Abstract
Background
While commonly used to describe liver resections at risk for post-operative complications, no standard definition of ‘major hepatectomy’ exists. The objective of the present retrospective study is to specify the extent of hepatic resection that should describe a major hepatectomy.
Methods
Demographics, diagnoses, surgical treatments and outcomes from patients who underwent a liver resection at two high-volume centres were reviewed.
Results
From 2002 to 2009, 1670 patients underwent a hepatic resection. Post-operative mortality and severe, overall and hepatic-related morbidity occurred in 4.4%, 29.7%, 41.6% and 19.3% of all patients. Mortality (7.4% vs. 2.7% vs. 2.6%) and severe (36.7% vs. 24.7% vs. 24.1%), overall (49.3% vs. 40.6% vs. 35.9%) and hepatic-related (25.6% vs. 16.4% vs. 15.2%) morbidity were more common after resection of four or more liver segments compared with after three or after two or fewer segments (all P < 0.001). There were no significant differences in any post-operative outcome after resection of three and two or fewer segments (all P > 0.05). On multivariable analysis, resection of four or more liver segments was independently associated with post-operative mortality and severe, overall, and hepatic-related morbidity (all P < 0.01).
Conclusions
A major hepatectomy should be defined as resection of four or more liver segments.
Keywords: liver, resection, major hepatectomy
Introduction
While it is widely recognized that the risks of liver resection are directly related to the volume and function of the liver remnant, these measures may be difficult to determine pre-operatively and are widely under reported among studies analysing post-operative outcomes after liver resection. Hence, most investigators define a major liver resection by the volume of liver resected. Stratification by extent of resection has been used to analyse mortality1–17 and morbidity3–5,11,14,15,17–25 after a partial hepatectomy. In these settings, patients undergoing a major hepatectomy are at the highest risk of adverse post-operative outcomes. Thus, novel treatments aimed at improving the overall safety profile of liver resection are often focused on this subgroup.26–33 Yet no standard definition of a major hepatectomy exists. Resections of two, three, four or five liver segments and a hemihepatectomy have been previously used by us and other investigators as a threshold for a major liver resection. This inconsistency not only hinders comparisons between studies, but also hampers an adequate assessment of morbidity and mortality risk when counselling patients regarding liver resection. The objective of the present study was to determine the extent of resection that should define a major hepatectomy by reviewing liver resections performed at two high-volume academic centres during the contemporary era and identifying those patients at highest risk for post-operative mortality and morbidity.
Methods
After obtaining approval from the Institutional Review Board at both institutions, demographics, clinicopathological data, surgical treatments and post-operative outcomes from patients who underwent a liver resection at the Liver Cancer Center at the University of Pittsburgh Medical Center (UPMC) and at the Duke University Medical Center (DUMC) were reviewed. Patients whose only hepatic procedure was a liver biopsy or radiofrequency ablation were excluded from the present study. Most hepatic lesions were detected pre-operatively with computed tomography, magnetic resonance imaging and/or positron emission tomography. Intra-operative ultrasonography was used to detect and localize all lesions with respect to major vessels. The extent of hepatic resection was at the discretion of the operating surgeon with the aim of achieving negative surgical margins and a liver remnant of sufficient volume to maintain hepatic function with intact vascular inflow, vascular outflow and biliary drainage. Hepatic resections are described using Brisbane 2000 terminology.34 To determine the extent of resection, wedge resections were counted as one-half of a segment and the number of resected segments were rounded down to the nearest whole number. Importantly, any resections which did not follow anatomic planes were categorized as wedge resections. The volume of liver resected itself was not used to distinguish wedge and anatomic resections. Ninety-day post-operative morbidity and mortality were recorded. Post-operative complications were graded according to the Dindo–Clavien classification35 with the following exceptions: (i) grade I complications were largely not recorded except for wound infection and ascites requiring diuresis and (ii) the need for a blood transfusion was not regarded as a complication. Complications grade III and above were considered severe. Hepatic-related morbidity included hepatic abscess or fluid collection requiring drainage, hyperbilirubinemia (≥7.0 mg/dl) bile leak, cholangitis, ascites or liver failure.
