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One-stage ultrasonographically guidedhepatectomy for multiple bilobar

colorectal metastases: A feasible andeffective alternative to the 2-stageapproachGuido 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, limitedonly by itstechnical feasibility.1 Thekeytotheproce-dure’s success is leaving enoughremnant liver to en-

sure patientsurvival. In cases of multiple and bilobar

CLM, the most commonly used operative approachis a 2-stage hepatectomy.2 This multistep strategy uses limited resections and major hepatectomies

with or without preresection portal vein emboliza-

tion (PVE).2,3

This method also allows extendingoperative indications to those patients previously

judged to be unresectable, because the metastaticdisease would demand the removal of too muchliver parenchyma for the resection to be curative.This approach, however, has some drawbacks. Twooperations are needed, each of which is associated

with mortality and morbidity. In addition, somepatients do not complete this treatment approachbecause of tumor progression during the intervalbetween the 2 surgical procedures or after PVE.

A possible alternative, however, does exist. We

have shown, both for primary and metastatic liver

Supported in part by a research grant from the Cesare BannoFoundation for Cancer Research.

Accepted for publication February 13, 2009.

Reprint requests: Guido Torzilli, MD, PhD, Associate Professorof Surgery, Chief, Liver Surgery Unit, Third Department of Sur-gery, University of Milan, IRCCS Istituto Clinico Humanitas, ViaManzoni 56, 20089 Rozzano, Milan, Italy. E-mail: [email protected] .

0039-6060/$ - see front matter

2009 Mosby, Inc. All rights reserved.

doi:10.1016/j.surg.2009.02.017

60 SURGERY

mailto:[email protected]






neoplasms, that a well-defined policy of ultrason-ically guided hepatectomy allows us to carry out radical operations safely and without major re-moval of liver parenchyma in the vast majority of

patients, even when the tumors have complexpresentations such as multiplicity and vascularinvasion.4-7 Using information gleaned from thisexperience, we explored the feasibility, safety,and effectiveness of a 1-stage operative procedurein 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 t his study is based on theBrisbane classification.8 Hepatic resections are

considered major when at least 3 adjacent segmentsare removed. The hepatic vein (HV) at the cavalconfluence, the so-called hepatocaval confluence ,

was defined as the last 4 cm of the HV before itsconfluence into the inferior vena cava (IVC). Post-operative death was analyzed at 30 days and 90 daysafter operation. Any adverse event that requiredadditional operative treatment or any invasivecorrective procedure was considered a majorpostoperative morbidity. Liver failure was consid-ered mild when the total serum bilirubin concen-tration 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 postoper-atively.9 Local tumor recurrence was defined asrecurrence at the cut-edge (true local recurrence),

and was analyzed after a minimum follow-up of 6 months.

Eligibility criteria. Inclusion criteria for thecurrent study were as follows: (1) patients present-ing with resectable CLM; (2) 4 or more lesions;(3) bilobar involvement of the liver; (4) contact orclose adjacency (<0.5 cm) of at least 1 CLM with amajor intrahepatic vascular structures (first- orsecond-order portal branches and/or HV at cavalconfluence). A criterion for nonresectability wasthe presence of bilateral tumor involvement of thefirst-order portal branches for $1/3 vessel circum-

ference, even with minimal bile duct dilation at any imaging modality.

Pre-operative work-up. Preoperative imaging work-up consisted of abdominal transcutaneousultrasonography (US), computed tomography (CT), or magnetic resonance imaging (MRI), andchest spiral CT for every patient. From 2004,18-fluoro-2-deoxy-glucose positron emission tomog-raphy (18F FDG-PET) imaging was also included.Patients were selected for 1-stage resection basedon technical feasibility, regardless of size or numberof metastases, after a multidisciplinary meeting

with our medical oncologists. Technical feasibility

CLM

HV

DL

CLM

PB

AG

DL

CLM

PB

AG

DLA B C

CLM

HV

DLCLM

PB

AG

DL

D E

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

Surgery Volume 146, Number 1

Torzilli et al 61



was established if residual liver volume (RLV) withoptimal 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 (oreven steatotic) liver, if it represented $50% of the whole liver volume in the presence of cirrhoticliver, or if the total serum bilirubin level rangedbetween 1 and 1.5 mg/dL. In the event of diseasedliver parenchyma and a total serum bilirubinlevel ranging between 1.5 and 2 mg/dL, tumorec-tomy alone was considered acceptable. In addi-tion, hepatic resection was contraindicated if serum bilirubin level was $2 mg/dL. Using CTor MRI, surgeons calculated the liver volume by

adding together the liver areas determined foreach slice.

