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isks after Extended Resection in Noncirrhotic Livertéphanie Truant, PhD, Olivier Oberlin, MD, Géraldine Sergent, MD, Gilles Lebuffe, PhD,uc Gambiez, MD, Olivier Ernst, PhD, François-René Pruvot, MD

BACKGROUND: Before extended hepatectomy of five or more segments, the remnant liver volume (RLV) isusually calculated as a ratio of RLV to total liver volume (RLV-TLV) and must be � 20% to25%. This method can lead to compare parts of normal liver parenchyma to others compro-mised by biliary or vascular obstruction or by portal vein embolization. Extrapolating fromliving-donor liver transplantation, we hypothesized that RLV to body weight ratio (RLV-BWR)could accurately assess the functional limit of hepatectomy.

STUDY DESIGN: From September 2000 to December 2004, volumetric measurements of RLV using computedtomography were obtained before right-extended hepatectomy in 31 patients. RLV-BWR of0.5% as a critical point for patient course was compared with stratification by RLV-TLV(� 25% or � 25% and � 20% or � 20%).

RESULTS: Three-month morbidity and mortality were not significantly different between groups RLV-TLV � and � 25% and between groups RLV-TLV � and � 20%, but increased significantlyin group RLV-BWR � 0.5% compared with group RLV-BWR � 0.5% (p � 0.038 and p �0.019, respectively) with an non-significant increase in death from liver failure (p � 0.077).

CONCLUSIONS: RLV-BWR was more specific than RLV-TLV in predicting postoperative course after extendedhepatectomy. Patients with an anticipated RLV � 0.5% of body weight are at considerable riskfor hepatic dysfunction and postoperative mortality. ( J Am Coll Surg 2007;204:22–33. © 2007
by the American College of Surgeons)
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n patients with normal liver, only extended hepatic re-ection of more than four segments, mainly right or leftepatic trisectionectomies, carries a high risk of postop-rative complications associated with hepatic insuffi-iency,1 requiring determination preoperatively of futureemnant liver volume (RLV). RLV is usually expressed asratio of RLV to total liver volume (RLV-TLV)2,3 aftereasurement of these volumes by CT. It is considered

hat a hepatectomy leaving an RLV of as much as 25% to0% of the liver can be performed safely,2,4-6 but Abdalla

ompeting Interests Declared: None.resented at the Journée Francophones de Pathologie Digestive, Paris, France,pril 2005, and the IHPBA Congress, Edinburgh, Scotland, September006.

eceived January 19, 2006; Revised September 7, 2006; Accepted September2, 2006.rom the Departments of Digestive and Transplantation Surgery (Truant,berlin, Gambiez, Pruvot), Radiology (Sergent, Ernst), and Anesthesiology

Lebuffe), University Hospital, Hospital Huriez, Lille, France.orrespondence address: François-René Pruvot, MD, Service de Chirurgieigestive et Transplantation, Hôpital Huriez, 59037 Lille Cedex, France.

pmail: [email protected]

222007 by the American College of Surgeons

ublished by Elsevier Inc.

nd colleagues4 have shown that this limit can be de-reased to 20% without a high death rate. RLV calcu-ated through this ratio can be misestimated in the casef huge or multiple metastases, the volume of whichust be subtracted from the TLV, or in the presence of

reas of nonfunctional liver resulting from biliary or vas-ular obstruction.7 To reduce these difficulties, some au-hors have used the method of “standardized measure-ent of the RLV,” where total liver volume is estimated

y a formula that closely correlates the volume measuredy CT with the body surface area (BSA) or body weightn adult patients.2,8-10 The calculated total liver size dif-ered substantially according to the formula used.11,12 Inhe case of extended hepatectomies with an anticipatedLV-TLV close to the limit of 25%, this ratio might note accurate enough to predict postoperative course orhe need for preoperative portal vein embolizationPVE). In the case of repeat hepatectomy, in which ac-ual TLV does not reach initial TLV because of incom-
lete recovery,13 this ratio is ineffective.
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23Vol. 204, No. 1, January 2007 Truant et al Extended Resection in Noncirrhotic Liver

