Remnant Liver Volume to Body Weight Ratio > 0.

5%: A New Cut-Off to Estimate Postoperative Risks after Extended Resection in Noncirrhotic Liver
Stphanie Truant, PhD, Olivier Oberlin, MD, Graldine Sergent, MD, Gilles Lebuffe, PhD, Luc Gambiez, MD, Olivier Ernst, PhD, Franois-Ren Pruvot, MD
Before extended hepatectomy of five or more segments, the remnant liver volume (RLV) is usually calculated as a ratio of RLV to total liver volume (RLV-TLV) and must be 20% to 25%. This method can lead to compare parts of normal liver parenchyma to others compromised by biliary or vascular obstruction or by portal vein embolization. Extrapolating from living-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 computed tomography were obtained before right-extended hepatectomy in 31 patients. RLV-BWR of 0.5% 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 RLVTLV and 25% and between groups RLV-TLV and 20%, but increased significantly in 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 extended hepatectomy. Patients with an anticipated RLV 0.5% of body weight are at considerable risk for hepatic dysfunction and postoperative mortality. (J Am Coll Surg 2007;204:2233. 2007 by the American College of Surgeons)
BACKGROUND:

In patients with normal liver, only extended hepatic resection of more than four segments, mainly right or left hepatic trisectionectomies, carries a high risk of postoperative complications associated with hepatic insufficiency,1 requiring determination preoperatively of future remnant liver volume (RLV). RLV is usually expressed as a ratio of RLV to total liver volume (RLV-TLV)2,3 after measurement of these volumes by CT. It is considered that a hepatectomy leaving an RLV of as much as 25% to 30% of the liver can be performed safely,2,4-6 but Abdalla
Competing Interests Declared: None. Presented at the Journe Francophones de Pathologie Digestive, Paris, France, April 2005, and the IHPBA Congress, Edinburgh, Scotland, September 2006. Received January 19, 2006; Revised September 7, 2006; Accepted September 12, 2006. From the Departments of Digestive and Transplantation Surgery (Truant, Oberlin, Gambiez, Pruvot), Radiology (Sergent, Ernst), and Anesthesiology (Lebuffe), University Hospital, Hospital Huriez, Lille, France. Correspondence address: Franois-Ren Pruvot, MD, Service de Chirurgie Digestive et Transplantation, Hpital Huriez, 59037 Lille Cedex, France. email: frpruvot@chru-lille.fr

and colleagues4 have shown that this limit can be decreased to 20% without a high death rate. RLV calculated through this ratio can be misestimated in the case of huge or multiple metastases, the volume of which must be subtracted from the TLV, or in the presence of areas of nonfunctional liver resulting from biliary or vascular obstruction.7 To reduce these difficulties, some authors have used the method of standardized measurement of the RLV, where total liver volume is estimated by a formula that closely correlates the volume measured by CT with the body surface area (BSA) or body weight in adult patients.2,8-10 The calculated total liver size differed substantially according to the formula used.11,12 In the case of extended hepatectomies with an anticipated RLV-TLV close to the limit of 25%, this ratio might not be accurate enough to predict postoperative course or the need for preoperative portal vein embolization (PVE). In the case of repeat hepatectomy, in which actual TLV does not reach initial TLV because of incomplete recovery,13 this ratio is ineffective.

2007 by the American College of Surgeons Published by Elsevier Inc.

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ISSN 1072-7515/07/$32.00 doi:10.1016/j.jamcollsurg.2006.09.007

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Abbreviations and Acronyms

BSA LDLT PT PVE RLV RLV-BWR RLV-TLV

body surface area living-donor liver transplantation prothrombin time preoperative portal vein embolization remnant liver volume ratio of remnant liver volume to body weight ratio of remnant liver volume to total liver volume