Operative technique. A J-shaped laparotomy wasusually performed. For those patients with tu-mor(s) close to the hepatocaval confluence or inthe paracaval portion of segment 1, a J-shapedthoracoabdominal incision was carried out. Intra-operative ultrasonography (IOUS) was performedusing an Aloka SDD 5500 and, more recently, an

Aloka Alpha 10 (Aloka, Tokyo, Japan), bothequipped with the standard 2--6 MHz convexprobe, 5--10 MHz T-shaped, and the 5--10 MHz

microconvex probe. The staging was completed

with contrast-enhanced intraoperative ultrasonog-raphy (CEIOUS); the contrast agent consisted of 4.8 mL of microbubbles filled with sulfur hexa-

fluoride (SonoVue; Bracco Imaging, Italy), which was injected intravenously.10,11

At this point, based on the IOUS criteria fortumor--vessel relations reported previously,4,5 theoperative strategy was defined. In particular, ves-sels were spared if IOUS showed the following:(1) the portal branch or HV was separated by athin 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 ). Inall the other conditions (Type C), Vessel resection

was carried out (Fig 1, D and E ), In particular, in acondition similar to type B (Fig 1, C ), but betweena CLM and an HV, the vessel was considered in-

vaded and therefore resected (Type Cb) (Fig 1, E ).To determine the extent of resection, paren-

chyma fed by the portal branch that is to beresected must be considered.4 In the case of resect-ing 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:

Fig 2. The inferior right hepatic vein (IRHV) as it ap-pears at intraoperative ultrasonography. The main fea-ture is that it runs behind the main right (RPV) andright sectional (P5-8 and P6-7) portal branches. IVC , In-ferior vena cava.

Fig 3. eFlow mode shows the hepatopetal flow (arrows )in the sectional (P5-8 and P6-7) portal branches (red inP5-8: blood flow toward the probe; blue in P6-7: bloodflow opposite to the probe) once the right hepatic vein(RHV) is clamped by finger compression (no color insidethe vessel).

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62 Torzilli et al



d IOUS showing accessory HVs (Fig 2);

d 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

tumor

5

(Fig 3);d 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);

d eFlow mode IOUS directly detecting collateral circula-

tion and showing the HV to be resected connecting

with the one adjacent to it (Fig 5).

HVs were encircled and clamped when they wereto be resected at their caval confluence. In contrast,these HVs were compressed only by IOUS-guidedfinger 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 theright and left triangular and coronary ligaments.Mobilization together with the J-shaped incision(and, in selected patients, according to the afore-mentioned criteria, the J-shaped thoracoabdomi-nal approach) allowed the liver to be retracted tothe right or the left. This method enabled thesurgeon to approach lesions located in the poster-osuperior and paracaval segments.

Theareasforresectionweredemarcated(Fig6, 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 sur-face, which resulted in a shadow visible on IOUS.

Another method to draw the resection area on theliver surface with the aid of IOUS was to use the fin-

gertips. With the thin tip of the electrocautery device positioned between the probe and the liversurface, the surgeon used a fingertip to push onthe opposite side, thus making the liver’s profile vis-ible on IOUS. As a result, spatial relationshipsbetween the fingertip, the shadow of theelectrocautery device, and the tumor edge couldbe estimated precisely and the resection areamarked on both liver surfaces (Fig 7).

