International Study Group Of Liver Surgery Research Articles

Preliminary clinical study of the safety of hepatectomy predicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced T1 mapping magnetic resonance imaging.

Background and AimStudies have found that gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced T1 mapping magnetic resonance imaging (MRI) could assess liver fibrosis, cirrhosis, and function with high effectiveness. The aim of this study is to explore the efficacy of MRI in predicting the safety of hepatectomy.MethodsForty‐nine patients who underwent liver resection were recruited. Gd‐EOB‐DTPA‐enhanced MRI examination was performed 1 week before surgery, and the rate of T1 relaxation time reduction (ΔT120min%) of liver parenchyma was calculated. Posthepatectomy liver failure (PHLF) was defined by the “50–50 criteria” and International Study Group of Liver Surgery (ISGLS) classification, respectively, and posthepatectomy complications (PHC) were defined by the Clavien‐Dindo grading system. The effectiveness of ΔT120min% in predicting the occurrence of PHLF and PHC was analyzed.ResultsThe area under the curve (AUC) for ΔT120min% predicting PHLF meeting “50–50 criteria” was 0.957, with a cutoff value of 0.497, sensitivity of 100%, and specificity of 89.1%. The AUC for predicting ISGLS grade B/C (severe) PHLF was 0.84, with a cutoff value of 0.5232, sensitivity of 63.6%, and specificity of 92.6%. The AUC for predicting PHC of Clavien‐Dindo grades 3–5 (severe) was 0.882, with a cutoff value of 0.5646, sensitivity of 87.5%, and specificity of 75.8%. Univariate and multivariate analyses showed that ΔT120min% < 0.4970 (P < 0.01) was an independent risk factor for the development of PHLF (50–50 criteria). Univariate and multivariate analyses showed that liver stiffness measurement and ΔT120min% were risk factors for severe PHLF and severe PHC.ConclusionsGd‐EOB‐DTPA‐enhanced T1 mapping MRI accurately predicts the safety of hepatectomy.

Evaluation of the ISGLS Criteria for Post-hepatectomy Liver Failure: Insights from Consideration of the Comprehensive Complication Index as a Measure of Morbidity

Purpose: We aimed to evaluate the International Study Group of Liver Surgery (ISGLS) definition and grading system for post-hepatectomy liver failure (PHLF) using the Comprehensive Complication Index (CCI), a standardized morbidity measure. Methods: Adult patients who underwent major hepatic resection between 2010-2020 were included from twelve international centers. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) INR >1.7 and serum bilirubin >3 mg/dL (Balzan), or 3) peak serum bilirubin >7 mg/dL (Mullen). We compared the 90-day mortality and major morbidity predicted by each definition. We then tabulated the distribution of CCI by ISGLS grade and used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grade. Results: Among 1654 patients, 444 (26.8%) met ISGLS PHLF criteria. Of the three PHLF definitions, the ISGLS definition had the highest AUC (0.72) and sensitivity (69.4) for prediction of 90-day mortality. Patients with ISGLS PHLF grades B and C were at increased odds of CCI>40 (Grade B OR 3.7; 95% CI: 2.0-6.9; and Grade C OR 96.1; 95% CI: 45.8-201.3) and 90-day mortality (Grade B OR 2.8; 95% CI: 1.0-7.4; and Grade C OR 108.0; 95% CI: 53.3, 218.7). ISGLS grade A PHLF was not associated with CCI>40 or 90-day mortality (Table 1). Conclusions: In this diverse, international cohort of patients undergoing major hepatectomy, ISGLS grade A was not associated with significant morbidity or mortality, calling into question the current classification of patients in this group as having clinically significant PHLF.FP08.06_Table 1Comparison of Morbidity and Mortality by ISGLS Grade (n=1654)No ISGLS PHLF n=1210ISGLS A n=287ISGLS B n=103ISGLS C n=54CCI, median (IQR)0 (0-20.9)8.7 (0-26.2)27.6 (20.9-35.9)100 (44.9-100)P<0.001 CCI: 0672 (55.5)138 (48.1)0 (0)0 (0) CCI: 1-20110 (9.1)21 (7.3)12 (11.7)0 (0) CCI: 20-40375 (31.0)111 (38.7)76 (73.8)10 (18.5) CCI: 40-6032 (2.6)9 (3.1)14 (13.6)9 (16.7) CCI: 60-802 (0.2)0 (0)0 (0)1 (1.9) CCI: 80-10019 (1.6)8 (2.8)1 (0.97)34 (63.0)OR for CCI>40 (95% CI)-1.37 (0.78-2.41)3.72 (2.02-6.87)96.05 (45.84-201.27)AUC=0.72OR for 90-day mortality (95% CI)-1.75 (0.80-3.83)2.76 (1.02-7.43)108.00 (53.33-218.72)AUC=0.78 Open table in a new tab

