World J Surg (2009) 33:1711–1719 DOI 10.1007/s00268-009-0093-4 Value of MELD and MELD-Based Indices in Surgical Risk Evaluation of Cirrhotic Patients: Retrospective Analysis of 190 Cases Beatriz P. Costa Æ F. Castro Sousa Æ Marco Serôdio Æ César Carvalho Published online: 10 June 2009 Ó Société Internationale de Chirurgie 2009 Abstract Background Recent studies have suggested that the Model for End-Stage Liver Disease (MELD) may represent a promising alternative to the Child-Turcotte-Pugh classification as a predictive factor of operative mortality and morbidity. This study was designed to evaluate the value of MELD and four MELD-based indices (iMELD: integrated MELD; MESO: MELD to sodium ratio; MELD-Na: MELD with incorporation of sodium; MELD-XI: MELD excluding the International Normalized Ratio) in the quantification of surgical risk for patients with cirrhosis and compare its prognostic value with the Child-TurcottePugh classification and two derived scores (proposed by Huo and Giannini, respectively). Methods A retrospective study of 190 patients with cirrhosis, operated on in our department between 1993 and 2008, was undertaken. Results Forty-three percent of patients were included in Child-Turcotte-Pugh A class, and their mean MELD score was 12.2 ± 4.9 (range, 6.4–35.2). Mortality and morbidity rates were 13% and 24%, respectively. In global analysis of mortality, MELD-based indices presented an acceptable prognostic performance (auROC = 71–77%), similar to the three analyzed Child-Turcotte-Pugh-derived scores. iMELD demonstrated the highest prognostic capacity (auROC = 77%; 95% confidence interval (CI), 66–88; p = 0.0001); operative death probability was 4% (95% CI, 3.6– 4.4) when the score was inferior to 35, 16.1% (95% CI, 14.4–17.9) between 35 and 45, and 50.1% (95% CI, B. P. Costa (&)
F. Castro Sousa
M. Serôdio
C. Carvalho IIIrd Surgical Department, Coimbra University Medical School and Hospitals, Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal e-mail: beatrizpcosta@huc.min-saude.pt 42.2–58.1) when superior to 45. In elective surgical procedures, iMELD represented a useful prognostic factor of operative mortality (auROC = 80%; 95% CI, 63–97; p = 0.044) with significant correlation and better accuracy then MELD and Child-Turcotte-Pugh-derived indices. Conclusions In this study, iMELD was a useful predictive parameter of operative mortality for patients with cirrhosis submitted to elective procedures. Further studies are necessary to define the relevance of MELD-based indices in the individual surgical risk evaluation. Abbreviations iMELD Integrated MELD MESO MELD to sodium ratio MELD-Na MELD with incorporation of sodium MELD-XI MELD excluding the international normalized ratio r Spearman’s correlation coefficient. Introduction Hepatic cirrhosis represents a recognized surgical risk factor that is important to quantify during the preoperative evaluation. In 2003, del Olmo et al. showed that in extrahepatic operations, cirrhosis was associated with a higher operative mortality (16.3 vs 3.5%) [1]. Child-TurcottePugh classification [2, 3], based on values of bilirubinemia, albuminemia, and prothrombin time, presence, and severity of ascites and hepatic encephalopathy, is currently used for surgical risk evaluation. In 1997, Mansour et al. [4] demonstrated, in abdominal surgery, an operative mortality of 10%, 30%, and 82% for A, B, and C classes, respectively [5]. Nevertheless, this classification, described for more 123 1712 than 30 years, includes five variables empirically selected, with equal relative value and some subjectivity, leading to stratification in three heterogeneous categories with low discriminative capacity [6]. Recent studies have suggested that