ALPPS：Breaks the barrier between resectable and unresectable

HASAN Mohammad Mahboob，MA Junyong，YAN Zhenlin

1.Combined Military Hospital Dhaka，Bangladesh；2.Department of Hepatic SurgeryⅣ，Eastern Hepatobiliary Surgery Hospital，The Second Military Medical University，Shanghai200438，China

ALPPS：Breaks the barrier between resectable and unresectable

HASAN Mohammad Mahboob1，MA Junyong2，YAN Zhenlin2

1.Combined Military Hospital Dhaka，Bangladesh；2.Department of Hepatic SurgeryⅣ，Eastern Hepatobiliary Surgery Hospital，The Second Military Medical University，Shanghai200438，China

Liver failure is still the main issue for post hepatectomy mortality.The main obstacle for hepatectomy is insufficient future liver remnant（FLR）.Safety markers of hepatic resection are borderline liver function and sufficient volume of FLR.Associated liver partition and portal vein ligation for staged hepatectomy（ALPPS）is a new innovation to increase FLR to the desired volume perm itting extended hepatectomy for patients with initially insufficient FLR.This article reviews the emergent and surgical aspect of ALPPS in comparison to traditional methods to increase FLR. Pathophysiology of liver hypertrophy following ALPPS and other method are discussed in details.Outcome and prognosisare also reviewed through relevant literatures.

Portal vein embolization；Two-stage hepatectomy；Associated liver partition and portal vein ligation for staged hepatectomy；Future liver remnant

Introduction

Hepatic resection with clear surgicalmargins is the main potentially curative treatment for primary liver cancer or livermetastases（along with resection of primary lesion）.The volume and function of the future liver remnant（FLR） determine whether hepatic resection is safe or not.Preservation of adequate FLR is the most important factor to avoid postoperative liver failure（PLF）.In general，the right hem iliver accounts for approximately two-thirds of total liver volume（TLV）whereas the left hemiliver accounts for approximately a third[1]. When preoperative liver function is normal，an FLR of 30% is generally regarded as sufficient for adequate liver function[2].In the setting of chemotherapy-related injury or cirrhosis but without portal hypertensionrequire a FLR of at least 40%[2-7]，Truant and her associates recommend an estimated FLR to body weight ratio of greater than 0.5[8].

In patients with borderline volume of FLR，surgeons have difficulty to choose either resection of the hepatic tumor with potential risk of postoperative liver failure（PLF）or giving palliative treatment to the patient，such as using transcatheter arterial chemoembolization or local ablative therapy to avoid PLF.

Over the last 20 years，advances in liver surgery have come as a result of manipulations to redistribute portal venous blood flow to the liver by portal vein occlusion（PVO） ，resulting in compensatory hypertrophy of the FLR.Two-stage hepatectomies have been described to deal with bilobar liver tumors，and this can be used in conjunction with portal vein ligation（PVL） ，or percutaneous portal vein embolization（PVE）[9-15].The most common reason for non-resection was progression of disease（10%）followed by inadequate hypertrophy of the remnant liver（2%）[16].

Associating liver partition and portal vein ligation for staged hepatectomy（ALPPS）is a new two-stage surgical strategy that has been demonstrated to induce rapid and extensive hypertrophy and has challenged the concept of unresectability[17-18]. However，much controversy has surrounded this procedure，and both safety and long-term oncologic outcomes have been questioned[19-20].

Measures to increase resectibility

Some strategies have been developed to increase resectability in patients undergoing major hepatic resection.One of them is portal vein occlusion and the other is two-staged hepatic resection.This occlusion can be done through embolization by radiology or surgical portal vein ligation.This approach is able to induce atrophy of the tumor-bearing lobe with subsequent hypertrophy in the contralateral lobe by diverting the portal venous flow.

Preoperative portalvein embolization（PVE）

Preoperative portal vein embolization（PVE） was first introduced into clinical practice in the 1980s by Makuuchi and his associates[10]. Selective embolization techniques increase tolerance to major hepatic resection by reducing the liver volume that requires resection and inducing hypertrophy of the FLR to approximate target lim its in patients with large tumors or abnormal liver function.Criteria for selection of patients for PVE prior to major hepatectomy are FLR size，factors compromising liver function including previous chemotherapy，hepatitis，and cirrhosis and the planned complexity of the procedure.PVE is recommended when predicted FLR is less than 20%to 25%in a normal liver and less than 40%in a liver with compromised function. Stimulation by PVE increases circulating IL-6 and TNF-α，with activation of the mitogenic cascade similar to partial hepatectomy.A significant increase in DNA synthesis and mRNA expression of hepatocyte grow th factor（HGF）has been observed in the nonligated lobe，whereas HGF expression is only slightly elevated；negative regulators of hepatocyte proliferation，such as TGF-β and IL-1β，are strongly expressed in the shrinking ligated/ embolized lobe[21].

