Simultaneous portal and hepatic vein embolization is better than portal embolization or ALPPS for hypertrophy of future liver remnant before major hepatectomy: A systematic review and network meta-analysis

Background:Post-hepatectomy liver failure(PHLF)is the Achilles’heel of hepatic resection for colorectal liver metastases.The most commonly used procedure to generate hypertrophy of the functional liver remnant(FLR)is portal vein embolization(PVE),which does not always lead to successful hypertrophy.Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been proposed to overcome the limitations of PVE.Liver venous deprivation(LVD),a technique that includes simultaneous portal and hepatic vein embolization,has also been proposed as an alternative to ALPPS.The present study aimed to conduct a systematic review as the first network meta-analysis to compare the efficacy,effectiveness,and safety of the three regenerative techniques.Data sources:A systematic search for literature was conducted using the electronic databases Embase,PubMed(MEDLINE),Google Scholar and Cochrane.Results:The time to operation was significantly shorter in the ALPPS cohort than in the PVE and LVD cohorts by 27 and 22 days,respectively.Intraoperative parameters of blood loss and the Pringle maneuver demonstrated non-significant differences between the PVE and LVD cohorts.There was evidence of a significantly higher FLR hypertrophy rate in the ALPPS cohort when compared to the PVE cohort,but non-significant differences were observed when compared to the LVD cohort.Notably,the LVD cohort demonstrated a significantly better FLR/body weight(BW)ratio compared to both the ALPPS and PVE cohorts.Both the PVE and LVD cohorts demonstrated significantly lower major morbidity rates compared to the ALPPS cohort.The LVD cohort also demonstrated a significantly lower 90-day mortality rate compared to both the PVE and ALPPS cohorts.Conclusions:LVD in adequately selected patients may induce adequate and profound FLR hypertrophy before major hepatectomy.Present evidence demonstrated significantly lower major morbidity and mortality rates in the LVD cohort than in the ALPPS and PVE cohorts.

CD4^(+)CD25^(+) regulatory T cells decreased future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy

BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned stage 2 ALPPS is future liver remnant(FLR)volume growth,but the exact mechanism has not been elucidated.The correlation between regulatory T cells(Tregs)and postoperative FLR regeneration has not been reported.AIM To investigate the effect of CD4^(+)CD25^(+)Tregs on FLR regeneration after ALPPS.METHODS Clinical data and specimens were collected from 37 patients who developed massive HCC treated with ALPPS.Flow cytometry was performed to detect changes in the proportion of CD4^(+)CD25^(+)Tregs to CD4^(+)T cells in peripheral blood before and after ALPPS.To analyze the relationship between peripheral blood CD4^(+)CD25^(+)Treg proportion and clinicopathological information and liver volume.RESULTS The postoperative CD4^(+)CD25^(+)Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume,proliferation rate,and kinetic growth rate(KGR)of the FLR after stage 1 ALPPS.Patients with low Treg proportion had significantly higher KGR than those with high Treg proportion(P=0.006);patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion(P=0.043).The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume,proliferation rate,and KGR were all greater than 0.70.CONCLUSION CD4^(+)CD25^(+)Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients’livers.Treg percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.