The parenchymal transection was performedusing intermittent clamping by the Pringle ma-neuver12 using Pean forceps, the crush-clamping

method, and bipolar electrocautery for vessel coag-ulation. Vessels thicker than 2 mm were ligated with 2-0 or 3-0 sutures. Ultrasonographic guidance was used to direct the dissection plane, which ap-peared 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 thedissection plane, the so-called hooking techniq ue

was used to avoid erroneous vessel ligation.13

This technique involves encircling the vessel witha suture that is visible on IOUS as an echogenicspot with a posterior shadow. Ultrasonographicguidance enables the stitch to be hooked to the

Fig 4. Arrows in the image on the left are showing flow directions toward the inferior vena cava (IVC) in the right he-patic vein (RHV) and middle hepatic vein (MHV), using the eFlow mode. On the right, after finger compression is ap-plied 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 seg-ment 8 ventral (P8v) and 8 dorsal (P8d) remains hepatopetal (red and blue , respectively).


Torzilli et al 63



exposed vessel; the vessel can then gently be pulledup, which causes it to stretch slightly, outlining thetraction point on IOUS.

To improve guidance along the proper trajec-tory of the dissection plane, the surgeon’s finger-tips were positioned at the posterior aspect of theresection area. Once resection was accomplished,

the specimen and the liver cut surface were

examined with IOUS to be sure of completenodule removal. The specimen was studied withthe water bath technique, which consists of real-time control to assure that the targeted nodule wasentirely present within the specimen removedfrom the liver (Fig 9). In addition, the cut surfaceof the liver was refilled with saline to avoid the

artifacts generated by the residual air bubbles

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.

Surgery July 2009

64 Torzilli et al



and clots, and then re-imaged with IOUS. If resid-ual 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 re-generated cellulose (Fibrillar Tabotamp; Ethicon,Somerville, NJ) and/or fibrin glue (either Tissucolpurchased from Baxter [Deerfield, IL] or Quixilobtained from Ethicon). To rule out bile leakage,

we performed a careful examination of the resec-tion area, but did not routinely perform intraoper-ative cholangiography.14 Multihole, 19-French,closed-suction drains were always left near the re-

section area. Drains were removed on the 7th post-operative day (POD) or when the bilirubin level inthe drain discharge (sampled routinely on the 3rd,5th, and 7th POD) showed a decrement, asdescribed previously.15 A chest tube was left inpatients undergoing thoracoabdominal incision.

Outcome measures. We studied the morbidity,mortality, amount of blood loss, and rate of bloodtransfusions, as well as the serum levels of totalbilirubin, aspartate aminotransferase (AST), andalanine 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 therate of true local recurrence (at the resection mar-gin) after a minimum follow-up of 6 months. Thepatients were followed in our institution by an ex-pert hepatobiliary team every 3 months with aphysical examination, liver function tests, serumcarcinoembryonic 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. Percutaneousablation therapy was proposed when hepatic recur-rence was visible at US, < 2 cm, and not close to any

visceral cavities such as the stomach or colon.Patients. Among 144 consecutive patients re-

ferred to our unit between September 2001 andDecember 2007, 100 (69%) underwent liver resec-tion. A total of 44 patients were excluded becauseof 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 amean age of 63 years (range, 36--82). The totalnumber of preoperative metastatic lesions was163, with a median of 5 lesions per patient (range,2--20). The median size of the largest CLM was4 cm (range, 2--13).

Of the 29 patients, 19 (66%) received chemo-therapy before resection; 2 patients underwent 1 limited resection at the same time as the colonresection, and 2 underwent intraoperative ablationtherapy at the time of the colon resection. Che-motherapy was associated with disease progression

in 10 patients, stable disease in 7, and tumor

Fig 7. At intraoperative ultrasonography, the electrocau-tery device positioned between the liver surface (arrows )and the surgeon’s fingertip positioned on the oppositeside of the liver ( F ) allow the surgeon to draw an idealplane for dissection (white arrows ).

Fig 8. The dissection plane (arrows ) is visible at intrao-perative ultrasonography and is passing just adjacent to

the portal branch to segment 5 and 8 (P5-8) along a sys-tematic extended right posterior sectionectomy (SERPS)procedure.


Torzilli et al 65



reduction in 2. At follow-up, 1 patient underwent percutaneous ablation for 2 CLM with incompletetumor necrosis, and 2 patients were referred to ourUnit without any previous treatment. All the pre-operative treatments were carried out in othercenters before referral.

Statistical analysis. Continuous variables arepresented as medians and ranges, whereas propor-tions are presented as numbers and percentages.