Statistical analyses were performed with PASW version 18 (Chicago, IL, USA) software. For univariable and multivariable analyses, diagnoses were grouped as benign, metastatic and primary hepatobiliary malignancy. Data distribution was tested for normality by examining the mean and standard error of the kurtosis and skewness. Comparisons were performed using the Mann–Whitney U- or Kruskal–Wallis tests for non-normally distributed continuous variables. χ2 analyses were used for categorical variable comparisons. Logistic regression was employed to test predictors of morbidity and mortality. Predictors for each model were chosen based on significant associations (P≤ 0.05) between the predictor and dependent variable using univariable analyses.
Results
Overall cohort
From 2002 to 2009, 1670 consecutive patients underwent a liver resection at the Liver Cancer Center at UPMC or at DUMC. In all, 879 (52.6%) patients underwent resection at UPMC and most patients at both centres were Caucasian (Table 1). 354 (21.9%) underwent resection for benign disease and the most common malignant indications for surgery included colorectal cancer metastases, hepatocellular carcinoma and other metastatic disease (Table 1) and 222 (13.3%) patients underwent laparoscopic resection. Simultaneous major non-hepatic procedures were performed in 428 (25.6%) patients. Colorectal, diaphragm and bile duct resections were the most commonly performed simultaneous procedures (Table 1). Most patients had an American Society of Anesthesiology (ASA) score of II or III. The largest component of each resection stratified by the total number of liver segments resected is reported in Table 2. For example, a liver resection encompassing a posterior sectionectomy and two left-sided wedge resections would be categorized as a three segment resection where the largest component of the resection was a bisegmentectomy. In the entire cohort, post-operative mortality, severe morbidity, overall morbidity and hepatic-related morbidity occurred in 74 (4.4%), 496 (29.7%), 695 (41.6%) and 323 (19.3%) patients, respectively.
Table 1.
Demographics, clinicopathological tumour characteristics, pre-operative laboratory values and surgical treatments stratified by extent of hepatic resection
| All patients (n = 1670) | ≤Two segments (n = 814) | Three segments (n = 219) | ≥Four segment (n = 637) | P | |
|---|---|---|---|---|---|
| Age (years)* | 59 (49–69) | 58 (48–68) | 62 (50–72) | 59 (50–69) | 0.013 |
| Male gender | 782 (47.5%) | 413 (50.8%) | 117 (53.4%) | 346 (54.4%) | 0.385 |
| Ethnicity | <0.001 | ||||
| Caucasian | 1430 (86.7%) | 690 (84.8%) | 192 (87.7%) | 548 (86.0%) | |