Extrapolating the example of living-donor liver trans-lantation (LDLT) to hepatic resection, we assumedhat the ratio of RLV to body weight (RLV-BWR) of theatient—by considering RLV only—could be used as aore relevant calculation method of the minimum RLV

olerable after extended hepatectomy of five or moreegments, as reflected by the postoperative clinical andiochemical parameters. In LDLT, the minimum toler-ble volume of the graft is higher than the 25% to 30%f RLV tolerated after hepatectomy, owing to less-ffective liver regeneration,2,14,15 and ranges from 40% to0% of the ideal TLV of the recipient.16-18 In this setting,he adequacy between graft volume and recipient weights generally estimated by the graft body weight ratio, andhe minimum tolerable volume of the graft is about 0.8%f body weight.19-21 Nevertheless, in cases of urgent trans-lantation, ie, fulminant hepatic failure, some patientsere successfully transplanted with small-for-size grafts

epresenting only 0.6% of their body weight.22

In this prospective study, patients with noncirrhoticiver who were candidates for a right hepatic trisec-ionectomy underwent measurement of RLV by liverolumetry using CT. We first studied the associationf a conventional RLV-TLV of � 25% or 20% to theostoperative course of the patients. Afterward weompared the value of RLV-BWR to that of RLV-TLV inredicting morbidity and mortality after a right hepaticrisectionectomy.

ETHODSatient selectionmong 186 major hepatectomies of 3 or moreouinaud segments23 performed at our institution be-

ween September 2000 and December 2004, 5328.5%) were right hepatic trisectionectomies, as de-ined (resection of Couinaud segments IV to VIII). To

Abbreviations and Acronyms

BSA � body surface areaLDLT � living-donor liver transplantationPT � prothrombin timePVE � preoperative portal vein embolizationRLV � remnant liver volumeRLV-BWR � ratio of remnant liver volume to body weightRLV-TLV � ratio of remnant liver volume to total liver

volume

pecifically assess the impact of a small RLV on postop- T

rative course, 10 patients were excluded from this studyor the following reasons: presence of chronic liver dis-ase (n � 1), persistent malignant obstructive jaundiceespite biliary drainage (n � 6), or association of liveresection with resection of another organ (eg, colon,ancreas) (n � 3).5,24-27 Among the remaining 43 pa-ients, who were considered to have normal liver paren-hyma, 31 underwent preoperative measurement of theLV using CT because of an anticipated small RLV andntered this prospective study. There were 17 men and4 women, whose median age was 60 years (range 36 to9) (Table 1). Indications for right hepatic trisectionec-omy were hepatocellular carcinoma (n � 1), biliaryalignancies (n � 5), colorectal liver metastases

n � 22), noncolorectal liver metastases (n � 2), andngioma (n � 1). Preoperative chemotherapy was per-ormed in 23 (74.2%) of 31 patients.

easurement of liver volumes using helical CTerial abdominal transverse sections were taken withontrast-enhanced CT at 0.5-cm intervals in each pa-ient. On each slice, both TLV and volume of the liver toe resected were outlined and the sum of the slices cal-ulated by integrated software techniques.7 Tumor vol-mes were considered to be nonfunctional liver paren-hyma and were subtracted from the TLV.28,29 Theumor volume was calculated using the mean of at leastperpendicular diameters (D) measured on the resected

pecimens as follows: [Tumor volume � 4/3 * � (D/)3].2 The volumetric data were calculated either afterVE when performed (n � 9 patients with an antici-ated RLV of � 20%) or within 1 month before lapa-otomy. We then calculated the RLV to total liver vol-me ratio (RLV-TLV, expressed as a percentage of theLV) and the RLV to body weight ratio (RLV-BWR,

xpressed as a percentage of the body weight). Then,onsidering a cut-off of 0.6% as the minimum tolerableolume of the graft in LDLT in association with thelower liver regeneration in this setting,15 a cut-off of.5% of the body weight was selected as a hypotheticalut point to be analyzed for its use in terms of patientutcomes. Patients were stratified in 3 different ways asollows: RLV-TLV � or � 25%, RLV-TLV � or

20%, and RLV-BWR � or � 0.5%.