PVE can now be safely carried out using ultrasound-guided percutaneous transhepatic puncture under local anesthesia[22].Portal vein occlusion is able to increase the future liver remnant up to 40%within three to eight weeks.In some patients however，sufficient hypertrophy is not always achieved，and there is still concern about the potential for faster grow th of the tumor during the period prior to resection[23-27].

Drawbacks of PVE are：a.Complete redirection of portal flow to one hemiliver can lead to portal hypertension，similar to the portal hypertension seen in“small for size” syndrome[28-30]. The term “small-for-size”syndrome was first used in liver transplantation，although the mechanism is similar to that in PLF-insufficient liver mass for the resultant blood flow[28，31].b.Enhanced tumour grow th after PVE can be recognized.Changes in cytokines and grow th factors，alterations in hepatic blood supplyand enhanced cellular host response can promote local tumour grow th after PVE；c.Patients showing slow grow th of FLR or with persistently small FLR volume after 3 weeks of PVE are unlikely to exhibit further liver regeneration beyond this time point.d. Small metastases in the FRL or peritoneal carcinomatosis can escape detection from medical imaging and are only detected during laparotomy.e. Under radiological procedure，sometimes it is difficult to embolize the two branches of right portal vein.f.Ectopic embolization might take place，because the right portal vein is short and hard to handle. g. There is possibility of injury to contralateral lobe，portal vein thrombosis，hepatic ductand hepatic artery injury.

Two-stage hepatectomy

The two-stage hepatectomy was pioneered by surgeons at the Hôpital Paul Brousse in the 2000s. The operation was designed when it was impossible to remove allmalignant lesions in the liver in a single procedure[15].The intention of the first procedure was to keep the final FLR clear of allmalignant lesions. During thewaiting time to second operation，the FLR hypertrophies can be induced making the hepatectomy feasible and potentially curative[32]. Under this principle，a variety of methods of two-stage hepatectomy were developed.Jaeck[14]routinely used right PVE which resulted in hypertrophy of the left liver after the initial removal of all the tumors located in the left liver（the FLR），allowing a safer curative right or extended-right hem ihepatectomy.Clavien[2]modified the procedure by combining wedge resections of all the left-sided tumors in the FLR and concomitant right portal vein ligation in the first operation，and then followed by extended right hepatectomy a few weeks later.This modification is based on evidences that portal vein ligation triggers a similar or better regenerative response than PVE[23].On this basis，Adam and his colleagues[15]combined ligature or/and absolute alcohol injection into the right portal vein at time of first operation involving resection of all the left sided malignant lesions in FLR.The ligature precluded any backflow of alcohol into themain/left portal vein as well as cavernous transformation of the ligated portal system.These improvements enormously shorten the interval between two hepatectomies.

However，the major reason for failure of the two-stage hepatectomy is tumor progression during a too long waiting period for the FLR to hypertrophy or an insufficient volume increase after portal vein occlusion[33-35]. There are other disadvantages[36-38]：firstly，liver regeneration can be impaired or altered by prolonged use of some chemotherapeutic agents. Secondly，patients have to be carefully selected to slow tumor progression with well-differentiated tumors allowing a sufficient delay for regeneration of FLR.Thirdly，in addition to the fibrous adhesions after the first hepatectomy，the atrophy-hypertrophy complex related to the right portal ligation changes the dissection plane of the right hepatectomy，thus，making it potentially dangerous to perform the second hepatectomy.

Innovation of ALPPS technique：Professor Hans Schlitt in Regensburg，Germany，performed the first new two-step technique in 2007.This great procedure was invented by chance.He planned to carry out extended right hepatectomy in a patient with hilar cholangiocarcinoma.Intraoperatively he assumed that the FLR was too small to sustain the patient's life postoperatively.Then he decided to perform only selective left hepatico-jejunostomy for palliation.He divided liver parenchyma along falciform ligament for positioning of hepatico-jejunostomy，thereby completely devascularizing segment 4.He also ligated right portal vein in order to induce hypertrophy of left lateral section of liver.Out of curiosity，he performed a computed tomography scan on 8thpostoperative day.To his surprise，the left lateral section had grown enormously in size.Then he performed another operation and successfully removed the diseased part of the liver.An editorial in 2012 by de Santibanes and Clavien proposed a name-Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy（ALPPS）.This technique has been used around the world withexcellent results[17，39-42].