| African–American | 173 (10.5%) | 86 (10.6%) | 17 (7.8%) | 70 (11.0%) | |
| Asian | 24 (1.5%) | 13 (1.6%) | 3 (1.4%) | 8 (1.3%) | |
| Hispanic | 5 (0.3%) | 4 (0.5%) | 0 | 1 (0.2%) | |
| Native American | 7 (0.4%) | 5 (0.6%) | 2 (0.9%) | 0 | |
| Other | 10 (0.6%) | 6 (0.7%) | 1 (0.5%) | 3 (0.5%) | |
| NA | 21 (1.3%) | 10 (1.2%) | 4 (1.8%) | 7 (1.1%) | |
| Institution | <0.001 | ||||
| DUMC | 791 (47.4%) | 349 (49.2%) | 144 (65.8%) | 298 (53.2%) | |
| UPMC | 879 (52.6%) | 465 (57.1%) | 75 (34.2%) | 339 (46.8%) | |
| Diagnoses | <0.001 | ||||
| Benign | 354 (21.9%) | 226 (27.8%) | 44 (20.1%) | 84 (13.5%) | |
| Colorectal cancer metastases | 624 (38.5%) | 290 (35.6%) | 55 (25.1%) | 279 (43.8%) | |
| Hepatocellular carcinoma | 228 (14.1%) | 113 (13.9%) | 38 (17.4%) | 77 (12.4%) | |
| Other metastatic disease | 224 (13.8%) | 115 (14.1%) | 20 (9.1%) | 89 (14.3%) | |
| Cholangiocarcinoma | 121 (7.5%) | 15 (1.8%) | 32 (14.6%) | 74 (11.6%) | |
| Gallbladder carcinoma | 57 (3.5%) | 28 (3.4%) | 16 (7.3%) | 13 (2.1%) | |
| Other primary malignancy | 11 (0.7%) | 3 (0.4%) | 1 (0.5%) | 7 (1.1%) | |
| NA | 51 (3.1%) | 24 (2.9%) | 13 (5.9%) | 14 (2.2%) | |
| Laparoscopic resection | 222 (13.3%) | 187 (23.0%) | 25 (11.4%) | 10 (1.6%) | <0.001 |
| Simultaneous non-hepatic procedures | 428 (25.6%) | 192 (23.6%) | 48 (21.9%) | 188 (29.5%) | 0.024 |
| Bile duct resection | 117 (7.0%) | 22 (2.7%) | 27 (12.3%) | 68 (10.7%) | |
| Colorectal resection | 113 (6.8%) | 66 (8.1%) | 6 (2.7%) | 41 (6.4%) | |
| Diaphragm resection | 92 (5.5%) | 44 (5.4%) | 5 (2.3%) | 43 (6.8%) | |
| Upper gastrointestinal resection | 58 (3.5%) | 34 (4.2%) | 5 (2.3%) | 19 (3.0%) | |
| Vascular resection and reconstruction | 30 (1.8%) | 4 (0.5%) | 6 (2.7%) | 20 (3.1%) | |
| Pancreatic resection | 16 (1.0%) | 8 (1.0%) | 1 (0.5%) | 7 (1.1%) | |
| Other | 107 (6.4%) | 63 (7.7%) | 10 (4.6%) | 34 (5.3%) | |
| ASA Score | 0.091 | ||||
| I | 41 (2.6%) | 25 (3.2%) | 1 (0.5%) | 15 (2.5%) | |
| II | 542 (34.1%) | 285 (36.7%) | 69 (33.5%) | 188 (31.1%) | |
| III | 946 (59.6%) | 441 (56.8%) | 129 (62.6%) | 376 (62.1%) | |
| IV | 59 (3.7%) | 26 (3.3%) | 7 (3.4%) | 26 (4.3%) | |
| NA | 82 (4.9%) | 37 (4.5%) | 13 (5.9%) | 32 (5.0%) | |
| Pre-operative bilirubin (mg/dl)* | 0.5 (0.3–0.7) | 0.5 (0.3–0.7) | 0.5 (0.3–0.8) | 0.5 (0.3–0.7) | 0.403 |
| Pre-operative albumin (mg/dl)* | 4.0 (3.7–4.3) | 4.1 (3.7–4.4) | 4.0 (3.6–4.3) | 4.0 (3.7–4.3) | 0.068 |
| Pre-operative INR* | 1 (1.0–1.1) | 1.0 (1.0–1.1) | 1.0 (1.0–1.1) | 1.0 (1.0–1.1) | 0.002 |
Continuous variables are reported as median (25th–75th perecentiles).
NA, not applicable; ASA, American Society of Anesthesiology; INR, international normalized ratio.
Table 2.