urgical techniquesll patients underwent right hepatic trisectionectomy.23

he liver was approached through a right or bilateral

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24 Truant et al Extended Resection in Noncirrhotic Liver J Am Coll Surg

ubcostal incision in all patients. Extraparenchymatousontrol of the hepatic artery and the portal and hepaticeins was carried out in all patients before resection.iver transection was performed using an ultrasonic dis-ector (Dissectron, Satelec Medical, Integra). All opera-ions were performed under low central venous pressureonditions.30 Total vascular exclusion of the liver wassed in one patient who underwent en bloc vena cavaesection. Other resections were performed without he-atic inflow occlusion (n � 23) or under intermittentortal triad clamping (n � 7) (clamping period of 15inutes separated each by 5 minutes of release). Addi-

ional procedures were performed in 10 patients32.3%), including resection of the common bile ductn � 4), portal vein (n � 1), portal vein and commonile duct (n � 3) or inferior vena cava (n � 2), andesections of one or more left tumor(s) or caudate lobe

able 1. Distribution of 31 Patients According to Ratio Useemnant Liver Volume to Total Liver Volume or Ratio of the Rlogic and Intraoperative Characteristics for Each Group

Total RLV-T

ut-off value � 25%31 17

LV-TLV (median %) 24.3 22.1LV-TLV range (%) 16.1–41.1 16.2–24.8LV-BWR (median %) 0.59 0.52LV-BWR range (%) 0.35–1.00 0.35–0.83edian age (y) 60 58ale-to-female ratio (n) 17:14 11:6

SA score 2 1hemotherapy (n) 23 13

ndications (n)Metastases 24 14Liver cancer 6 2Angioma 1 1

VE (n) 9 6esected nodules (n) 2 3.5esected segments (n) 5 5lamping (n) 8 3ascular or biliary resection (n) 10 5dditional resection of left tumor

or caudate lobe (n) 11 5lood loss (mL) 600 525perative time (min) 330 330

ontinuous variables were expressed as median and compared using the Manlogic and intraoperative data, except for age for groups � and � 0.5%.Mann-Whitney U test, p � 0.021.SA, American Society of Anesthesiologists; PVE, portal vein embolizationeight; RLV-TLV, ratio of remnant liver volume to total liver volume.

ere carried out in 4 and 7 patients, respectively. l

nalysisreoperative, intraoperative, and postoperative dataere collected prospectively in a computerized database.nly variables previously shown to affect outcomes were

tudied,31 ie, clinical background, including age,11 gen-er, viral markers such as hepatitis B or C infections,iabetes mellitus,32 the American Society of Anesthesi-logists Physical Status Scores (ASA score),27 indicationsor resection and performance of preoperative chemo-herapy,33 and intraoperative findings including opera-ive time, blood loss,30,34 and vascular clamping.30 Liverunction tests, which were preoperatively normal for allatients, were recorded on postoperative days 1, 3, 5, 7,0, and 15, and kidney function evaluated by Cockroftormula. Liver failure was defined as both a prothrombinime (PT; expressed as a percentage of the normal level ofrothrombin activity) � 50% and total serum bilirubin

r Calculation of the Remnant Liver Volume (Either Ratio ofant Liver Volume to Body Weight) and Principal Clinicopath-

RLV-TLV RLV-BWR

25% � 20% � 20% � 0.5% � 0.5%4 6 25 9 222.4 19 27.3 21.6 27.3–41.1 16.1–20.4 21.6–41.1 16.1–31.2 20.3–41.10.73 0.44 0.6 0.41 0.64–1 0.35–0.66 0.37–1 0.35–0.5 0.52–12.5 66 58 70* 56.5*:8 3:3 14:11 6:3 11:11

2 1.5 2 2 10 4 19 8 15

0 5 19 9 154 1 5 0 60 0 1 0 13 3 6 3 61.5 3.5 2 3 15 5.1 5 5 55 0 8 1 75 2 8 3 7

6 3 8 2 90 600 575 750 5500 330 330 330 330

itney U test. For each ratio, groups were comparable in terms of clinicopath-

, remnant liver volume; RLV-BWR, ratio of remnant liver volume to body

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o Hospital Beaujon’s criteria.2,35 Main outcomes mea-ures were durations of ICU stay and hospitalization,ostoperative morbidity and mortality, defined as eventsccurring during the same hospital stay or within 3onths after resection.8 Morbidity was defined as any

erioperative complication, including ascites or pleuralffusion requiring drainage; biliary fistula or biloma;epsis or hemorrhage; wound complications; pneumo-ia or pulmonary embolism; atelectasis requiring bron-hoscopy; cardiac complications; and kidney or liverailure.2 Complications were defined as major when theyequired reoperation or interventional radiology or re-ulted in organ failure or patient death. The biochemicalnd clinical course of patients was studied for its associ-tion with the RLV expressed either as the RLV-TLV ors the RLV-BWR.