RESULTS

Feasibility and intraoperative findings. One-

stage, complete resection of CLM was feasible in

26 of 29 patients. At exploratory laparotomy, 3patients had diffuse peritoneal carcinomatosis.

After IOUS, 103 new lesions were detected in 18patients. In 14 of the 21 patients studied withCEIOUS, 9 additional lesions were found, all of

which were confirmed at pathology together withthe 157 lesions detected preoperatively. Therefore,the total number of resected lesions was 269, corre-sponding to a median of 6 lesions per patient (range, 4--49).

Of the 26 patients, 16 (61%) had tumors at thehepatocaval confluence. In 20 patients (77%),IOUS confirmed 29 CLM with macrovascular inva-sion (28 type C and 1 Cb subtype, according to the

IOUS criteria for tumor--vessel relations4,5). IOUSdisclosed a type A relation for 27 CLM in 17 pa-tients, a type B relation for 5 CLM in 4 patients,and type A + C combined relations for 6 CLM in6 patients. There were 67 tumor--vessel relationsclassified at IOUS (Table).

Operative procedures. All procedures, includ-ing operations, IOUS, and CEIOUS, wereperformedby the same surgeon (G.T.). A thoracoabdominalincision was carried out in 7 patients (27%). Themedian operation time was 555 minutes (range, 299--958).Median clamping time was 116minutes (range,

65--348). In 1 patient, an overall clamping time of 348minutes was required to resect 49 lesions (Fig 6, A and B ). Preconditioning was never used. Theoverall median blood loss was 500 mL (range, 50--1,000 mL). Only 4 patients (15%) received bloodtransfusions.

Each type of operative resection is outlined inthe Table. Only 1 of 26 patients (4%) underwent aright hepatectomy associated with 2 limited left-sided resections, which represents the only majorhepatectomy. An extended right posterior sectio-nectomy (a so-called systematic e xt ended right posterior

sectionectomy [SERPS procedure ]),7

was performed in

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

Fig 10. A tiny residual CLM (asterisk ) is visualized with in-traoperative ultrasonography (IOUS) exploring the cut surface (arrows ) after tissue removal was accomplished;transparent arrows indicate the resection margin that isdefined on the cut surface with the electrocautery deviceunder IOUS guidance.

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66 Torzilli et al



5 patients. All these resections were combined withlimited left-sided resections. A wedge resection of right-sided lung metastases was combined in 2 pa-tients for 2 lung CLM, and was accomplishedthrough the thoracoabdominal incision. Drains

were removed from all but 3 patients on the 7t hPOD, based on our policy described previously.14

Pathology. All resected nodules proved to bemetastases from adenocarcinoma. Minimum resec-tion margins ranged from 0 to 8 mm. Margins of 0mm 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 liverparenchyma was steatotic in 12 patients, normal in12, 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 re-quired reoperation. Major morbidity occurred in1 patient and consisted of pulmonary embolism.Minor morbidity consisted of transient fever in 2patients and increased bilirubin level (#89 mg/dL)

in the output of 1 drain in 3 patients; the drains

Table. Type of liver resections

Patient No.

lesions IOUS class CLM-vessel

relation Type of resection

1 4 1 A HV ; 1 A P1 PRS2 (1 les.); PRS3 (1 les.); PRS4inf-5 (1 les.); PRS6-7 (1 les.)2 4 1 A HV ; 1 C+A HV ; 1 CP2 PRS2 (1 les.); PRS5 (1 les.); PRS6-7 (2 les.)

3 6 1 C P2+HV +A P2; 3 CP3 PRS2-3 (1 les.); SS4sup (1 les.); SERPS (4 les.)4 4 2 A HV ; 1 CP3 PRS2-4sup (1 les.); PRS1cl (1 les.); SS6 (1 les.); PRS7 (1 les.)5 5 1 A P1; 2 CP3; 1 CHV PRS2-3 (1 les.); PRS1cp (1 les.); PRS6 (1 les.); PRS7 (1 les.); PRS8d (1 les.)6 5 1 CP2+A HV ; 1 CP3 SS2 (1 les.); PRS6-7 (2 les.); SS5 (1 les.); PRS8d (1 les.)7 6 1 C P2+HV ; 1 CP3 PRS3 (1 les.); PRS4 (1 les.); ext. S4inf RH (1 les.)8 6 1 A P1; 1 CP2 PRS2-3 (1 les.); PRS1pp (1 les.); PRS4inf-5 (1 les.); PRS5 (1 les.); PRS6

(1 les.); PRS5+SS8 (1 les.).9 6 1 CHV ; 1 CP3 LL (1 les.); PRS4inf-5 (1 les.); PRS5 (1 les.); PRS7 (2 les.); PRS8v (1 les.).