Surgical treatments stratified by total number of segments resected. The largest component of each liver resection is reported
| Total (n = 1670) | |
|---|---|
| Four or more hepatic segments | |
| Extended right hepatectomy | 139 (8.3%) |
| Extended left hepatectomy | 58 (3.5%) |
| Right hepatectomy | 420 (25.1%) |
| Left hepatectomy | 20 (1.2%) |
| Three hepatic segments | |
| Left hepatectomy | 167 (10.0%) |
| Central liver resection | 41 (2.5%) |
| Bisegmentectomy | 11 (0.7%) |
| Two or fewer hepatic segments | |
| Bisegmentectomy | 529 (31.7%) |
| Monosegmentectomy | 53 (3.2%) |
| Wedge resection | 225 (13.5%) |
| Miscellaneous | 7 (0.4%) |
Comparisons by extent of resection
In all, 814 (48.7%), 219 (13.1%) and 637 (38.1%) patients underwent resection of two or less, three and four or more hepatic segments, respectively. One hundred and fifty-three (9.1%) patients underwent complete or wedge resections of the caudate as a component of the overall hepatic resection. Twenty-one (2.6%), 6 (2.7%), and 126 (19.8%) patients underwent caudate resection among patients who underwent resection of two or fewer, three and four or more liver segments. Patients who underwent resection of four or more segments more often had a caudate resection compared with three and two or fewer segments (P < 0.05). There were significant differences in patient age and ethnicity between these groups (Table 1). Patients at DUMC more often underwent larger volume resections (particularly resection of three liver segments) compared with those at UPMC. For the most part, larger volume resections were more often performed for malignant indications. As expected, laparoscopic resections comprising four or more, three, and two or less segments were decreasingly common. Rates of simultaneous non-hepatic procedures were highest with resections encompassing four or more segments. Pre-operative albumin tended to be slightly higher among patients undergoing resection of two or less segments (Table 1). In spite of a similar median international normalized ratio (INR) for each group, comparisons of the non-normal distributions of INR between groups revealed statistical differences as a result of the extremes at the upper end of each respective distribution.
Comparing all three groups, post-operative mortality (7.4% vs. 2.7% vs. 2.6%) and severe (36.7% vs. 24.7% vs. 24.1%), overall (49.3% vs. 40.6% vs. 35.9%), and hepatic related morbidity (25.6% vs. 16.4% vs. 15.2%) were all more common after resection of four or more liver segments compared with three and two or fewer segments (all P < 0.001). Rates of each endpoint were higher among patients who underwent resection of four or more segments compared with two or fewer segments (all P < 0.001). Similarly, rates of all endpoints were all higher after resection of four or more segments compared with three segments (all P < 0.05), Fig. 1. In contrast, no significant difference in each endpoint was observed after resection of three and two or less segments.
Figure 1.
Post-operative mortality and severe, overall, and hepatic morbidity by extent of resection. No significant difference in each endpoint was observed after resection of three and two or fewer liver segments. *P < 0.05 compared with three liver segments and two or less liver segments
Univariable and multivariable analyses
On univariable analysis, age greater than 50 years, male gender, diagnosis, simultaneous non-hepatic procedure, laparoscopic resection, ASA score, extent of resection, pre-operative albumin, bilirubin and INR were all significantly associated with post-operative mortality (Table 3). On multivariable analysis, male gender, primary hepatobiliary malignancy, simultaneous non-hepatic procedure, pre-operative albumin and resection of four or more liver segments were all independently associated with post-operative mortality (Table 4). Laparoscopic resection, diagnosis, simultaneous non-hepatic procedure, ASA score, extent of resection, pre-operative albumin, bilirubin and INR were all significantly associated with severe post-operative morbidity on univariable analysis (Table 2). On multivariable analysis, primary hepatobiliary malignancy, simultaneous non-hepatic procedure and resection of four or more liver segments were all independently associated with severe post-operative morbidity (Table 5). Age greater than 50 years, male gender, diagnosis, simultaneous non-hepatic procedure, laparoscopic resection, ASA score, extent of resection, pre-operative albumin, bilirubin and INR were all significantly associated with overall post-operative morbidity on univariable analysis (Table 2). On multivariable analysis, age greater than 50 years, primary hepatobiliary malignancy, laparoscopic liver resection, simultaneous non-hepatic procedure, ASA score of II (relative to I) and resection of four or more liver segments was independently associated with overall post-operative morbidity (Table 6). Male gender, site of liver resection, diagnosis, laparoscopic resection, simultaneous non-hepatic procedure, ASA score, extent of resection, pre-operative albumin, bilirubin and INR were all significantly associated with hepatic-related post-operative morbidity on univariable analysis (Table 2). On multivariable analysis, male gender, site of liver resection, primary hepatobiliary malignancy, simultaneous non-hepatic procedure, pre-operative bilirubin and resection of four or more liver segments were independently associated with hepatic-related post-operative complications (Table 7).
Table 3.