Extrapolating the example of living-donor liver transplantation (LDLT) to hepatic resection, we assumed that the ratio of RLV to body weight (RLV-BWR) of the patientby considering RLV onlycould be used as a more relevant calculation method of the minimum RLV tolerable after extended hepatectomy of five or more segments, as reflected by the postoperative clinical and biochemical parameters. In LDLT, the minimum tolerable volume of the graft is higher than the 25% to 30% of RLV tolerated after hepatectomy, owing to lesseffective liver regeneration,2,14,15 and ranges from 40% to 50% of the ideal TLV of the recipient.16-18 In this setting, the adequacy between graft volume and recipient weight is generally estimated by the graft body weight ratio, and the minimum tolerable volume of the graft is about 0.8% of body weight.19-21 Nevertheless, in cases of urgent transplantation, ie, fulminant hepatic failure, some patients were successfully transplanted with small-for-size grafts representing only 0.6% of their body weight.22 In this prospective study, patients with noncirrhotic liver who were candidates for a right hepatic trisectionectomy underwent measurement of RLV by liver volumetry using CT. We first studied the association of a conventional RLV-TLV of 25% or 20% to the postoperative course of the patients. Afterward we compared the value of RLV-BWR to that of RLV-TLV in predicting morbidity and mortality after a right hepatic trisectionectomy. METHODS
Patient selection

erative course, 10 patients were excluded from this study for the following reasons: presence of chronic liver disease (n 1), persistent malignant obstructive jaundice despite biliary drainage (n 6), or association of liver resection with resection of another organ (eg, colon, pancreas) (n 3).5,24-27 Among the remaining 43 patients, who were considered to have normal liver parenchyma, 31 underwent preoperative measurement of the RLV using CT because of an anticipated small RLV and entered this prospective study. There were 17 men and 14 women, whose median age was 60 years (range 36 to 79) (Table 1). Indications for right hepatic trisectionectomy were hepatocellular carcinoma (n 1), biliary malignancies (n 5), colorectal liver metastases (n 22), noncolorectal liver metastases (n 2), and angioma (n 1). Preoperative chemotherapy was performed in 23 (74.2%) of 31 patients.
Measurement of liver volumes using helical CT

Among 186 major hepatectomies of 3 or more Couinaud segments23 performed at our institution between September 2000 and December 2004, 53 (28.5%) were right hepatic trisectionectomies, as defined (resection of Couinaud segments IV to VIII). To specifically assess the impact of a small RLV on postop-

Serial abdominal transverse sections were taken with contrast-enhanced CT at 0.5-cm intervals in each patient. On each slice, both TLV and volume of the liver to be resected were outlined and the sum of the slices calculated by integrated software techniques.7 Tumor volumes were considered to be nonfunctional liver parenchyma and were subtracted from the TLV.28,29 The tumor volume was calculated using the mean of at least 2 perpendicular diameters (D) measured on the resected specimens as follows: [Tumor volume 4/3 * (D/ 2)3].2 The volumetric data were calculated either after PVE when performed (n 9 patients with an anticipated RLV of 20%) or within 1 month before laparotomy. We then calculated the RLV to total liver volume ratio (RLV-TLV, expressed as a percentage of the TLV) and the RLV to body weight ratio (RLV-BWR, expressed as a percentage of the body weight). Then, considering a cut-off of 0.6% as the minimum tolerable volume of the graft in LDLT in association with the slower liver regeneration in this setting,15 a cut-off of 0.5% of the body weight was selected as a hypothetical cut point to be analyzed for its use in terms of patient outcomes. Patients were stratified in 3 different ways as follows: RLV-TLV or 25%, RLV-TLV or 20%, and RLV-BWR or 0.5%.
Surgical techniques

All patients underwent right hepatic trisectionectomy.23 The liver was approached through a right or bilateral

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Table 1. Distribution of 31 Patients According to Ratio Used for Calculation of the Remnant Liver Volume (Either Ratio of Remnant Liver Volume to Total Liver Volume or Ratio of the Remnant Liver Volume to Body Weight) and Principal Clinicopathologic and Intraoperative Characteristics for Each Group
Total RLV-TLV RLV-TLV RLV-BWR

Cut-off value N RLV-TLV (median %) RLV-TLV range (%) RLV-BWR (median %) RLV-BWR range (%) Median age (y) Male-to-female ratio (n) ASA score Chemotherapy (n) Indications (n) Metastases Liver cancer Angioma PVE (n) Resected nodules (n) Resected segments (n) Clamping (n) Vascular or biliary resection (n) Additional resection of left tumor or caudate lobe (n) Blood loss (mL) Operative time (min)

