Extended hepatectomy (EH) is the only curative treatment for large primary or bilobar metastatic hepatic malignancies that improves long-term survival [
Several studies have evaluated different predictive factors for PHLF and other postoperative clinical outcomes [
The aim of this study was to investigate the association of the preoperative platelet count and postoperative clinical outcomes following EH in patients without portal hypertension, splenomegaly, or cirrhosis. To do this, we investigated the effect of preoperative thrombocytopenia on PHLF, morbidity, and mortality after EH.
We investigated all patients who underwent liver resection to treat primary, metastatic, or benign liver disease at the department of General, Visceral, and Transplantation Surgery at the University of Heidelberg between October 2001 and September 2016. All patients were followed up until September 2017. Only patients who underwent EH were included in the study. EH was defined as resection of five or more hepatic segments based on the Brisbane 2000 classification [
PHLF was diagnosed and graded (grade A, B, or C) according to the proposed definition by the International Study Group of Liver Surgery (ISGLS) [
The severity of postoperative morbidities were classified as grade I to V based on the Clavien-Dindo classification [
All preoperative clinical evaluations including medical history, physical examination, and laboratory findings were recorded. All patients underwent cross-sectional contrast-enhanced computed tomography or magnetic resonance imaging of the chest, abdomen, and pelvis to assess the resectability of the tumor and to plan the hepatectomy. The preoperative platelet count was measured on the day of surgery and thrombocytopenia was defined as a platelet count <150 x 109/L.
Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp. Released 2013. Armonk, NY). Categorical data were presented as frequencies and proportions, and continuous data were presented as means ± standard deviations. Categorical data were compared using chi-square test of association or Fisher's exact test. Continuous data were compared using Student’s t-test. Univariate and multivariate logistic regression analyses were performed to determine independent preoperative predictive factors of PHLF, major morbidity, and 30-day mortality. Variables with a
The mean age of patients was 60.8±11.7 years and 50.7% were female. Primary hepatic malignancy was the most common indication for EH (57.7% of patients), and 35.8% of patients received preoperative systemic chemotherapy. PHLF was detected in 26.3% of patients, major complications (grade III–IV) in 26.8% of patients, and 30-day mortality in 11.3% of patients. Detailed patient demographics and clinical data are shown in Table
Clinicopathologic characteristics of patients who underwent extended hepatectomy.
| |
---|---|
| |
Age (years) | 60.8 ±11.7 |
Gender | |
Female/male | 108/105 |
BMI (kg/m2) | 25.53 ± 4.44 |
ASA score | |
Class 1 | 4 (2.5%) |
Class 2 | 76 (46.9%) |
Class 3 | 82 (50.6%) |
| |
Cirrhosis | |
Yes | 7 (3.2%) |
Indication of extended hepatectomy | |
Benign liver disease | 9 (4.2%) |
Primary malignancy | 123 (57.7%) |
Cholangiocarcinoma | 105 (85.4) |
Hepatocellular carcinoma | 18 (14.6%) |
Metastatic disease | 81 (38.0%) |
Preoperative chemotherapy | |
Yes | 73 (35.8%) |
Preoperative platelet count (x 109/L) | |
Mean (SD) | 300.1 ± 121.5 |
| |
Intraoperative blood loss (ml) | 1638.21 ± 1535.49 |
Transfusion of RBC | |
Patient | 60 (31.1%) |
Unit | 1.52 ± 3.34 |
Transfusion of FFP | |
Patient | 44 (22.8%) |
Unit | 1.43 ± 3.64 |
Operation time (min) | 293.78 ± 115.15 |
| |
PHLF | 56 (26.3%) |
Grade A | 16 (28.6%) |
Grade B | 14 (25.0%) |
Grade C | 26 (46.4%) |
Major morbidity | 57 (26.8%) |
ICU stay (days) | 8.14 ± 13.47 |
Hospitalization (days) | 23.43 ± 16.68 |
30-day mortality | 24 (11.3%) |
BMI: body mass index; ASA: American Society of Anesthesiologists; SD: standard deviation; RBC: red blood cells; FFP: fresh-frozen plasma; PHLF: posthepatectomy liver failure; ICU: intensive care unit.
