International Study Group Of Liver Surgery Research Articles

The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study.

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.

The impact of post-hepatectomy liver failure on long-term survival after liver resection for perihilar cholangiocarcinoma

BackgroundAlthough post-hepatectomy liver failure (PHLF) can accurately predict short-term mortality of liver resection for perihilar cholangiocarcinoma (pCCA), its significance in predicting long-term overall survival (OS) is still uncertain. MethodsRetrospective analysis was performed on patients with pCCA who underwent liver resection between October 2013 and December 2018. The patients were divided into 3 groups; No PHF, PHLF (all grade) and grade B/C PHLF according to The International Study Group of Liver Surgery (ISGLS) criteria. ResultsA total of 177 patients were enrolled, 65 (36.7%) had PHLF; 25 (14.1%) had grade A, and 40 (22.6%) had grade B/C. Prior to surgery, patients with PHLF showed significantly greater bilirubin levels and CA 19-9 level than those without (11.5 vs 6.7 mg/dL, p = 0.002 and 232.4 vs 85.9 U/mL, p = 0.005, respectively). Additionally, pre-operative future liver remnant volume in PHLF group was lower than no PHLF group significantly (39.6% vs 43.5%, p = 0.006). Major complication and 90-day mortality were higher in PHLF group than no PHLF group (69.2% vs 20.5%, p < 0.001 and 29.2% vs 3.6%, p < 0.001, respectively). The OS in both grade A PHLF and grade B/C PHLF was significantly worse compared to no PHLF, with median survival times of 8.4, 3.3, and 19.2 months, respectively (p < 0.001 and p < 0.001, respectively). Multivariable analysis revealed that PHLF was independently prognostic factor for long-term survival. ConclusionTo achieve negative resection margin, the surgical resection in pCCA was aggressive, however this increased the risk of PHLF, which also affects the OS. Consequently, it is necessary for establishing a balance between aggressive surgery and PHLF.

Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis

This study aims to clarify the perioperative risk factors and short-term prognosis of central bisectionectomy (CB) for hepatocellular carcinoma (HCC). Surgical data from 142 selected patients out of 171 HCC patients who underwent anatomical CB (H458) between 2005 and 2020 were collected from 17 expert institutions in a single-arm retrospective study. Morbidities recorded by the International Study Group of Liver Surgery (ISGLS) from grade BC post-hepatectomy liver failure (PHLF) and bile leakage (PHBL), or complications requiring intervention were observed in 37% of patients. A multivariate analysis showed that increased blood loss (iBL) > 1500 mL from PHLF (risk ratio [RR]: 2.79), albumin level < 4 g/dL for PHBL (RR, 2.99), involvement of segment 1, a large size > 6 cm, or compression of the hepatic venous confluence or cava by HCC for all severe complications (RR: 5.67, 3.75, 6.51, and 8.95, respectively) (p < 0.05) were significant parameters. Four patients (3%) died from PHLF. HCC recurred in 50% of 138 surviving patients. The three-year recurrence-free and overall survival rates were 48% and 81%, respectively. Large tumor size and surrounding tumor involvement, or compression of major vasculatures and the related iBL > 1500 mL were independent risk factors for severe morbidities in patients with HCC undergoing CB.

A critical appraisal of the ISGLS definition of biliary leakage after liver resection