31 24.3 16.141.1 0.59 0.351.00 60 17:14 2 23 24 6 1 9 2 5 8 10 11 600 330

25% 17 22.1 16.224.8 0.52 0.350.83 58 11:6 1 13 14 2 1 6 3.5 5 3 5 5 525 330

25% 14 32.4 25.341.1 0.73 0.411 62.5 6:8 2 10 10 4 0 3 1.5 5 5 5 6 700 330

20% 6 19 16.120.4 0.44 0.350.66 66 3:3 1.5 4 5 1 0 3 3.5 5.1 0 2 3 600 330

20% 25 27.3 21.641.1 0.6 0.371 58 14:11 2 19 19 5 1 6 2 5 8 8 8 575 330

0.5% 9 21.6 16.131.2 0.41 0.350.5 70* 6:3 2 8 9 0 0 3 3 5 1 3 2 750 330

0.5% 22 27.3 20.341.1 0.64 0.521 56.5* 11:11 1 15 15 6 1 6 1 5 7 7 9 550 330

Continuous variables were expressed as median and compared using the Mann-Whitney U test. For each ratio, groups were comparable in terms of clinicopathologic and intraoperative data, except for age for groups and 0.5%. *Mann-Whitney U test, p 0.021. ASA, American Society of Anesthesiologists; 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 total liver volume.

subcostal incision in all patients. Extraparenchymatous control of the hepatic artery and the portal and hepatic veins was carried out in all patients before resection. Liver transection was performed using an ultrasonic dissector (Dissectron, Satelec Medical, Integra). All operations were performed under low central venous pressure conditions.30 Total vascular exclusion of the liver was used in one patient who underwent en bloc vena cava resection. Other resections were performed without hepatic inflow occlusion (n 23) or under intermittent portal triad clamping (n 7) (clamping period of 15 minutes separated each by 5 minutes of release). Additional procedures were performed in 10 patients (32.3%), including resection of the common bile duct (n 4), portal vein (n 1), portal vein and common bile duct (n 3) or inferior vena cava (n 2), and resections of one or more left tumor(s) or caudate lobe were carried out in 4 and 7 patients, respectively.

Analysis

Preoperative, intraoperative, and postoperative data were collected prospectively in a computerized database. Only variables previously shown to affect outcomes were studied,31 ie, clinical background, including age,11 gender, viral markers such as hepatitis B or C infections, diabetes mellitus,32 the American Society of Anesthesiologists Physical Status Scores (ASA score),27 indications for resection and performance of preoperative chemotherapy,33 and intraoperative findings including operative time, blood loss,30,34 and vascular clamping.30 Liver function tests, which were preoperatively normal for all patients, were recorded on postoperative days 1, 3, 5, 7, 10, and 15, and kidney function evaluated by Cockroft formula. Liver failure was defined as both a prothrombin time (PT; expressed as a percentage of the normal level of prothrombin activity) 50% and total serum bilirubin level 50 mol/L after postoperative day 4 according

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5000
Resected liver volumetric measuremement (mL)

4500 4000 3500 3000 2500 2000 1500 1000 500 500

750

1000

1250

1500 1750 2000 2250 Resected liver volume (mL)

2500

2750

3000

3250

Figure 1. Correlation between the volume (or weight) of the resected right lobe and its volumetric assessment by CT for 26 of 31 patients (p 0.0001; Spearmans coefcient of rank correlation p 0.83).

to Hospital Beaujons criteria.2,35 Main outcomes measures were durations of ICU stay and hospitalization, postoperative morbidity and mortality, defined as events occurring during the same hospital stay or within 3 months after resection.8 Morbidity was defined as any perioperative complication, including ascites or pleural effusion requiring drainage; biliary fistula or biloma; sepsis or hemorrhage; wound complications; pneumonia or pulmonary embolism; atelectasis requiring bronchoscopy; cardiac complications; and kidney or liver failure.2 Complications were defined as major when they required reoperation or interventional radiology or resulted in organ failure or patient death. The biochemical and clinical course of patients was studied for its association with the RLV expressed either as the RLV-TLV or as the RLV-BWR.
Statistical analysis

values of 0.5% and the RLV-TLV with a cut-off value of 20% and 25%, were calculated for postoperative mortality. Statistical significance was defined as p 0.05. Statistical analysis was performed using StatView software, version 4.55 (Abacus Concepts). RESULTS
Liver volumes assessment and volumetric data