the Model for End-Stage Liver Disease (MELD)—a score calculated from three laboratory variables (serum bilirubin, creatinine levels, and International Normalized Ratio (INR)) and initially developed for evaluation of short-term prognosis of patients submitted to transjugular intrahepatic portosystemic shunt and used by United Network for Organ Sharing (UNOS) since 2002 in the definition of priorities for liver transplantation—may represent a functional hepatic reserve parameter and a predictive factor of operative mortality and morbidity, with good correlation and, eventually, with a higher prognostic accuracy than the traditional Child-Turcotte-Pugh classification [1, 3, 7–17]. More recently, other MELD-based indices have been proposed, including the ‘‘Integrated MELD’’ (iMELD), the ‘‘MELD with incorporation of sodium’’ (MELD-Na), and the ‘‘MELD to sodium ratio’’ (MESO), incorporating other independent predictive factors, such as natremia and age, to improve its prognostic potential [18–21]. Simultaneously, several authors have suggested modifications of the Child-Turcotte-Pugh classification, including subdivision of classes (Heuman et al. 2005), introduction of a new D class (Huo et al., 2006), and addition of creatininemia as a sixth variable (Giannini et al. 2004) [22–26]. A retrospective study of 190 patients, who were operated on in our department between 1993 and 2008, was performed to evaluate the relevance of MELD and four MELD-based indices (iMELD, MELD-Na, MESO, and MELD-XI) in the quantification of surgical risk of patients with cirrhosis and to compare its prognostic value with Child-Turcotte-Pugh classification and two derived scores. Materials and methods Adult patients with cirrhosis operated on at the IIIrd Surgical Department of Coimbra University Hospitals, between 1993 and 2008, were identified through the informatics’ medical registry based on ICD-9 (‘‘International Classification of Diseases, 9th Revision Code). Diagnosis of cirrhosis was confirmed by clinical criteria (typical signs and symptoms, previous episodes of hepatic encephalopathy or variceal bleeding), imaging (dysmorphic or atrophic liver, portal hypertension), endoscopic (esophageal varices), peroperative, and/or histological suggestive findings. Chronic renal failure under dialyze therapy and oral anticoagulants were considered exclusion criteria, such as insufficient data available to determine MELD and Child-Turcotte-Pugh scores. The study was 123 World J Surg (2009) 33:1711–1719 based on review of clinical charts and results of laboratory variables at the moment of hospital admission. The variables studied included age, sex, associated diseases, etiology of liver disease, presence and grade of ascites and hepatic encephalopathy (definition based on West Haven criteria [27]), and laboratory values (bilirubinemia, albuminemia, creatininemia, natremia, prothrombinemia, and INR). The type of surgical procedure (urgent vs elective surgery, abdominal vs extraabdominal surgery, major vs minor surgery) and the type of anesthesia (general anesthesia vs other types) were recorded. The American Society of Anesthesiology (ASA) classification, the Charlson’s age–comorbidity index, and the Surgical Risk Scale score were determined [28–32]. The first has been accepted, for study purposes, as a method to describe the risk of death in perioperative context and is calculated by adding the points corresponding to several associated diseases and one point for each decade of age older than 49 years. The Surgical Risk Scale, described in 2002 by Sutton et al. [31], has been used as a risk scoring system, using a scale of 3 to 14 points, and incorporates the classifications of the ‘‘Confidential Enquiry Into