Major liver resections,perioperative issues and posthepatectomy liver failure:A comprehensive update for the anesthesiologist

Significant advances in surgical techniques and relevant medium-and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections.To support these outstanding results and to reduce perioperative complications,anesthesiologists must address and master key perioperative issues(preoperative assessment,proactive intraoperative anesthesia strategies,and implementation of the Enhanced Recovery After Surgery approach).Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate.Among postoperative complications,posthepatectomy liver failure(PHLF)occurs in different grades of severity(A-C)and frequency(9%-30%),and it is the main cause of 90-d postoperative mortality.PHLF,recently redefined with pragmatic clinical criteria and perioperative scores,can be predicted,prevented,or anticipated.This review highlights:(1)The systemic consequences of surgical manipulations anesthesiologistsmust respond to or prevent,to positively impact PHLF(a proactive approach);and(2)the maximal intensivetreatment of PHLF,including artificial options,mainly based,so far,on Acute Liver Failure treatment(s),to buytime waiting for the recovery of the native liver or,when appropriate and in very selected cases,toward livertransplant.Such a clinical context requires a strong commitment to surgeons,anesthesiologists,and intensivists towork together,for a fruitful collaboration in a mandatory clinical continuum.

Preoperative Evaluation of Posthepatectomy Liver Failure Using MRI-Based Liver Function Indices in Child-Pugh Class A Patient

Purpose: To evaluate posthepatectomy liver failure (PHLF) using gadoxetic acid-enhanced magnetic resonance imaging (MRI) with a measure of relative liver enhancement (RLE) on hepatobiliary phase images, thereby facilitating safe liver resection. Methods: Twenty patients in Child-Pugh class A underwent tumor excision surgery and indocyanine green (ICG) clearance of future remnant liver (FRL) (ICG-Krem) values were >0.05. PHLF was evaluated using the grading system of the International Study Group of Liver Surgery (ISGLS). The RLE value was defined as the signal gain percentage between the precontrast and hepatocellular images. In the whole liver and FRL, theRLE value measured the tumor-free liver parenchyma in RLE images. We examined the correlation between indocyanine green clearance (ICG-K) and MRI-based liver function in the whole liver. Preoperative PHLF evaluation was predicted using remnant hepatocellular uptake index (rHUI), remnant RLE (rRLE), coefficient variation of Rrle [Cv(rRLE)], and ICG-Krem corrected by heterogeneous liver function(HLF-ICG-Krem). Results: HLF-ICG-Krem and rRLE values correlated with INRs after postoperative day five (r = -0.55 and 0.46, p = 0.01 and 0.04, respectively). Furthermore, HLF-ICG-Krem values ≤0.05 detected two patients with higher INRs after postoperative day five. On the other hand, neither rHUI nor Cv(rRLE) was correlated with INRs after postoperative day five (r = 0.28, and -0.03, respectively;p >0.05 for both). HLF-ICG-Krem was significantly lower with PHLF than without PHLF (p = 0.005). Conclusion: HLF-ICG-Krem is useful for evaluating PHLF more correctly.

Heparin is an effective treatment for preventing liver failure after hepatectomy

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver resection.Heparin,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver failure.AIM To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.METHODS The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were not.The statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU mortality.Logistic regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two groups.RESULTS In this study,1388 patients who underwent liver cancer hepatectomy were analyzed.PSM yielded 213 matched pairs from the heparin-treated and control groups.Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples.Further analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU mortality.CONCLUSION Liver failure is an important hazard following hepatic surgery.During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure.This indicates that heparin may provide a hopeful option for controlling PHLF.