Randomised controlled trial to evaluate a new sealant to prevent biliary fistula in liver surgery: should we reconsider bile leak classification?

Background: Biliary fistula (BF) is the most common post hepatectomy complication. Different definitions have been proposed. The International Study Group of Liver Surgery (ISGLS) definition is the most used. The definition adopted in Humanitas Research Hospital (HRH) defines BF as bilirubin concentration in the drain fluid greater than 10 mg/dL on or after POD 3. Various topical haemostatic agents have been developed, their usefulness in preventing BF remains unclear and needs to be assessed. Purpose: First endpoint: assess the clinical benefit of using Hemopatch to prevent post-operative BF. Secondary endpoint: evaluate the clinical impact of the two definitions. Methods: We designed a randomized controlled study on 220 patients: 110 Hemopatch group (group-A) and 110 standard group (group-B), who underwent hepatic resection from 2018 to 2020. All patients were drained. Drains were removed with drain bilirubin concentration less than 10 mg/dL on POD 7. Results: BF (ISGLS definition) occurred in 139(63.5%) patients, 67(60.9%) in group-B and 72(66.1%) in group-A (P = 0,515). One-hundred- twenty fistulas (54.5%) were grade A, 18(9%) grade B, 1(0.5%) grade C. Considering HRH definition, BF occurred in 19(8.7%) patients, 6(5.5%) in group-B and 13(11.9%) in group-A(P=0.144). Sixteen (84.2%) were treated conservatively, 2(10.5%) performed ERCP, 1(5.3%) underwent relaparotomy. At multivariate analysis the only factor associated with BF increased risk was transection of the main portal branch (OR=54.35; P=0.026). Conclusions: Hemopatch does not reduce the incidence of biliary fistula, considering both the ISGLS and HRH definition. The different rate of BF in the two classification may lead to reconsider its definition.

Primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma

Purpose: The aim of this study was to investigate the incidence and risk factors of primary and secondary LF after major liver resection for pCCA. Method: All patients who underwent a major liver resection for suspected pCCA between 2000 and 2020 at two tertiary-referral hospitals were included. LF was defined according to the International Study Group for Liver Surgery (ISGLS) criteria and only grade B/C was considered clinically relevant. Primary LF was defined as failure without any underlying postoperative cause, and secondary as LF with an onset after an underlying postoperative complication as a cause. Results: The incidence of LF and 90-day mortality were 20.9% and 17.0% in the 253 included patients. The incidences of primary LF was 9.1% and secondary 11.9%. Abdominal sepsis, portal vein thrombosis, and arterial thrombosis were the most frequent causes. The absence of preoperative remnant liver assessment and blood loss were independent risk factors for primary LF. Independent risk factors for secondary LF were ECOG performance status, percutaneous biliary drainage, and preoperative cholangitis. Conclusion: LF after major liver resection for pCCA occurred in one of every five patients. Preoperative assessment of the remnant liver seems essential to avoid primary LF with concomitant postoperative mortality.