10 11 1 A HV ; 1 C+A P2; 1 CP2 PRS2-3 (2 les.); PRS4 (1 les.); SERPS (8 les.)11 10 2 A HV PRS4sup (1 les.); PRS2 (2 les.); PRS4inf (1 les.); PRS4inf-5 (1 les.); PRS6-7

(3 les.); PRS7 (2 les.)12 12 1 A P2; 1 BUP; 1 BP1; 1 CHV PRS2-3 (1 les.); PRS3-4inf (1 les.); PRS4inf (1 les.); SERPS (9 les.)13 11 1 BP1; 1 CHV ext S4sup LL (3 les.); PRS4inf (2 les.); PRS1pp (2 les.); PRS5 (1 les.); PRS8

(3 les.).14 13 1 BUP; 1 CHV PRS2 (1 les.); PRS3-4-5 (6 les.); SERPS (4 les.); PRS8v (2 les.)15 5 1 CHV ; 1 CHV +A P2 ext S4sup LL (1 les.); PRS4inf-5 (3 les.); SS7-8 with RHV in IRHV+ (1 les.)16 7 1 A HV ; 1 CHV ; 1 CHV +A P2 ext S4sup LL (2 les.); PRS4inf-5 (3 les.); PRS6 (1 les.); PRS7 (1 les.)17 18 3 A HV ; 1 CP2 PRS4sup-8d (3 les.); PRS2-3 (5 les.); PRS4inf (1 les.); PRS5-6 (3 les.); PRS8v

(2 les.); PRS7 (3 les.); PRS8d (1 les.)18 17 1 A HV ; 1 CHV LL (2 les.); PRS4-5-8 (2 les.); PRS5 (4 les.); PRS6 (2 les.); PRS6-7 (5 les.);

PRS8 (2 les.)19 22 2 A HV ; 1 CP2; 2 CHV 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.)20 5 3 A HV PRS3 (1 les.); PRS7 (3 les.); PRS5-8 (1 les.)21 6 1 A HV PRS2 (1 les.); PRS3 (2 les.); PRS5-6 (1 les.); PRS8 (2 les.)22 49 3 A HV ; 1 BP2 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.)

23 11 1A HV ; 1Cb PRS3 (1 les.); PRS3 (2 les.); PRS2 (1 les.); PRS2 (1 les.); PRS4sup (3 les.);SS7-8 with RHV in IRHV+ (3 les.)

24 9 2 CP3 PRS2 (1 les.); PRS5 (1 les.); PRS8 (4 les.); PRS6-7 (3 les.)25 12 1 A P1 SS2 (1 les.); PRS6-7 (5 les.); PRS4-5-8 (6 les.);26 5 1 CP2 PRS3 (1 les.); PRS4sup (1 les.); SS6-7 (1 les.); PRS8 (2 les.)Total 269 67

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.


Torzilli et al 67



were left in place until the bilirubin level in thedrain output decreased to <10 mg/dL. The drain

was then removed, and the patients were dischargedon the 13th, 16th, and 23rd POD, respectively.Serum levels of bilirubin, AST, and ALT returned

to normal usually by POD 5. The median hospitalstay was 9 days (range, 8--33).Long-term outcome. After a median follow-up

of 14 months (mean, 17; range, 6--54), 3 patientsdied from both liver and extrahepatic recurrence(12%), but we did not observe any local recurrenceat the resection margin. Of the 26 patients, 12(46%) are alive without disease, and 11 (42%) arealive with disease. Among the latter, 5 patients havehad both liver and extrahepatic recurrences: 5hepatic recurrences only and 1 extrahepatic recur-rence only. Liver recurrences occurred bilaterally in 7 patients, in the side where more CLM wereremoved in 3, and in the opposite side in theremaining 3 patients.