PurposeThe International Study Group of Liver Surgery (ISGLS) defined post-hepatectomy biliary leakage as drain/serum bilirubin ratio > 3 at day 3 or the interventional/surgical revision due to biliary peritonitis. We investigated the definition’s applicability.MethodsA retrospective evaluation of all liver resections over a 6-year period was performed. ROC analyses were performed for drain/serum bilirubin ratios on days 1, 2, and 3 including grade A to C (analysis I) and grade B and C biliary leakages (analysis II) to test specific cutoff values.ResultsA total of 576 patients were included. One hundred nine (18.9%) postoperative bile leakages occurred (19.6% of the whole population grade A, 16.5% grade B/C). Areas under the curve (AUC) for analysis I were 0.841 (day 1), 0.846 (day 2), and 0.734 (day 3). The highest sensitivity (78% on day 1/77% on day 2) and specificity (78% on day 1/79% on day 2) in analysis I were obtained for a drain/serum bilirubin ratio of 2.0. AUCs for analysis II were similar: 0.788 (day 1), 0.791 (day 2), and 0.650 (day 3). The highest sensitivity (73% on day 1/71% on day 2) and specificity (74% on day 1/76% on day 2) in analysis II were detected for a drain/serum bilirubin ratio of 2.0 on postoperative day 2.ConclusionBiliary leakages should be defined if the drain/serum bilirubin ratio is > 2.0 on postoperative day 2.

Developing and validating a nomogram based on skeletal muscle index and clinical scoring system for prediction of liver failure after hepatectomy.

Hepatectomy is the preferred treatment for patients with liver tumors. Post-hepatectomy liver failure (PHLF) remains one of the most fatal postoperative complications. We aim to explore the risk factors of PHLF and create a nomogram for early prediction of PHLF. We retrospectively analyzed patients undergoing hepatectomy at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University between 2015 and 2022, and the patients were divided into training and internal validation cohorts at an 8:2 ratio randomly. The patients undergoing liver resection from the Affiliated Huaian Hospital of Xuzhou Medical University worked as external validation. Then, a nomogram was developed which was based on multivariate analyses to calculate the risk of PHLF. The area under the ROC curve (AUROC) and Hosmer -Lemeshow test was used to evaluate the prediction effect of the model. A total of 421 eligible patients were included in our study. Four preoperative variables were identified after multivariate analysis as follows, ASA (American Society of Anesthesiologists) score, Child-Pugh score, SMI (Skeletal muscle index), and MELD (Model for end-stage liver disease) score as independent predictors of PHLF. The area under the ROC curve of the predictive model in the training, internal, and external validation cohorts were 0.89, 0.82, and 0.89. Hosmer -Lemeshow P values in the training, internal, and external validation cohorts were 0.91, 0.22, and 0.15. The Calibration curve confirmed that our nomogram prediction results were in accurate agreement with the actual occurrence of PHLF. We construct a nomogram to predict the grade B/C PHLF of ISGLS (International Study Group of Liver Surgery) in patients who underwent hepatic resection based on risk factors. This tool can provide a visual and accurate preoperative prediction of the grade B/C PHLF and guide the next step of clinical decision-making.

Assessment of serum and drain fluid bilirubin concentrations in liver transplantation patients

Bile leakage is a major complication after liver transplantation and remains as a significant source of morbidity and mortality. In 2011, the International Study Group of Liver Surgery (ISGLS) defined bile leakage as a drain/serum bilirubin ratio ≥3. However, to our knowledge there is no literature assessing serum and drain bilirubin concentrations after liver transplantation. The aim of this study was to describe the natural postoperative changes in serum and drain fluid bilirubin concentrations in patients after liver transplantation. We included 32 patients who underwent liver transplantation at Kobe University Hospital from January 2007 to December 2020. We enrolled 34 living donors who had no complications as the control group. The recipient serum total/direct bilirubin concentration were higher compared with the donors from postoperative day (POD) 1 to 5 with a statistical difference (P < .05). The recipient drain/serum total bilirubin ratio was lower than donors on POD 3 (0.89 ± 0.07 vs 1.53 ± 0.07: P < .0001), which was also confirmed by the recipient drain/serum direct bilirubin ratio (0.64 ± 0.10 vs 1.18 ± 0.09: P < .0001). On POD 3, the drain fluid volume (647.38 ± 89.47 vs 113.43 ± 86.8 mL: P < .001) and serum total bilirubin concentration (6.73 ± 0.61 vs 1.23 ± 0.60 mg/dL: P < .001) was higher in the recipients than in donors. Categorized in 2 groups, the higher drain fluid volume and bilirubin concentration recipients showed lower drain/serum total bilirubin ratio compared with the other group (P=.03) CONCLUSION: The drain/serum bilirubin ratio in the transplanted patients could be calculated lower compared with the hepatectomy patients because of high drain fluid volume and hyperbilirubinemia. Great care should be taken when assessing the bile leakage in liver transplant recipients using the ISGLS definition.