The role of hepatobiliary scintigraphy combined with spect/ct in predicting severity of liver failure before major hepatectomy: a single-center pilot study

Hepatobiliary scintigraphy (HBS) has been demonstrated to predict post-hepatectomy liver failure (PHLF). However, existing cutoff values for future liver remnant function (FLR-F) were previously set according to the “50–50 criteria” PHLF definition. Methods of calculation and fields of application in liver surgery have changed in the meantime. The aim of this study was to demonstrate the role of HBS combined with single photon emission computed tomography (SPECT/CT) in predicting severity of PHLF, according to the International Study Group of Liver Surgery (ISGLS). All patients submitted to major hepatectomy with preoperative HBS-SPECT/CT between November 2016 and December 2019, were analyzed. Patients were resected according to hepatic volumetry. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoffs of FLR function for predicting PHLF according to ISGLS definition and grading. Of the 38 patients enrolled, 26 were submitted to one-stage hepatectomy (living liver donors = 4) and 12 to two-stage procedures (portal vein embolization = 4, ALPPS = 8). Overall, 18 patients developed PHLF according to ISGLS criteria: 12 of grade A (no change in the patient’s clinical management) and 6 of grade B (change in clinical management). ROC analysis established increasingly higher cutoffs of FLR-F for predicting PHLF according to the “50–50 criteria”, ISGLS grade B and ISGLS grade A/B, respectively. HBS with SPECT/CT may help to assess severity of PHLF following major hepatectomy. Prospective multicenter trials are needed to confirm the effective role of HBS-SPECT/CT in liver surgery.

Nomogram for prediction of the international study Group of Liver Surgery (ISGLS) grade B/C Posthepatectomy liver failure in HBV-related hepatocellular carcinoma patients: an external validation and prospective application study

BackgroundTo develop a nomogram for predicting the International Study Group of Liver Surgery (ISGLS) grade B/C posthepatectomy liver failure (PHLF) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients.MethodsPatients initially treated with hepatectomy were included. Univariate regression analysis and stochastic forest algorithm were applied to extract the core indicators and reduce redundancy bias. The nomogram was then constructed by using multivariate logistic regression, and validated in internal and external cohorts, and a prospective clinical application.ResultsThere were 900, 300 and 387 participants in training, internal and external validation cohorts, with the morbidity of grade B/C PHLF were 13.5, 11.0 and 20.2%, respectively. The nomogram was generated by integrating preoperative total bilirubin, platelet count, prealbumin, aspartate aminotransferase, prothrombin time and standard future liver remnant volume, then achieved good prediction performance in training (AUC = 0.868, 95%CI = 0.836–0.900), internal validation (AUC = 0.868, 95%CI = 0.811–0.926) and external validation cohorts (AUC = 0.820, 95%CI = 0.756–0.861), with well-fitted calibration curves. Negative predictive values were significantly higher than positive predictive values in training cohort (97.6% vs. 33.0%), internal validation cohort (97.4% vs. 25.9%) and external validation cohort (94.3% vs. 41.1%), respectively. Patients who had a nomogram score < 169 or ≧169 were considered to have low or high risk of grade B/C PHLF. Prospective application of the nomogram accurately predicted grade B/C PHLF in clinical practise.ConclusionsThe nomogram has a good performance in predicting ISGLS grade B/C PHLF in HBV-related HCC patients and determining appropriate candidates for hepatectomy.

Development and validation of the bile leakage grading criterion in patients following Roux-en-Y hepaticojejunostomy

The present research aimed to propose a severity grading criterion for bile leakage in pediatric patients after Roux-en-Y hepaticojejunostomy for choledochal cysts. Despite a bile leakage classification system from the International Study Group of Liver Surgery (ISGLS) has been developed, a commonly used grading system for pediatric patients after Roux-en-Y hepaticojejunostomy has not yet been established. A review of clinical, laboratory, and ultrasonographic parameters were used to develop a grading system for classifying the severity of bile leakage. A total of 267 patients with bile leakage were retrospectively assessed to review the system. We developed a grading system for bile leakage severity for use in pediatric patients following Roux-en-Y hepaticojejunostomy. By applying the criteria to 267 patients, grade I, II, or III bile leakage was determined in 103 patients (8.7%), 115 patients (9.8%), and 49 patients (4.2%) patients, respectively. The most severe bile leakage grade (grade III), was associated with significantly higher γ-glutamyl transpeptidase and amylase levels, greater drain fluid output, more intensive care unit (ICU) admissions, and longer postoperative hospital stay. Interestingly, patients with grade II leakage who underwent reoperation had significantly more ICU admissions, longer postoperative hospital stays (p<0.05), and higher overall hospitalization cost (p<0.05) compared with those who underwent conservation management. Of the patients with bile duct stricture and common bile duct (CBD) stones, there were no differences among the different grades of postoperative bile leakage. The proposed bile leakage criteria may optimize objective diagnosis and therapeutic modalities.