Functional transition:Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUND Preoperative portal vein embolization(PVE)is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant.PVE induces hypertrophy of the future liver remnant(FLR)and a shift of the functional reserve to the FLR.However,whether the increase of the FLR volume(FLRV)corresponds to the functional transition after PVE remains unclear.AIM To investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional(3D)computed tomography(CT)and 99mTc-galactosyl-human serum albumin(99mTc-GSA)singlephoton emission computed tomography(SPECT)fusion images.METHODS Thirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I,Hokkaido University Hospital between October 2013 and March 2018 were enrolled.Three-phase dynamic multidetector CT and 99mTc-GSA SPECT scintigraphy were performed at pre-PVE,and at 1 and 2 wk after PVE;3D 99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system.Functional FLRV(FFLRV)was defined as the total liver volume×(FLR volume counts/total liver volume counts)on the 3D 99m Tc-GSA SPECT CT-fused images.The calculated FFLRV was compared with FLRV.RESULTS FFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE(P<0.01).The increase in FFLRV and FLRV was 55.1%±41.6%and 26.7%±17.8%(P<0.001),respectively,at 1 wk after PVE,and 64.2%±33.3%and 36.8%±18.9%(P<0.001),respectively,at 2 wk after PVE.In 3 of the 33 patients,FFLRV levels decreased below FLRV at 2 wk.One of the three patients showed rapidly progressive fatty changes in FLR.The biopsy at 4 wk after PVE showed macroand micro-vesicular steatosis of more than 40%,which improved to 10%.Radical resection was performed at 13 wk after PVE.The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSION The functional transition lagged behind the increase in FLRV after PVE in some cases.Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.

Current strategies to induce liver remnant hypertrophy before major liver resection

Hepatic resection is the gold standard for patients affected by primary or metastatic liver tumors but is hampered by the risk of post-hepatectomy liver failure.Despite recent impro-vements,liver surgery still requires excellent clinical judgement in selecting patients for surgery and,above all,efficient pre-operative strategies to provide adequate future liver remnant.The aim of this article is to review the literature on the rational,the preliminary assessment,the advantages as well as the limits of each existing technique for preparing the liver for major hepatectomy.

Portal vein embolization for induction of selective hepatic hypertrophy prior to major hepatectomy: rationale,techniques, outcomes and future directions

The ability to modulate the future liver remnant(FLR) is a key component of modern oncologic hepatobiliary surgery practice and has extended surgical candidacy for patients who may have been previously thought unable to survive liver resection. Multiple techniques have been developed to augment the FLR including portal vein embolization(PVE), associating liver partition and portal vein ligation(ALPPS), and the recently reported transhepatic liver venous deprivation(LVD). PVE is a well-established means to improve the safety of liver resection by redirecting blood flow to the FLR in an effort to selectively hypertrophy and ultimately improve functional reserve of the FLR. This article discusses the current practice of PVE with focus on summarizing the large number of published reports from which outcomes based practices have been developed. Both technical aspects of PVE including volumetry, approaches, and embolization agents; and clinical aspects of PVE including data supporting indications, and its role in conjunction with chemotherapy and transarterial embolization will be highlighted. PVE remains an important aspect of oncologic care; in large part due to the substantial foundation of information available demonstrating its clear clinical benefit for hepatic resection candidates with small anticipated FLRs.

Neoadjuvant chemotherapy for colorectal liver metastases:A contemporary review of the literature

Colorectal carcinoma(CRC)is one of the leading causes of cancer-related deaths worldwide,and up to 50%of patients with CRC develop colorectal liver metastases(CRLM).For these patients,surgical resection remains the only opportunity for cure and long-term survival.Over the past few decades,outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy,as well as improvements in operative technique and perioperative care.Chemotherapy in the modern era of oxaliplatin-and irinotecancontaining regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents.The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery.Consequently,the use of neoadjuvant strategies is becoming progressively more established.For patients with CRLM,the primary advantage of neoadjuvant chemotherapy(NCT)is the potential to down-stage metastatic disease in order to facilitate hepatic resection.On the other hand,the routine use of NCT for patients with resectable metastases remains controversial,especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy.Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk,reserving NCT for patients with borderline resectable or unresectable disease and high operative risk.Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability.In light of the growing number of treatment options available to patients with metastatic CRC,it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.

Minimizing the risk of small-for-size syndrome after liver surgery

Background: Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant(FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-forsize syndrome(SFSS). Data sources: This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specifc modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. Results: Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. Conclusions: With those techniques the indications of radical treatment for patients with liver tumors have signifcantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modifcation of interventions and the right timing of surgery.