tatistical analysisontinuous variables were expressed as median (range)

nd compared using the Mann-Whitney U test. Cate-orical variables, expressed as frequencies and percent-ges, were compared using Fisher’s exact test. Correla-ions between variables were assessed using Spearman’sank correlation coefficient p. The sensitivity and speci-

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Figure 1. Correlation between the volume (or weight) oCT for 26 of 31 patients (p � 0.0001; Spearman’s co

icity of the three ratios, ie, the RLV-BWR with cut-off T

alues of 0.5% and the RLV-TLV with a cut-off value of0% and 25%, were calculated for postoperative mor-ality. Statistical significance was defined as p � 0.05.tatistical analysis was performed using StatView soft-are, version 4.55 (Abacus Concepts).

ESULTSiver volumes assessment and volumetric datas liver density is close to 1,36 the actual weight of the

esected liver, which was documented for 26 patients,as considered equal to its volume. The comparisonetween the volume of the resected right lobe and itsolumetric assessment by CT showed a very goodorrelation (Fig. 1, p � 0.0001; Spearman’s rank cor-elation coefficient, p � 0.83), allowing us to validatehe volumetric measurements by CT. Distribution ofhe 31 patients according to ratio of RLV used (eitherLV-TLV or RLV-BWR) and median values of pre-perative RLV-TLV and RLV-BWR for each group are re-orted in Table 1. As TLV is correlated to bodyeight,12,37 there was good correlation between RLV-WR and RLV-TLV (Fig. 2, p � 0.0001, Spearman’sank correlation coefficient p � 0.72).2 Some discor-ant results were observed, eg, a patient with RLV-

volume (mL)2000 2250 25002000 2250 2500 2750 3000 3250

volume (mL)volume (mL)2000 2250 25002000 2250 2500 2750 3000 3250

volume (mL)

resected right lobe and its volumetric assessment byent of rank correlation p � 0.83).

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anges of RLV-TLV and RLV-BWR groups over-apped one another (Table 1, Fig. 2).

atientsain clinicopathologic data are presented for each

roup in Table 1. For each ratio, groups were compa-able in terms of preoperative data, with the exceptionf a higher median age in group RLV-BWR � 0.5%hen compared with group � 0.5% (70 versus 56.5ears; p � 0.021). Three patients who had an RLV of

20% at presentation could not have effective PVE,lthough the rate of PVE did not differ betweenroups. Similarly, intraoperative characteristics,ainly surgical time, estimated blood loss, or portal

riad clamping, did not differ between groups (Table). Histology of explanted specimen confirmed thatone of the patients had underlying liver disease. Forach ratio, there was no difference between groups inerms of pre- and intraoperative characteristics, allow-ng us to specifically study the potential impact ofLV, expressed either as the RLV-TLV or as the RLV-WR, on the postoperative course.

ostoperative liver function testso clarify the impact of RLV on postoperative liver func-

15

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Figure 2. Correlation between the ratio of remnant liveliver volume to body weight (RLV-BWR) (p � 0.0001, Spa positive correlation between both ratios, some disco� 25% or 20% could have an RLV-BWR � 0.5%.

ion tests, one patient with an unrelated postoperative com- p

lication (iatrogenic colonic perforation) was excludedrom this portion of the analysis. Importantly, no patienteceived fresh-frozen plasma transfusion.38 Whatever theatio used, PT did not correlate with RLV: all patients ex-erienced a decrease of PT on postoperative day 1 thatrogressively normalized thereafter, irrespective of RLVdata not shown). By contrast, postoperative total serumilirubin was inversely correlated to the RLV-TLV (day 1, p�0.59, p � 0.0007; day 3, p � �0.71, p � 0.0001; day

, p � �0.66, p � 0.0004; day 7, p � �0.53, p � 0.005;ay 10, p � �0.49, p � 0.009; day 15, p � �0.49, p �.012; data not shown) and to the RLV-BWR (day 1, p �0.47, p � 0.012; day 3, p � �0.53, p � 0.004; day 5, p�0.63, p � 0.0006; day 7, p � �0.60, p � 0.001; day