A Nomogram Based on Preoperative Lab Tests, BMI, ICG-R15, and EHBF for the Prediction of Post-Hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background: Liver cancer is one of the most common malignant tumors, and worldwide, its incidence ranks sixth, and its morality third. Post-hepatectomy liver failure (PHLF) is the leading cause of death in patients who have undergone liver resection. This retrospective study investigated the risk factors for PHLF by predicting and constructing an index to evaluate the risk. This was achieved by combining the lab tests with an indocyanine green (ICG) clearance test. Methods: The study analyzed 1081 hepatocellular carcinoma (HCC) patients who had received liver resection at Sun Yat-sen University Cancer Center between 2005 and 2020. The patients were divided into a PHLF group (n = 113) and a non-PHLF group (n = 968), according to the International Study Group of Liver Surgery (ISGLS) criteria. Receiver operating characteristics (ROC) curves were then used to estimate the optimal cut-off values. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors. Finally, a nomogram was constructed where the calibration plot, the areas under the ROC curve (AUC), and the decision curve analysis (DCA) showed good predictive ability. Results: Correlation analysis revealed that body mass index (BMI) was positively correlated with ICG-R15 and with effective hepatic blood flow (EHBF). Univariate and multivariate logistics regression analysis revealed that BMI, ICG-R15, international normalized ratio (INR), tumor size, hepatic inflow occlusion (HIO) time, and operation method were independent predictive factors for PHLF. When these factors and EHBF were included in the nomogram, the nomogram showed a good predictive value, with a C-index of 0.773 (95% Confidence Interval [CI]: 0.729-0.818). The INR had the largest ROC areas (AUC INR = 0.661). Among the variables, ICG-R15 (AUC ICG-R15 = 0.604) and EHBF (AUC EHBF = 0.609) also showed good predictive power. Conclusions: The risk of PHLF in HCC patients can be precisely predicted by this model prior to the operation. By integrating EHBF into the model, HCC patients at higher risk for PHLF can be identified more effectively.

Lean body mass predicts postoperative liver failure in patients with hepatocellular carcinoma.

Post-hepatectomy liver failure (PHLF) is a severe complication of liver surgery in hepatocellular carcinoma (HCC) patients. Reduced lean body mass (LBM) decreases the immune activity and increases adverse clinical outcomes among cancer patients. We aimed to assess the association between LBM and PHLF in HCC patients. PHLF was defined and graded based on the International Study Group of Liver Surgery (ISGLS) criteria. Patients with Grade B or Grade C were included in PHLF ⩾ Grade B group, while others in PHLF < Grade B group. LBM was measured via preoperative computed tomography images. Binary logistic regression was applied for investigating the association between LBM and PHLF. The receiver operating characteristic curve was used to identify potential cut-off values and assess the predictive ability of the measured variables. The PHLF ⩾ Grade B group had significantly lower LBM levels (means ± standard deviation: 57.0 ± 14.1) than PHLF < Grade B group (67.2 ± 15.7) (p< 0.001). After controlling other variables, LBM was an independent protective factor for PHLF ⩾ Grade B (Odds Ratio: 0.406, 95% confidence interval: 0.172-0.957, p= 0.039). The prevalence of PHLF ⩾ Grade B in each quartile of LBM was 29.4% (15/51), 25.5% (13/51), 19.2% (10/52) and 4.0% (2/50), respectively (ptrend< 0.001). LBM might be a protective factor for PHLF in HCC patients. Our findings might help to develop a novel strategy to reduce the occurrence of hepatic dysfunction following major liver resection. Multicentric prospective studies and further molecular biologic investigation are needed.