Perioperative Deaths’’ (elective, scheduled, urgent, and emergent), the ‘‘British United Provident Association’’ (minor, intermediate, major, major plus, and major complex) and ASA for each surgical procedure. Child-Turcotte-Pugh [2, 3] classification was determined and Child-Turcotte-Pugh-modified scoring systems, described respectively by Huo et al. [23] and Giannini et al. [24], were calculated. MELD and four MELD-based indices were determined: iMELD, MELDNa, MESO index, and MELD-XI (Table 1) [3, 7, 18–21, 33]. The operative mortality and morbidity rates (primary end points) and duration of postoperative hospitalization were determined. Perioperative mortality was defined as death within 30 days or during the hospitalization after the operation. Complications were considered to be any deviation from the normal postoperative course other than normal sequelae (inherent to a specific surgical procedure), failure of therapy (goal of treatment not attained), or death. Data management and statistical analysis were performed with SPSSÒ version 15 for Windows (SPSS, Inc., Chicago; IL), including v2 and Student’s t tests, logistic regressions, Spearman’s correlations, ROC (receiver operating characteristic) curves, and Analyse It (comparison of ROC curves). For all tests, P value \ 0.05 was considered statistically significant. The study was conformed to the standards of the Declaration of Helsinki. Results The study included 190 patients: 81% were male and the mean age was 61 years (Table 2). The etiology of cirrhosis World J Surg (2009) 33:1711–1719 1713 Table 1 Formulas of the analyzed MELD-based and Child-Turcotte-Pugh-modified scores Score Study Formula MELD Freeman [3] 9.57 Loge creatininemia mg/dl ? 3.78 Loge bilirubinemia mg/dl ? 11.2 Loge ‘‘International Normalized Ratio’’ ? 6.43 iMELD Luca et al. [18] MELD? 0.3 age years - 0.7 natremia mEq/L?100 Minimal values were set to 1.0 and maximal serum creatinine level was considered 4.0 mg/dl MELD-Na Biggins et al. [19] MELD? 1.59 (135-natremia mEq/L) MESO Huo et al. [20] (MELD/natremia mEq/L)100 Maximum and minimum natremia values of 135 and 120 mEq/L, respectively MELD-XI Modified Child’s score Heuman et al. [33] Huo et al. [23] 5.11 Loge bilirubinemia mg/dl ? 11.76 Loge creatininemia mg/dl ? 9.44 Included an additional class D (16–18 points) resulting from attribution of one point when albuminemia \2.3 g/dl, bilirubinemia [8 mg/dl, or prothrombin time prolongation [11 s Creatinine-modified Child’s score Giannini et al. [24] Estimated by adding one to three points to the original score: 1 if creatininemia B media of the cohort; 2 if between median and median ? standard deviation; 3 if C to median ? standard deviation Table 2 Characteristics of patients with cirrhosis who underwent operation (n = 190) n (%) Male gender 153 81 Age (yr) 61.4 ± 12 (32–94) Etiology of cirrhosis Alcoholic 165 87 Viral 12 6 Other 13 7 ASA classificationm II 46 24 III 91 48 IV 53 28 Charlson’s modified indexa 6.5 ± 2.5 (3–15) Data are (%) or median ± standard deviation a Charlson’s modified index: summation of points from comorbid conditions: (1) myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, ‘‘connective tissue disease’’, peptic ulcer, uncomplicated diabetes mellitus; (2) moderate-severe renal disease, diabetes mellitus with end organ damage, hemiplegia, neoplasia, leukemia, lymphoma; (3) moderate-severe liver disease; (6) metastatic solid tumor, AIDS; one point for each decade of age older than 49 years (Charlson et al. [30]) was alcoholic in 87% of the cases. Forty-eight percent of patients were included in ASA III class, and the mean value of Charlson’s age–comorbidity index was 6.5. Forty-three percent of patients were included in