0, p � �0.57, p � 0.002; day 15, p � �0.57, p �.0037; Fig. 3) with a very good correlation observed forhe group RLV-BWR 0.5% until postoperative day 15.here was no evidence of a correlation between RLV-TLVr RLV-BWR and the other liver function tests (aspartate-minotransferase/alanine-aminotransferase level, factor V,lkaline phosphatase, �-glutamyl transpeptidase, serum al-umin) or kidney function (data not shown).

hree-month morbidity and durations of staysmong the 31 patients, 11 experienced one or more

,7 ,8 ,9 1 1,1BWR (%)

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me to total liver volume (RLV-TLV) and ratio of remnantan’s coefficient of rank correlation p � 0.72). Despiteresults were observed, eg, a patient with an RLV-TLV

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ostoperative complications (overall morbidity rate of

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5.5%; Table 2). The most frequent complications werescites (n � 2) or pleural effusion (n � 3), wound com-lications (n � 3), biliary fistula (n � 2) or biloma (n �), colonic perforation (n � 1), kidney failure (n � 1),r liver failure (n � 2). Among these 11 patients, 6 hadajor complications, requiring interventional radiology

r reoperation (n � 3) or resulting in patient death (n �). The analysis for each ratio showed that overall mor-idity rates were higher when the RLV was smaller, noatter which ratio was used (Table 2). This increase in

verall morbidity was statistically significant only whenhe RLV-BWR was used (p � 0.038). We also observedigher rates of major complications in the groups withmall RLV, whichever ratio was used, although theseifferences were not statistically significant (Table 2).urations of ICU stay and hospitalization were compa-

able between groups (Table 2).

hree-month mortalityhree patients (9.7%) died in the postoperative pe-

iod, 2 (6.5%) from liver failure. These two patients

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Figure 3. Correlation between the ratio of remnant livetotal serum bilirubin (in horizontal axis) on postoperat

ad received neoadjuvant chemotherapy for colorec- n

al liver metastasis, but did not display adverse sideffects on the nontumoral liver at two histologicxaminations.39

Patient 1: Seventy-two years old, ASA score � 3, co-orbidities include arrhythmia, Raynaud’s phenome-

on, 9 preoperative cycles of oxaliplatine-based chemo-herapy, right hepatic trisectionectomy (5 segments)ithout contralateral resection or additional procedure,perative time of 360 minutes, blood loss of 400 mL,elective portal triad clamping without Pringle maneu-er; postoperative course: hyperbilirubinemia (270 atostoperative day 15) and death from liver and multiplergan failure at day 25.

Patient 2: Seventy-seven years old, ASA score � 2,omorbidities include hypertension, dyslipemia, 2reoperative cycles of oxaliplatine-based chemother-py, right hepatic trisectionectomy (5 segments) with-ut contralateral resection or additional procedure,perative time of 210 minutes, blood loss of 200 mL,elective portal triad clamping without Pringle ma-

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Day 7P =0.001

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me to body weight (RLV-BWR) (in vertical axis) and theys 1, 3, 5, 7, 10, and 15.

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160 at postoperative day 15) and death from liverailure at day 53.

The third patient died from a nonspecific complica-ion (peritonitis secondary to iatrogenic colonic perfo-ation). Distribution of patients’ deaths among groups iseported in Table 2. There was an increase in the rates ofverall mortality or deaths from liver failure in theroups with an RLV-TLV � 25% or 20% comparedith the groups with a higher RLV-TLV, although theseifferences were not statistically significant. By contrast,verall mortality was significantly higher in the groupLV-BWR � 0.5% compared with the group � 0.5%

p � 0.019). About rates of deaths from liver failure, theifference was not statistically significant when compar-

ng groups RLV-BWR � 0.5% and � 0.5% (p �.077). Two patients who died from liver failure had anLV-BWR � 0.5%. For prediction of postoperativeortality, the RLV-TLV 20% had the best specificity

89%), but low sensitivity (33%), and the RLV-TLV5% had a 100% sensitivity but low specificity (46%).LV-BWR 0.5% had a 100% sensitivity in associationith an excellent specificity (78%).

