Liver surgery is performed nowadays more frequently than in previous decades 1. Analysis of the Nationwide Inpatient Sample (NIS) shows that the number of liver operations almost doubled from 1988 to 2000, with ∼7000 operations performed in the USA in 2000. As diagnostic techniques advance and surgical outcomes improve, the rate of utilization of liver surgery for various indications will continue to increase. Published literature suggests a reduction in morbidity and mortality rates in recent years, with many high-volume centers reporting mortality rates less than 5% 2–5. Advances in perioperative management and surgical techniques have reduced mortality rates; however, reported morbidity rates remain high and range from 23 to 56% depending on indication for surgery 6,7.
In 2008, Sokol and Wilson 8 attempted to provide a sophisticated definition of surgical complications; they defined a complication as an undesirable, unintended, and direct result of an operation affecting the patient that would not have occurred had the operation gone as well as could reasonably be hoped. Dindo and Clavien 9 defined complication in 2008 as any deviation from the ideal postoperative course that is not inherent in the procedure and does not comprise a failure to cure.
Classification of surgical complications
Modified classification of surgical complications 10 was adopted in the current study. Table 1 shows its components.
History of MELD score
Model for end-stage liver disease (MELD) was originally developed at the Mayo Clinic, and at that point, was called the ‘Mayo End-stage Liver Disease’ score. It was derived in a series of patients undergoing transjugular intrahepatic portosystemic shunt procedures. The original version also included a variable based on the underlying etiology (cause) of the liver disease 11. The score turned out to be predictive of prognosis in chronic liver disease in general, and – with some modifications – came to be applied as an objective tool in assigning need for a liver transplant. The etiology turned out to be relatively unimportant and was also considered as relatively subjective; it was therefore removed from the score 12. Schroeder et al.13 evaluated the predictive indices of the MELD in 2006 for all liver resection including minor hepatic resection; they disputed the conclusion that MELD should not be used in the setting of elective hepatic resection.
As the extended hepatic surgery can be performed with a low morbidity and mortality in the hands of trained and experienced hepatic surgeons, the present study attempted to explore the preoperative and intraoperative predictors of postoperative complications including preoperative MELD score after major hepatic resection only (hemihepatectomy and extended hemihepatectomy operations).
Patients and methods
This study included a retrospective analysis of the clinical data of 144 patients who underwent either right hemihepatectomy, left hemihepatectomy, extended right hemihepatectomy, or extended left hemihepatectomy, provided that these data were as complete as possible.
Source of data
The data were obtained from the medical records of Georg August University Hospital 2002–2012.
All cases of atypical liver resection or any liver resection smaller than hemihepatectomy were excluded. The outcomes were either postoperative complications or death of the patient (within 3 months from the end of the operation). The complications included either in-hospital or out-of-hospital occurrences. Mortality is defined as death within 3 months of surgery.
The MELD is a scoring system for assessing the severity of chronic liver disease. It was initially developed to predict death within 3 months of surgery in patients who had undergone a transjugular intrahepatic portosystemic shunt procedure 11, and was subsequently found to be useful in determining prognosis and prioritizing for recipients of a liver transplant 12,14. This score is now used by the United Network for Organ Sharing 15 and Eurotransplant for prioritizing allocation of liver transplants instead of the older Child–Pugh score.
Determination of MELD score
MELD uses the patient’s values for serum bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time (PT) to predict survival. It is calculated according to the following formula: 14
United Network for Organ Sharing has made the following modifications to the score 15:
If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0.
Any value less than one is assigned a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result).
Patients with a diagnosis of liver cancer will be assigned a MELD score on the basis of how advanced the cancer is.
INR results were not available at Georg August University Hospital and were calculated on the basis of PT.
Measurement of prothrombin time/international normalized ratio
Patient samples for PT/INR estimation in this study were collected using 3.0 ml plastic plasma tubes (S-Monovettes) with sodium citrate, predosed as a 0.106 molar solution, which is equivalent to 3.2% trisodium citrate (Sarstedt AG & Co., Nümbrecht, Germany). PT was measured at 37°C on an ACL TOP 700 system using the HemosIL RecombiPlasTin 2G reagents on the basis of recombinant human tissue factor (Instrumentation Laboratory Company, Bedford, Massachusetts, USA).
