Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity.
ABSTRACT: BACKGROUND AND AIMS:Antithrombin III (ATIII) has been reported to be associated with liver pathologies and was shown to predict outcome in patients undergoing liver resection for hepatocellular carcinoma. We now aimed to assess whether perioperative ATIII-activity could predict postoperative outcome in patients without underlying liver disease, as well as in a routine clinical setting of patients undergoing hepatic resection. METHODS:ATIII-activity was evaluated preoperatively and on the first (POD1) and fifth day after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC). We further aimed to prospectively validate our results in a set of 177 consecutive patients undergoing hepatic resection. RESULTS:Patients developing postoperative liver dysfunction (LD) had a more pronounced postoperative decrease in ATIII-activity (P<0.001). ATIII-activity on POD1 significantly predicted postoperative LD (P<0.001, AUC = 84.4%) and remained independent upon multivariable analysis. A cut-off value of 61.5% ATIII-activity was determined using ROC analysis. This cut-off was vital to identify high-risk patients for postoperative LD, morbidity, severe morbidity and mortality (P<0.001, respectively) with a highly accurate negative predictive value of 97%, which could be confirmed for LD (P<0.001) and mortality (P = 0.014) in our independent validation cohort. Further, mCRC patients below our cut-off suffered from a significantly decreased overall survival (OS) at 1 and 3 years after surgery (P = 0.011, P = 0.025). CONCLUSIONS:The routine laboratory parameter ATIII-activity on POD1 independently predicted postoperative LD and was associated with clinical outcome. Patients with a postoperative ATIII-activity <61.5% might benefit from close monitoring and timely initiation of supportive therapy. TRIAL REGISTRATION:ClinicalTrials.gov NCT01700231.
Project description:Background:To date, definitions of liver dysfunction (LD) after hepatic resection rely on late postoperative time points. Further, the used parameters are markedly influenced by perioperative management. Thus, we aimed to establish a very early postoperative score to predict postoperative mortality. Methods:Liver related parameters were evaluated after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC) and subsequent validation in a prospective set of 482 consecutive patients from 4 independent institutions undergoing hepatic resection was performed. Results:C-reactive protein (CRP, AUC =0.739, P<0.001) and antithrombinIII-activity (ATIII, AUC =0.844, P<0.001) on the first postoperative day (POD) were found to be elevated in patients with LD. Cut-off values for CRP at 3 mg/dL and for ATIII at 60% significantly identified high-risk patients for postoperative LD and mortality (P<0.001) and thus defined the 3-60 criteria on POD1. The 3-60 criteria showed superior sensitivity and specificity compared to established criteria for LD [3-60 criteria: total positive patients: 26 patients (70% mortality detected), odds ratio (OR): 48.8; International Study Group for Liver Surgery: total positive patients: 43 (70% mortality detected), OR: 23.3; Peak7: total positive patients: 9 (30% mortality detected), OR: 27.8; 50-50: total positive patients: 9 (30% mortality detected), OR: 27.8]. These results could be validated in a multi-center analysis and ultimately the 3-60 criteria remained an independent predictor of postoperative mortality upon multivariable analysis. Conclusions:The 3-60 criteria on POD1 predict postoperative LD and mortality early after liver resection with a comparable or better accuracy than established criteria, allowing for immediate identification of high-risk patients.
Project description:Recently, von-Willebrand-Factor (vWF) has been shown to correlate with postoperative liver dysfunction (LD). Accordingly, "disintegrin-like metalloprotease with thrombospondin type1 motif" (ADAMTS13) is known to cleave vWF in less active fragments. Thus, we aimed to evaluate the diagnostic potential of ADAMTS13-activity (ADAMTS13-AC) to identify patients with postoperative LD after hepatectomy. Accordingly 37 patients undergoing hepatectomy for different neoplastic entities were included in this study. Plasma ADAMTS13-AC and vWF-Ag were measured 1?day prior to (preOP), 1 and 5 days (POD1/5) after hepatectomy. In accordance to the ISGLS-criteria LD was prospectively recorded. In this context, perioperative ADAMTS13-AC- and vWF-Ag/ADAMTS13-AC-ratio- levels revealed a significant increase after hepatectomy. Accordingly, elevated vWF-Ag/ADAMTS13-AC-ratio significantly predicted LD (preOP AUC: 0.75, p?=?0.02; POD1 AUC: 0.80, p?=?0.03). Patients who fulfilled our perioperative vWF-Ag/ADAMTS13-AC-ratio cut-off-levels (preOP: ?116, POD1: ?165) suffered from significantly higher incidences of LD (preOP: 70% vs. 30%, p?=?0.01; POD1: 83% vs. 17%, p?=?0.001). In conclusion, perioperative ADAMTS13-AC measurement may serve as a useful parameter to early detect high-risk patients developing postoperative LD prior to liver resection in patients suffering from hepatic malignancies. Indeed, further investigations have to be performed to consolidate its role as a predictive marker for LD.