Seventeen patients (8.0%) had a preoperative platelet count of <150 x 109/L (mean platelet count=122.3±22.3 x 109 per L), and the remaining 196 (92.0%) patients had a preoperative platelet count of ≥150 x 109/L (mean platelet count=315.5±114.0 x 109 per L). Baseline characteristics and clinical outcome of the patients with preoperative thrombocytopenia are shown in Table
Clinicopathologic characteristics of patients with a preoperative platelet count of <150 x 109/L.
| |
---|---|
| |
Age (years) | 63.1 ±12.5 |
Gender | |
Female/male | 8/9 |
BMI (kg/m2) | 25.08 ± 3.88 |
ASA score | |
Class 1 | 0 (0.0%) |
Class 2 | 8 (57.1%) |
Class 3 | 6 (42.9%) |
| |
Cirrhosis | |
Yes | 0 (0.0%) |
Indication of extended hepatectomy | |
Benign liver disease | 2 (11.8%) |
Primary malignancy | 9 (52.9%) |
Cholangiocarcinoma | 9 (100%) |
Hepatocellular carcinoma | 0 (0.0%) |
Metastatic disease | 6 (35.3%) |
Preoperative chemotherapy | |
Yes | 5 (29.4%) |
Preoperative platelet count (x 109/L) | |
Mean (SD) | 122.3 ± 22.3 |
| |
Intraoperative blood loss (ml) | 3352.94 ± 2019.32 |
Transfusion of RBC | |
Patient | 8 (50.0%) |
Unit | 4.38 ± 6.26 |
Transfusion of FFP | |
Patient | 9 (56.3%) |
Unit | 4.31 ± 5.91 |
Operation time (min) | 381.29 ± 136.05 |
| |
PHLF | 10 (58.8%) |
Grade A | 0 (0.0%) |
Grade B | 2 (20.0%) |
Grade C | 8 (80.0%) |
Major morbidity | 6 (35.3%) |
ICU stay (days) | 16.65 ± 9.50 |
Hospitalization (days) | 30.18 ± 15.20 |
30-day mortality | 6 (35.3%) |
BMI: body mass index; ASA: American Society of Anesthesiologists; SD: standard deviation; RBC: red blood cells; FFP: fresh-frozen plasma; PHLF: posthepatectomy liver failure; ICU: intensive care unit.
To investigate the impact of the preoperative platelet count on postoperative outcomes including PHLF, morbidity, and 30-day mortality, we performed univariate and multivariate regression analysis. Univariate analysis (Table
Univariate and multivariate analysis of predictive factors of PHLF, major morbidity, and 30-day mortality after extended hepatectomy.