The INR is the PT ratio of a test sample compared with a normal PT (derived from the log mean normal prothrombin time of 20 normal donors) corrected for the sensitivity of the thromboplastin used in the test. It is the value for the PT ratio that has been obtained using the first WHO reference thromboplastin with an international sensitivity index (ISI) of 1.0.
The INR value was calculated according to the following equation:The ISI web software and the certified plasmas of the HemosIL ISI Calibrate set (Instrumentation Laboratory Company) were used to establish a laboratory’s instrument/reagent-specific local ISI.
Data were analyzed using SPSS software, version 19 (SPSS Inc., Chicago, Illinois, USA). Preoperative variables that correlated with postoperative complications were identified using bivariate analyses. Categorical variables were assessed using the χ2-test and continuous variables were assessed using Student’s t-test or Mann–Whitney test (abnormally distributed variables) for comparison of two groups and one-way analysis of variance test for comparison of more than two groups or the Kruskal–Wallis test (abnormally distributed variables). A cut-off level of 9 for the MELD score was utilized in the analysis (median value). A P-value less than 0.05 was considered statistically significant.
Prevalence of postoperative complications after hemihepatectomy
The study included 144 patients who underwent either right hemihepatectomy, left hemihepatectomy, extended right hemihepatectomy, or extended left hemihepatectomy during the study period (2002–2012). As can be seen in Fig. 1, postoperative complications were reported among 75 patients of 144 (52.1%).
Figure 2 shows that postoperative complication grades 1, 3a, 2, and 3b were reported among 49.3, 17.4, 12.5%, and 11.8 of patients, respectively.
Table 2 summarizes postoperative complications according to their sites. The most frequent complications were pleural effusion (26.7%), biliary leakage (21.3%), wound dehiscence (13.3%), ascites, and intra-abdominal abscess (6.7%). Death was reported among six cases (8%).
Association of preoperative MELD scores with posthemihepatectomy complications
As shown in Table 3, 46.8% of patients whose preoperative MELD score was below 9 developed posthemihepatectomy Complications compared with 84.2% of those whose preoperative MELD score ranged between 9 and 18. The association between preoperative MELD score and development of posthemihepatetomy was statistically significant, P=0.002.
Association between preoperative MELD score and grades of postoperative complications after hemihepatectomy operations
The MELD score preoperatively was higher among patients with postoperative complications grades 5 and 3b than those of other grades. However, this difference was borderline statistically significant, P=0.057 (Table 4).
Association between preoperative AST, INR, creatinine, bilirubin levels, and posthemihepatectomy complications
Table 5 shows that there was no significant difference between preoperative aspartate aminotransferase (AST), bilirubin, creatinine, and INR levels among those who developed posthemihepatectomy complications and those who did not develop such complications.
The relationship between different factors and development of postoperative complications after hemihepatectomy operations
From Table 6, it is evident that exactly half of nonmalignant cases (50%) and more than half of malignant cases (53.2%) compared with none of living donor liver transplantation cases developed postoperative complications after liver resection. However, this difference was statistically not significant, P=0.323. More than half (60%) of the patients in the age group 51–60 years and slightly more than half of those older than 60 years of age (52.5%) compared with only 40% of patients aged 50 years or younger had postliver hemihepatectomy complications, P=0.405. BMI, sex, and duration of the operation were not significantly associated with the development of postoperative complications.
Association between preoperative AST level and postoperative grade of complications after hemihepatectomy operations
Table 7 shows that the AST level preoperatively was not significantly associated with posthemihepatectomy grade of complications, P=0.130.
Association between preoperative creatinine level and postoperative grade of complications after hemihepatectomy operations
As can be seen in Table 8, the preoperative creatinine level was not significantly associated with the grade of posthemihepatectomy complications, P=0.138.
Association between bilirubin level and postoperative grade of complications after hemihepatectomy operations
The preoperative bilirubin level was not significantly associated with the grade of posthemihepatectomy complications as can be seen in Table 9.
Association between INR level and postoperative grade of complications after hemihepatectomy operations
The INR level preoperatively was not significantly associated with grades of postoperative complications (Table 10).
There were four cases of hepatic cirrhosis (one macroscopic and three microscopic). Two of the microscopic cases had no postoperative complications (grade 1), whereas one case had grade 3a and the macroscopic case had postoperative complication grade 1. Their MELD scores ranged between 6 and 10 preoperatively. Death was reported in six cases, yielding a mortality rate of 4.17%.