IMPACT OF EXTENDED LIVING DONOR CRITERIA ON DONOR SAFETY IN LIVING DONOR LIVER TRANSPLANTATION

Introduction: Donor safety has been the primary focus of transplant programs that perform living donor liver transplantation (LDLT) and major living donor complications could be avoidable under the strict selection criteria of living donors. Recently, strict donor selection criteria has been modified to expand the donor pool in LDLT but the concept for extended donor is not clearly defined yet. Herein, we describe out center’s experience for extended criteria donors in LDLT focusing on donor safety. Materials and Methods: We retrospectively reviewed the outcomes of 424 living donor right hepatectomy (LDRH) including 105 extended criteria donors who performed at our institution from January 2010 to June 2019. Extended Donor criteria was defined as follows; 1) old donor (age >40 years) with remnant liver volume of <35%, 2) young donor (age ≤40 years) with remnant liver volume <29% and minimal fatty change (<15%), 3) young donor with mild hepatosteatosis (15%-30%) and remnant liver volume of < 35%. The outcomes in extended living donors were compared with those in living donors using conventional criteria focusing on donor safety. Posthepatectomy liver failure (PHLF) was defined according to the International Study Group of Liver Surgery (ISGLS) criteria. We also included statistical analysis of risk factors that are related to PHLF. Results: PHLF occurred in 43 donors (10.1%) and most cases were grade A except one case in conventional donor group (grade B) and PHLF did not occur more frequently in extended donor group. (7.6% vs. 11.0% % P = 0.32) and the incidence of major complications requiring radiological or surgical interventions did not differ between the 2 groups. Moreover, no difference in either posttransplant graft function or survival was apparent between the 2 groups. In multivariate logistic regression analyses, only major complication (OR, 3.002; 95% CI, 1.042-8,649; P = 0.04) was associated with PHLF but not related to our extended donor criteria. Conclusion: LDRH under our extended criteria could be performed to expand donor pools without adverse effects on donor safety.

Transient Biliary Fistula After Pancreatoduodenectomy Increases Risk of Biliary Anastomotic Stricture

BackgroundBiliary fistula after pancreatoduodenectomy (PD) is associated with significant morbidity and mortality. The aim of this study was to determine the risk of early postoperative biliary fistula for developing biliary anastomotic stricture after PD. MethodsRetrospective review of all PD performed for various indications at a single institution between 2013 and 2018. Postoperative biliary fistulae were graded according to the International Study Group of Liver Surgery (ISGLS) as grade A–C. Multivariable analysis was performed for all comparative patient subgroups. ResultsA total of 843 patients underwent PD for malignant (68%) and benign (32%) indications. Postoperative biliary fistula developed in 66 (8%) patients; ISGLS grade A in 29 (3%), grade B in 32 (4%), and grade C in 5 (0.6%). Ninety-day mortality was 3% (25 patients). The remaining 818 patients were evaluated with a median follow-up of 16 months (IQR, 5–32 months). Biliary anastomotic stricture developed in 41 (5%) patients at a median of 10 months (IQR, 6–18 months) postoperatively. Strictures were managed with percutaneous (27 patients, 66%) or endoscopic (14 patients, 34%) stenting. No biliary stricture required operative anastomotic revision. Postoperative biliary fistula (HR, 4.4; 95% CI, 2.0–9.9; P = 0.0002) was associated with biliary anastomotic stricture; an increased risk for biliary anastomotic stricture was seen in patients with grade A (HR, 6.4; 95% CI, 2.4–16.9; P = 0.0002) and grade B (HR, 3.6; 95% CI, 1.2–10.9; P = 0.02) postoperative biliary fistula. ConclusionPostoperative biliary fistula after pancreatoduodenectomy, including clinically insignificant, transient biliary fistula, is associated with an increased risk of a late biliary anastomotic stricture requiring stenting.