Project description:BACKGROUND AND AIMS:Thrombopoietin (TPO) has been implicated in the process of liver regeneration and was found to correlate with hepatic function in patients with liver disease. With this investigation we aimed to determine if perioperative TPO levels were associated with postoperative outcome in patients undergoing liver resection. METHODS:Perioperative TPO was analyzed prior to liver resection as well as on the first and fifth postoperative day in 46 colorectal cancer patients with liver metastasis (mCRC) as well as 23 hepatocellular carcinoma patients (HCC). Serum markers of liver function within the first postoperative week were used to define liver dysfunction. RESULTS:While circulating TPO levels significantly increased one day after liver resection in patients without liver cirrhosis (mCRC) (P < 0.001), patients with underlying liver disease (HCC) failed to significantly induce TPO postoperatively. Accordingly, HCC patients had significantly lower TPO levels on POD1 and 5. Similarly, patients with major resections failed to increase circulating TPO levels. Perioperative dynamics of TPO were found to specifically predict liver dysfunction (AUC: 0.893, P < 0.001) after hepatectomy and remained an independent predictor upon multivariate analysis. CONCLUSIONS:We here demonstrate that perioperative TPO dynamics are associated with postoperative LD. Postoperative TPO levels were found to be lowest in high-risk patients (HCC patients undergoing major resection) but showed an independent predictive value. Thus, a dampened TPO increase after liver resection reflects a poor capacity for hepatic recovery and may help to identify patients who require close monitoring or intervention for potential complications.
Project description:BACKGROUND:Neoadjuvant chemotherapy (NeoCTx) is performed for most patients with colorectal cancer liver metastases (CRCLM). However, chemotherapy-associated liver injury (CALI) has been associated with poor postoperative outcome. To date, however, no clinically applicable and noninvasive tool exists to assess CALI before liver resection. METHODS:Routine blood parameters were assessed in 339 patients before and after completion of NeoCTx and before surgery. The study assessed the prognostic potential of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), the albumin-bilirubin grade (ALBI), and their combinations. Furthermore, an independent multi-center validation cohort (n = 161) was included to confirm the findings concerning the prediction of postoperative outcome. RESULTS:Higher ALBI, APRI, and APRI + ALBI were found in patients with postoperative morbidity (P = 0.001, P = 0.064, P = 0.001, respectively), liver dysfunction (LD) (P = 0.009, P = 0.012, P < 0.001), or mortality (P = 0.037, P = 0.045, P = 0.016), and APRI + ALBI had the highest predictive potential for LD (area under the curve [AUC], 0.695). An increase in APRI + ALBI was observed during NeoCTx (P < 0.001). Patients with longer periods between NeoCTx and surgery showed a greater decrease in APRI + ALBI (P = 0.006) and a trend for decreased CALI at surgery. A cutoff for APRI + ALBI at - 2.46 before surgery was found to identify patients with CALI (P = 0.002) and patients at risk for a prolonged hospital stay (P = 0.001), intensive care (P < 0.001), morbidity (P < 0.001), LD (P < 0.001), and mortality (P = 0.021). Importantly, the study was able to confirm the predictive potential of APRI + ALBI for postoperative LD and mortality in a multicenter validation cohort. CONCLUSION:Determination of APRI + ALBI before surgery enables identification of high-risk patients for liver resection. The combined score seems to dynamically reflect CALI. Thus, APRI + ALBI could be a clinically relevant tool for optimizing timing of surgery in CRCLM patients after NeoCTx.