Effect of postoperative administration of nafamostat mesilate on posthepatectomy liver failure

To investigate whether the administration of nafamostat mesilate (NM) reduces the risk of posthepatectomy liver failure (PHLF) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). We retrospectively reviewed the 1114 patients who underwent hepatectomy for HCC between 2004 and 2020. NM was selectively administered to patients undergoing major hepatectomy with an estimated blood loss of >500mL. NM group was administered via intravenous of 20mg of NM from immediately after surgery until postoperative day 4. We performed 1:1 propensity score matching and included 56 patients in each group. PHLF was defined according to the International Study Group of Liver Surgery (ISGLS). The incidence of PHLF was lower in the NM group than control group (P=0.018). The mean peak total bilirubin (P=0.006), aspartate transaminase (P=0.018), and alanine aminotransferase (P=0.018) levels postoperatively were significantly lower in the NM group. The mean hospital stays (P=0.012) and major complication rate (P=0.023) were also significantly lower in the NM group. Prophylactic administration of NM reduced the risks of complication and decreased the frequency of PHLF after hepatectomy. A further prospective study is needed to verify our findings.

Functional assessment of liver regeneration after major hepatectomy.

BackgroundLiver regeneration is crucial to restore the functional liver mass after liver resection. The aim of this study was to evaluate the early postoperative changes in remnant liver function, volume and liver stiffness after major liver resection and their correlation with postoperative outcomes.MethodsPatients undergoing major liver resection (≥3 segments) between February and November 2018 underwent both functional assessment using technetium-99m mebrofenin hepatobiliary scintigraphy (HBS) and CT-volumetry of the (future) remnant liver on preoperative day 1, the 5th postoperative day, and 4–6 weeks after resection. At the same time points, patients underwent transient elastography (TE) for the assessment of liver stiffness. Severe postoperative complications (Clavien-Dindo ≥ 3A) and mortality were correlated with the functional and volumetric increases of the remnant liver. Liver failure was graded according to the International Study Group of Liver Surgery (ISGLS) criteria.ResultsA total of 18 patients were included of whom 10 (56%) had severe complications and one patient (5%) developed liver failure. Function and volume of the remnant liver had increased by the 5th postoperative day from 6.9 (5.4–10.9) to 9.6 (6.7–13.8) %/min/m2, P=0.004 and from 795.5 (538.3–1,037.5) to 1,080.0 (854.0–1,283.3) mL, P<0.001, respectively. After 4–6 weeks, remnant liver volume had further increased [from 1,080.0 (854.0–1,283.3) to 1,222.0 (1,016.0–1,380.5) mL, P=0.035], however, liver function did not show any significant, further increase [from 9.6 (6.7–13.8) to 10.9 (8.8–13.6) %/min/m2, P=0.177]. Liver elasticity of the future remnant liver (FRL) increased [from 10.8 (5.7–18.7) to 17.5 (12.4–22.6) kPa, P=0.018] and gradually recovered after 4–6 weeks to a median of 10.9 (5.7–18.8) kPa (T3 vs. T4, P=0.079). Patients who had severe postoperative complications did not show a significant increase in liver function on the 5th postoperative day (P=0.203), despite increase of volume (P<0.01).ConclusionsFunctional regeneration of the remnant liver predominantly occurs during the first 5 days after resection. In case of severe complications, functional regeneration is delayed, in contrast to volume increase.

Impact of post-hepatectomy liver failure on morbidity and short- and long-term survival after major hepatectomy.