Careful preoperative evaluations of the patients’ condition are essential for the successful surgical management of patients who have undergone hepatic resection 16.
Liver surgery involves various operations of the liver for different disorders. The most common operation performed on the liver is a resection (removal of a portion of the liver). The most typical indication for liver resection is a malignant tumor 17.
Although the rates of complications following liver resection have decreased over the years, complication rates remain high, with 52.1% of the patients in the current study developing at least one complication. In the National Surgical Quality Improvement Programme-Patient Safety Study (NSQIP PSS) sample, 22.6% of patients experienced at least one complication and 5.2% underwent a second operation for complications 18. There has been significant variation in both the reported rates and the definitions of complication across the literature. Complication rates in large studies of unselected patients range from 22 to 45% 2–7. Furthermore, definitions for complications are not standardized and varying criteria for complication make the results of different studies difficult to compare. In addition, all patients in the present work underwent hemihepatectomy and extended hemihepatectomy, which are the more extensive operations that can be performed on the liver. Also, the results of single-center studies may not be reliable indicators of population-wide results as single-center studies are more sensitive to institution-specific case mix.
In 2007, Enrico et al. 19 analyzed the causes and foreseeable risk factors for liver resective surgery linked to postoperative morbidity on the basis of data derived from a single-center surgical population. The morbidity rate was 47.7%, caused by an increase in ascites (10%), temporary hepatic insufficiency (19%), biliary fistula (6%), hepatic abscess (25%), hemoperitoneum (10%), and pleural effusion (30%), or sometimes a combination 19.
The most frequent complications in our study were pleural effusion (26.7%), biliary leakage (21.3%), wound dehiscence (13.3%), ascites, and intra-abdominal abscess (6.7%).
The 4.17% overall 3-month mortality rate in this study is slightly higher than other mortality rates published on the basis of population-wide data for unselected patients. For example, on the basis of data from the NIS, Dimick et al.1 reported that the rate of mortality for liver resection decreased from 10.4% (1988–1999) to 5.3% (1998–2000). A mortality rate of 2.6% has been reported in the NSQIP PSS study. High-volume hospitals (17) (>10 resections per year) in the NIS data set reported a 3.9% overall mortality rate from 1998 to 2000, although there are important differences between NSQIP, NIS, and our study data sets (e.g. the 3-month mortality rate reported in the current study, 30-day mortality reported in the NSQIP study, and in-hospital mortality reported in NIS). Because the majority of hospitals included in the NSQIP PSS data set reported more than 30 liver resections over the 3-year time period, the results of that study are representative of ‘high-volume’ hospitals.
Schroeder et al.13 evaluated the predictive indices of the MELD, Child–Turcotte–Pugh scores, and the American Society of Anesthesiology physical status classification on morbidity and mortality for patients after hepatic resection. American Society of Anesthesiology and Child–Turcotte–Pugh scores were predictive of mortality but not morbidity, but MELD had no predictive value 13. Nagorney and Kamath 20 reported that the application of MELD as a prognostic tool for patients other than those awaiting hepatic transplantation requires further investigation before clinical application. In addition, they disputed the conclusion that MELD should not be used in the setting of elective hepatic resection 20. The contradiction between our results and the aforementioned results could be attributed to the fact that in our study, we included the preoperative MELD score as a predictive value of morbidity after hemihepatectomy or extended hemihepatectomy.
MELD was developed as a reliable objective method to determine the risk of mortality in patients with cirrhosis only 11. Nagorney and Kamath 20 documented that the conclusion on MELD cannot be drawn without data on the specific number of patients with cirrhosis and the exclusion of patients with chronic renal failure and anticoagulants that affect serum creatinine and INR (essential components of MELD score calculation). However, the applicability of MELD in patients without cirrhosis, irrespective of intervention, is unknown 20.
Nagorney and Kamath concluded from their study in 2006 that there was no index that is clinically useful in predicting operative risk, either morbidity or mortality, in this group of patients 20.
In the present work, the preoperative MELD score was significantly associated with posthemihepatectomy complications after adjusting for other confounders in a logistic-regression model and confirmation that there are no associations between bilirubin, serum creatinine, and INR and posthemihepatectomy complications.