Project description:Treatment options and reliable predictive marker to determine patients at risk to develop postoperative LD and to define the optimal time point of liver resection are limited. Accordingly, there is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery, specifically as current markers are often expensive, time consuming and sometimes invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic and treatment response biomarkers for several diseases. Using next-generation sequencing as an unbiased systematic approach 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative LD after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature - consisting of miRNAs 151a-5p, 192-5p and 122-5p - that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real-time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a-5p to 192-5p and 122-5p to 151a-5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stay and even mortality prior to surgery with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Given the clinical relevance of predicting potentially fatal postoperative clinical outcome after liver resection, our data demonstrate the clinical utility of a novel miRNA-based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in tailoring the optimal time point of surgery to each individual patient. Thereby, our data might help to tailor surgical strategies to the specific risk profile of individual patients. Overall design: Examination of 48 baseline plasma samples by Illumina NextSeq 500 sequencing taken prior to partial hepatectomy. 21 samples from patients with post-operative liver dysfunction. 27 samples from patients without post-operative liver dysfunction. Please note that there are two patients who received hepatic surgery because of liver cirrhosis, but did not suffer from a cancerous disease (characteristics: cancer type = none). The main outcome of this study was post-operative liver dysfunction (characteristics: Liver Dysfunction) and the type of cancer was provided as supporting information to give background about the reason why patients required liver surgery. Mostly, lesions due to three types of cancer were the reason for surgery, and, in only two cases, cirrhosis.
Project description:BACKGROUND:Delta neutrophil index (DNI) can be used as a biomarker for infection to predict patient outcomes. We aimed to investigate the relationship between DNI and clinical outcomes in trauma patients who underwent abdominal surgery. MATERIALS AND METHODS:We retrospectively analyzed injured patients who underwent emergent abdominal surgery in the regional trauma center of Wonju Severance Christian Hospital between March 2016 and May 2018. Patient characteristics, operation type, preoperative and postoperative laboratory findings, and clinical outcomes were evaluated. Logistic regression analysis was performed for risk factors associated with mortality. RESULTS:Overall, 169 patients (mean age, 53.8 years; 66.3% male) were enrolled in this study, of which 19 (11.2%) died. The median injury severity score (ISS) was 12. The non-survivors had a significantly higher ISS [25(9-50) vs. 10(1-50), p<0.001] and serum lactate level (9.00±4.10 vs. 3.04±2.23, p<0.001) and more frequent shock (63.2% vs 23.3%, p<0.001) and solid organ injury (52.6% vs. 25.3%, p = 0.013) than the survivors. There were significant differences in postoperative DNI between the two groups (p<0.009 immediate post-operation, p = 0.001 on postoperative day 1 [POD1], and p = 0.013 on POD2). Logistic regression analysis showed that the independent factors associated with mortality were postoperative lactate level (odds ratio [OR] 1.926, 95% confidence interval [CI] 1.101-3.089, p = 0.007), postoperative sequential organ failure assessment score (OR 1.593, 95% CI 1.160-2.187, p = 0.004), and DNI on POD1 (OR 1.118, 95% CI 1.028-1.215, p = 0.009). The receiver operating characteristics curve demonstrated that the area under the curve of DNI on POD1 was 0.887 (cut-off level: 7.1%, sensitivity 85.7%, and specificity 84.4%). CONCLUSIONS:Postoperative DNI may be a useful biomarker to predict mortality in trauma patients who underwent emergent abdominal surgery.
Project description:There is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery and thereby determine the optimal time point of liver resection, specifically as current markers are often expensive, time consuming, and invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic, and treatment-response biomarkers for several diseases. Using next-generation sequencing as an unbiased systematic approach, 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative liver dysfunction (LD) after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature-consisting of miRNAs 151a-5p, 192-5p, and 122-5p-that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real-time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a-5p to 192-5p and 122-5p to 151a-5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stays, and even mortality before an operation with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Our data demonstrate the clinical utility of an miRNA-based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in individualized patient treatment. Thereby, our data might help to tailor surgical strategies to the specific risk profile of patients.
