Bile Acid Overload Induced by Bile Duct and Portal Vein Ligation Improves Survival after Staged Hepatectomy in Rats

Objective Compared to portal vein ligation(PVL),simultaneous bile duct and portal vein ligation(BPL)can significantly enhance hypertrophy of the intact liver.This study aimed to investigate whether BPL could improve survival after extended hepatectomy independently of an increased remnant liver.Methods We adopted rat models of 90%BPL or 90%PVL.To investigate the role of bile acids(BAs)the BA pools in the PVL and BPL groups were altered by the diet.Staged resection preserving 10%of the estimated liver weight was performed 3 days after BPL;PVL;or sham operation.Histology,canalicular network(CN)continuity;and hepatocyte polarity were evaluated.Results At 3 days after BPL;PVL;or sham operation when the volumetric difference of the intended liver remained insignificant,the survival rates after extended hepatectomy were 86.7%,47%,and 23.3%,respectively(P<0.01).BPL induced faster restoration of canalicular integrity along with an intensive but transient BA overload.Staged hepatectomy after BPL shortened the duration of the bile CN disturbance and limited BA retention.Decreasing the BA pools in the rats that underwent BPL could compromise these effects,whereas increasing the BA pools of rats that underwent PVL could induce similar effects.The changes in CN restoration were associated with activation of LKB1.Conclusion In addition to increasing the future remnant liver,BPL shortened the duration of the spatial disturbance of the CN and could significantly improve the tolerance of the hypertrophied liver to staged resection.BPL may be a safe and efficient future option for patients with an insufficient remnant liver.

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.

Associating liver partition and portal vein ligation for staged hepatectomy： the current role and development

BACKGROUND： Associating liver partition and portal vein ligation for staged hepatectomy （ALPPS） has recently been developed to induce rapid liver hypertrophy and reduce posthepatectomy liver failure in patients with insufficient future liver remnant （FLR）. ALPPS is still considered to be in an early developmental phase because surgical indications and techniques have not been standardized. This article aimed to review the current role and future developments of ALPPS. DATA SOURCES： Studies were identified by searching MED- LINE and PubMed for articles from January 2007 to October 2016 using the keywords ＂associating liver partition and portal vein ligation for staged hepatectomy＂ and ＂ALPPS＂ Addi- tional papers were identified by a manual search of references from key articles. RESULTS： ALPPS induces more hypertrophy of the FLR in less time than portal vein embolization or portal vein ligation. The benefits of ALPPS include rapid hypertrophy 47%-110% of the liver over a median of 6-16.4 days, and 95%-100% com- pletion rate of the second stage of ALPPS. The main criticisms of ALPPS are centered on its high morbidity and mortality rates. Morbidity rates after ALPPS have been reported to be 15.3%-100%, with ≥ the Clavien-Dindo grade III morbidity of 13.6%-44%. Mortality rates have been reported to be 0%-29%. The important questions to ask even if oncologic long-term results are acceptable are： whether the gain in quality and quantity of life can be off balance by the substantial risks of morbidity and mortality, and whether stimulation of rapid liver hypertrophy also accelerates rapid tumor progression and spread. Up till now, the documentations of the ALPPS procedure come mainly from case series, and most of these series include heterogeneous groups of malignancies. The numbers are also too small to separately evaluate survival for different tumor etiologies. CONCLUSIONS： Currently, knowledge on ALPPS is limited, and prospective randomized studies are lacking. From the reported preliminary results, safety of the ALPPS procedure remains questionable. ALPPS should only be used in experienced, high-volume hepatobiliary centers.

Role of associating liver partition and portal vein ligation for staged hepatectomy in colorectal liver metastases:A review

Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant(FLR) to allow for resection directly. There are therefore strategies todecrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion(PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS(associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.

Evolution of associating liver partition and portal vein ligation for staged hepatectomy: Simpler, safer and equally effective methods

Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) has been recently demonstrated as a method to induce rapid and extensive hypertrophy within a short time and has been employed for a variety of primary and metastatic liver tumors. However, controversies remain due to its high morbidity and mortality. To enable safer surgery, liver surgeons have searched for better technical modifications, such as partial ALPPS, mini-ALPPS, minimally invasive ALPPS, and Terminal branches portal vein Embolization Liver Partition for Planned hepatectomy(TELPP). It seems that TELPP is very promising, because it has the main advantage of ALPPS-the rapid increase of future liver remnant volume, but the morbidity and mortality are much lower because only one surgical operation is required.