In our study, only four cases of hepatic cirrhosis (one macroscopic and three microscopic) were included. Two of the microscopic cases had no postoperative complications (grade 1), whereas one case had grade 3a and the macroscopic case had postoperative complication grade 1; the patient was a known case of hepatitis C. Their MELD scores ranged between 6 and 10 preoperatively. Death was reported in six cases, yielding a mortality rate of 4.17%. In our study, the preoperative MELD score was not significantly associated with posthemihepatectomy mortality as four of the patients had MELD scores below 9 and two had MELD scores of 13 and 16.
Teh et al. 21 showed that the MELD score is predictive of postoperative mortality after hepatic resection for patients with cirrhosis and hepatocellular cancer. However, others have shown that MELD is predictive of perioperative mortality after other operations in patients with cirrhosis 22–24. Our study could not confirm any of the aforementioned findings because there were six deaths and four patients with cirrhosis in our cohort as it was an exclusion criterion as mentioned before. We did not focus on the cirrhotic patients; our aim was to determine the significance of the MELD score even in noncirrhotic patients undergoing major hepatic operations to predict complications.
Breitenstein et al.25 developed a simple score in 2010 to predict postoperative complications by severity after liver resection using readily available preoperative risk factors. Complications were assessed prospectively in 615 consecutive noncirrhotic patients undergoing liver resection at the same institution. In a randomly selected 60% of the population, multivariate logistic-regression analysis was used to develop a score to predict severe complications defined as complication grades III, IV, and mortality (grade V) (Clavien–Dindo classification). The score was validated by calibration in the rest of the 40% of the patients. Grade III–V complications occurred in 159 (26%) of the 615 patients after liver resection; 90 (15%) were grade III, 48 (8%) were grade IV, and 21 (3%) were grade V. Four preoperative parameters were identified as independent predictors including American Society of Anesthesiologists category, transaminases levels (AST), extent of liver resection (>3 vs. <3 segments), and the need for an additional hepaticojejunostomy or colon resection. A prediction score was calculated on the basis of 60% of the population (369 patients) using the four independent predictors ranging from 0 to 10 points. The risk of developing serious postoperative complications was 16% in ‘low-risk’ patients (0–2 points), 37% in ‘intermediate-risk’ patients (3–5 points), and 60% in ‘high-risk’ patients (6–10 points). The predicted mean for absolute risk for grade III–V complications was 27% in the validation population including 40% of the patients (n=246), whereas the observed risk was 24%. Predicted and observed risks were similar throughout the different risk categories (P=0.8). The score was significantly associated with hospital and intensive care unit stays. Costs of the entire procedure doubled among the three risk groups.
In the present work, grade III–V complications occurred in 54 (37.5%) of the 144 patients after hemihepatectomy or extended hemihepatectomy; 41 (28.5%) were grade IIIa and IIIb, 7 (4.9%) were grade IVa and b, and 6 (4.17%) were grade V.
AST level preoperatively was not significantly associated with posthemihepatectomy complications and grade of complication. One of the preoperative predictors in the previous study was a liver resection of more than three segments; however, all the patients in our study underwent hemihepatectomy or extended hemihepatectomy.
Preoperative hepatic function as assessed by the serum bilirubin level was a potent predictor of postoperative complication as reported by Sitzmann and Greene 26. In the present survey, bilirubin was not a predictor for posthemihepatectomy complications.
In 2009, Armstrong et al. 27 evaluated the predictive indices of creatinine, that is, whether elevated preoperative serum creatinine increased the risk of renal failure and nonrenal complications after liver resection. Data were studied from 1535 consecutive liver resections. Outcomes in patients with preoperative creatinine up to 124 μmol/l (group 1) were compared with those with preoperative creatinine of at least 125 μmol/l (group 2). Despite the differences in age and comorbidity, this study showed no difference in the rate of surgical complications between the two groups. Systemic complications accounted for the higher rates of postoperative morbidity in patients with elevated serum creatinine 27. In our study, creatinine was not significantly associated with posthemihepatectomy complications and also the grade of complication. In the present work, creatinine was also not associated with the mortality as five out of six patients who died had normal preoperative creatinine levels, whereas only one patient had a preoperative creatinine level of 2.6 mg/dl. This can most probably be attributed to the relatively small sample size in our research.
The authors thank PD Dr. med T. Lorf for his fruitful directions, useful advice, professional cooperation, and endless support during the conduction of this work and they also thank Prof. Moataz M. Abdel-Fattah for his great support during the statistical analysis of this research work.
There are no conflicts of interest.
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