Univariable analysis for mortality, severe morbidity, overall morbidity, cardiopulmonary morbidity and hepatic morbidity
| Mortality | Severe morbidity | Overall morbidity | Hepatic morbidity | |||||
|---|---|---|---|---|---|---|---|---|
| P | P | P | P | |||||
| Age | <0.001 | 0.083 | <0.001 | 0.216 | ||||
| ≤50 years (n = 489) | 7 (1.4%) | 130 (26.5%) | 172 (35.2%) | 85 (17.4%) | ||||
| >50 years (n = 1181) | 67 (5.7%) | 366 (31.0%) | 523 (44.3%) | 238 (20.2%) | ||||
| Gender | <0.001 | 0.767 | <0.001 | <0.001 | ||||
| Male (n = 876) | 52 (6.6%) | 229 (29.3%) | 369 (47.2%) | 180 (23.0%) | ||||
| Female (n = 792) | 22 (2.5%) | 265 (30.1%) | 325 (36.6%) | 143 (16.1%) | ||||
| Ethnicity | 0.198 | 0.921 | 0.290 | 0.769 | ||||
| Caucasian (n = 1430) | 60 (4.2%) | 429 (30.0%) | 595 (41.6%) | 278 (19.4%) | ||||
| Non-Caucasian (n = 219) | 14 (6.3%) | 61 (30.6%) | 100 (45.7%) | 45 (20.5%) | ||||
| Institution | 0.712 | 0.827 | 0.174 | 0.004 | ||||
| UPMC (n = 791) | 33 (4.2%) | 237 (29.9%) | 315 (39.8%) | 129 (16.3%) | ||||
| Duke (n = 879) | 41 (4.7%) | 258 (29.4%) | 380 (43.2%) | 194 (22.1%) | ||||
| Diagnosis | <0.001 | <0.001 | <0.001 | <0.001 | ||||
| Benign (n = 354) | 2 (0.6%) | 76 (21.5%) | 117 (33.1%) | 52 (14.7%) | ||||
| Primary malignant (n = 417) | 45 (10.8%) | 170 (40.7%) | 255 (61.2%) | 141 (33.8%) | ||||
| Metastatic disease (n = 848) | 27 (3.2%) | 240 (28.3%) | 323 (38.1%) | 130 (15.3%) | ||||
| Laparoscopic resection | 0.021 | <0.001 | <0.001 | 0.050 | ||||
| Yes (n = 222) | 3 (1.4%) | 43 (19.4%) | 59 (26.6%) | 32 (14.4%) | ||||
| No (n = 1448) | 71 (4.9%) | 453 (31.3%) | 636 (43.9%) | 291 (20.1%) | ||||
| Simultaneous procedures | <0.001 | <0.001 | <0.001 | <0.001 | ||||
| Yes (n = 428) | 37 (8.6%) | 180 (42.1%) | 238 (55.6%) | 124 (29.0%) | ||||
| No (n = 1242) | 37 (3.0%) | 316 (25.4%) | 457 (36.8%) | 199 (16.0%) | ||||
| ASA Score | <0.001 | <0.001 | <0.001 | <0.001 | ||||
| I (n = 41) | 1 (2.4%) | 7 (17.1%) | 11 (26.8%) | 5 (12.2%) | ||||
| II (n = 542) | 8 (1.5%) | 132 (24.4%) | 191 (35.2%) | 85 (15.7%) | ||||
| III (n = 946) | 52 (5.5%) | 304 (32.1%) | 425 (44.9%) | 189 (20.0%) | ||||
| IV (n = 59) | 9 (15.3%) | 28 (47.5%) | 37 (62.7%) | 30 (50.8%) | ||||
| Extent of resection | <0.001 | <0.001 | <0.001 | <0.001 | ||||
| ≤2 segments (n = 814) | 21 (2.6%) | 196 (24.1%) | 292 (35.9%) | 124 (15.2%) | ||||
| 3 segments (n = 219) | 6 (2.7%) | 65 (24.7%) | 89 (40.6%) | 36 (16.4%) | ||||
| ≥4 segments (n = 637) | 47 (7.4%) | 235 (36.9%) | 314 (49.3%) | 163 (25.6%) | ||||
| Pre-operative bilirubin (mg/dl)* | 0.7 vs. 0.5 | <0.001 | 0.5 vs. 0.5 | <0.001 | 0.5 vs. 0.5 | <0.001 | 0.6 vs. 0.5 | <0.001 |
| Pre-operative albumin (mg/dl)* | 3.7 vs. 4.0 | <0.001 | 4.1 vs. 3.9 | <0.001 | 3.9 vs. 4.1 | <0.001 | 3.9 vs. 4.1 | <0.001 |
| Pre-operative INR* | 1.1 vs. 1.0 | <0.001 | 1.0 vs. 1.0 | <0.001 | 1.0 vs. 1.0 | 0.002 | 1.0 vs. 1.0 | 0.002 |
Medians are reported for continuous variable comparisons.