From conventional two-stage hepatectomy to ALPPS:Fifteen years of experience in a hepatobiliary surgery unit

Background:Hepatectomy in patients with large tumor load may result in postoperative liver failure and associated complications due to excessive liver parenchyma removal.Conventional two-stage hepatectomy(TSH)and associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)technique are possible solutions to this problem.Colorectal liver metastases(CRLM)is the most frequent indication,and there is a need to assess outcomes for both techniques to improve surgical and long-term oncological outcomes in these patients.Methods:A single-center retrospective study was designed to compare TSH with ALPPS in patients with initially unresectable bilateral liver tumors between January 2005 and January 2020.ALPPS was performed from January 2012 onwards as the technique of choice.Long-term overall survival(OS)and disease-free survival(DFS)were evaluated as primary outcome in CRLM patients.Postoperative morbidity,mortality and liver growth in all patients were also evaluated.Results:A total of 38 staged hepatectomies were performed:17 TSH and 21 ALPPS.Complete resection rate was 76.5%(n=13)in the TSH group and 85.7%(n=18)in the ALPPS group(P=0.426).Overall major morbidity(Clavien-Dindo≥3 a)(stage 1+stage 2)was 41.2%(n=7)in TSH and 33.3%(n=7)in ALPPS patients(P=0.389),and perioperative 90-day mortalities were 11.8%(n=2)vs.19.0%(n=4)in each group,respectively(P=0.654).Intention-to-treat OS rates at 1 and 5 years in CRLM patients for TSH(n=15)were 80%and 33%,and for ALPPS(n=17)76%and 35%,respectively.DFS rates at 1 and 5 years were 36%and 27%in the TSH group vs.33%and 27%in the ALPPS group,respectively.Conclusions:ALPPS is an effective alternative to TSH in bilateral affecting liver tumors,allowing higher resection rate,but patients must be carefully selected.In CRLM patients similar long-term OS and DFS can be achieved with both techniques.

The significance of severe postoperative complications on liver regeneration

The liver is an extraordinary organ known for its remarkable regenerative capacity(1).This regenerative ability lays the foundation for various therapeutic approaches,such as partial hepatectomy(PHx),split-liver transplantation,live-donor liver transplantation,and associated liver partition and portal vein ligation for staged hepatectomy(ALPPS).

Functional assessment of liver regeneration after major hepatectomy

Background: Liver 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. Methods: Patients 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. Results: A 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). Conclusions: Functional 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.

Simultaneous splenectomy improving the outcomes of patients with hepatocellular carcinoma,cirrhosis and portal hypertension treated with hepatectomy

Aims:Patients with cirrhosis and clinically significant portal hypertension(CSPH)usually have concomitant secondary hypersplenism,and splenectomy(Spx)is an option for treating these patients in the Asia‐Pacific region.CSPH is the most important risk factor for postoperative liver dysfunction(PLD)in patients with hepatocellular carcinoma(HCC)and cirrhosis undergoing liver resection.However,the impact of simultaneous Spx and hepatectomy in patients with HCC and CSPH remains unclear.In this study,we aimed to determine the impact of simultaneous Spx on the posthepatectomy outcomes in these patients.Methods:This study included 691 consecutive patients with hepatitis B virusrelated HCC,cirrhosis,and CSPH.These included 565 patients who underwent hepatectomy only(non‐Spx group)and 126 who underwent simultaneous hepatectomy and splenectomy(Spx group).We analyzed the effect of 25 preoperative and 5 intraoperative factors on postoperative outcomes using logistic regression.To overcome any possible selection bias,confounders were balanced by propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses,and subgroup analyses were performed within the PSM‐matched groups.Results:Logistic regression analyses revealed that Spx was an independent protective factor for severe postoperative liver dysfunction(SPLD;odds ratio[OR]=0.22,95%confidence interval[CI]:0.11–0.43,p<0.001)and 90‐day SPLD‐related mortality(OR=0.21,95%CI:0.06–0.55,p=0.004),respectively.Spx was also independently associated with a higher overall survival rate(hazard ratio=0.63,95%CI=0.47–0.85,p=0.002)based on Cox regression analysis.PSM and IPTW models showed that the benefit of Spx was also consistent across the major and minor hepatectomy subgroups examined.Conclusion:Simultaneous Spx improved the outcomes of patients with HCC,cirrhosis,and CSPH treated with hepatectomy,including patients who underwent major and minor hepatectomies.