Continuous variables were expressed as median (range) and compared using the Mann-Whitney U test. Categorical variables, expressed as frequencies and percentages, were compared using Fishers exact test. Correlations between variables were assessed using Spearmans rank correlation coefficient p. The sensitivity and specificity of the three ratios, ie, the RLV-BWR with cut-off

As liver density is close to 1,36 the actual weight of the resected liver, which was documented for 26 patients, was considered equal to its volume. The comparison between the volume of the resected right lobe and its volumetric assessment by CT showed a very good correlation (Fig. 1, p 0.0001; Spearmans rank correlation coefficient, p 0.83), allowing us to validate the volumetric measurements by CT. Distribution of the 31 patients according to ratio of RLV used (either RLV-TLV or RLV-BWR) and median values of preoperative RLV-TLV and RLV-BWR for each group are reported in Table 1. As TLV is correlated to body weight,12,37 there was good correlation between RLVBWR and RLV-TLV (Fig. 2, p 0.0001, Spearmans rank correlation coefficient p 0.72).2 Some discordant results were observed, eg, a patient with RLVTLV 25% could have RLV-BWR 0.5%, and

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45

40

35 RLV-TLV (%)

30

25

20

15 ,3 ,4 ,5 ,6 ,7 RLVBWR (%) ,8 ,9 1 1,1

Figure 2. Correlation between the ratio of remnant liver volume to total liver volume (RLV-TLV) and ratio of remnant liver volume to body weight (RLV-BWR) (p 0.0001, Spearmans coefcient of rank correlation p 0.72). Despite a positive correlation between both ratios, some discordant results were observed, eg, a patient with an RLV-TLV 25% or 20% could have an RLV-BWR 0.5%.

ranges of RLV-TLV and RLV-BWR groups overlapped one another (Table 1, Fig. 2).
Patients

Main clinicopathologic data are presented for each group in Table 1. For each ratio, groups were comparable in terms of preoperative data, with the exception of a higher median age in group RLV-BWR 0.5% when compared with group 0.5% (70 versus 56.5 years; p 0.021). Three patients who had an RLV of 20% at presentation could not have effective PVE, although the rate of PVE did not differ between groups. Similarly, intraoperative characteristics, mainly surgical time, estimated blood loss, or portal triad clamping, did not differ between groups (Table 1). Histology of explanted specimen confirmed that none of the patients had underlying liver disease. For each ratio, there was no difference between groups in terms of pre- and intraoperative characteristics, allowing us to specifically study the potential impact of RLV, expressed either as the RLV-TLV or as the RLVBWR, on the postoperative course.
Postoperative liver function tests

plication (iatrogenic colonic perforation) was excluded from this portion of the analysis. Importantly, no patient received fresh-frozen plasma transfusion.38 Whatever the ratio used, PT did not correlate with RLV: all patients experienced a decrease of PT on postoperative day 1 that progressively normalized thereafter, irrespective of RLV (data not shown). By contrast, postoperative total serum bilirubin was inversely correlated to the RLV-TLV (day 1, p 0.59, p 0.0007; day 3, p 0.71, p 0.0001; day 5, p 0.66, p 0.0004; day 7, p 0.53, p 0.005; day 10, p 0.49, p 0.009; day 15, p 0.49, p 0.012; 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 10, p 0.57, p 0.002; day 15, p 0.57, p 0.0037; Fig. 3) with a very good correlation observed for the group RLV-BWR 0.5% until postoperative day 15. There was no evidence of a correlation between RLV-TLV or RLV-BWR and the other liver function tests (aspartateaminotransferase/alanine-aminotransferase level, factor V, alkaline phosphatase, -glutamyl transpeptidase, serum albumin) or kidney function (data not shown).
Three-month morbidity and durations of stays