ASA, American Society of Anesthesiology; INR, international normalized ratio.
Table 4.
Multivariable analysis for post-operative mortality
| Beta | Odds ratio | 95% CI | P | |
|---|---|---|---|---|
| Age greater than 50 years | 1.026 | 2.789 | 0.980–7.939 | 0.055 |
| Male gender | 1.142 | 3.133 | 1.681–5.837 | <0.001 |
| Diagnosis (ref: Benign) | ||||
| Primary hepatobiliary malignancy | 1.123 | 3.073 | 1.684–5.607 | <0.001 |
| Metastatic disease | −0.540 | 0.582 | 0.125–2.711 | 0.491 |
| Laparoscopic resection | 0.069 | 1.071 | 0.301–3.809 | 0.916 |
| Simultaneous non-hepatic procedure | 0.651 | 1.918 | 1.066–3.453 | 0.030 |
| ASA score (ref: I) | ||||
| II | −0.338 | 0.713 | 0.064–7.907 | 0.783 |
| III | −0.899 | 0.407 | 0.043–3.870 | 0.434 |
| IV | −1.588 | 0.204 | 0.020–2.057 | 0.178 |
| Pre-operative bilirubin | 0.067 | 1.070 | 0.870–1.315 | 0.523 |
| Pre-operative albumin | −0.806 | 0.447 | 0.284–0.702 | <0.001 |
| Pre-operative INR | 0.151 | 1.163 | 0.330–4.099 | 0.815 |
| Four or more liver segment resection | 0.941 | 2.561 | 1.424–4.606 | 0.002 |
ASA, American Society of Anesthesiology; INR, international normalized ratio.
Table 5.
Multivariable analysis for severe post-operative morbidity
| Beta | Odds ratio | 95% CI | P | |
|---|---|---|---|---|
| Diagnosis (ref: Benign) | ||||
| Primary hepatobiliary malignancy | 0.571 | 1.770 | 1.335–2.347 | <0.001 |
| Metastatic disease | 0.173 | 1.188 | 0.825–1.713 | 0.355 |
| Laparoscopic resection | 0.229 | 1.257 | 0.815–1.940 | 0.301 |
| Simultaneous non-hepatic procedure | 0.707 | 2.027 | 1.550–2.652 | <0.001 |
| ASA (ref: I) | ||||
| II | 1.119 | 3.061 | 0.950–9.859 | 0.061 |
| III | 0.859 | 2.360 | 0.866–6.431 | 0.093 |
| IV | 0.578 | 1.783 | 0.653–4.869 | 0.259 |
| Pre-operative bilirubin | 0.054 | 1.055 | 0.916–1.216 | 0.454 |
| Pre-operative albumin | 0.192 | 1.212 | 0.583–2.518 | 0.606 |
| Pre-operative INR | −0.164 | 0.849 | 0.678–1.062 | 0.152 |
| Four or more liver segment resection | 0.496 | 1.642 | 1.281–2.104 | <0.001 |
ASA, American Society of Anesthesiology; INR, international normalized ratio.
Table 6.