In 2012，an international ALPPS registry was created.Currently there are more than 430 ALPPS procedures registered from 75 centers across the world（www.alpps.net/q=registry）[3].

Features of ALPPS：ALPPS has recently been described as a new strategy to induce a rapid and large FLR volume increase.There are two important characteristics of ALPPS：rapid hypertrophy and fundamental auxiliary role undertaken by deportalized and diseased liver during time interval between in situ liver splitting（ISLS）and second operation.Although the arterialized liver containing tumor is excluded and deprived of its portal blood supply，it still can act as an auxiliary liver to assist the grow ing FLR in metabolic，synthetic，and detoxifying functions until the contralateral liver has grown enough to entirely take up the physiological function[22，41，43].

Reasons for rapid hypertrophy is the increase in portal flow to the FLR after PVO is an important trigger for liver regeneration and is the most amenable to surgical manipulation.Wilms et al. identified portal neo-collaterals to segments of the liver with occluded portal flow by performing ex-situ angiography after PVE and PVL[44]. This recanalization of branches of the embolized portal vein has been suggested as one of the reasons for failure of adequate hypertrophy after technically successful PVE[3,45].The addition of ISLS to PVL prevents the formation of vascular collaterals，which may explain the greater hypertrophy seen in ALPPS. Manipulation of the liver intraoperatively in the first stage of ALPPS also creates a traumatic stimulus，whichmay also contribute to the hypertrophy[3].

PVL or PVE are traditional approaches to induce liver hypertrophy of the FLR prior to hepatectomy in primarily non-resectable liver tumors.However，these approaches fail in about 14 percent of patients. Adequate hypertrophy of FLR using PVL or PVE generally takes more than four weeks.A lthough the grow th rate after PVE can be increased by portal CD133-positive stem cell application，this still cannot grow as fast as the FLR hypertrophy after ISLS. ALPPS can induce rapid grow th of FLR，which is greater than that of reported w ith portal vein embolization or occlusion alone.Recent studies have confirmed marked hypertrophy of FLR by 40%to 80%within 6 to 9 days or 22%per day after ISLS compared with approximately 3% after PVE[46]. Furthermore，ALPPS allows earlier post-operative chemotherapy.

Indications and contraindications of ALPPS：ALPPS is indicated for the patients with FLR of less than 30%in normal livers or less than 40%in diseased livers resulting from cholestasis，macrosteatosis，fibrosis or pathologic changes associated with chemotherapy.Indications include marginally resectable or locally advanced unresectable liver tumors of any origin with an insufficient FLR either in volume or quality.The pathologies that commonly applied include colorectal liver metastases，hilar cholangiocarcinoma and hepatocellular carcinoma.In addition，major liver resection combined with synchronous resection of other organs，such as colorectal cancer and liver metastases，neuroendocrine pancreatic and intestinal tumors with massive liver metastases，are also potential indications.ALPPS ismainly applicable to those who needed extended right hepatectomy. Contraindications are unresectable liver metastases in the FLR，unresectable extrahepatic metastases，severe portal hypertension，high anesthetic risks，poor medical conditions formajor surgery[22，47].

Steps of operation： A fter exploratory laparotomy，the liver is completely mobilized from its attachments.Segments 2 and 3 are cleared of tumor with wedge resections as required.The structures within the port ahepatis are then skeletonized. Subsequently the right portal vein is ligated and divided while preserving the right hepatic duct and right hepatic artery.It is of paramount importance to avoid any damage to hepatic artery of diseased liver and to the vasculobiliary structures of FLR.Hepatic parenchymal transection is carried out on right side of falciform ligament，separating liver segments 2 and 3from the rest of liver.Cholangiography is routinely performed through cystic ductafter liver parenchymal transection to detect any bile leak.At the end of the first operation，the hepatic pedicle of diseased liver，the hepatic veins，and the cystic duct are encircled with a black silk to facilitate their identification during second stage of the operation.The use of fibrin sealant on the raw surface or a plastic bag around the liver facilitates the second procedure by m inim izing postoperative adhesions and avoiding bile peritonitis due to bile leak.Prophylactic antibiotics are given because of the presence of an ischem ic diseased liver and a foreign body in the abdominal cavity.

After a mean interval of 9 days，CT volumetry is utilized to confirm hypertrophy of the FLR.In the second stage of the operation，intraoperative ultrasound is used on the FLR to detect any tumor that might have been missed during the first operation.If new tumors are found，either resection or ablative therapy can be performed.The plastic bag is removed.The right hepatic artery is ligated and divided along with the right hepatic duct.The right and middle hepatic vein，which provide venous drainage，into the vena cava，are ligated and divided. When necessary，the biliary system is reconstructed with a Roux-en-Y hepaticojejunostomy.The FLR is fixed to the anterior abdominal wall to prevent rotation.Drainsare placed in the surgical bed[3，22].