To clarify the impact of RLV on postoperative liver function tests, one patient with an unrelated postoperative com-

Among the 31 patients, 11 experienced one or more postoperative complications (overall morbidity rate of

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1,1 1

1,1

RLVBWR (%)

,9 ,8 ,7 ,6 ,5 ,4 ,3 0 10 20 30 40 50 60

RLVBWR (%)

Day 1 P =0.012

1 ,9 ,8 ,7 ,6 ,5 ,4 ,3

Day 3 P =0.004

70

80

20

40

60

80

100

120

140

160

180

Serum bilirubin (mol/L)

1,1 1 1,1

Serum bilirubin (mol/L)

RLVBWR (%)

,9 ,8 ,7 ,6 ,5 ,4 ,3 0 10 20 30 40 50 60 70 80

RLVBWR (%)

Day 5 P =0.0006

1 ,9 ,8 ,7 ,6 ,5 ,4 ,3

Day 7 P =0.001

90

100

110

20

40

60

80

100

120

Serum bilirubin (mol/L)

1,1 1 1,1

Serum bilirubin (mol/L)

RLVBWR (%)

RLVBWR (%)

,9 ,8 ,7 ,6 ,5 ,4 ,3 0 20 40 60 80 100 120

Day 10 P =0.002

1 ,9 ,8 ,7 ,6 ,5 ,4 ,3 0 50 100 150 200 250

Day 15 P =0.0037

140

160

300

350

Serum bilirubin (mol/L)

Serum bilirubin (mol/L)

Figure 3. Correlation between the ratio of remnant liver volume to body weight (RLV-BWR) (in vertical axis) and the total serum bilirubin (in horizontal axis) on postoperative days 1, 3, 5, 7, 10, and 15.

35.5%; Table 2). The most frequent complications were ascites (n 2) or pleural effusion (n 3), wound complications (n 3), biliary fistula (n 2) or biloma (n 1), colonic perforation (n 1), kidney failure (n 1), or liver failure (n 2). Among these 11 patients, 6 had major complications, requiring interventional radiology or reoperation (n 3) or resulting in patient death (n 3). The analysis for each ratio showed that overall morbidity rates were higher when the RLV was smaller, no matter which ratio was used (Table 2). This increase in overall morbidity was statistically significant only when the RLV-BWR was used (p 0.038). We also observed higher rates of major complications in the groups with small RLV, whichever ratio was used, although these differences were not statistically significant (Table 2). Durations of ICU stay and hospitalization were comparable between groups (Table 2).
Three-month mortality

Three patients (9.7%) died in the postoperative period, 2 (6.5%) from liver failure. These two patients had received neoadjuvant chemotherapy for colorec-

tal liver metastasis, but did not display adverse side effects on the nontumoral liver at two histologic examinations.39 Patient 1: Seventy-two years old, ASA score 3, comorbidities include arrhythmia, Raynauds phenomenon, 9 preoperative cycles of oxaliplatine-based chemotherapy, right hepatic trisectionectomy (5 segments) without contralateral resection or additional procedure, operative time of 360 minutes, blood loss of 400 mL, selective portal triad clamping without Pringle maneuver; postoperative course: hyperbilirubinemia (270 at postoperative day 15) and death from liver and multiple organ failure at day 25. Patient 2: Seventy-seven years old, ASA score 2, comorbidities include hypertension, dyslipemia, 2 preoperative cycles of oxaliplatine-based chemotherapy, right hepatic trisectionectomy (5 segments) without contralateral resection or additional procedure, operative time of 210 minutes, blood loss of 200 mL, selective portal triad clamping without Pringle maneuver; postoperative course: hyperbilirubinemia

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Table 2. Three-Month Morbidity and Mortality and Duration of Stays

Total RLV-TLV RLV-TLV RLV-BWR

Cut-off value N Morbidity overall, n (%) RLV versus , p value Major, n (%) RLV versus , p value Duration of hospitalization (d) RLV versus , p value Duration of ICU stay (d) RLV versus , p value Overall mortality, n (%) RLV versus , p value Death from liver failure, n (%) RLV versus , p value

31 11 (35.5) 6 (19.4) 13 4 3 (9.7) 2 (6.5)