Albumin-Indocyanine Green Evaluation (ALICE) grade predicts bile leakage after hepatic resection.

We investigated the predictors of bile leakage after hepatic resection. The data of 270 consecutive patients who underwent curative hepatic resection in our institute between January, 2016 and April, 2019 were reviewed retrospectively. The patients were assigned to one of two groups according to the presence of bile leakage and the clinicopathological and surgical outcomes were analyzed. Bile leakage was defined by the International Study Group of Liver Surgery (ISGLS) grade. There were no hospital deaths. The median intraoperative blood loss volume was 167ml. Bile leakage occurred in 12 patients (4.4%), as ISGLS grade A leakage in 1 and as ISGLS grade B leakage in 11. The mean hospital stay was significantly longer for patients with bile leakage. High-risk procedures, hepatocellular carcinoma, and Albumin-Indocyanine Green Evaluation (ALICE) grade 3 were independent predictors of ISGLS grade B or C postoperative bile leakage. In patients with three high-risk factors, the incidence of bile leakage was 53.9%. Based on this retrospective analysis, high-risk procedures, hepatocellular carcinoma, and ALICE grade 3 were independent predictors of bile leakage in patients undergoing hepatic resection. Thus, special care must be taken during surgery to prevent bile leakage in patients with these risk factors.

The incidence and severity of post-hepatectomy bile leaks is affected by surgical indications, preoperative chemotherapy, and surgical procedures.

Bile leaks are one of the most common complications after liver resection. The International Study Group of Liver Surgery (ISGLS) established a uniform bile leak definition including a severity grading. However, a risk factor assessment according to ISGLS grading as well as the clinical implications has not been studied sufficiently so far. The incidence and grading of bile leaks according to ISGLS were prospectively documented in 501 consecutive liver resections between July 2012 and December 2016. A multivariate regression analysis was performed for risk factor assessment. Association with other surgical complications, 90-day mortality as well as length of hospital stay (LOS) was studied. The total rate of bile leaks in this cohort was 14.0%: 2.8% grade A, 8.0% grade B, and 3.2% grade C bile leaks were observed. Preoperative chemotherapy or biliary intervention, diagnosis of hilar cholangiocarcinoma, colorectal metastasis, central minor liver resection, major hepatectomy, extended hepatectomy or two-stage hepatectomy, were some of the risk factors leading to bile leaks. The multivariate regression analysis revealed that preoperative chemotherapy, major hepatectomy and biliodigestive reconstruction remained significant independent risk factors for bile leaks. Grade C bile leaks were associated not only with surgical site infection, but also with an increased 90-day mortality and prolonged LOS. The preoperative treatment as well as the surgical procedure had significant influence on the incidence and the severity of bile leaks. Grade C bile leaks were clinically most relevant, and led to significant increased LOS, rate of infection, and mortality.

The Analysis of Posthepatectomy Liver Failure Incidence and Risk Factors Among Right Liver Living Donors According to International Study Group of Liver Surgery Definition

AimThere is a well-known risk of the emergence of hepatic failure in living donor transplant cases on whom are performed a right donor hepatectomy (RDH). There are different prevalence ratios in literature on this phenomenon. In our study, we aim to depict the prevalence of hepatic failure and risk factors in our cases regarding the most recent description criteria related to hepatic failure. Patients and MethodsWe included right liver donor hepatectomy cases who fit the donor evaluation algorithm at the Dokuz Eylul University Liver Transplantation Unit between the period of June 2000 and September 2017. The patients were evaluated regarding preoperative data. Liver failure was defined according to the International Study Group of Liver Surgery (ISGLS) criteria. We also included statistical analysis of risk factors that are potentially related to liver failure. ResultsWe included a total of 276 patients. In 27 (9.7%) patients, we observed posthepatectomy liver failure (PHLF). In 26 (9.4%) patients, we observed Grade A liver failure; in 1 (0.3%) patient, we observed Grade B liver failure. We did not observe any Grade C hepatic failure. In patients with hepatic failure, we observed a significantly longer period of hospitalization (P = .007). Old age (odds ratio = 1.065, 95% confidence interval, 1.135–29.108, P = .035) and preoperatory red blood cell (RBC) transfusion (odds ratio = 5.749, 95% confidence interval, 1.019–1.113, P = .005) were shown as independent risk factors for PHLF. ConclusionPosthepatectomy liver failure is a vital complication of RDH. The risk can be decreased by careful selection of donor candidates. Elderly donor candidates and intraoperative RBC are independent risk factors for PHLF.

