedure.
Fig 7. At intraoperative ultrasonography, the electrocautery device positioned between the liver surface (arrows)
and the surgeons fingertip positioned on the opposite
side of the liver (F) allow the surgeon to draw an ideal
plane for dissection (white arrows).

and clots, and then re-imaged with IOUS. If residual lesions were observed, the same procedure of
demarcation was repeated on the cut surface,
and resection was accomplished (Fig 10).
Finally, the cut surfaces of the liver (Fig 6, B)
were secured by suture control of vessels and, if
necessary, by electrocautery, fibrillar-oxidated regenerated cellulose (Fibrillar Tabotamp; Ethicon,
Somerville, NJ) and/or fibrin glue (either Tissucol
purchased from Baxter [Deerfield, IL] or Quixil
obtained from Ethicon). To rule out bile leakage,
we performed a careful examination of the resection area, but did not routinely perform intraoperative cholangiography.14 Multihole, 19-French,
closed-suction drains were always left near the resection area. Drains were removed on the 7th postoperative day (POD) or when the bilirubin level in
the drain discharge (sampled routinely on the 3rd,
5th, and 7th POD) showed a decrement, as
described previously.15 A chest tube was left in
patients undergoing thoracoabdominal incision.
Outcome measures. We studied the morbidity,
mortality, amount of blood loss, and rate of blood
transfusions, as well as the serum levels of total
bilirubin, aspartate aminotransferase (AST), and
alanine aminotransferase (ALT) on the 1st, 3rd,
5th, and 7th POD. Because the secondary outcome
for this study was the reliability of the procedure

from an oncologic standpoint, we studied the

rate of true local recurrence (at the resection margin) after a minimum follow-up of 6 months. The
patients were followed in our institution by an expert hepatobiliary team every 3 months with a
physical examination, liver function tests, serum
carcinoembryonic antigen levels, US (twice a
year), and CT or MRI (twice a year). Re-resection
of recurrences was always considered without or
with resectable extrahepatic disease. Percutaneous
ablation therapy was proposed when hepatic recurrence was visible at US, < 2 cm, and not close to any
visceral cavities such as the stomach or colon.
Patients. Among 144 consecutive patients referred to our unit between September 2001 and
December 2007, 100 (69%) underwent liver resection. A total of 44 patients were excluded because
of massive liver involvement in 13, multiple distant
metastases in 23, or lymph node metastases in 8.
Based on the above criteria, we selected 29 patients
(29%) including 16 males and 13 females with a
mean age of 63 years (range, 36--82). The total
number of preoperative metastatic lesions was
163, with a median of 5 lesions per patient (range,
2--20). The median size of the largest CLM was
4 cm (range, 2--13).
Of the 29 patients, 19 (66%) received chemotherapy before resection; 2 patients underwent
1 limited resection at the same time as the colon
resection, and 2 underwent intraoperative ablation
therapy at the time of the colon resection. Chemotherapy was associated with disease progression
in 10 patients, stable disease in 7, and tumor

66 Torzilli et al

Surgery
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Fig 9. Once the specimen is removed, the presence of the tiny CLM (arrows) is confirmed with intraoperative ultrasonography (A) and with the water bath technique (B). G, Gauze.

Fig 10. A tiny residual CLM (asterisk) is visualized with intraoperative ultrasonography (IOUS) exploring the cut
surface (arrows) after tissue removal was accomplished;
transparent arrows indicate the resection margin that is
defined on the cut surface with the electrocautery device
under IOUS guidance.

reduction in 2. At follow-up, 1 patient underwent

percutaneous ablation for 2 CLM with incomplete
tumor necrosis, and 2 patients were referred to our
Unit without any previous treatment. All the preoperative treatments were carried out in other
centers before referral.
Statistical analysis. Continuous variables are
presented as medians and ranges, whereas proportions are presented as numbers and percentages.
RESULTS
Feasibility and intraoperative findings. Onestage, complete resection of CLM was feasible in