Associating liver partition and portal vein ligation for staged hepatectomy in the treatment of colorectal cancer liver metastases

Colorectal cancer(CRC)is a common malignancy of the digestive system.Colorectal liver cancer metastasis(CRLM)occurs in approximately 50%of the patients and is the main cause of CRC mortality.Surgical resection is currently the most effective treatment for CRLM.However,given that the remnant liver volume after resection should be adequate,only a few patients are suitable for radical resection.Since Dr.Hans Schlitt first performed the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for CRLM in 2012,ALPPS has received considerable attention and has continually evolved in recent years.This review explains the technical origin of the ALPPS procedure for CRLM and evaluates its efficacy,pointing to its favorable postoperative outcomes.We also discuss the patient screening strategies and optimization of ALPPS to ensure long-term survival of patients with CRLM in whom surgery cannot be performed.Finally,further directions in both basic and clinical research regarding ALPPS have been proposed.Although ALPPS surgery is a difficult and high-risk technique,it is still worth exploration by experienced surgeons.

Abdominal cross-sectional imaging of the associating liver partition and portal vein ligation for staged hepatectomy procedure

Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) is a recently introduced technique aimed to perform two-stage hepatectomy in patients with a variety of primary or secondary neoplastic lesions. ALPSS is based on a preliminary liver resection associated with ligation of the portal branch directed to the diseased hemiliver(DH), followed by hepatectomy after an interval of time in which the future liver remnant(FLR) hypertrophied adequately(partly because of preserved arterialization of the DH). Multidetector computed tomography(MDCT) and magnetic resonance imaging(MRI) play a pivotal role in patients' selection and FLR assessment before and after the procedure, as well as in monitoring early and late complications, as we aim to review in this paper. Moreover, we illustrate main abdominal MDCT and MRI findings related to ALPPS.

Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma

BACKGROUND The role of tumor-infiltrating lymphocytes(TILs)in the growth and progression of hepatocellular carcinoma(HCC)has attracted widespread attention.AIM To evaluate the feasibility of associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for massive HCC by exploring the role of TIL in the tumor microenvironment.METHODS Fifteen massive HCC patients who underwent ALPPS treatment and 46 who underwent hemi-hepatectomy were selected for this study.Propensity score matching was utilized to match patients in ALPPS and hemi-hepatectomy groups(1:1).Quantitative analysis of TILs in tumor and adjacent tissues between the two groups was performed by immunofluorescence staining and further analyses with oncological characteristics.In the meantime,trends of TILs in peripheral blood RESULTS Continuous measurement of tumor volume and necrosis volume showed that the proportion of tumor necrosis volume on the seventh day after stage-I ALPPS was significantly higher than the pre-operative value(P=0.024).In the preoperative period of stage-I ALPPS,the proportion of tumor necrosis volume in the high CD8+T cell infiltration group was significantly higher than that in the low group(P=0.048).CONCLUSION TIL infiltration level maintained a dynamic balance during the preoperative period of ALPPS.Compared with right hemi-hepatectomy,the ALPPS procedure does not cause severe immunosuppression with the decrease in TIL infiltration and pathological changes in immune components of peripheral blood.Our results suggested that ALPPS is safe and feasible for treating massive HCC from the perspective of immunology.In addition,high CD8+T cell infiltration is associated with increasing tumor necrosis in the perioperative period of ALPPS.

Extrahepatic right portal vein ligation allows parenchyma-sparing en bloc resection of segments 7, 8 and 4a for liver tumors engaging the right and middle hepatic veins

Right trisectionectomy for posterior liver tumors engaging the right and middle hepatic veins may lead to post-hepatectomy liver failure if the anticipated liver remnant is small. In such patients we developed a parenchymasparing one-step approach, that includes extrahepatic right portal vein ligation accompanied by en bloc resection only of segments 7, 8 and 4a and resection of the right and middle hepatic veins. The technique was applied in 3 patients with normal liver function, where according to the preoperative computed tomography the volume of segments 1, 2 and 3 ranged between 17% and 20% of the total liver volume. In all patients liver biochemistry improved rapidly postoperatively and a doubling of volume of segments 1, 2 and 3 was achieved by the third postoperative week, as extrahepatic right portal vein ligation ameliorated reperfusion injury of the remaining segments 5 and 6 and induced hypertrophy of segments 1, 2, 3 and 4b. There was no mortality or long-term complications.Patients are alive and free of disease 74, 50 and 17 months after the operation, respectively. We propose that the term ＂extended upper right sectionectomy＂ may be considered for the en bloc resection of segments 7, 8 and 4a, in future revisions ofthe Brisbane 2000 terminology of hepatic anatomy and resections.