ISCUSSIONn this prospective study, we showed for the first timehat the RLV-BWR was a new and easy calculationethod of the RLV and that its use was relevant in

ssessing the minimum RLV tolerable after an extended

able 2. Three-Month Morbidity and Mortality and DurationTotal RLV-

ut-off value � 25%31 17

orbidity overall, n (%) 11 (35.5) 8 (47)LV � versus �, p value 0.1ajor, n (%) 6 (19.4) 4 (23.5)

LV � versus �, p value 0.6uration of hospitalization (d) 13 13LV � versus �, p value 0.7uration of ICU stay (d) 4 4LV � versus �, p value 0.6verall mortality, n (%) 3 (9.7) 3 (17.6)LV � versus �, p value 0.2eath from liver failure, n (%) 2 (6.5) 2 (11.8)LV � versus �, p value 0.4

ontinuous variables are expressed as median. Liver failure was defined as botostoperative day 4 according to Hospital Beaujon’s criteria.2,35

LV, remnant liver volume; RLV-BWR, ratio of remnant liver volume to bod

epatectomy of five or more segments. Our study al- u

owed us to analyze a cut-off value of 0.5% as a criticaloint associated with patient postoperative course.ight hepatic trisectionectomy resulting in an RLV-WR of � 0.5% of body weight in patients with normal

iver was associated with substantially increased morbid-ty and mortality rates.

RLV-BWR, which was translated from the LDLTodel, is based on a correlation between TLV and bodyeight or BSA.12,37 In our study, we first hypothesized

hat the lower limit of RLV-BWR would be � 0.6% ofody weight tolerated for grafts in case of urgentDLT.16-22 Liver regeneration is slower after LDLT thanfter hepatic resection,15 resulting from a large spectrumf factors, including absence of contralateral hypertro-hy, as the liver is strictly normal in living donor, ageismatch,40 anatomic graft congestion after hepatic ve-

ous reconstruction,41 regeneration-induced acceleratedejection,20 antiproliferative action of glucocorticoids orirolimus,42 and ischemia-reperfusion injury,2,14,15 whichan be aggravated by exposure of the small-for-size graftso excessive portal perfusion.43 In light of these data, weould determine a cut-off value of RLV-BWR of 0.5% ascritical point for postoperative course in our series.

atients with an RLV-BWR � 0.5% showed a threefoldncrease in overall complication rate (66.5% versus2.5%; p � 0.038) and a significant increase in overallortality rate (33% versus 0%; p � 0.019) when com-

ared with patients with a higher RLV-BWR. In partic-

taysRLV-TLV RLV-BWR

25% � 20% � 20% � 0.5% � 0.5%14 6 25 9 22(21.5) 4 (66.5) 7 (28) 6 (66.5) 5 (22.5)

0.15 0.038(14) 2 (33) 4 (16) 3 (33) 3 (13.5)

0.57 0.3213.5 14.5 12 14 12.5

0.1 0.44 4 4 5 4

0.80 0.12(0) 1 (16.7) 2 (8) 3 (33) 0 (0)

0.49 0.019(0) 1 (16.7) 1 (4) 2 (22) 0 (0)

0.35 0.077

othrombin time � 50% and a total serum bilirubin level � 50 �mol/L after

ght; RLV-TLV, ratio of remnant liver volume to total liver volume.

of STLV

�

33

2

5

40

30

9

h a pr

lar, the 2 cases of lethal liver failure observed in our

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eries occurred in group RLV-BWR � 0.5%. Death andiver failure rates stand out compared with earlier stud-es, although few data exist about very extended hepa-ectomies. The death and liver failure rates stand outompared to prior studies, although few data exist re-arding very extended hepatectomies. Our study popu-ation was highly selected, including only patients whoequired liver volumetry because of an anticipated smallLV and who underwent (for one third of them) a com-lex hepatectomy associated with biliary or vascular re-onstruction. By contrast, our mortality rate among 402epatectomies (3.8%) performed in our institutionince September 2000 was comparable to those reportedn the literature. Laboratory values for RLV-BWR wereignificantly correlated to postoperative serum bilirubinhrough day 15 (day 1, P � 0.012; day 3, P � 0.004; day, P � 0.0006; day 7, P � 0.001; day 10, P � 0.002; day5, P � 0.0037; Fig. 3), with a delayed recovery in groupLV-BWR � 0.5%. Although the early peak of serumilirubin reflects surgical injury and initial liver regener-tion, its delayed recovery in patients with smaller RLV-WR suggests the possibilities of more profound hepaticysfunction or ongoing liver damage of the “small-for-ize remnant liver” that is exposed to a dramatic increasef portal flow.44 Our results showed that RLV-BWR al-owed for better identification of patients at risk for liverailure and better stratification of patients than the RLV-LV (Table 3). Similarly, applying the correlation be-