26 of 29 patients. At exploratory laparotomy, 3

patients had diffuse peritoneal carcinomatosis.
After IOUS, 103 new lesions were detected in 18
patients. In 14 of the 21 patients studied with
CEIOUS, 9 additional lesions were found, all of
which were confirmed at pathology together with
the 157 lesions detected preoperatively. Therefore,
the total number of resected lesions was 269, corresponding to a median of 6 lesions per patient
(range, 4--49).
Of the 26 patients, 16 (61%) had tumors at the
hepatocaval confluence. In 20 patients (77%),
IOUS confirmed 29 CLM with macrovascular invasion (28 type C and 1 Cb subtype, according to the
IOUS criteria for tumor--vessel relations4,5). IOUS
disclosed a type A relation for 27 CLM in 17 patients, a type B relation for 5 CLM in 4 patients,
and type A + C combined relations for 6 CLM in
6 patients. There were 67 tumor--vessel relations
classified at IOUS (Table).
Operative procedures. All procedures, including operations, IOUS, and CEIOUS, were performed
by the same surgeon (G.T.). A thoracoabdominal
incision was carried out in 7 patients (27%). The
median operation time was 555 minutes (range, 299-958). Median clamping time was 116 minutes (range,
65--348). In 1 patient, an overall clamping time of 348
minutes was required to resect 49 lesions (Fig 6, A
and B). Preconditioning was never used. The
overall median blood loss was 500 mL (range, 50-1,000 mL). Only 4 patients (15%) received blood
transfusions.
Each type of operative resection is outlined in
the Table. Only 1 of 26 patients (4%) underwent a
right hepatectomy associated with 2 limited leftsided resections, which represents the only major
hepatectomy. An extended right posterior sectionectomy (a so-called systematic extended right posterior
sectionectomy [SERPS procedure]),7 was performed in

Torzilli et al 67

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Table. Type of liver resections