Risk factors of liver dysfunction for donor after extended right lobe graft donation

Introduction: Extended right lobe graft are often used in living donor liver transplantation(LDLT), in the donors with sufficient future liver remnant (FLR) volume. The aim of this study is to review retrospectively and to find risk factors of liver dysfunction for donor after extended right lobe graft donation. Method: From November 2005 to May 2018, a total of 52 living liver donors who underwent extended right lobectomy were included in this study.The subjects were divided into 2 groups.The hazard group was defined as the donors showing at least one of the following criteria:(1)postoperative serum peak bilirubin > 3.0mg/dL; (2) postoperative peak INR > 2.0, (3) posthepatectomy liver failure(PHLF) grade B or C of International Study Group of Liver Surgery(ISGLS), (4) ascites > 500cc on or after pod 5. Other donors with no criteria mentioned above were included in the safety group. Result: In hazard group, they had smaller volume of left lateral section(LLS) compared to safety group and the ratio of left liver volume(LLV) and left lateral section volume(LLSV) to total liver volume (TLV) in hazard group were smaller than in safety group. The mean and median values of the ratio of LLV to TLV(LLV/TLV); 38%, and the ratio of LLSV to TLV(LLSV/TLV); 20%, were used as the cut-off value. In hazard group, there were more patients whose LLV/TLV was less than 38% and whose LLSV/TLV was less than 20%. Using each cut-off values regarded as risk factors, three groups were categorized. This indicates that donors with smaller LLV/TLV or/and LLSV/TLV are more prone to liver dysfunction. Conclusion: The extent of donor hepatectomy must be contemplated based on a careful preoperative evaluation, including the volumetry. In this study, the LLV/TLV less than 38% and/or LLSV/TLV less than 20% were the major risk factors for postoperative liver dysfunction.

Analysis of the international study group of hepatic surgery definitions of typical complications after liver surgery

Background: The International Study Group of Liver Surgery (ISGLS) established the first internationally standardized definitions and grading for posthepatectomy hemorrhage (PHH), posthepatic liver failure (PHLF) and bile leakage. We aimed to evaluate and validate these new definitions in a center. Methods: 415 patients underwent hepatic surgery between 2004 and 2014. Uni- and multivariate analyses were made for correlations of PHH, PHLF and bile leakage with perioperative parameters and mortality. Results: 25 (6.1%) patients developed a PHH Grade A, 3 (0.7%) patients a PHH Grade B and one (0.2%) patient a PHH Grade C. 23 (5.5%) patients had a PHLF Grade A, 24 (5.8%) patients a PHLF Grade B and 7 patients (1.6%) a PHLF Grade C. Bile leakage Grade A occurred in 10 (2.4%) patients, bile leakage Grade B occurred in 24 (5.8%) patients, and bile leakage Grade C occurred in 7 (1.6%) patients. Mortality was significantly increased in patients with PPH Grades B and C and in patients with PHLF Grades A, B, and C. Three (42.9%) patients with bile leakage Grade C died. Conclusion: Our data indicate that the new definitions correlate well with mortality and duration of hospital stay.

Interstage assessment of remnant liver function in ALPPS using hepatobiliary scintigraphy: introduction of the HIBA index