ween TLV and BSA, Shirabe and colleagues1 showedhat a ratio of RLV to BSA of � 250 mL/m2 was asso-iated with an increased risk of liver failure in hepatitis- or C-positive patients who underwent rightepatectomy.Importantly, only right hepatic trisectionectomy was

elected for this study, to allow for uniform comparisonetween patients with very small future RLV. The aver-ge proportion of left lateral section to TLV was 17% �% (range 11 to 29) in 155 living donors,45 and innother series of 102 patients with normal liver, the leftateral section contributed � 20% of TLV in � 75% ofatients.3 This type of hepatectomy also avoided theonsiderations on liver volume at risk for devasculariza-ion or venous congestion because of regular portal andepatic venous distribution of the left lateral liver sec-ion. As reported in a recent study46 on virtual resection,here was no substantial difference between two-imensional CT and computer-assisted risk analysis of
epatic circulation in calculation of future RLV before right f
epatic trisectionectomy in contrast to left trisectionec-omy or central hepatectomy.To specifically assess the min-mum RLV-BWR that was compatible with a safe postop-rative course, we excluded from our study patients withhronic liver disease, preoperative jaundice, or associ-ted extrahepatic procedure, factors that are known toffect postoperative course.27 We performed resectionssing a standardized technique, namely under low cen-ral venous pressure conditions and without portal triadlamping when possible, to avoid both deleteriousackflow bleeding from hepatic veins and ischemia-eperfusion injury,24,30,34,47 allowing good preservation ofhe small remnant liver.48 About postoperative liverunction tests, patients received neither fresh-frozenlasma nor massive blood transfusion, which might havead an effect on postoperative PT or serum bilirubin

evels independent of RLV.38 Patients with unrelatedomplications were excluded from this portion of thenalysis, to ensure that the kinetics of liver function testsere a function of the RLV rather than primarily related

o postoperative complications. On the other hand, ourtudy had some limitations. First, it included primaryiver tumors and metastatic colorectal cancer. The me-ian age of patients was higher in the group RLV-BWR

0.5% compared with group RLV-BWR � 0.5% (70ersus 56.5 years), which might have impaired liver re-eneration in the former. Several studies49-51 have shownhat postoperative liver function and mortality rates af-er hepatectomy in patients older than 65 years wereimilar to those in younger patients, provided that el-erly patients were strictly selected before operation.welve of 43 patients who did not undergo preoperativeeasurement of the future RLV as deemed sufficientere not included in this study and might have led to a

election bias. Like most previous studies, segment I,hich was generally preserved, was not considered inolumetric analysis, although accounting for 2% � 1%f TLV.3 Finally, about two-thirds of our patients hadeceived preoperative chemotherapy, which has been as-ociated with adverse side effects,39 although this condi-ion might be difficult to avoid in patients withalignancies.The main advantage of RLV calculated through the

LV-BWR is that it is anticipated with regard to bodyeight of the patient and subsequently to the metabolicemand. Contrary to RLV-TLV, the RLV-BWR doesot lie on the assumption of a homogeneously preserved
unction of the whole liver. Indeed, Imamura and col-

Table 3. Previous and Current Studies Analyzing the Impact of Remnant Liver Volume on Postoperative Course