No.
Patient lesions

IOUS class CLM-vessel

relation

4
4
6
4
5
5
6
6

9
10
11

6
11
10

1 CHV; 1 CP3
1 AHV; 1 C+AP2; 1 CP2
2 AHV

12
13

12
11

1 AP2; 1 BUP; 1 BP1; 1 CHV

1 BP1; 1 CHV

14
15
16
17

13
5
7
18

1
1
1
3

18

17

1 AHV; 1 CHV

19

22

2 AHV; 1 CP2; 2 CHV

20
21
22

5
6
49

3 AHV
1 AHV
3 AHV; 1 BP2

23

11

1AHV; 1Cb

24
25
26
Total

9
12
5
269

1
1
1
2
1
1
1
1

AHV; 1 AP1
AHV; 1 C+AHV; 1 CP2
C P2+HV+AP2; 3 CP3
AHV; 1 CP3
AP1; 2 CP3; 1 CHV
CP2+AHV; 1 CP3
C P2+HV; 1 CP3
AP1; 1 CP2

1
2
3
4
5
6
7
8

BUP; 1 CHV
CHV; 1 CHV+AP2
AHV; 1 CHV; 1 CHV+AP2
AHV; 1 CP2

2 CP3
1 AP1
1 CP2
67

Type of resection
PRS2 (1 les.); PRS3 (1 les.); PRS4inf-5 (1 les.); PRS6-7 (1 les.)
PRS2 (1 les.); PRS5 (1 les.); PRS6-7 (2 les.)
PRS2-3 (1 les.); SS4sup (1 les.); SERPS (4 les.)
PRS2-4sup (1 les.); PRS1cl (1 les.); SS6 (1 les.); PRS7 (1 les.)
PRS2-3 (1 les.); PRS1cp (1 les.); PRS6 (1 les.); PRS7 (1 les.); PRS8d (1 les.)
SS2 (1 les.); PRS6-7 (2 les.); SS5 (1 les.); PRS8d (1 les.)
PRS3 (1 les.); PRS4 (1 les.); ext. S4inf RH (1 les.)
PRS2-3 (1 les.); PRS1pp (1 les.); PRS4inf-5 (1 les.); PRS5 (1 les.); PRS6
(1 les.); PRS5+SS8 (1 les.).
LL (1 les.); PRS4inf-5 (1 les.); PRS5 (1 les.); PRS7 (2 les.); PRS8v (1 les.).
PRS2-3 (2 les.); PRS4 (1 les.); SERPS (8 les.)
PRS4sup (1 les.); PRS2 (2 les.); PRS4inf (1 les.); PRS4inf-5 (1 les.); PRS6-7
(3 les.); PRS7 (2 les.)
PRS2-3 (1 les.); PRS3-4inf (1 les.); PRS4inf (1 les.); SERPS (9 les.)
ext S4sup LL (3 les.); PRS4inf (2 les.); PRS1pp (2 les.); PRS5 (1 les.); PRS8
(3 les.).
PRS2 (1 les.); PRS3-4-5 (6 les.); SERPS (4 les.); PRS8v (2 les.)
ext S4sup LL (1 les.); PRS4inf-5 (3 les.); SS7-8 with RHV in IRHV+ (1 les.)
ext S4sup LL (2 les.); PRS4inf-5 (3 les.); PRS6 (1 les.); PRS7 (1 les.)
PRS4sup-8d (3 les.); PRS2-3 (5 les.); PRS4inf (1 les.); PRS5-6 (3 les.); PRS8v
(2 les.); PRS7 (3 les.); PRS8d (1 les.)
LL (2 les.); PRS4-5-8 (2 les.); PRS5 (4 les.); PRS6 (2 les.); PRS6-7 (5 les.);
PRS8 (2 les.)
PRS2 (1 les.); PRS2-3 (3 les.); PRS4-5 (5 les.); PRS5 (3 les.); PRS6 (1 les.);
PRS7 (4 les.); PRS8v (3 les.); PRS8d (2 les.)
PRS3 (1 les.); PRS7 (3 les.); PRS5-8 (1 les.)
PRS2 (1 les.); PRS3 (2 les.); PRS5-6 (1 les.); PRS8 (2 les.)
PRS1cl (1 les.); PRS1cp (1 les.); PRS2-3 (14 les.); PRS4sup (1 les.); PRS4inf-5
(8 les.); PRS5-6 (7 les.); PRS6 (3 les.); PRS7-8 (11 les.); PRS7 (1 les.); PRS8
(2 les.)
PRS3 (1 les.); PRS3 (2 les.); PRS2 (1 les.); PRS2 (1 les.); PRS4sup (3 les.);
SS7-8 with RHV in IRHV+ (3 les.)
PRS2 (1 les.); PRS5 (1 les.); PRS8 (4 les.); PRS6-7 (3 les.)
SS2 (1 les.); PRS6-7 (5 les.); PRS4-5-8 (6 les.);
PRS3 (1 les.); PRS4sup (1 les.); SS6-7 (1 les.); PRS8 (2 les.)

IOUS, Intraoperative ultrasonography; CLM, colorectal liver metastases; cl, caudate lobe; cp, caudate process; IRHV, inferior right hepatic vein; HV, hepatic
vein; LL, left lobectomy (segments 2 and 3); P1, first-order portal branch; P2, second-order portal branch; P3, third-order portal branch; pp, paracaval
portion; PR, partial resection; RH, right hepatectomy; RHV, right hepatic vein; SERPS, systematic extended right posterior sectionectomy; SX, segment
X; SSX, segmental resection segment X; UP, umbilical portion.

5 patients. All these resections were combined with

limited left-sided resections. A wedge resection of
right-sided lung metastases was combined in 2 patients for 2 lung CLM, and was accomplished
through the thoracoabdominal incision. Drains
were removed from all but 3 patients on the 7th
POD, based on our policy described previously.14
Pathology. All resected nodules proved to be
metastases from adenocarcinoma. Minimum resection margins ranged from 0 to 8 mm. Margins of 0
mm were obtained in all 5 patients with CLM
having a B pattern at IOUS, and in 7 of the 21

patients with an A pattern at IOUS. The liver

parenchyma was steatotic in 12 patients, normal in
12, cirrhotic in 1, and showed signs of previously
diagnosed chronic hepatitis in 1.
Postoperative outcome. In-hospital mortality
and 90-day mortality was nil. The overall morbidity
rate was 23% (6/26). None of the patients required reoperation. Major morbidity occurred in
1 patient and consisted of pulmonary embolism.
Minor morbidity consisted of transient fever in 2
patients and increased bilirubin level (#89 mg/dL)
in the output of 1 drain in 3 patients; the drains