Novel liver vein deprivation technique that promotes increased residual liver volume(with video):A case report

BACKGROUND Inadequate volume of future liver remnant(FLR)is a major challenge for hepatobiliary surgeons treating large or multiple liver tumors.As an alternative to associating liver partition and portal vein ligation(ALPPS)for staged hepatectomy and liver venous deprivation(LVD)using stage 1 interventional radiology for vascular embolization combined with stage 2 open liver resection have been used.CASE SUMMARY A novel modified LVD technique was performed in a patient with pancreatic neuroendocrine tumor with liver metastases by using stage 1 laparoscopic ligation of the right hepatic vein,right posterior portal vein,and short hepatic veins combined with local excision of three liver metastases in the left hemiliver.The operation was followed three days later by interventional radiology to embolize an anomalous right anterior portal vein to complete LVD.A stage 2 laparoscopic right hemihepatectomy and pancreaticosplenectomy were then carried out.CONCLUSION The minimally invasive technique promoted a rapid increase,comparable to ALPPS,in volume of the FLR after the stage 1 operation to allow the laparoscopic stage 2 resection to be performed.

Optimization of the future remnant liver:review of the current strategies in Europe

Liver resection still represent the treatment of choice for liver malignancies,but in some cases inadequate future remnant liver(FRL)can lead to post hepatectomy liver failure(PHLF)that still represents the most common cause of death after hepatectomy.Several strategies in recent era have been developed in order to generate a compensatory hypertrophy of the FRL,reducing the risk of post hepatectomy liver failure.Portal vein embolization,portal vein ligation,and ALLPS are the most popular techniques historically adopted up to now.The liver venous deprivation and the radio-embolization are the most recent promising techniques.Despite even more precise tools to calculate the relationship among volume and function,such as scintigraphy with^(99m)Tc-mebrofenin(HBS),no consensus is still available to define which of the above mentioned augmentation strategy is more adequate in terms of kind of surgery,complexity of the pathology and quality of liver parenchyma.The aim of this article is to analyse these different strategies to achieve sufficient FRL.

Preoperative portal vein embolization for hepatocellular carcinoma: consensus and controversy

Thirty years have passed since the first report of portal vein embolization(PVE),and this procedure is widely adopted as a preoperative treatment procedure for patients with a small future liver remnant(FLR).PVE has been shown to be useful in patients with hepatocellular carcinoma(HCC)and chronic liver disease.However,special caution is needed when PVE is applied prior to subsequent major hepatic resection in cases with cirrhotic livers,and volumetric analysis of the liver segments in addition to evaluation of the liver functional reserve before PVE is mandatory in such cases.Advances in the embolic material and selection of the treatment approach,and combined use of PVE and transcatheter arterial embolization/chemoembolization have yielded improved outcomes after PVE and major hepatic resections.A novel procedure termed the associating liver partition and portal vein ligation for staged hepatectomy has been gaining attention because of the rapid hypertrophy of the FLR observed in patients undergoing this procedure,however,application of this technique in HCC patients requires special caution,as it has been shown to be associated with a high morbidity and mortality even in cases with essentially healthy livers.

Sequential transcatheter arterial chemoembolization and portal vein embolization before right hemihepatectomy in patients with hepatocellular carcinoma