Comparison of percutaneous transhepatic portal vein embolization and unilateral portal vein ligation

AIM： To compare the effect of percutaneous transhepatic portal vein embolization （PTPE） and unilateral portal vein ligation （PVL） on hepatic hemodynamics and right hepatic lobe （RHL） atrophy.METHODS： Between March 2005 and March 2009, 13 cases were selected for PTPE （n = 9） and PVL （n = 4） in the RHL. The PTPE group included hilar bile duct carcinoma （n = 2）, intrahepatic cholangiocarcinoma （n = 2）, hepatocellular carcinoma （n = 2） and liver metastasis （n = 3）. The PVL group included hepatocellular carcinoma （n = 2） and liver metastasis （n = 2）. In addition, observation of postoperative hepatic hemodynamics obtained from computed tomography and Doppler ultrasonography was compared between the two groups.RESULTS： Mean ages in the two groups were 58.9 ± 2.9 years （PVL group） vs 69.7 ±3.2 years （PTPE group）, which was a significant difference （P = 0.0002）. Among the indicators of liver function, including serum albumin, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, platelets and indocyanine green retention rate at 15 min, no significant differ- ences were observed between the two groups. Preop-erative RHL volumes in the PTPE and PVL groups were estimated to be 804.9 ±181.1 mL and 813.3 4±129.7 mL, respectively, with volume rates of 68.9% ± 2.8% and 69.2% ±4.2%, respectively. There were no significant differences in RHL volumes （P = 0.83） and RHL volume rates （P = 0.94）, respectively. At 1 mo after PTPE or PVL, postoperative RHL volumes in the PTPE and PVL groups were estimated to be 638.4±153.6 mL and 749.8 ± 121.9 mL, respectively, with no significant difference （P = 0.14）. Postoperative RHL volume rates in the PTPE and PVL groups were estimated to be 54.6% ± 4.2% and 63.7% ± 3.9%, respectively, which was a significant difference （P = 0.0056）. At 1 mo after the operation, the liver volume atrophy rate was 14.3% ± 2.3% in the PTPE group and 5.4%± 1.6% in the PVL group, which was a significant difference （P = 0.0061）.CONCLUSION： PTPE is a more effective procedure than PVL because PTPE is able to occlude completely the portal branch throughout the right peripheral vein.

Associating liver partition and portal vein ligation or combined transarterial chemo-embolisation and portal vein embolisation for staged hepatectomy for HBV-related hepatocellular carcinoma

Many patients with hepatocellular carcinoma are diagnosed with large tumours at an advanced stage.In addition,conditions such as liver fibrosis,cirrhosis,portal hypertension,viral load,and portal vein thrombosis due to either non-neoplastic or portal vein tumour thrombus limit the indications for surgical management to a select subset of individuals(1).

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)-a fine balance

We read with interest the paper by Li et al.entitled“Associating liver partition and portal vein ligation for staged hepatectomy versus sequential transarterial chemoembolization and portal vein embolization in staged hepatectomy for HBV-related hepatocellular carcinoma:a randomized comparative study”(1).

Associating liver partition and portal vein ligation for staged hepatectomy versus sequential transarterial chemoembolization and portal vein embolization in staged hepatectomy for HBV-related hepatocellular carcinoma:a randomized comparative study