Of those 10 patients operated for CLM who hadprogression during chemotherapy, 1 patient (10%) died; 5 (50%) are alive with disease; and 4(40%) are alive disease-free. The median follow-upfor this subgroup was 8 months. Re-resection wascarried out in 2 of the 5 patients who had only liverrecurrences; for the other 3 patients, percutaneousablation was carried out in 2, and the third patient refused any other treatment. Of the 8 patients whohad hepatic relapses combined with extrahepatic

disease, liver resection was combined with totalabdominal hysterectomy and salpingo-oophorec-tomy in 1; percutaneous ablation was carried out in3; and systemic chemotherapy was administered inthe remaining 4. Systemic chemotherapy was alsogiven to the patient with extrahepatic relapsesonly.

DISCUSSION

Two-stage hepatectomy combining limited re-section 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 completethe treatment strategy.2,3 Furthermore, major hep-atectomies are still associated with appreciablerates of mortalit y and major morbidity includingliver failure,2,8,16 although more recent series de-scribe greater levels of safety.17 PVE itself is associ-ated with morbidity; although reported at only 2%,18 it still results in additional morbidity forthe treatment strategy as a whole. In addition,15% of patients do not benefit from PVE, mainly

because of disease progression or insufficient

remnant liver hypertrophy,18 whereas others havea worse outcome because of a greater rate of new lesions in the remnant liver compared withpatients who did not undergo PVE.3,19-23

Using the experience gained from our estab-

lished policy,

4-6

we herein explored the possibility of providing at least the same therapeutic resultsof the 2-stage approach with a 1-stage approach.Rather than making major resections safer, ouraim was to establish a surgical procedure that maximizes parenchymal-sparing and allows cura-tive resection in 1 stage. Indeed, follo wing andexpanding on previous experiences,24 we haveshown how, with the aid of IOUS, it is possible tospare liver parenchyma in most circumstances, de-spite complex presentations.4-7 For this reason, it

was feasible to limit the use of a formal right hep-atectomy to just 1 of the 26 patients (4%) in ourseries, with no need for a two-stage approach.This policy, however, often resulted in resectionmargins of 0 mm.

It is noteworthy that, although we never achieveda minimal resection margin of 1 cm, there was norecurrence at the resection margin during a meanfollow-up similar to that of the 2 major reports on2-stage hepatectomies: 17 (median, 14) of our series

versus 22 (median, not reported),2 and 19 (median,12),3 respectively. Moreover, contrar y to the 2 majorreports on 2-stage hepatectomies,2,3 we never adop-ted intraoperative ablation therapies, which we

believe are suboptimal ev en when compared with0-mm margin resection.25

In contrast, several studies have demonstratedthat a limited tumor-free margin is not a contra-indication for resection by showing that the risk of recurrence at the resect ion margin does not ap-pear t o be greater.26,27 Based on precise crite-ria,4,5,7 IOUS guidance helps maximize thepossibility of getting closer to the tumor. Indeed,other authors in the 1990s showed that 16% to18% of patients with hepatocellular carcinoma

who underwent liver resection without IOUS

guidance had positive margins, whereas none of the patients who underwent liver resectionunder the guidance of IOUS had residualtumor.28,29

Performing more conservative hepatic resec-tions allows for repeat hepatectomies should anew CLM be detected.1 Indeed, in cases of recur-rence, procedures that preserve major vascularstructures allow more surgical options than a ma-

jor hepatectomy. As a consequence, re-resection was possible in 2 of the 5 patients with hepaticrelapses only in our series, and in 1 patient with

hepatic recurrences and resectable extrahepatic

Surgery July 2009

68 Torzilli et al



disease. Furthermore, all 5 patients with hepaticrelapses only, except the 1 patient who refusedboth reoperation and percutaneous ablation ther-apy, were able to receive local treatment withradical intent. In this sense, the multimodal

approach has a fundamental role that should bediscussed 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 thisapproach.