PHLF
| | | ||||
---|---|---|---|---|---|---|
OR | 95% CI | | OR | 95% CI | | |
Age | 1.015 | 0.988–1.043 | 0.280 | |||
Gender | 0.963 | 0.523–1.772 | 0.902 | |||
BMI (kg/m2) | 0.989 | 0.914–1.071 | 0.793 | |||
ASA score | 1.429 | 0.743–2.751 | 0.285 | |||
| ||||||
Indication of extended hepatectomy | ||||||
Benign liver disease | Reference | Reference | Reference | Reference | Reference | Reference |
Primary malignancy | 1.367 | 0.256–7.290 | 0.714 | 0.810 | 0.120–5.470 | 0.828 |
Metastatic disease | 2.306 | 1.159–4.591 | 0.017 | 1.897 | 0.806–4.463 | 0.141 |
Preoperative chemotherapy | 1.679 | 0.723–3.896 | 0.228 | |||
Platelet count <150 x 109/L | 4.658 | 1.678–12.929 | 0.003 | 4.351 | 1.266–14.953 | 0.020 |
| ||||||
Intraoperative blood loss (L) | 1.159 | 1.036–1.297 | 0.010 | 0.884 | 0.615–1.271 | 0.506 |
Intraoperative RBC/FFP transfusion | 2.617 | 1.343–5.098 | 0.005 | 2.226 | 0.859–5.769 | 0.099 |
Operation time (hour) | 1.264 | 1.076–1.484 | 0.004 | 1.167 | 0.961–1.417 | 0.120 |
Major morbidity
| | | ||||
---|---|---|---|---|---|---|
OR | 95% CI | | OR | 95% CI | | |
Age | 1.036 | 1.010–1.062 | 0.006 | 1.050 | 1.020–1.083 | 0.001 |
Gender | 1.148 | 0.669–1.969 | 0.617 | |||
BMI (kg/m2) | 1.011 | 0.944–1.083 | 0.758 | |||
ASA score | 1.329 | 0.752–2.346 | 0.328 | |||
| ||||||
Indication of extended hepatectomy | ||||||
Benign liver disease | Reference | Reference | Reference | Reference | Reference | Reference |
Primary malignancy | 2.017 | 0.497–8.187 | 0.326 | 1.347 | 0.195–9.291 | 0.762 |
Metastatic disease | 3.331 | 1.827–6.072 | <0.001 | 2.387 | 1.111–5.127 | 0.026 |
Preoperative chemotherapy | 0.626 | 0.274–1.428 | 0.266 | |||
Platelet count <150 x 109/L | 10.427 | 2.321–46.845 | 0.002 | 4.923 | 0.922–26.296 | 0.062 |
| ||||||
Intraoperative blood loss (L) | 1.365 | 1.181–1.577 | <0.001 | 1.309 | 0.863–1.985 | 0.206 |
Intraoperative RBC/FFP transfusion | 2.880 | 1.555–5.336 | 0.001 | 1.285 | 0.491–3.363 | 0.610 |
Operation time (hour) | 1.431 | 1.215–1.685 | <0.001 | 1.237 | 1.007–1.520 | 0.042 |
30-day mortality
| | | ||||
---|---|---|---|---|---|---|
OR | 95% CI | | OR | 95% CI | | |
Age | 1.038 | 0.997–1.082 | 0.073 | 1.038 | 0.994–1.085 | 0.094 |
Gender | 1.720 | 0.718–4.124 | 0.224 | |||
BMI (kg/m2) | 1.032 | 0.928–1.147 | 0.564 | |||
ASA score | 1.179 | 0.504–2.762 | 0.704 | |||
| ||||||
Indication of extended hepatectomy | ||||||
Benign liver disease | Reference | Reference | Reference | Reference | Reference | Reference |
Primary malignancy | 2.406 | 0.239–24.220 | 0.456 | 1.784 | 0.078–40.796 | 0.717 |
Metastatic disease | 3.517 | 1.150–10.754 | 0.027 | 3.460 | 0.856–13.980 | 0.081 |
Preoperative chemotherapy | 0.570 | 0.126–2.568 | 0.464 | |||
Platelet count <150 x 109/L | 5.394 | 1.784–16.311 | 0.003 | 4.430 | 1.055–18.777 | 0.043 |
| ||||||
Intraoperative blood loss (L) | 1.342 | 1.085–1.659 | 0.007 | 1.166 | 0.753–1.805 | 0.492 |
Intraoperative RBC/FFP transfusion | 3.216 | 1.295–7.986 | 0.012 | 1.604 | 0.435–5.921 | 0.478 |
Operation time (hour) | 1.261 | 1.023–1.555 | 0.030 | 1.093 | 0.839–1.425 | 0.509 |
OR: odds ratio; CI: confidence interval; BMI: body mass index; ASA: American Society of Anesthesiologists; RBC: red blood cells; FFP: fresh-frozen plasma.