BackgroundPost-hepatectomy liver failure (PHLF) is one of the most serious postoperative complications after hepatectomy. The aim of this study was to assess the impact of the International Study Group of Liver Surgery (ISGLS) definition of PHLF on morbidity and short- and long-term survival after major hepatectomy.MethodsThis was a retrospective review of all patients who underwent major hepatectomy (three or more liver segments) for various liver tumours between 2010 and 2018 at two Swedish tertiary centres for hepatopancreatobiliary surgery. Descriptive statistics, regression models, and survival analyses were used.ResultsA total of 799 patients underwent major hepatectomy, of which 218 patients (27 per cent) developed ISGLS-defined PHLF, including 115 patients (14 per cent) with ISGLS grade A, 76 patients (10 per cent) with grade B, and 27 patients (3 per cent) with grade C. The presence of cirrhosis, perihilar cholangiocarcinoma, and gallbladder cancer, right-sided hemihepatectomy and trisectionectomy all significantly increased the risk of clinically relevant PHLF (grades B and C). Clinically relevant PHLF increased the risk of 90-day mortality and was associated with impaired long-term survival. ISGLS grade A had more major postoperative complications compared with no PHLF but failed to be an independent predictor of both 90-day mortality and long-term survival. The impact of PHLF grade B/C on long-term survival was no longer present in patients surviving the first 90 days after surgery.ConclusionsThe presently used ISGLS definition for PHLF should be reconsidered regarding mortality as only PHLF grade B/C was associated with a negative impact on short-term survival; however, even ISGLS grade A had clinical implications.

Validation of the ISGLS classification of bile leakage after pancreatic surgery: A rare but severe complication

IntroductionHepaticoenterostomy is an important step of reconstruction during hepatopancreatobiliary (HPB) surgery with a subsequent bile leakage rate of up to 5%. The International Study Group of Liver Surgery (ISGLS) proposed a severity grading system for defining bile leakage after HPB surgery, which has not been validated after pancreatic surgery in a large patient cohort. The present study aimed to validate the ISGLS definition for bile leakage in pancreatic surgery and to investigate the postoperative outcomes of bile leakage after pancreatic resections. Materials and methodsData from the prospectively maintained database for pancreas surgery were extracted for any type of pancreatectomy with hepaticoenterostomy between 2006 and 2019. The severity of bile leakage was graded according to the ISGLS definition. The influence of our standardized hepaticoenterostomy technique and of the complexity of the surgical procedure on the rate of clinically relevant bile leakages (B and C) were assessed in three different timeframes. ResultsBile leakage was detected in 152 of 5,300 patients (2.9%). Clinically relevant bile leakages included seventy patients with grade B and eighty-two patients with grade C bile leakages (46.1% and 53.9%, respectively). During the study period, the overall rate of bile leakage showed to be stable (from 3.5% to 2.4%). Patients with grade C bile leakage had a higher rate of postoperative wound infection (P < 0.001) and longer ICU stays and hospital stays compared to patients with grade B bile leakage (P = 0.03 and P < 0.001 respectively). These parameters were significantly higher in patients with late grade C bile leakage but were similar between patients with grade B bile leakage and early grade C bile leakage (<5th day POD). In the whole patients’ cohort, the 90-day mortality rate was 3.2% (174/5,300), with a rate of 25% in patients with bile leakage (38/152). ConclusionThe ISGLS classification is a valid method for classifying postoperative bile leak after pancreas surgery. Standardization of our hepaticoenterostomy technique resulted in a stable rate of bile leakage. Although rare, bile leakage following pancreas surgery is a severe complication that has a major impact on patient outcomes and contributes significantly to morbidity and mortality, even in the absence of POPF.

Preservation of the round ligament to accommodate transient portal hypertension after major hepatectomy

PurposePosthepatectomy liver failure (PHLF) remains a leading cause of death after extensive liver resection. Apart from the size and function of the remaining liver remnant, the development of postresection portal hypertension (pHT) plays a crucial role in the development of PHLF. We hypothesize that the umbilical vein in the preserved round ligament (RL) may recanalize in response to new-onset pHT after extended hepatectomy, thus providing a natural portosystemic shunt.MethodsIn this exploratory study, RL was preserved in 10 consecutive patients undergoing major liver resection. Postoperative imaging was pursued to obtain evidence of reopened umbilical vein in the RL. The postoperative course, including the occurrence of PHLF, as well as the rate of procedure-specific complications were recorded.ResultsNone of the 10 cases presented with an adverse event due to preservation of the RL. In 6 cases, postoperative imaging demonstrated reopening of the umbilical vein with hepatofugal flow in the RL. The rates of procedure-related surgical complications were lower than would be expected in this population; in particular, the rate of occurrence of PHLF as defined by the International Study Group of Liver Surgery (ISGLS) was low.ConclusionOur results support the theoretical concept of portosystemic pressure relief via a preserved umbilical vein after major liver surgery. As preservation of the RL is easily done, we suggest keeping it intact in extended hepatectomy cases and in patients with preexistent pHT.