Background:Both portal vein embolization(PVE)and associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)have merits and demerits when used in patients with unresectable liver cancers due to insufficient volumes in future liver remnant(FLR).Methods:This study was a single-center,prospective randomized comparative study.Patients with the diagnosis of hepatitis B related hepatocellular carcinoma(HCC)were randomly assigned in a 1:1 ratio to the 2 groups.The primary endpoints were tumor resection and three-year overall survival(OS)rates.Results:Between November 2014 to June 2016,76 patients with unresectable HBV-related HCC due to inadequate volume of FLR were randomly assigned to ALPPS groups(n=38)and TACE+PVE groups(n=38).Thirty-seven patients(97.4%)in the ALPPS group compared with 25 patients(65.8%)in the TACE+PVE group were able to undergo staged hepatectomy(risk ratio 1.48,95%CI:1.17-1.87,P<0.001).The three-year OS rate of the ALPPS group(65.8%)(95%CI:50.7-80.9)was significantly better than the TACE+PVE group(42.1%)(95%CI:26.4-57.8)(HR 0.50,95%CI:0.26-0.98,two-sided P=0.036).However,no significant difference in the OS rates between patients who underwent tumor resection in the 2 groups of patients was found(HR 0.80,95%CI:0.35-1.83,two-sided P=0.595).Major postoperative complications rates after the stage-2 hepatectomy were 54.1%in the ALPPS group and 20.0%in the TACE+PVE group(risk ratio 2.70,95%CI:1.17-6.25,P=0.007).Conclusions:ALPPS resulted in significantly better intermediate-term OS outcomes,at the expenses of a significantly higher perioperative morbidity rate compared with TACE+PVE in patients who had initially unresectable HBV-related HCC.

No difference in mortality among ALPPS,two-staged hepatectomy,and portal vein embolization/ligation:A systematic review by updated traditional and network meta-analyses

Background:There is an ongoing debate on the feasibility,safety,and oncological efficacy of the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)technique.The aim of this study was to compare ALPPS,two-staged hepatectomy(TSH),and portal vein embolization(PVE)/ligation(PVL)using updated traditional meta-analysis and network meta-analysis(NMA).Data sources:Electronic databases were used in a systematic literature search.Updated traditional metaanalysis and NMA were performed and compared.Mortality and major morbidity were selected as primary outcomes.Results:Nineteen studies including 1200 patients were selected from the pool of 436 studies.Of these patients,315(31%)and 702(69%)underwent ALPPS and portal vein occlusion(PVO),respectively.Ninetyday mortality based on updated traditional meta-analysis,subgroup analysis of the randomized controlled trials(RCTs),and both Bayesian and frequentist NMA did not demonstrate significant differences between the ALPPS cohort and the PVE,PVL,and TSH cohorts.Moreover,analysis of RCTs did not demonstrate significant differences of major morbidity between the ALPPS and PVO cohorts.The ALPPS cohort demonstrated significantly more favorable outcomes in hypertrophy parameters,time to operation,definitive hepatectomy,and R0 margins rates compared with the PVO cohort.In contrast,1-year disease-free survival was significantly higher in the PVO cohort compared to the ALPPS cohort.Conclusions:This study is the first to use updated traditional meta-analysis and both Bayesian and frequentist NMA and demonstrated no significant differences in 90-day mortality between the ALPPS and other hepatic hypertrophy approaches.Furthermore,two high quality RCTs including 147 patients demonstrated no significant differences in major morbidity between the ALPPS and PVO cohorts.

The role of associating liver partition and portal vein ligation for staged hepatectomy in the management of patients with colorectal liver metastasis

Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)approach emerged as a promising surgical strategy for rapid and large hypertrophy of the future liver remnant(FLR)when a major liver resection is necessary.Colorectal liver metastasis(CRLM)is their main indication.However,the promising results published so far,are very difficult to interpret since they usually focus on the technique and not on the underlying disease.Moreover,they are usually made up of complex populations,which received different chemotherapy schemes,with the ALPPS technical variations implemented over time and without consistent long-term follow-up results as well.Whereby,its role in CRLM should be analyzed as carefully as possible to indicate and select the best candidates who will benefit the most from this approach.We conducted a computerized search using PubMed and Google Scholar for reports published so far,using mesh headings and keywords related to the ALPPS and CRLM.