Project description:Background:Postoperative day 1-drains amylase (POD1-DA) values are commonly used to predict the risk of pancreatic fistula (PF) after pancreaticoduodenectomy (PD). Perioperative inflammatory biomarkers have been associated to higher risk of complications in different oncological surgeries. Aim of this study was to investigate the utility of the combination of preoperative inflammatory biomarkers (PIBs) with POD1-DA levels in predicting grade C PF. Materials and methods:From a prospective collected database of 317 consecutive pancreaticoduodenectomies, data regarding POD1-DA levels and PIBs as neutrophil-to-lymphocyte ratio (NRL), derived neutrophil-to-lymphocyte ratio (dNRL), platelet-to-lymphocyte ratio (PLR) were analyzed in 227 cases. P-values <0.05 were considered statistically significant. Receiver operating characteristic (ROC) curves defined the optimal thresholds for biomarkers and drains amylase values and their accuracy to predict PF. Furthermore, the Positive Predictive Value (PPV) was computed to evaluate the probability to develop PF combining PIBs and drains amylase values. Combination of drains amylase and different PIBs cut-offs were used to evaluate the risk of grade C PF. Results:A POD1-DA level of 351 U/L significantly predicted PF (sensitivity 82.7%, specificity 76%, AUC 0.836; p < 0.001) with a PPV of 76.5% and a NPV of 82.6%.POD1-DA levels ?807 U/L significantly predicted grade C PF (sensitivity 72.7%, specificity 64.4%, AUC 0.676; p = 0.004) with a PPV of 17.8% and a NPV of 95.6%.Notably, this last PPV increased from 17.8% to 89% when PIBs, at different cut-offs, were combined with POD1-DA at the value ? 807 U/L. Conclusion:PIBs significantly improve POD1-DA ability in predicting grade C PF after PD.
Project description:Background Capillary refill time (CRT) is a non-invasive technique to evaluate tissue perfusion, and quantitative CRT (Q-CRT) adapted to pulse oximetry was developed with patients with sepsis and compared to blood lactate and sepsis scores. In post liver transplantation, large amounts of fluid administration are necessary for maintaining tissue perfusion to grafted liver against intravascular hypovolemia. This study aimed to evaluate whether Q-CRT can predict poor outcomes by detecting peripheral tissue perfusion abnormality in patients with liver transplantations who were treated with massive fluid administration. Methods In this single-center prospective cohort study, we enrolled adult patients with liver transplantations between June 2018 and July 2019. Measurement of Q-CRT was conducted at intensive care units (ICU) admission and postoperative day 1 (POD1). Results A total of 33 patients with liver transplantations were enrolled. Significant correlations of Q-CRT and ?Ab, a tissue oxygen delivery parameter calculated by pulse oximetry data, at ICU admission with the postoperative outcomes such as length of ICU and hospital stay and total amount of ascitic fluid discharge were observed. Quantitative CRT and ?Ab at ICU admission were significantly associated with these postoperative outcomes, even after adjusting preoperative and operative factors (MELD score and bleeding volume, respectively). However, quantitative CRT and ?Ab at POD1 and changes from ICU admission to POD1 failed to show significant associations. Conclusions Q-CRT values were significantly associated with postoperative outcomes in liver transplantation. Although the mechanisms of this association need to be clarified further, Q-CRT may enable identification of high-risk patients that need intensive postoperative managements.
Project description:Postoperative liver dysfunction remains a major concern following hepatic resection. In order to identify patients who are at risk of developing liver dysfunction, indocyanine green (ICG) clearance has been proposed to predict postoperative liver function. All patients who underwent liver resection at the Medical University Vienna, Austria between 2006 and 2015 with preoperative ICG clearance testing (PDR, R15) were analyzed in this study. Postoperative liver dysfunction was analyzed as defined by the International Study Group of Liver Surgery. Overall, 698 patients (male: 394 (56.4%); female: 304 (43.6%)) with a mean age of 61.3 years (SD: 12.9) were included in this study, including 313 minor liver resections (44.8%) and 385 major liver resections (55.2%). One hundred and seven patients developed postoperative liver dysfunction after liver resection (15.3%). Factors associated with liver dysfunction were: male sex (p = 0.043), major liver resection (p < 0.0001), and preoperative ICG clearance (PDR (p = 0.002) and R15 (p < 0.0001)). Notably ICG clearance was significantly associated with liver dysfunction in minor and major liver resections respectively and remained a predictor upon multivariable analysis. An optimal cut-off for preoperative ICG clearance to accurately predict liver dysfunction was PDR < 19.5%/min and R15 > 5.6%. To the best of our knowledge, this is the largest study analyzing the predictive value of preoperative ICG clearance assessment in patients undergoing liver resection. ICG clearance is useful to identify patients at risk of postoperative liver dysfunction.