Validation of the ISGLS Classification of Bile Leakage after Pancreatic Surgery: A Rare but Severe Complication

Introduction: Hepaticoenterostomy is an important step in hepatopancreatobiliary (HPB) surgery with a subsequent bile leakage (BL) rate of up to 5%. The International Study Group of Liver Surgery (ISGLS) proposed a grading system for BL after HPB surgery. This study aimed to validate this grading system for BL in pancreatic surgery (PS) and to investigate the postoperative outcomes of BL after PS. Methods: Data were extracted for any type of pancreatectomy with hepaticoenterostomy between 2006 and 2019. The BL was graded according to the ISGLS classification. The influence of our standardized hepaticoenterostomy technique and the complexity of the surgery on BL rate were assessed in different time frames. Results: BL was detected in 156 of 5,300 patients (2.9%, Table 1). During the study period, the overall rate of Type-B and C BL showed a slight reduction from 3.5% to 2.4%. Patients with Type-C BL had higher wound infection rate and longer ICU-stay. Patients with Type-C BL receiving late surgical revision (>5th day postoperative) had higher mortality rate compared to patients with Type-B and early Type-C BL (Table 2). Conclusion: The ISGLS classification is valid for classifying BL after PS. The BL rate is influenced by the complexity of surgery (Figure 1). Patients with early Type-C BL who undergo reoperation in the first five days have better outcomes than late onset Type-C BL patients. Although rare, BL following PS is a severe complication with a major impact on patient outcome contributing significantly to morbidity and mortality.Tabled 1EP02D-052Grade B(n= 70)Early grade C+(n= 39)Late grade C‡(n= 43)P-valuen (%) or median (range)Wound infection10 (14.3%)14 (35.9%)21 (48.9%)< 0.001Intervention (CT-guided drainage and/or PTCD)70 (100%)20 (51.3%)24 (55.8%)0.001Re-intubation14 (20%)12 (30.8%)16 (37.2%)0.16ICU stay (days)7 (0–76)10 (0–131)18 (2–173)<0.001*Hospital stay (days)40.5 (15–109)35 (9–182)43 (14–235)0.22∗30-day mortality9 (12.9%)7 (17.9%)14 (32.6 %)0.0390-day mortality13 (18.6%)9 (23.1%)16 (37.2%)0.08 Open table in a new tab

Using the Comprehensive Complication Index to Rethink the ISGLS Criteria for Post-hepatectomy Liver Failure in an International Cohort of Major Hepatectomies.

To compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication Index (CCI)" and 90-day mortality. PHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF. Adults who underwent major hepatectomies at twelve international centers (2010-2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades. Among 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2-7.2; grade C OR 137.0; 95% CI: 59.2-317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6-232.1). Grade A was not associated with CCI> 40 or 90-day mortality. In this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.