Multivariable analysis for overall post-operative morbidity
| Beta | Odds ratio | 95% CI | P | |
|---|---|---|---|---|
| Male gender | 0.189 | 1.207 | 0.914–1.595 | 0.184 |
| Age greater than 50 years | 0.308 | 1.361 | 1.083–1.710 | 0.008 |
| Diagnosis (ref: Benign) | ||||
| Primary hepatobiliary malignancy | 0.593 | 1.809 | 1.382–2.367 | <0.001 |
| Metastatic disease | 0.309 | 1.362 | 0.969–1.915 | 0.075 |
| Laparoscopic resection | 0.445 | 1.560 | 1.060–2.295 | 0.024 |
| Simultaneous non-hepatic procedure | 0.684 | 1.981 | 1.529–2.568 | <0.001 |
| Pre-operative bilirubin | 0.133 | 1.142 | 0.977–1.335 | 0.096 |
| Pre-operative albumin | −0.175 | 0.840 | 0.679–1.039 | 0.108 |
| Pre-operative INR | −0.138 | 0.871 | 0.434–1.749 | 0.698 |
| ASA (ref: I) | ||||
| II | 1.063 | 2.895 | 1.029–8.143 | 0.044 |
| III | 0.575 | 1.778 | 0.777–4.069 | 0.173 |
| IV | 0.328 | 1.389 | 0.611–3.155 | 0.433 |
| Four or more liver segment resection | 0.425 | 1.530 | 1.213–1.929 | <0.001 |
ASA, American Society of Anesthesiology; INR, international normalized ratio.
Table 7.
Multivariable analyses for hepatic related post-operative morbidity
| Beta | Odds ratio | 95% CI | P-value | |
|---|---|---|---|---|
| Male gender | 0.377 | 1.458 | 1.092–1.946 | 0.011 |
| Resection at UPMC | 0.342 | 1.408 | 1.049–1.889 | 0.023 |
| Diagnosis (ref: Benign) | ||||
| Primary hepatobiliary malignancy | 0.721 | 2.057 | 1.489–2.843 | <0.001 |
| Metastatic disease | 0.225 | 1.252 | 0.808–1.939 | 0.314 |
| Laparoscopic resection | −0.289 | 0.749 | 0.454–1.236 | 0.258 |
| Simultaneous non-hepatic procedure | 0.566 | 1.762 | 1.288–2.410 | <0.001 |
| ASA (ref: I) | ||||
| II | 0.656 | 1.926 | 0.583–6.366 | 0.282 |
| III | 0.133 | 1.142 | 0.414–3.149 | 0.797 |
| IV | −0.043 | 0.958 | 0.346–2.648 | 0.934 |
| Pre-operative bilirubin | 0.190 | 1.209 | 1.041–1.403 | 0.013 |
| Pre-operative albumin | −0.172 | 0.842 | 0.649–1.093 | 0.197 |
| Pre-operative INR | −0.296 | 0.744 | 0.302–0.835 | 0.521 |
| Four or more liver segment resection | 0.691 | 1.996 | 1.491–2.672 | <0.001 |
UPMC, University of Pittsburgh Medical Center; ASA, American Society of Anesthesiology; INR, international normalized ratio.
Discussion
Remnant liver volume is widely considered the key factor in predicting complications after a partial hepatectomy. As this measurement is difficult, inconsistent and unreported in most resection series, extent of resection is used as a surrogate for remnant liver volume. In the present study of a large series of liver resections for a wide variety of indications at two high volume academic centres, resection of four or more liver segments was independently associated with post-operative mortality and severe, overall and hepatic-related morbidity. Importantly, this finding was independent of other factors expected to increase mortality and morbidity risk, including primary hepatobiliary malignancy, simultaneous non-hepatic procedures, advanced patient age and ASA score. In contrast, there were no differences in post-operative outcomes after resection of three and two or less liver segments. Therefore, in the modern era of enhanced anaesthetic and critical care, a better understanding of hepatic segmental anatomy and improved transection techniques, a standard left hepatectomy (resection of three segments using Brisbane criteria) should not be considered a major hepatic resection. These results are in accordance to that reported by Aloia et al.15 who analysed 2313 hepatic resections in the National Surgical Quality Improvement Program dataset from 2005–2007. Rates of all categories of severe morbidity were similar after a left hepatectomy (a three segment resection) compared with after a lesser hepatectomy. In contrast, severe morbidity was higher after a right and extended hepatectomy. Thirty-day post-operative mortality after a lesser, left, right and extended hepatectomy were 1.8%, 0.9%, 3.7% and 5.2%, respectively. The extent of a hepatic resection was associated with severe morbidity (OR 1.8, P = 0.0001) but not mortality.