25% 17 8 (47) 0.13 4 (23.5) 0.6 13 0.75 4 0.64 3 (17.6) 0.23 2 (11.8) 0.49

25% 14 3 (21.5) 2 (14) 13.5 4 0 (0) 0 (0)

20% 6 4 (66.5) 0.15 2 (33) 0.57 14.5 0.1 4 0.80 1 (16.7) 0.49 1 (16.7) 0.35

20% 25 7 (28) 4 (16) 12 4 2 (8) 1 (4)

0.5% 9 6 (66.5) 0.038 3 (33) 0.32 14 0.4 5 0.12 3 (33) 0.019 2 (22) 0.077

0.5% 22 5 (22.5) 3 (13.5) 12.5 4 0 (0) 0 (0)

Continuous variables are expressed as median. Liver failure was defined as both a prothrombin time 50% and a total serum bilirubin level 50 mol/L after postoperative day 4 according to Hospital Beaujons criteria.2,35 RLV, remnant liver volume; RLV-BWR, ratio of remnant liver volume to body weight; RLV-TLV, ratio of remnant liver volume to total liver volume.

(160 at postoperative day 15) and death from liver failure at day 53. The third patient died from a nonspecific complication (peritonitis secondary to iatrogenic colonic perforation). Distribution of patients deaths among groups is reported in Table 2. There was an increase in the rates of overall mortality or deaths from liver failure in the groups with an RLV-TLV 25% or 20% compared with the groups with a higher RLV-TLV, although these differences were not statistically significant. By contrast, overall mortality was significantly higher in the group RLV-BWR 0.5% compared with the group 0.5% (p 0.019). About rates of deaths from liver failure, the difference was not statistically significant when comparing groups RLV-BWR 0.5% and 0.5% (p 0.077). Two patients who died from liver failure had an RLV-BWR 0.5%. For prediction of postoperative mortality, the RLV-TLV 20% had the best specificity (89%), but low sensitivity (33%), and the RLV-TLV 25% had a 100% sensitivity but low specificity (46%). RLV-BWR 0.5% had a 100% sensitivity in association with an excellent specificity (78%). DISCUSSION In this prospective study, we showed for the first time that the RLV-BWR was a new and easy calculation method of the RLV and that its use was relevant in assessing the minimum RLV tolerable after an extended hepatectomy of five or more segments. Our study al-

lowed us to analyze a cut-off value of 0.5% as a critical point associated with patient postoperative course. Right hepatic trisectionectomy resulting in an RLVBWR of 0.5% of body weight in patients with normal liver was associated with substantially increased morbidity and mortality rates. RLV-BWR, which was translated from the LDLT model, is based on a correlation between TLV and body weight or BSA.12,37 In our study, we first hypothesized that the lower limit of RLV-BWR would be 0.6% of body weight tolerated for grafts in case of urgent LDLT.16-22 Liver regeneration is slower after LDLT than after hepatic resection,15 resulting from a large spectrum of factors, including absence of contralateral hypertrophy, as the liver is strictly normal in living donor, age mismatch,40 anatomic graft congestion after hepatic venous reconstruction,41 regeneration-induced accelerated rejection,20 antiproliferative action of glucocorticoids or sirolimus,42 and ischemia-reperfusion injury,2,14,15 which can be aggravated by exposure of the small-for-size grafts to excessive portal perfusion.43 In light of these data, we could determine a cut-off value of RLV-BWR of 0.5% as a critical point for postoperative course in our series. Patients with an RLV-BWR 0.5% showed a threefold increase in overall complication rate (66.5% versus 22.5%; p 0.038) and a significant increase in overall mortality rate (33% versus 0%; p 0.019) when compared with patients with a higher RLV-BWR. In particular, the 2 cases of lethal liver failure observed in our