How should liver hypertrophy be stimulated?A comparison of upfront associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)and portal vein embolization(PVE)with rescue possibility

Background:The role of associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)in comparison to portal vein embolization(PVE)is debated.The aim of this study was to compare successful resection rates(RR)with upfront ALPPS vs.PVE with rescue ALPPS on demand and to compare the hypertrophy of the liver between ALPPS and PVE plus subsequent rescue ALPPS.Methods:A retrospective analysis of all patients treated with PVE for colorectal liver metastasis(CRLM)or ALPPS(any diagnosis,rescue ALPPS included)at five Scandinavian university hospitals during the years 2013-2016 was conducted.A Chi-square test and a Mann-Whitney U test were used to assess the difference between the groups.A successful RR was defined as liver resection without a 90-day mortality.Results:A total of 189 patients were included.Successful RR was in 84.5%of the patients with ALPPS upfront and in 73.3%of the patients with PVE and rescue ALPPS on demand(P=0.080).The hypertrophy of the future liver remnants(FLRs)with ALPPS upfront was 71%(48-97%)compared to 96%(82-113%)after PVE and rescue ALPPS(P=0.010).Conclusions:Upfront ALPPS offers a somewhat higher successful RR than PVE with rescue ALPPS on demand.The sequential combination of PVE and ALPPS leads to a higher overall degree of hypertrophy than upfront ALPPS.

Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment(CAPRA)score:is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)?

Background:Preoperative patient selection in Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)is not always reliable with currently available scores,particularly in patients with primary liver tumor.This study aims to(I)to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and(II)to create a score predicting 90-day mortality preoperatively.Methods:Thirteen high-volume centers participated in this retrospective multicentric study.A risk analysis based on patient characteristics,underlying disease and procedure type was performed to identify risk factors and model the Comprehensive ALPPS Preoperative Risk Assessment(CAPRA)score.A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index(CCI),the age-adjusted CCI(aCCI),the ALPPS risk score before Stage 1(ALPPS-RS1)and Stage 2(ALPPS-RS2).The model was internally validated applying bootstrapping.Results:A total of 451 patients were included.Mortality was 14.4%.The CAPRA score is calculated based on the following formula:(0.1×age)−(2×BSA)+1(in the presence of primary liver tumor)+1(in the presence of severe cardiovascular disease)+2(in the presence of moderate or severe diabetes)+2(in the presence of renal disease)+2(if classic ALPPS is planned).The predictive ability was 0.837 for the CAPRA score,0.443 for CCI,0.519 for aCCI,0.693 for ALPPS-RS1 and 0.807 for ALPPS-RS2.After 1,000 cycles of bootstrapping the C statistic was 0.793.The accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of 4.70.Conclusions:Comorbidities play an important role in ALPPS and should be carefully considered when planning the procedure.By assessing the patient’s preoperative condition in relation to ALPPS,the CAPRA score has a very good ability to predict postoperative mortality.

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.

Portal vein embolization failure:Current strategies and future perspectives to improve liver hypertrophy before major oncological liver resection

Portal vein embolization(PVE)is currently considered the standard of care to improve the volume of an inadequate future remnant liver(FRL)and decrease the risk of post-hepatectomy liver failure(PHLF).PHLF remains a significant limitation in performing major liver surgery and is the main cause of mortality after resection.The degree of hypertrophy obtained after PVE is variable and depends on multiple factors.Up to 20%of patients fail to undergo the planned surgery because of either an inadequate FRL growth or tumor progression after the PVE procedure(usually 6-8 wk are needed before surgery).The management of PVE failure is still debated,with a lack of consensus regarding the best clinical strategy.Different additional techniques have been proposed,such as sequential transarterial chemoembolization followed by PVE,segment 4 PVE,intra-portal administration of stem cells,dietary supplementation,and hepatic vein embolization.The aim of this review is to summarize the up-to-date strategies to overcome such difficult situations and discuss future perspectives on improving FRL hypertrophy.

Simultaneous bile duct and portal venous branch ligation in two-stage hepatectomy

Hepatectomy is an effective surgical treatment for multiple bilobar liver metastases from colon cancer;however,one of the primary obstacles to completing surgical resection for these cases is an insufficient volume of the future remnant liver,which may cause postoperative liver failure.To induce atrophy of the unilateral lobe and hypertrophy of the future remnant liver,procedures to occlude the portal vein have been conventionally used prior to major hepatectomy.We report a case of a 50-year-old woman in whom two-stage hepatectomy was performed in combination with intraoperative ligation of the portal vein and the bile duct of the right hepatic lobe.This procedure was designed to promote the atrophic effect on the right hepatic lobe more effectively than the conventional technique,and to the best of our knowledge,it was used for the first time in the present case.Despite successful induction of liver volume shift as well as the following procedure,the patient died of subsequent liver failure after developing recurrent tumors.We discuss the first case in which simultaneous ligation of the portal vein and the biliary system was successfully applied as part of the first step of two-stage hepatectomy.