Sparing a substantial amount of the liver pa-renchyma by our aggressive parenchymal-sparingtechnique does not seem to expose patients to agreater risk of recurrence. We noted that 54% of patients developed disease during the follow-up(50% involving the liver) in our study comparedto 64% (48% involving the liver) reported by

Jaeck et al3 and 69% (61% involving the liver)reported by Adam et al.2 Furthermore, in thespared hemiliver with the greatest number of CLM to be removed, there did not appear to bea 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 majormorbidity.2,3,19-23 The operative technique we pro-posed herein is not simple because it involves mul-tiple combined procedures that account for the

long durations of the operative procedure andthe long clamping times. Such long operationshave often been associated with those series featur-ing the best results in terms of safety,1,30 even incirrhotic patients.6,31 A long and careful proceduremay be required to achieve optimal hemostasis andthe prevention of biliary leak.4,5,7 Intermittent he-patic inflow clamping has been shown in several se-ries to be safe and effective compared to noclamping and to continuous clamping with or

without preconditioning.32-34 We were able to ob-tain good results with up to 348 minutes of clamp-

ing time similar t o that of 322 minutes reported by Sakamoto et al.35 Although these intermittent clamping times are quite long, serum levels of bil-irubin, AST, and ALT returned to normal usually by POD 5. Furthermore, the inflow occlusion,

which minimized blood transfusion rates (15% inthis series), has beneficial effects on both short-and long-term outcomes.36,37

This prospective cohort of patients was com-pared 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

conditions compared w ith those considered forthe 2-stage procedure.2,3 We included patients witha minimum of 4 bilobar CLM, patients with CLMhaving relations with major intrahepatic vascularstructures, and patients with disease progression

after chemotherapy. Furthermore, the 3 patientssubmitted to exploratory laparotomy for diffusecarcinomatosis also would not have been consid-ered suitable for the 2-stage operation. All theseconsiderations should help in the concerns about major selection bias and, furthermore, show that this approach is not just an alternative to the2-stage policy, but may allow the opportunity to oper-ate on patients otherwise considered unresectableby the conventional approaches.

A possible criticism of our approach is that the procedure is based on intraoperative findingsand, for this reason, cannot be applied systemati-cally. Our approach, however, does not ignore thepreoperative findings. In fact, the preoperative

workup was crucial in allowing us to expect thefeasibility of a 1-stage approach by means of aggressive parenchymal sparing.4-7 By using the cri-teria we have outlined, many lesions that wouldappear to require a major hepatic resection by conventional criteria can actually be resected with-out a major hepatic resection as shown in the hereinpresented series. With our approach, a completeresection using a 1-stage, parenchymal-sparing ap-proach may even lead to a greater overall resection

rate than a 2-stage approach, although we acknowl-edge that we have not included a comparable con-trol group undergoing a 2-stage approach.

The intraoperative detection of 112 new lesionsby IOUS and CEIOUS, representing 42% of all thelesions removed, is worthy of discussion. MultipleCLM lesions are associated generally with a greaterrate of missed lesions at preoperative imaging.38,39

PET, however, seems inadequate for accurate intra-hepatic staging,39 especially for those patients un-dergoing operation after chemotherapy,40 whorepresented 66% of our series. These consider-

ations highlight the central and crucial role playedby IOUS and CEIOUS in treating these patients.

There are limitations of IOUS and CEIOUS,including the cost of state-of-the-art ultrasoundmachines and the need for hepatic surgeons to be

well trained in their use. However, a wide range of prices for suitable ultrasound machine exists, andcourses are available to train surgeons in the use of ultrasound in surgical practice. The American Col-lege of Surgeons has recognized recently the needfor specifically trained surgeons in the United Statesand, similarly, we have started a School for Surgical

Ultrasonography in Europe.


Torzilli et al 69



In conclusion, we have shown that IOUS-guidedresection based on strict criteria allows a radicalbut parenchymal-sparing, 1-stage hepatectomy/metastasectomy in patients with multiple bilobarCLM. This strategy limits the need for 2-stage

hepatectomy and, in so doing, may rise abovemany of the limitations and consequences of a2-stage approach.

The authors thank Ms Rosalind Roberts for hereditorial assistance during manuscript preparation.

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one stage hepatectomy

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