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series occurred in group RLV-BWR 0.5%. Death and liver failure rates stand out compared with earlier studies, although few data exist about very extended hepatectomies. The death and liver failure rates stand out compared to prior studies, although few data exist regarding very extended hepatectomies. Our study population was highly selected, including only patients who required liver volumetry because of an anticipated small RLV and who underwent (for one third of them) a complex hepatectomy associated with biliary or vascular reconstruction. By contrast, our mortality rate among 402 hepatectomies (3.8%) performed in our institution since September 2000 was comparable to those reported in the literature. Laboratory values for RLV-BWR were significantly correlated to postoperative serum bilirubin through day 15 (day 1, P 0.012; day 3, P 0.004; day 5, P 0.0006; day 7, P 0.001; day 10, P 0.002; day 15, P 0.0037; Fig. 3), with a delayed recovery in group RLV-BWR 0.5%. Although the early peak of serum bilirubin reflects surgical injury and initial liver regeneration, its delayed recovery in patients with smaller RLVBWR suggests the possibilities of more profound hepatic dysfunction or ongoing liver damage of the small-forsize remnant liver that is exposed to a dramatic increase of portal flow.44 Our results showed that RLV-BWR allowed for better identification of patients at risk for liver failure and better stratification of patients than the RLVTLV (Table 3). Similarly, applying the correlation between TLV and BSA, Shirabe and colleagues1 showed that a ratio of RLV to BSA of 250 mL/m2 was associated with an increased risk of liver failure in hepatitis B- or C-positive patients who underwent right hepatectomy. Importantly, only right hepatic trisectionectomy was selected for this study, to allow for uniform comparison between patients with very small future RLV. The average proportion of left lateral section to TLV was 17% 4% (range 11 to 29) in 155 living donors,45 and in another series of 102 patients with normal liver, the left lateral section contributed 20% of TLV in 75% of patients.3 This type of hepatectomy also avoided the considerations on liver volume at risk for devascularization or venous congestion because of regular portal and hepatic venous distribution of the left lateral liver section. As reported in a recent study46 on virtual resection, there was no substantial difference between twodimensional CT and computer-assisted risk analysis of hepatic circulation in calculation of future RLV before right

hepatic trisectionectomy in contrast to left trisectionectomy or central hepatectomy. To specifically assess the minimum RLV-BWR that was compatible with a safe postoperative course, we excluded from our study patients with chronic liver disease, preoperative jaundice, or associated extrahepatic procedure, factors that are known to affect postoperative course.27 We performed resections using a standardized technique, namely under low central venous pressure conditions and without portal triad clamping when possible, to avoid both deleterious backflow bleeding from hepatic veins and ischemiareperfusion injury,24,30,34,47 allowing good preservation of the small remnant liver.48 About postoperative liver function tests, patients received neither fresh-frozen plasma nor massive blood transfusion, which might have had an effect on postoperative PT or serum bilirubin levels independent of RLV.38 Patients with unrelated complications were excluded from this portion of the analysis, to ensure that the kinetics of liver function tests were a function of the RLV rather than primarily related to postoperative complications. On the other hand, our study had some limitations. First, it included primary liver tumors and metastatic colorectal cancer. The median age of patients was higher in the group RLV-BWR 0.5% compared with group RLV-BWR 0.5% (70 versus 56.5 years), which might have impaired liver regeneration in the former. Several studies49-51 have shown that postoperative liver function and mortality rates after hepatectomy in patients older than 65 years were similar to those in younger patients, provided that elderly patients were strictly selected before operation. Twelve of 43 patients who did not undergo preoperative measurement of the future RLV as deemed sufficient were not included in this study and might have led to a selection bias. Like most previous studies, segment I, which was generally preserved, was not considered in volumetric analysis, although accounting for 2% 1% of TLV.3 Finally, about two-thirds of our patients had received preoperative chemotherapy, which has been associated with adverse side effects,39 although this condition might be difficult to avoid in patients with malignancies. The main advantage of RLV calculated through the RLV-BWR is that it is anticipated with regard to body weight of the patient and subsequently to the metabolic demand. Contrary to RLV-TLV, the RLV-BWR does not lie on the assumption of a homogeneously preserved function of the whole liver. Indeed, Imamura and col-

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Table 3. Previous and Current Studies Analyzing the Impact of Remnant Liver Volume on Postoperative Course
PVE First author n RLV calculation Cut-off n n % Morbidity (%) p Value Liver failure (%) p Value Overall mortality (%) p Value