68 Torzilli et al

were left in place until the bilirubin level in the

drain output decreased to <10 mg/dL. The drain
was then removed, and the patients were discharged
on the 13th, 16th, and 23rd POD, respectively.
Serum levels of bilirubin, AST, and ALT returned
to normal usually by POD 5. The median hospital
stay was 9 days (range, 8--33).
Long-term outcome. After a median follow-up
of 14 months (mean, 17; range, 6--54), 3 patients
died from both liver and extrahepatic recurrence
(12%), but we did not observe any local recurrence
at the resection margin. Of the 26 patients, 12
(46%) are alive without disease, and 11 (42%) are
alive with disease. Among the latter, 5 patients have
had both liver and extrahepatic recurrences: 5
hepatic recurrences only and 1 extrahepatic recurrence only. Liver recurrences occurred bilaterally
in 7 patients, in the side where more CLM were
removed in 3, and in the opposite side in the
remaining 3 patients.
Of those 10 patients operated for CLM who had
progression during chemotherapy, 1 patient
(10%) died; 5 (50%) are alive with disease; and 4
(40%) are alive disease-free. The median follow-up
for this subgroup was 8 months. Re-resection was
carried out in 2 of the 5 patients who had only liver
recurrences; for the other 3 patients, percutaneous
ablation was carried out in 2, and the third patient
refused any other treatment. Of the 8 patients who
had hepatic relapses combined with extrahepatic
disease, liver resection was combined with total
abdominal hysterectomy and salpingo-oophorectomy in 1; percutaneous ablation was carried out in
3; and systemic chemotherapy was administered in
the remaining 4. Systemic chemotherapy was also
given to the patient with extrahepatic relapses
only.
DISCUSSION
Two-stage hepatectomy combining limited resection and major hepatectomies with or without
PVE is a multistep strategy for the treatment of
otherwise unresectable multiple bilobar CLM.
However, 19--24% of patients do not complete
the treatment strategy.2,3 Furthermore, major hepatectomies are still associated with appreciable
rates of mortality and major morbidity including
liver failure,2,8,16 although more recent series describe greater levels of safety.17 PVE itself is associated with morbidity; although reported at only
2%,18 it still results in additional morbidity for
the treatment strategy as a whole. In addition,
15% of patients do not benefit from PVE, mainly
because of disease progression or insufficient

Surgery
July 2009
remnant liver hypertrophy,18 whereas others have
a worse outcome because of a greater rate of new
lesions in the remnant liver compared with
patients who did not undergo PVE.3,19-23
Using the experience gained from our established policy,4-6 we herein explored the possibility
of providing at least the same therapeutic results
of the 2-stage approach with a 1-stage approach.
Rather than making major resections safer, our
aim was to establish a surgical procedure that
maximizes parenchymal-sparing and allows curative resection in 1 stage. Indeed, following and
expanding on previous experiences,24 we have
shown how, with the aid of IOUS, it is possible to
spare liver parenchyma in most circumstances, despite complex presentations.4-7 For this reason, it
was feasible to limit the use of a formal right hepatectomy to just 1 of the 26 patients (4%) in our
series, with no need for a two-stage approach.
This policy, however, often resulted in resection
margins of 0 mm.
It is noteworthy that, although we never achieved
a minimal resection margin of 1 cm, there was no
recurrence at the resection margin during a mean
follow-up similar to that of the 2 major reports on
2-stage hepatectomies: 17 (median, 14) of our series
versus 22 (median, not reported),2 and 19 (median,
12),3 respectively. Moreover, contrary to the 2 major
reports on 2-stage hepatectomies,2,3 we never adopted intraoperative ablation therapies, which we
believe are suboptimal even when compared with
0-mm margin resection.25
In contrast, several studies have demonstrated
that a limited tumor-free margin is not a contraindication for resection by showing that the risk of
recurrence at the resection margin does not appear to be greater.26,27 Based on precise criteria,4,5,7 IOUS guidance helps maximize the
possibility of getting closer to the tumor. Indeed,
other authors in the 1990s showed that 16% to
18% of patients with hepatocellular carcinoma
who underwent liver resection without IOUS
guidance had positive margins, whereas none of
the patients who underwent liver resection
under the guidance of IOUS had residual
tumor.28,29
Performing more conservative hepatic resections allows for repeat hepatectomies should a
new CLM be detected.1 Indeed, in cases of recurrence, procedures that preserve major vascular
structures allow more surgical options than a major hepatectomy. As a consequence, re-resection
was possible in 2 of the 5 patients with hepatic
relapses only in our series, and in 1 patient with
hepatic recurrences and resectable extrahepatic