Background:Recent studies showed that sequential selective transcatheter arterial chemoembolization(TACE)and portal vein embolization(PVE)provided better future liver remnant(FLR)regeneration rate and disease-free survival following surgery compared with PVE alone.The present study aimed to clarify whether preoperative sequential TACE and PVE before right hemihepatectomy can reduce postoperative hepatocellular carcinoma(HCC)recurrence and improve long-term disease-free and overall survival.Methods:Recurrence and survival outcomes were retrospectively evaluated in 205 patients with HCC who underwent right hemihepatectomy by a single surgeon from November 1993 to November 2017.Patients were divided into four groups according to the procedure performed before the surgery:sequential TACE and PVE(TACE-PVE),PVE-only,TACE-only,or na?ve control groups.The baseline patient and tumor characteristics,postoperative outcomes,recurrence-free survival and overall survival were analyzed.Results:Baseline patient and tumor characteristics upon diagnosis were similar in all four groups,while sequential TACE and PVE were well tolerated.The TACE-PVE group had a higher mean increase in percentage FLR volume compared with that of the PVE-only group(17.46%±6.63%vs.12.14%±5.93%;P=0.001).The TACE-PVE group had significantly better overall and disease-free survival rates compared with the other groups(both P<0.001).Conclusions:Sequential TACE and PVE prior to surgery can be an effective therapeutic strategy for patients with HCC scheduled for major hepatic resection.The active application of preoperative sequential TACE and PVE for HCC would allow more patients with marginal FLR volume to become candidates for major hepatic resection by promoting compensatory FLR hypertrophy without the deterioration of basal hepatic functional reserve or tumor progression.

Simultaneous transcatheter arterial chemoembolization and portal vein embolization for patients with large hepatocellular carcinoma before major hepatectomy

BACKGROUND Sequential transarterial chemoembolization(TACE)and portal vein embolization(PVE)are associated with long time interval that can allow tumor growth and nullify treatments'benefits.AIM To evaluate the effect of simultaneous TACE and PVE for patients with large hepatocellular carcinoma(HCC)prior to elective major hepatectomy.METHODS Fifty-one patients with large HCC who underwent PVE combined with or without TACE prior to hepatectomy were included in this study,with 13 patients in the simultaneous TACE+PVE group,17 patients in the sequential TACE+PVE group,and 21 patients in the PVE-only group.The outcomes of the procedures were compared and analyzed.RESULTS All patients underwent embolization.The mean interval from embolization to surgery,the kinetic growth rate of the future liver remnant(FLR),the degree of tumor size reduction,and complete tumor necrosis were significantly better in the simultaneous TACE+PVE group than in the other groups.Although the patients in the simultaneous TACE+PVE group had a higher transaminase levels after PVE and TACE,they recovered to comparable levels with the other two groups before surgery.The intraoperative course and the complication and mortality rates were similar among the three groups.The overall survival and disease-free survival were higher in the simultaneous TACE+PVE group than in the other two groups.CONCLUSION Simultaneous TACE and PVE is a safe and effective approach to increase FLR volume for patients with large HCC before major hepatectomy.

Associating liver partition and portal vein ligation for staged hepatectomy for colorectal liver metastasis:a single-center experience

Background:Associated liver partition and portal vein ligation for staged hepatectomy(ALPPS)is increasingly used for the treatment of primarily unresectable colorectal liver metastases(CRLM)because of the insufficient future liver remnant(FLR).The aim of this study was to share our experience with ALPPS for advanced CRLM and review the role of ALPPS in the management of patients with CRLM.Methods:Consecutive patients(n=10)with CRLM who underwent ALPPS at our center between December 2014 and October 2021 were retrospectively studied.Results:The median age of patients was 58 years(range 49–70 years).Five patients had metachronous CRLM and the other 5 patients had synchronous CRLM.Five patients had unilateral CRLM and the other 5 patients had bilateral CRLM.All patients previously underwent neoadjuvant chemotherapy.The FLR volume increased by 45.3%(35.8%–61.6%)over 14 days(range 7–21 days).The absolute and relative kinetic growth rates were 17.9 mL/day(range 7.5–32.1 mL/day)and 4.6%/day(range 2.3%–8.8%/day),respectively.Overall morbidity rates were 20%(2/10)and 40%(4/10)after ALPPS stage 1 and stage 2,respectively.The 30-day and 90-day mortality rates were 0%and 10%,respectively.R0 resection was achieved for all patients,and the median disease-free survival was 18.7 months.Conclusions:ALPPS is an effective treatment option for advanced CRLM.It enables rapid hypertrophy of the FLR and achieves a high R0 resection rate with an acceptable oncological outcome.However,ALPPS should be reserved for selected patients because of its relatively high morbidity and mortality.