Background: ALPPS remains controversial given the high rate of liver-related mortality after stage-2. Hepatobiliary scintigraphy (HBS) combined with single photon emission computed tomography (SPECT) could accurately estimates future liver remnant (FLR) function. Our aim was to evaluate interstage liver function in ALPPS using HBS and whether this may help to predict posthepatectomy liver failure (PHLF). Methods: Between 2011 and 2016, 20/39 patients (51.3%) underwent SPECT-HBS before ALPPS stage-2 for primary (n=3) or secondary liver tumors (n=17). PHLF was defined by the International Study Group of Liver Surgery (ISGLS) criteria, 50-50 criteria or peak bilirubin >7 mg/dl. Grade A PHLF was excluded, as it requires no change in clinical management. Different HBS parameters were evaluated. Results: Interstagely, 3 HBS parameters differed significantly between patients with (n=4) and without PHLF (n=16) after stage-2. Among these, the HIBA-index best predicted PHLF, with a cutoff value of 15%. The risk of PHLF in patients with HIBA-index<15% was 80%, whereas no patient withHIBA-index ≥15% developed PHLF Conclusion: Interstage HBS could help to predict clinically significant PHLF after ALPPS stage-2. An HIBA-index cutoff of 15% seemed to give the best diagnostic performance. While further studies are needed to confirm our findings, the routine application of this non-invasive low-cost exam could facilitate decision-making in institutions performing ALPPS

Analysis of the International Study Group of Hepatic Surgery definitions of typical complications after liver surgery

Background: The International Study Group of Liver Surgery (ISGLS) established the first internationally standardized definitions and grading for posthepatectomy hemorrhage (PHH), posthepatic liver failure (PHLF) and bile leakage. We aimed to evaluate and validate these new definitions in a center. Methods: 415 patients underwent hepatic surgery between 2004 and 2014. Uni- and multivariate analyses were made for correlations of PHH, PHLF and bile leakage with perioperative parameters and mortality. Results: 25 (6.1%) patients developed a PHH Grade A, 3 (0.7%) patients a PHH Grade B and one (0.2%) patient a PHH Grade C. 23 (5.5%) patients had a PHLF Grade A, 24 (5.8%) patients a PHLF Grade B and 7 patients (1.6%) a PHLF Grade C. Bile leakage Grade A occurred in 10 (2.4%) patients, bile leakage Grade B occurred in 24 (5.8%) patients, and bile leakage Grade C occurred in 7 (1.6%) patients. Mortality was significantly increased in patients with PPH Grades B and C and in patients with PHLF Grades A, B, and C. Three (42.9%) patients with bile leakage Grade C died. Conclusion: Our data indicate that the new definitions correlate well with mortality and duration of hospital stay.

Post-hepatectomy liver failure in cirrhotic patients undergoing extensive liver resections – An Asian experience

Aim: To determine the prevalence of post-hepatectomy liver failure/insufficiency (PHLF/I) in extensive hepatic resections for hepatocellular carcinoma (HCC) and to assess the predictive value of preoperative factors for post-hepatectomy liver failure or insufficiency (PHLF/I). Methods: A retrospective review of patients who underwent liver resections for HCC between 2001-2013 was conducted. Preoperative parameters were assessed and analyzed for their predictive value of PHLF/I. Definitions used included the 50-50, International Study Group of Liver Surgery (ISGLS) and Memorial Sloan Kettering Cancer Centre (MSKCC) criteria. Results: 848 patients underwent liver resections for HCC between 2001-2013, of which 157 underwent right hepatectomy (RH) and extended right hepatectomy (ERH). The prevalence of PHLF/I was 7%, 41% and 28% for the 50-50, ISGLS and MSKCC criteria, respectively. There were no significant differences in PHLF/I between RH and ERH. Model for End-Stage Liver Disease (MELD) score and bilirubin were the strongest independent predictors for PHLF/I based on the 50-50 and ISGLS/MSKCC criteria, respectively. Predictive models were developed for each criteria with multiple logistic regression. Conclusion: MELD score, bilirubin, alpha-fetoprotein and platelet count had significant predictive value for PHLF/I (all p< 0.05). A composite score based on these factors can guide physicians to better select patients undergoing extensive resections to minimize PHLF.