Extended Resection in Noncirrhotic Liver

Shirabe1 Vauthey8 Abdalla4 Yigitler2 Shoup6

47* 15 42 138 33

Body surface area Standardized TLV9 Standardized TLV12 Standardized TLV10 Actual TLV Actual TLV

RLV 250 mL/m2 RLV-TLV 25% RLV-TLV 20% RLV-TLV 30% RLV-TLV 25% RLV-TLV 25% RLV-TLV 20% RLV-BWR 0.05%

Current study

31

Actual TLV Body weight

20 27 5 10 12 30 13 125 20 13 17 14 6 25 9 22

12 18 0 9 29 40 43

60 0 50 13 54 42 47 21.5 66.5 28 66.5 22.5

0.02 0.02 NS

0.13 0.15 0.038

38 0 8 5.6 90 0 11.8 0 16.7 4 22 0

0.0012

NS 0.0001 0.49 0.35 0.077

0 0 0 0 0 0.8 17.6 0 16.7 8 33 0

0.0008

NS

0.23 0.49 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 body surface 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.

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leagues52 found an abnormal indocyanine green retention rate at 15 minutes in 24% of neoplastic patients compared with 0% in the LDLT patients. One can hypothesize that this hepatic dysfunction is mostly a result of the diseased part of the liver, meaning that there is no uniform distribution of liver function within the entire liver volume. Interestingly, despite a global correlation between the RLV-TLV and the RLV-BWR, we observed some great discrepancies between both ratios for the same patient, eg, a patient with an RLV-TLV 25% or 20% could show an RLV-BWR 0.5%. These important differences might be because of the absence of correlation of the left lateral section volume with the body weight and its great interpatient variability in the TLV, and the difficulties estimating the TLV. In patients with multiple tumors, measurement of individual volumes cumulates the error variability associated with each measurement, and lesions beyond the resolution of imaging or areas of nonfunctional liver resulting from tumor growth or biliary dilation are underestimated, resulting in inaccurate estimate of the total tumor volume. This has led some authors to exclude these patients despite a risk for selection bias.2,28 In case of a large malignant tumor mass, the contralateral liver segments might have undergone a progressive compensatory hypertrophy, either because this tumor mass does not represent functional liver parenchyma or because it impairs the adjacent portal blood flow, resulting in misestimation of the actual RLV if expressed as a proportion of the TLV. Similarly, in patients undergoing PVE, volume measurement of the embolized liver is probably not appropriate given the histologic changes described in association with the procedure. The RLV-BWR could be particularly useful in the case of rehepatectomies. The liver regeneration observed after a first hepatectomy allows only part of the original liver volume to be recovered (about 85%), resulting in the inadequacy of the RLVTLV.13 In case of rehepatectomy, the minimum tolerable RLV calculated through the RLV-TLV ratio is unknown, probably 20% or 25%, but could be more appropriately anticipated by the RLV-BWR, which considers only the actual volume to be left. In conclusion, in our series, the RLV-BWR was more relevant than the RLV-TLV in predicting postoperative course after right hepatic trisectionectomy. Patients with an anticipated RLV of 0.5% of the body weight were at considerable risk for hepatic dysfunction and postoperative mortality, and no deaths occurred in patients

with an RLV-BWR 0.5%. These results now need to be confirmed in a larger series through a multicentric prospective study. In future studies, the prediction of postoperative morbidity and mortality should be based on an algorithm combining volumetric measurement through RLV-BWR and grading for liver disease and function, defining a functional remnant liver volume/ body weight ratio. Author Contributions Study conception and design: Truant, Pruvot Acquisition of data: Truant, Oberlin, Sergent, Lebuffe, Gambiez, Ernst Analysis and interpretation of data: Truant, Pruvot, Gambiez Drafting of manuscript: Truant, Pruvot Statistical expertise: Truant Supervision: Pruvot
Acknowledgment: We are indebted to Prof Gilles Mentha from University Hospital of Geneva, Switzerland, for his critical review of the article. We are also very grateful to Prof P Mathurin (Service dHpatogastroentrologie) and to Dr JL Desseyn (Unit INSERM 560), Lille, France, for their help with statistical analysis.

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