First author n RLV calculation Cut-off nPVE Morbidity

(%) p ValueLiver

failure (%) p ValueOverall

mortality (%) p Valuen %

Shirabe1 47* Body surface area RLV 250 mL/m2 � 20� 27

— ——

380

0.0012 ——

0.0008

Vauthey8 15 Standardized TLV9 RLV-TLV 25% � 5� 10

12 40 60†

0†0.02 —

—00

Abdalla4 42 Standardized TLV12 RLV-TLV 20% � 12� 30

18 43 5013

0.02 ——

00

Yigitler2 138 Standardized TLV10 RLV-TLV 30% � 13� 125

0 5442

NS 85.6

NS 00.8

NS

Shoup6 33 Actual TLV RLV-TLV 25% � 20� 13

— ——

900

� 0.0001 ——

Actual TLV RLV-TLV 25% � 17� 14

9 29 4721.5

0.13 11.80

0.49 17.60

0.23

Current study 31 Actual TLV RLV-TLV 20% � 6� 25

66.528

0.15 16.74

0.35 16.78

0.49

Body weight RLV-BWR 0.05% � 9� 22

66.522.5

0.038 220

0.077 330

0.019

Definition of liver failure was variable from one study to the other.*Study on hepatitis B- or C-positive patients. Standardized total liver volume (TLV) was calculated from published formula (see references) that closely correlates the volume measured by CT with the bodysurface area or body weight in adult patient, and actual TLV corresponds to measurement of the TLV by liver volumetry using CT.†Major complications only.PVE, portal vein embolization; RLV, remnant liver volume; RLV-BWR, ratio of remnant liver volume to body weight; RLV-TLV, ratio of remnant liver volume to TLV; TLV, total liver volume.

30

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urg

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eagues52 found an abnormal indocyanine green reten-ion rate at 15 minutes in 24% of neoplastic patientsompared with 0% in the LDLT patients. One can hy-othesize that this hepatic dysfunction is mostly a resultf the diseased part of the liver, meaning that there is noniform distribution of liver function within the entire

iver volume. Interestingly, despite a global correlationetween the RLV-TLV and the RLV-BWR, we observedome great discrepancies between both ratios for theame patient, eg, a patient with an RLV-TLV � 25% or0% could show an RLV-BWR � 0.5%. These impor-ant differences might be because of the absence of cor-elation of the left lateral section volume with the bodyeight and its great interpatient variability in the TLV,

nd the difficulties estimating the TLV. In patients withultiple tumors, measurement of individual volumes

umulates the error variability associated with each mea-urement, and lesions beyond the resolution of imagingr areas of nonfunctional liver resulting from tumorrowth or biliary dilation are underestimated, resultingn inaccurate estimate of the total tumor volume. Thisas led some authors to exclude these patients despite aisk for selection bias.2,28 In case of a large malignantumor mass, the contralateral liver segments might havendergone a progressive compensatory hypertrophy, ei-her because this tumor mass does not represent func-ional liver parenchyma or because it impairs the adja-ent portal blood flow, resulting in misestimation of thectual RLV if expressed as a proportion of the TLV. Sim-larly, in patients undergoing PVE, volume measure-

ent of the embolized liver is probably not appropriateiven the histologic changes described in associationith the procedure. The RLV-BWR could be particu-

arly useful in the case of rehepatectomies. The liveregeneration observed after a first hepatectomy allowsnly part of the original liver volume to be recoveredabout 85%), resulting in the inadequacy of the RLV-LV.13 In case of rehepatectomy, the minimum tolerableLV calculated through the RLV-TLV ratio is unknown,robably � 20% or 25%, but could be more appropri-tely anticipated by the RLV-BWR, which considersnly the actual volume to be left.

In conclusion, in our series, the RLV-BWR was moreelevant than the RLV-TLV in predicting postoperativeourse after right hepatic trisectionectomy. Patients withn anticipated RLV of � 0.5% of the body weight weret considerable risk for hepatic dysfunction and postop-
rative mortality, and no deaths occurred in patients
ith an RLV-BWR � 0.5%. These results now need toe confirmed in a larger series through a multicentricrospective study. In future studies, the prediction ofostoperative morbidity and mortality should be basedn an algorithm combining volumetric measurementhrough RLV-BWR and grading for liver disease andunction, defining a “functional remnant liver volume/ody weight ratio.”

uthor Contributions

tudy conception and design: Truant, Pruvotcquisition of data: Truant, Oberlin, Sergent, Lebuffe,Gambiez, Ernst

nalysis and interpretation of data: Truant, Pruvot, Gambiezrafting of manuscript: Truant, Pruvot

tatistical expertise: Truantupervision: Pruvot

cknowledgment: We are indebted to Prof Gilles Mentharom University Hospital of Geneva, Switzerland, for his crit-cal review of the article. We are also very grateful to Prof P

athurin (Service d’Hépatogastroentérologie) and to Dr JLesseyn (Unité INSERM 560), Lille, France, for their helpith statistical analysis.

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