Surgery
Volume 146, Number 1

disease. Furthermore, all 5 patients with hepatic

relapses only, except the 1 patient who refused
both reoperation and percutaneous ablation therapy, were able to receive local treatment with
radical intent. In this sense, the multimodal
approach has a fundamental role that should be
discussed with every patient with multiple CLM
when obtaining informed consent for the first
operative treatment. Patients should agree to their
willingness for re-treatment to not invalidate this
approach.
Sparing a substantial amount of the liver parenchyma by our aggressive parenchymal-sparing
technique does not seem to expose patients to a
greater risk of recurrence. We noted that 54% of
patients developed disease during the follow-up
(50% involving the liver) in our study compared
to 64% (48% involving the liver) reported by
Jaeck et al3 and 69% (61% involving the liver)
reported by Adam et al.2 Furthermore, in the
spared hemiliver with the greatest number of
CLM to be removed, there did not appear to be
a greater rate of liver recurrence, and recurrences
were bilateral.
The 1-stage procedure may also be safer than
the 2-stage approach with or without PVE; there
was no mortality or increased incidence of major
morbidity.2,3,19-23 The operative technique we proposed herein is not simple because it involves multiple combined procedures that account for the
long durations of the operative procedure and
the long clamping times. Such long operations
have often been associated with those series featuring the best results in terms of safety,1,30 even in
cirrhotic patients.6,31 A long and careful procedure
may be required to achieve optimal hemostasis and
the prevention of biliary leak.4,5,7 Intermittent hepatic inflow clamping has been shown in several series to be safe and effective compared to no
clamping and to continuous clamping with or
without preconditioning.32-34 We were able to obtain good results with up to 348 minutes of clamping time similar to that of 322 minutes reported by
Sakamoto et al.35 Although these intermittent
clamping times are quite long, serum levels of bilirubin, AST, and ALT returned to normal usually
by POD 5. Furthermore, the inflow occlusion,
which minimized blood transfusion rates (15% in
this series), has beneficial effects on both shortand long-term outcomes.36,37
This prospective cohort of patients was compared with historic data reported by other centers.
The resectability rate of our series from outpatient
clinic to exploration is rather high (>60%). Our
series includes those patients with unfavorable

Torzilli et al 69

conditions compared with those considered for

the 2-stage procedure.2,3 We included patients with
a minimum of 4 bilobar CLM, patients with CLM
having relations with major intrahepatic vascular
structures, and patients with disease progression
after chemotherapy. Furthermore, the 3 patients
submitted to exploratory laparotomy for diffuse
carcinomatosis also would not have been considered suitable for the 2-stage operation. All these
considerations should help in the concerns about
major selection bias and, furthermore, show that
this approach is not just an alternative to the
2-stage policy, but may allow the opportunity to operate on patients otherwise considered unresectable
by the conventional approaches.
A possible criticism of our approach is that
the procedure is based on intraoperative findings
and, for this reason, cannot be applied systematically. Our approach, however, does not ignore the
preoperative findings. In fact, the preoperative
workup was crucial in allowing us to expect the
feasibility of a 1-stage approach by means of
aggressive parenchymal sparing.4-7 By using the criteria we have outlined, many lesions that would
appear to require a major hepatic resection by
conventional criteria can actually be resected without a major hepatic resection as shown in the herein
presented series. With our approach, a complete
resection using a 1-stage, parenchymal-sparing approach may even lead to a greater overall resection
rate than a 2-stage approach, although we acknowledge that we have not included a comparable control group undergoing a 2-stage approach.
The intraoperative detection of 112 new lesions
by IOUS and CEIOUS, representing 42% of all the
lesions removed, is worthy of discussion. Multiple
CLM lesions are associated generally with a greater
rate of missed lesions at preoperative imaging.38,39
PET, however, seems inadequate for accurate intrahepatic staging,39 especially for those patients undergoing operation after chemotherapy,40 who
represented 66% of our series. These considerations highlight the central and crucial role played
by IOUS and CEIOUS in treating these patients.
There are limitations of IOUS and CEIOUS,
including the cost of state-of-the-art ultrasound
machines and the need for hepatic surgeons to be
well trained in their use. However, a wide range of
prices for suitable ultrasound machine exists, and
courses are available to train surgeons in the use of
ultrasound in surgical practice. The American College of Surgeons has recognized recently the need
for specifically trained surgeons in the United States
and, similarly, we have started a School for Surgical
Ultrasonography in Europe.

70 Torzilli et al

In conclusion, we have shown that IOUS-guided

resection based on strict criteria allows a radical
but parenchymal-sparing, 1-stage hepatectomy/
metastasectomy in patients with multiple bilobar
CLM. This strategy limits the need for 2-stage
hepatectomy and, in so doing, may rise above
many of the limitations and consequences of a
2-stage approach.
The authors thank Ms Rosalind Roberts for her
editorial assistance during manuscript preparation.
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