Child-Turcotte-Pugh’s A class, and the mean value of MELD was 12 (Table 3). Hepatocellular carcinomas, abdominal wall hernias, colorectal carcinomas, and gallstone disease represented the main elective surgical indications. Strangulated hernias, complicated peptic ulcers, acute cholecystitis, and complicated colorectal carcinomas predominated in urgent cases (Table 4). Surgical treatment was elective in 60% of cases and ‘‘major’’ in 77%; it included digestive operations in 73% and was performed under general anesthesia in 98%. Surgical procedures included hernioplasties (26%), hepatic resections (17%), cholecystectomies (12%), and colorectal resections (12%). The mean Surgical Risk Scale score was 8.9 (Table 5). Operative mortality and morbidity rates were 13% and 24%, respectively; mean postoperative hospitalization was 12.9 days (Table 6). For univariate analysis, the mortality rate was related with statistical significance to the Child-Turcotte-Pugh classification, modified Child-Turcotte-Pugh score (Huo et al. 2006 [23]), creatinine-modified Child-Turcotte-Pugh score (Giannini et al. 2004 [24]), MELD-derived indices and to patient’s age, ASA classification, and urgent operations (Table 7). In fact, the mean MELD score was higher in cases of operative death (17.3 ± 7 vs 11.5 ± 4; p = 0.0001). Patients with MELD C 15 (26%) had higher mortality rate (31.3 vs 6.1%; p = 0.0001; odds ratio = 5.1; accuracy = 77.1%). Similarly, mean Child-Turcotte-Pugh’s score was higher in cases of operative death (9.2 ± 2.5 vs 7.4 ± 2; p = 0.0001). Child-Turcotte-Pugh’s class C patients (19%) had higher mortality rate (31.4 vs 9.2%; p = 0.0001; odds ratio = 3.4; accuracy = 79.8%). Morbidity was not significantly related to any studied variables except age (Table 7). For multivariate analysis, age older than 70 years (p = 0.014; Exp(B) = 5.4; 95% confidence interval (CI), 1.4–20.8) and albuminemia B 3.1 g/dl (p = 0.049; Exp(B) = 3.6; 95% CI, 1–13.2) were independent factors of mortality. Globally, in the study of ROC curves for mortality, MELD-based indices presented an acceptable prognostic performance (area under the receiver operating characteristic curve (auROC) = 71–77%), similar to the three analyzed Child-Turcotte-Pugh-derived scores (auROC = 72–75%); only the difference between MESO and MELD-Na was statistically significant (p = 0.0433; Table 8; Fig. 1). iMELD demonstrated the highest 123 1714 Table 3 Child-Turcotte-Pugh classification, Child-TurcottePugh-modified scores, MELD, and MELD-based indices of cirrhotic patients submitted to surgery (n = 190) World J Surg (2009) 33:1711–1719 Study n (%) A 82 43 B 72 38 C 36 Child-Turcotte-Pugh classification Modified Child-Turcotte-Pugh score Data are (%) or median ± standard deviation 7.6 ± 2.2 (5–14) Freeman [3] Huo et al. [23] 19 7.8 ± 2.4 (5–15) Creatinine-modified Child-Turcotte-Pugh score Giannini et al. [24] 9 ± 2.5 (6–16) MELD Freeman [3] 12.2 ± 4.9 (6.4–35.2) 35.7 ± 7 (21.1–57.3) iMELD Luca et al. [18] MELD-Na Biggins et al. [19] 14.8 ± 7.4 (6.4–36.6) MESO Index Huo et al. [20] 9.1 ± 3.7 (4.2–24) MELD-XI Heuman et al. [33] 13.1 ± 4.4 (9.4–28.4) Table 4 Indications for surgery in 190 patients with cirrhosis Table 5 Surgical treatment in 190 patients with cirrhosis n (%) Hepatocellular carcinoma 34 18 Abdominal wall hernia 25 Colorectal carcinoma Gallstone disease n (%) Elective 113 60 ‘‘Major’’ 146 77 13 Under general anesthesia 187 98 19 16 10 8 Type of procedure 100 53 8 4 Extradigestive 53 27 37 20 Elective Gastric carcinoma Digestive extrahepatic Portal hypertension 3 2 Hepatic Status after Hartmann operation 2 1 Interventions Other 6 3 Hernioplasty/herniorrhaphy 56 26 Hepatic resection 36 17 Strangulated hernia of abdominal wall 19 10 