Impaired kinetic growth rate and increased posthepatectomy liver failure rates after ALPPS for colorectal liver metastasis

Introduction: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a fairly new operative technique, which pushes the limits of resectability of liver tumors. It has especially become a valid treatment option for patients with advanced colorectal liver metastasis (CRLM). It has the potential to facilitate much faster hypertrophy of the future liver remnant (FLR), thereby increasing resectability of previously unresectable CRLM, yet posthepatectomy liver failure (PHLF) as well as impaired hypertrophy of the FLR may still pose a problem in this setting. Methods: To further investigate and understand these issues, we retrospectively analyzed all consecutive patients undergoing ALPPS for resection of CRLM between January 2013 and March 2017 in search for potential risk factors. Cases of posthepatectomy liver failure (PHLF) were graded according to the consensus of the International Study Group of Liver Surgery (ISGLS). The kinetic growth rate (KGR, ml/d) was calculated as mean volume increase per day between the two stages of the ALPPS procedure. Results: A total of 22 patients were included in the analysis. Seven patients (31.8%) developed PHLF (all grade B). Multivariate regression analysis showed a statistically significant association between preoperative chemotherapy involving EGFR inhibitors (cetuximab, panitumumab) and grade B PHLF (p< 0.01) as well as a reduced KGR (p< 0.05). Conclusions: Impaired liver regeneration following EGFR signaling inhibition has been shown in rodents, but not in the clinical setting as of yet. Pending further investigation of these phenomena, we suggest caution when considering ALPPS in this subgroup of patients.

Risk factors of bile leak and its consequence – single center study of 501 consecutive liver resections

Bile leaks are one of the most common complications after liver resection. The International Study Group of Liver Surgery (ISGLS) established a uniform bile leak definition including a severity grading. The goal of our analysis was to assess risk factors discriminatingly for the three ISGLS bile leak grades. The study included a total of 501 liver resections between July 2012 and December 2016. The total rate of bile leaks was 14.0% (grade A/B/C, 2.8/8.0/3.2%). Univariate and a multivariate regression analyses were performed for risk factor assessment. Patients that had had chemotherapy recently before liver resection suffered more often from grade A and B bile leaks. Patients with a biliary disease (gall-bladder carcinoma, cholangiocarcinoma or benign biliary diseases) and patients who had required biliary interventions (ERC or PTC) before the operation and who usually received a bilio-digestive reconstruction, had an increased risk for grade C leaks. Major liver resections were associated with increased rates of all three grades. In univariate but not in multivariate analysis, staged hepatectomies (ALPPS) were a risk factor for bile leaks and liver fibrosis had a protective effect on the occurrence of bile leaks. Patients with all three grades of bile leaks had on average an increased length of hospital-stay. Mortality and surgical site infections were significantly increased in grad C leaks, only. Grad C bile leaks are clinically most relevant and are associated with malign and benign biliary diseases and preoperative biliary interventions as well as bilio-digesitve anastomoses. Especially these patient groups require increased awareness peri-operatively.

Post-hepatectomy liver failure is associated with tumor recurrence in patients with hilar cholangiocarcinoma

Purpose: For curative resection of hilar cholangiocarcinoma (HCCA), major hepatectomy with a high risk of hepatic insufficiency is often performed in combination with extrahepatic bile duct resection. However, the association between post-hepatectomy liver failure (PHLF) and oncologic outcomes in HCCA patients has not been described. Materials and methods: Between October 2001 and December 2013, 105 patients who underwent radical extrahepatic bile duct resection and major hepatectomy for HCCA were included in this study. Clinically relevant PHLF was defined as liver failure corresponding to grade B or C of the International Study Group of Liver Surgery (ISGLS) criteria. Results: The rates of 1-, 3-, and 5-year recurrence-free survival (RFS) were 49.8%, 19.5%, and 19.5%, respectively, for patients with PHLF (n = 47) and 73.9%, 47.3%, and 41.9%, respectively, for those without PHLF (n = 58) (P = 0.001). In addition, there was significant difference in overall survival (OS) between the two groups (P < 0.001). In multivariate analysis, PHLF was a significant prognostic factor for RFS (hazard ratio [HR] 2.320, 95% confidence interval [CI] 1.341 - 4.012; P = 0.003) and OS (HR 2.000, 95% CI 1.181 - 3.379; P = 0.010). Patients with PHLF had a higher cumulative incidence at all recurrence sites, with intrahepatic recurrence showing statistical significance (P = 0.039). Conclusion: PHLF is an independent prognostic factor for recurrence and survival after curative resection in HCCA patients. In particular, PHLF is strongly associated with intrahepatic recurrence.