Results of the present study have several implications for the field of hepatobiliary surgery. Although less commonly performed compared with resection of four or more and two or fewer liver segments, a three-segment hepatic resection (particularly a left hepatectomy) is a standard partial hepatectomy that has been regarded by many surgeons as a major liver resection.2,5,6,8,20,25,36,37 Yet the pesent study demonstrates higher relative risks of post-operative mortality (174.1%), severe morbidity (48.5%), overall morbidity (21.4%) and hepatic-related morbidity (56.1%) after resection of four or more segments relative to after resection of three segments. Moreover, there was no significant difference in post-operative outcomes after resection of three and two or fewer segments. An established definition of a major hepatectomy as resection of four or more segments allows for accurate comparison of post-operative outcomes between resection series. Novel surgical approaches, transection techniques, and intra-operative and post-operative treatments aimed at improving the safety profile of a partial hepatectomy should focus on those patients undergoing resection of at least four liver segments as these patients are at highest risk of post-operative morbidity and mortality. This criterion for major hepatic resection also allow for a more precise estimate of post-operative risk when counselling patients regarding liver resection.
Several limitations to the present study should be considered. Although pre-operative synthetic liver function (as measured by plasma albumin, bilirubin and INR) was recorded, chemotherapy associated liver disease, non-alcoholic fatty liver disease, fibrosis and cirrhosis were not directly accounted for in the present study. Thus, our conclusions may not apply in cases of severe liver disease where even low volume liver resections can have deleterious consequences. Disease in the non-tumour bearing liver (such as cirrhosis and cholestatic jaundice in the settings of hepatocellular carcinoma and extrahepatic cholangiocarcinoma, respectively) is probably the rationale why primary hepatobiliary malignancy was independently associated with poor post-operative outcomes. Because specific comorbidity data were not available for each patient, more accurate gauges of comorbidity, such as the Charleson comorbidity index, could not be calculated. We aimed to identify predictors of poor post-operative outcome based on pre-operatively identified factors. Thus intra-operative and post-operative variables, such as estimated blood loss and blood transfusion, which may worsen outcomes, were not accounted for in the present study. Several limitations owing to the retrospective nature of this study must be acknowledged. Retrospective data retrieval prevented verification that an assigned morbidity met the accepted published criteria for that particular complication when such a criteria exists. We relied upon individual physician interpretation of post-operative complications described in the medical record. Accurate assessments of wedge resection volume were unobtainable in this retrospective study. Because any nonanatomic resection was classified as a wedge resection (encompassing 0.5 segments), the amount of liver resected among those who underwent resection of two or fewer segments may have been underestimated. In spite of this potential bias, post-operative outcomes were no different compared with three-segment resections and were superior compared with resection of four or more liver segments. Multiple resections of separate segments and technically challenging resections (such as those involving the posterior sector) may be associated with worse post-operative outcomes regardless of the total number of segments resected. Thus all three and two or fewer segment resections may not have similar post-operative outcomes. By increasing the volume of the anticipated liver remnant, pre-operative portal vein embolization may improve post-operative outcomes after large volume liver resections.38,39 While used relatively infrequently before resections of four or more liver segments in this series, we did not account for this factor in our analyses. Liver volumetry using pre-operative imaging was not routinely performed before liver resection at either institution. These measurements were not available for the vast majority of patients who underwent liver resection at these two centres. All of these details were not accounted for in the present study and thus are important limitations to the applicability of the present results.
A major hepatectomy should be defined as resection of four or more liver segments. Studies evaluating post-operative outcomes and novel treatments aimed at improving the safety profile of a partial hepatectomy should focus on patients undergoing resection of four or more liver segments.
Conflicts of interest
None declared.
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