Peptic ulcer (perforation/hemorrhage) 19 10 Cholecystectomy Colo/rectal resection 27 26 12 12 Acute cholecystitis 9 5 Gastrectomy 15 7 Colorectal carcinoma (obstruction/perforation) 7 4 Explorative laparotomy/laparoscopy 8 4 Esophagus/gastric variceal bleeding 5 3 Troncular vagotomy and pyloroplasty 7 3 Abdominal trauma 5 3 Enterectomy 5 2 13 7 Gastrojejunostomy 5 2 Porto-caval shunt 5 2 28 13 Urgent Other prognostic capacity (auROC = 77%, 95% CI, 66–88; p = 0.0001); its mean value was higher in cases of operative death (42.8 ± 8.5 vs 34.6 ± 6.1; p = 0.0001). Patients with iMELD score C 40 (28%) had higher mortality rate (29.8 vs 6.6%; p = 0.0001; odds ratio = 4.5; accuracy = 75.6%). Operative death predicted probability, calculated from the logistic regression model, increased with iMELD (from 0.8–77.8%): 4% when inferior to 35 (95% CI, 3.6–4.4), 16.1% (95% CI, 14.4–17.9) between 35 and 45, and 50.1% (95% CI, 42.2–58.1) when [ 45 (Fig. 2). Regarding morbidity, predictive performance of the studied cirrhotic variables was low (auROC = 41–51%; not significant). In the analysis of mortality after elective surgical procedures, MELD-derived indices increased its prognostic advantages and iMELD was revealed to be a good predictive parameter of operative mortality (auROC = 80%, 123 Others Surgical Risk Scale score (Sutton et al., 2002): 8.9 ± 1.9 (5–13) 95% CI, 63–97; p = 0.044) with better predictive potential than MELD (p = 0.0226) and the three studied ChildTurcotte-Pugh-derived indices (p = 0.0005, p = 0.0003, and p = 0.001 compared with traditional, Huo, and Giannini scores, respectively); relations between all other variables did not reach statistical significance except MELD XI vs Child-Turcotte-Pugh-derived indices (Table 9). The iMELD score was superior in cases of mortality (40.1 ± 7.3 vs 33 ± 5.6; p = 0.016); in elective procedures, operative death probability was 0.7% (95% CI\ 0.6–0.8) when the score was \ 30, 3.2% (95% CI, 2.7–3.8) between 30 and 40, and 17.2% (95% CI, 11.1–23.3) when [ 40. World J Surg (2009) 33:1711–1719 1715 Table 6 Results of surgical treatment in 190 patients with cirrhosis Mortality n (%) 25 13 Sepsis 9 Hepatic insufficiency 8 Disseminated intravascular coagulation 3 Irreversible hypovolemic shock 3 Digestive hemorrhage 1 Acute pulmonary edema 1 Morbidity 46 Operative wound complications 22 Nosocomial pneumonia 6 Organ/space infection Pleural effusion 5 3 Intraperitoneal hemorrhage 3 Other 7 Postoperative hospitalization (days) 24 12.9 ± 13.4 (1–92) Data are (%) or median ± standard deviation Furthermore, the correlations between MELD and iMELD compared with Child-Turcotte-Pugh score were significant (Spearman’s r = 0.72; p = 0.0001 and Spearman’s r = 0.58; p = 0.0001, respectively). The correlation between MELD-XI and MELD was very good (Spearman’s r = 0.88; p = 0.0001). Discussion The particular relevance of our study relies on the direct comparison, in the perioperative context, of five MELDbased indices and three Child-Turcotte-Pugh derived scores. In this series, the population was characterized by high prevalence of associated diseases: the Charlson’s agecomorbidity index was 6.5 ± 2.5 (3–15) and 48% of patients were included in ASA III class. In relation to cirrhosis severity, 57% of our patients were included in Child-Turcotte-Pugh’s B and C classes and 34% had an MELD score [ 12. Surgical operations were mainly elective (60%) and digestive (73%, including 20% hepatic procedures) and were associated with a high mean Surgical Risk Score (8.9). Operative mortality (13%) and morbidity rates (24%) were similar to those published in recent literature (mortality between 9.8 and 28%) [9, 11]. Globally, this study suggested that MELD and MELDbased