Direct Bilirubin in Drainage Fluid 3 days after Hepatectomy Is Useful for Detecting Severe Bile Leakage

Introduction: The International Study Group of Liver Surgery (ISGLS) definition of bile leakage is an elevated total bilirubin concentration in the drainage fluid after post-operative day (POD) 3, which has been widely accepted. However, there were no reports about direct bilirubin in drainage fluid to predict bile leakage. Methods: Data from 257 patients who underwent hepatectomy were retrospectively reviewed. The optimal cut-off value was investigated using receiver-operating characteristic curves. The predictive power of drainage fluid total bilirubin (dTB) and drainage fluid direct bilirubin (dDB) to predict bile leakage, which was defined using ISGLS grade B or grade C, were compared. Results: ISGLS grade B bile leakage occurred in 16 patients (6.2%). Area under the curve (AUC) of dDB was always higher than that of dTB on each POD. The AUC of dDB was >0.75 on PODs 2, 3, and 5, and then it increased with the increasing POD. The dDB on POD 5 showed the highest accuracy (0.91) and positive predictive value (PPV) (0.67), which was followed by dTB/serum total bilirubin (sTB) on POD 3 (accuracy, 0.91; PPV, 0.33). Because the PPV of dDB increased as the POD increased, dDB was better than dTB for predicting clinically significant bile leakage. dDB on POD 3 showed the highest negative predictive value (0.97). The positive likelihood of dDB increased and the negative likelihood of dDB decreased on the basis of the POD. Among patients with dTB/sTB ≤3 on POD 3, 19.1% of these patients had bile leakage when dDB was >0.44 on POD 3. Conclusions: Measurement of both dDB and dTB, which are easy to perform, can be used to effectively predict clinically significant bile leakage.

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

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. First endpoint: assess the clinical benefit of using Hemopatch to prevent post-operative BF. Secondary endpoint: evaluate the clinical impact of the two definitions. 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. 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). Hemopatch does not reduce the incidence of BF, considering both the ISGLS and HRH definition. The different rate of BF in the two classification may lead to reconsider its definition.

Comparison between preoperative two-dimensional shear wave elastography and indocyanine green clearance test for prediction of post-hepatectomy liver failure.

Post-hepatectomy liver failure (PHLF) is one of the most serious complications and major causes of liver resection mortality. The purpose of this study is to investigate and compare the performance of preoperative two-dimensional shear wave elastography (2D-SWE) and the indocyanine green (ICG) clearance test for the prediction of PHLF. A total of 172 consecutive patients who were undergoing major liver resection were prospectively identified. Patients were evaluated by preoperative 2D-SWE and ICG clearance test. According to the International Study Group of Liver Surgery (ISGLS) recommendations, No PHLF, PHLF A, PHLF B, and PHLF C group classifications were defined. The differences in liver stiffness value (LSV) and ICG retention rate at 15 minutes (ICGR15) among the different PHLF classifications were investigated. The performance of LSV and ICGR15 for diagnosing different classifications of PHLF was compared. PHLF occurred in 43 (25.0%) patients, and 24 (14.0%) patients were grade A, 14 (8.1%) were grade B, and 5 (2.9%) were grade C. Both LSV and ICGR15 of the PHLF C group were significantly higher than those of the No PHLF group (P=0.025, P=0.001, respectively). According to univariate and multivariate logistic regression analysis, LSV and ICGR15 were significantly related to PHLF (P=0.051, P=0.084, respectively). For diagnosis of ≥ PHLF A, ≥ PHLF B, and ≥ PHLF C, the areas under the receiver operating characteristic curve (AUCs) for 2D-SWE were 0.624 [95% confidence interval (CI): 0.536-0.712, P=0.015], 0.699 (95% CI: 0.576-0.821, P=0.005), and 0.831 (95% CI: 0.737-0.925, P=0.01), respectively. The AUCs of the ICG clearance test were 0.631 (95% CI: 0.542-0.721, P=0.01), 0.570 (95% CI: 0.436-0.704, P=0.32), and 0.717 (95% CI: 0.515-0.920, P=0.098), respectively. The AUC of LSV for the diagnosis of ≥ PHLF A was comparable to that of ICGR15 (P=0.17). The AUCs of LSV were significantly higher than those of ICGR15 for the diagnosis of ≥ PHLF B (P=0.002) and C (P=0.038). 2D-SWE demonstrates the potential to aid in the prediction of the severity of PHLF. Our findings also suggest that the performance of 2D-SWE is better than the ICG clearance test.

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