According to multivariate analysis, patient age (OR 1.1, 95% CI 1.0–1.1,
After excluding patients with underlying cirrhosis (n = 7), we repeated univariate and multivariate analysis of PHLF, major morbidity and 30-day mortality. As presented in Supplementary Table
The six-month survival rate was 80.1%±2.8% in our cohort. Patients with a preoperative platelet count <150 x 109/L had a significantly lower six-month survival rate than patients with a preoperative platelet count ≥150 x 109/L (Figure
Six-month patient survival plot: significantly lower survival rates in patients with low preoperative platelet counts (<150 x 109/L) compared with normal preoperative platelet counts (≥150) (log-rank test p<0.001).
PHLF is a severe and potentially lethal complication after liver resection and is responsible for more than 60% of mortalities after EH [
We demonstrated that a low preoperative platelet count is a predictive factor of PHLF and higher mortality after EH. In our series of EHs, the odds of development of PHLF and 30-day mortality in patients with low platelet counts were more than 4 and 6 fold higher than patients with normal platelet count, respectively. Moreover, our results showed that long-term survival was lower in patients with low platelet count than patients with normal platelet count. These findings indicate that a low platelet count independently predicts short- and long-term outcomes after EH. We selected a cut-off value of 150 x 109/L for platelet counts because this is the minimum normal platelet count in our center and in most clinical settings.
In agreement with our findings, Alkozai et al. [
The predictive role of platelets on PHLF and postoperative mortality may be explained by various mechanisms. One proposed mechanism is the direct promotion of liver regeneration by platelets [
Furthermore, the association between low preoperative platelet count and high portal vein pressure suggests an alternative mechanism [
The retrospective design is a limitation of the present study. However, platelet counts, other laboratory measurements, morbidity, and mortality of all consecutive patients were all recorded prospectively during the study period. To minimize potential bias and estimate the independent effect of the platelet count as accurately as possible, we controlled factors that are known to affect post-EH morbidity and mortality. These potentially confounding factors included age, gender, BMI, American Society of Anesthesiologists (ASA) score, indication of EH, intraoperative blood loss and transfusion, and operation time using univariate and multivariate regression analyses. Therefore, we evaluated the predictive role of platelet count independent of these factors. Cirrhosis is also associated with low platelet count so may confound the effect of thrombocytopenia on posthepatectomy outcome [
In conclusion, preoperative thrombocytopenia seems to be a reliable predictor of PHLF and increased mortality after EH. This predictive role is independent of other related parameters, including age, cause of hepatectomy, intraoperative blood loss, and duration of surgery. Further randomized studies are required to evaluate the impact of increasing the preoperative platelet count (exogenous platelet infusion versus treatment of the underlying disease) on improving the postoperative outcomes after EH in patients with thrombocytopenia.
The data used to support the findings of this study are available from the corresponding author upon request.
This paper was (1) poster presentation at the annual meeting of the German Association for the Study of the Liver (GASL) on January 27, 2018, in Hamburg, Germany (Golriz, M., O. Ghamarnejad, E. Khajeh et al. Preoperative thrombocytopenia may predict poor surgical outcome after extended hepatectomy. Zeitschrift für Gastroenterologie 56, no. 01 (2018): A4-59.), and (2) poster presentation at the 135th congress of the Deutsche Gesellschaft für Chirurgie (DGCH) on April 18, 2018, in Berlin, Germany (Golriz, M., O. Ghamarnejad, E. Khajeh et al. Preoperative thrombocytopenia may predict poor surgical outcome after extended hepatectomy. Innov Surg Sci 2018; 3, (Suppl 1): s1–s231). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
The authors declare that there are no conflicts of interest regarding the publication of this article.
Supplementary Table S1. Subgroup analysis of predictive factors of PHLF, major morbidity, and 30-day mortality after extended hepatectomy in patients without cirrhosis.