indices are significant predictive parameters of operative mortality in patients with cirrhosis similar to Child-Turcotte-Pugh classification-derived scores (auROC = 71–77% and 72–75%, respectively). In fact, iMELD demonstrated the highest prognostic capacity, although the differences were not statistically significant. Interestingly, the prognostic advantages of MELD-based indices improved when considering only elective operations. In this group, iMELD represented a useful prognostic factor of operative mortality (auROC = 80%) with better predictive potential than MELD and Child-Turcotte-Pughderived scores. In reality, the operative risk evaluation seems to be much more important in the elective context. Nevertheless, MELD variables are susceptible to potential interferences that are associated with acute diseases (e.g., sepsis, dehydration, trauma coagulopathy), which do not reflect the severity of the underlying liver disease. The potential interest of MELD as a predictive factor of postoperative outcome for patients with cirrhosis has been confirmed by several authors in a wide variety of surgical operations [8, 9, 34]. In a retrospective study of 772 patients submitted to major digestive, orthopedic, and cardiac surgery, published in 2007 by Teh et al. [8], the operative mortality ranged from 5.6% when MELD score was \ 8 to more than 50% when MELD score was [ 20. There also was a mortality increase of 14% on the first and third months for each additional point in MELD score, of 15% during the first year and 6% during subsequent years; concordance (c-statistic) relative to first and third months were 0.78 and 0.82, respectively. Northup et al. reported, in a retrospective series of 130 patients undergoing general, orthopedic, cardiovascular, and urologic procedures, published in 2005, that operative mortality risk increased 1% for each additional point for MELD scores between 5 and 20 and 2% for values [20 (c = 0.72) [9, 35]. Other studies, such as Befeler et al. [11], Farnsworth et al. [12], and Perkins et al. [13], verified an increased risk of mortality and morbidity after surgery, mainly abdominal, in cases of MELD[8 to 14. Cucchetti et al. [10] reported that MELD [ 11 signifies an elevated risk of morbidity after hepatic resection for hepatocellular carcinoma (auROC = 85%), particularly hepatic insufficiency compared with values\9 (83.3 vs 8.1%, respectively). On the contrary, some studies did not notice advantages of MELD compared with ChildTurcotte-Pugh classification, such as Hoteit et al. [36] in a study of 195 patients submitted to extrahepatic surgery, Schroeder et al. [37] in elective hepatic operations, and others [38, 39]. Hyponatremia has been associated with severe complications of cirrhosis, including ascites, hepatorenal syndrome, and liver-related mortality [14]. Several authors have verified that natremia constituted an independent prognostic factor of mortality in cirrhotic candidates for transplantation and proposed its inclusion into MELD, creating new scores, e.g., iMELD, MELD-Na, and MESO [18–21, 40]. Luca et al. [18] showed that iMELD was associated with an increase in the accuracy of prediction of 123 1716 World J Surg (2009) 33:1711–1719 Table 7 Univariate analysis of operative mortality and morbidity of 190 patients with cirrhosis who underwent operation Mortality p Morbidity p Sex (male/female) 13.1 vs 13.5% NS 25.5 vs 18.9% NS Age (year) 67.1 ± 11.3 vs 60.6 ± 11.8 0.01 57.7 ± 13.7 vs 62.6 ± 11.1 0.016 Cirrhosis alcoholic/viral/other 13.3 vs 8.3 vs 15.4% NS 24.2 vs 41.7 vs 7.7% NS ASA classification (IV/III/II) 27.8 vs 8.9 vs 4.3% 0.001 18.5 vs 24.4 vs 30.4% NS Charlson’s modified index 7.3 ± 2.5 vs 6.4 ± 2.5 NS 6.2 ± 2.3 vs 6.6 ± 2.5 NS Albuminemia (g/dl) 2.8 ± 0.7 vs 3.6 ± 0.7 0.0001 3.6 ± 0.7 vs 3.4 ± 0.8 NS INR 1.8 ± 0.9 vs 1.3 ± 0.2 0,0001 1.3 ± 0.2 vs 1.4 ± 0.4 NS Creatininemia (mg/dl) 1.5 ± 0.7 vs 1 ± 0.4 0.0001 1.1 ± 0.4 vs 1.1 ± 0.5 NS Bilirubinemia (mg/dl) 2.4 ± 2.6 vs 1.8 ± 2.9 NS 1.8 ± 1.8 vs 1.9 ± 3.1 NS Natremia (mEq/l) 135.3 ± 7.7 vs 136.2 ± 4.7 NS 136.2 ± 5.6 vs 136 ± 5.1 NS Ascites (yes/no) Encephalopathy (yes/no) 26 vs 4.4% 14 vs 14% NS NS 19.6 vs 28.1% 22.2 vs 22.4% NS NS Child’s classification (C/B/A) 31.4 vs 14.1 vs 4.9% 0.001 25.7 vs 19.7 vs 26.8% NS Child’s score 9.2 ± 2.5 vs 7.4 ± 2.0 0.0001 7.5 ± 2.2 vs 7.7 ± 2.2 NS Modified Child’s scorea 9.5 ± 2.8 vs 7.5 ± 2.2 0.0001 7.6 ± 2.4 vs 7.8 ± 2.4 NS Creatinine-modified Child’s scoreb 11.2 ± 3 vs 8.7 ± 2.2 0.0001 8.8 ± 2.4 vs 9.1 ± 2.5 NS MELD 17.3 ± 7 vs 11.5 ± 4 0.0001 11.9 ± 3.9 vs 12.3 ± 5.2 NS iMELD 42.8 ± 8.5 vs 34.6 ± 6.1 0.0001 34 ± 6.4 vs 36.2 ± 7.1 NS MELD-Na 21.8 ± 9.3 vs 13.8 ± 6.5 0.001 14.6 ± 7.7 vs 14.9 ± 7.3 NS MESO 12.9 ± 5.1 vs 8.6 ± 3.1 0,001 8.9 ± 3 vs 9.2 ± 3.9 NS MELD-XI 16.7 ± 6 vs 12.5 ± 3.8 0.003 12.9 ± 4.1 vs 13.2 ± 4.4 NS Surgical Risk Scale 8.4 ± 2.4 vs 9 ± 1.8 NS 9.2 ± 1.8 vs 8.8 ± 2 NS Urgent procedure (yes/no) 26 vs 4.4 % 0.0001 23.4 vs 24.8 % NS ‘‘Digestive’’ procedure (yes/no) 15.2 vs 7.7 % NS 26.1 vs 19.2 % NS ‘‘Major’’ procedure (yes/no) 15.1 vs 6.8 % NS 25.3 vs 20.5 % NS General anesthesia (yes/no) 13.4 vs 0 % NS 24.6 vs 0 % NS Date (1993-1998/1999-2003/2004-2008) 13 vs 10.9 vs 15.2 % NS 17.4 vs 29.1 vs 27.3 % NS Data are (%) or median ± standard deviation INR International normalized ratio a Huo et al. [23], 2006 b Giannini et al. [24], 2004 mortality after transjugular intrahepatic portosystemic shunt (auROC = 78% vs 69%) and on the transplantation waiting list (auROC = 81% vs 75%), particularly in patients with MELD \ 15. The incorporation of natremia as a postoperative prognostic factor may be particularly important in cases with lower MELD scores (such as in our series) but may have disadvantages, namely, the susceptibility of natremia values to important oscillations with simple therapeutic measures (e.g., administration of diuretics), which do not always reflect modifications of the severity of liver disease. In our study, MELD-XI revealed a good correlation with MELD and similar statistic concordance in overall and elective surgery cohorts; its performance was significantly better than Child-Turcotte-Pugh-derived scores in elective procedures. MELD-XI, calculated only with serum bilirubin and creatinine levels, was originally 123 proposed in 2007 to prioritize cirrhotic candidates for liver transplantation under therapeutic anticoagulation and it may be especially useful in cases of possible dissociation of INR in relation to liver function (as occurs in cholestasis, pancreatic insufficiency, intestinal malabsorptive diseases, and disseminated intravascular coagulation, among others) and to monitor and correct discrepancies associated with the interlaboratory variability of INR measurements [33, 41]. Finally, there are several limitations of this study: retrospective design, potential selection bias (e.g., unknown number of patients with indication for surgery who were not operated on because of high surgical risk), low dimension of the sample, heterogeneity of the surgical procedures, and limited number of analyzed variables. Other aspects not included in the study are the influence of therapeutic maneuvers on MELD parameters and the World J Surg (2009) 33:1711–1719 1717 Table 8 Areas under the ROC curves for operative mortality and morbidity in 190 patients with cirrhosis Mortality vs Morbidity vs AUC (%) 95% CI p AUC (%) 95% CI p Charlson’s modified index 62 50–74 NS 53 42–64 NS Surgical Risk Scale 42 28–57 NS 55 46–65 NS Child’s score 72 61–83 0.001 48 37–58 NS Modified Child’s scorea 73 62–84 0.0001 47 37–58 NS Creatinine-modified Child’s scoreb 75 63–87 0.0001 47 37–58 NS MELD 76 64–89 0.0001 51 42–60 NS iMELD MELD-Na 77 76 66–88 64–87 0.0001 0.0001 41 48 31–52 38–58 NS NS MESO 76 63–88 0.0001 51 41–60 NS MELD-XI 71 59–83 0.001 51 41–60 NS AUC area under the ROC curve, CI confidence interval a Huo et al. [23], 2006 b Giannini et al. [24], 2004 Fig. 1 Comparison of ROC curves corresponding to Child-TurcottePugh score (auROC = 72%, p = 0.001), MELD (auROC = 76%; p = 0.0001), and iMELD (auROC = 77%; p = 0.0001) as predictive factors of operative mortality in 190 patients with cirrhosis eventual advantage of serial determinations (e.g., Delta MELD proposed in 2005 by Huo et al. [42]). A recent report by Lisman et al. [41] demonstrated clinically relevant interlaboratory variations of the calculated MELD, resulting mainly of differences on INR and creatinine measurements that justify adjustments and normalization. Further refinement and validation of MELD-based indices are needed and must include minimization of potential interferences into variables, due to different laboratory methods, sex and ethnic variations, acute occurrences (e.g., sepsis and dehydration), and therapeutic management. Other future investigational perspectives in Fig. 2 Relationship between the predicted probability of operative death and iMELD in 190 patients with cirrhosis who underwent operation this area will be to improve individual risk evaluation with definitions of ‘‘cutoffs,’’ correlation with quality of life and performance in cases of ascites, chronic encephalopathy, hepatopulmonary syndrome, and portopulmonary hypertension. Therefore, well-designed prospective studies, including a higher number of patients, specific surgical procedures, and analysis of additional variables are needed to clarify the interest and applicability of MELD-based indices on the daily clinical practice, particularly during the preoperative period. 123 1718 World J Surg (2009) 33:1711–1719 Table 9 Areas under the ROC curves for mortality and morbidity in 113 patients with cirrhosis submitted to elective surgery Mortality vs Morbidity vs AUC (%) 95% CI p AUC (%) 95% CI p Charlson’s modified index 78 62–94 0.034 55 36–56 NS Surgical risk scale 64 27–99 NS 56 44–67 NS Child’s score 54 24–84 NS 44 29–59 NS Modified Child’s score a 54 24–84 NS 44 29–58 NS Creatinine-modified Child’s scoreb 53 21–84 NS 44 29–59 NS MELD 61 27–94 NS 57 45–68 NS iMELD MELD-Na 80 62 63–97 28–96 0.044 NS 41 49 28–55 36–61 NS NS MESO 53 14–91 NS 54 41–67 NS MELD-XI 62 29–95 NS 55 44–67 NS AUC area under the ROC curve, CI confidence interval, NS not significant a Huo et al. [23], 2006 b Giannini et al. [24], 2004 Conclusions In this series, iMELD was revealed to be a useful predictive parameter of operative mortality in patients with cirrhosis submitted to elective procedures, with significant correlation with three studied Child-Turcotte-Pugh-derived scores (traditional, Huo et al., and Giannini et al., respectively) and MELD. Its simplicity, objectivity, and reproducibility may constitute additional advantages in relation to Child-Turcotte-Pugh-derived scores. Nevertheless, further studies are necessary to demonstrate the eventual interest of MELD-based indices in the surgical risk evaluation of patients with chronic hepatic diseases. References 1. del Olmo JA, Flor-Lorente B, Flor-Civera B et al (2003) Risk factors for nonhepatic surgery in patients with cirrhosis. World J Surg 27:647–652 2. Pugh RN, Murray-Lyon IM, Dawson JL et al (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649 3. 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