There are some important points on this operation：First，preoperative chemotherapy does not seem to influence the degree of liver hypertrophy[17]. Second，simultaneous surgery for primary tumor with ALPPS on synchronous liver metastases has been shown to be safe and effective in the first stage operation[47].Third，total laparoscopic ALPPS has been reported with effect of less adhesions during the second stage of operation[39，48].Fourth，ligation of bile duct of the diseased liver does not improve the degree of liver hypertrophy，but increases morbidity and mortality due to bile leak with possible injury of right hepatic artery during dissection[49].

The median time interval to have hypertrophic effect is nine days.De Santibanes observed a rapid grow th of the future liver remnant up to 83%in only six days.In contrast，hypertrophy using portal vein ligation or portal vein embolization is generally after four weeks and achieved a much lower degree of hypertrophy[50].

Outcome of ALPPS：The current evidence suggested that ALPPS offered a better chance of complete resection in patients who had primarily unresectable liver tumors at the cost of high operation morbidity and mortality.The morbidity rate has been reported to be as high as 70%，w ith high rates of procedure-related deaths of about 15%[18，28，40，47，48，51]. The main morbidity included bile leakage and sepsis，and the main cause of mortality included hepatic insufficiency.Another disadvantage of ALPPS is the use of foreign bodies such as plastic bags or sheets during the first stage of operation.If the second stage of operation cannot be performed for any reasons，the patients still need a reoperation to remove the foreign bodies[22].Bioactive sealants have been applied to the cut surface to prevent adhesions，with the advantage that they do not have to be removed.There have been reports of laparoscopic ALPSS with the proposed benefit of minimizing adhesions[52].In the early laparoscopic reports，the second stage is completed using an open technique.More recently Machado et al reported ALPPS performed totally by laparoscopy with minor adhesions[17，50，53，54].

Several series in the medical literature described a median of 74%－110%increase in FRL volume at a median of 9－15 days between the 2 steps of the operation[18，28，39，46，47，51].There have been few studies directly comparing ALPPS to conventional two-stage hepatectomies，although ALPPS is not intended to supplant conventional two-stage hepatectomies，but rather to expand the armamentarium for hepatic resection.Shindoh et al.published a retrospective review of 144 patients undergoing portal vein embolization and performed a comparative analysis to the 25 patients undergoing ALPPS from the original German paper[19].They showed that there were similar hypertrophy rates with 74%in ALPPS group and 62% in PVE group.Overall，majormorbidity（Clavien-Dindo≥ⅢA）was not significantly different between two groups（40%ALPPS versus 33%PVE），however bile leaks（24%versus 5.8%），sepsis（20%versus 0%），and re-laparotomy （28%versus 2.9%）were significantly higher in ALPPS group.Liver-related mortality was higher in ALPPS group（12%versus 5.8%），but this did not reach statistical significance[19].Furthermore，27.8%of the patients undergoing PVE did not reach the second stage due to short interval disease progression or insufficient liver regeneration[3].A review article by Vyas[55]comparing PVE and PVL found that 4.8%of subjects in PVE group and 7.4%of those in PVL group failed liver hypertrophy，with 17.46% and 29.29% ，respectively，showing interval disease progression.

Schadde et al. published a retrospective multicenter study comparing PVO to ALPPS using data obtained from four major centers[18].While they did recognize the trend toward highermorbidity and mortality associated with ALPPS when compared to PVO（15%versus 6%90-day mortality and 13% versus 9%PLF after the second stage），more patients in the ALPPS group achieved completion resection （83%versus 66%）and recurrence at 12 monthswas comparable（54%versus 52%）.In contrast to Aloia et al.，there was only a 34%increase in FLR in PVO group compared to 77%in ALPPS group，showing benefit from ALPPS in this regard[3].

Conclusion

PVE is still a widely used and preferable method.But obviously ALPPS has taken upper hand in respect of faster and considerable grow th in FLR. In other hand，high rate of mortality and morbidity takes away the light over the ALPPS.Due to high morbidity and mortality rates related to ALPPS procedure，the surgical candidates should be selected carefully.ALPPS is new in the field of hepatic surgery，thus the number of study and current evidence still appear too limited，further large scale studies are needed to evaluate its technical feasibility，safety and oncological outcome in comparison to other methods.Above all，we should remember that patient safety and benefit are uncompromizable.

Reference

[1]Mayo SC，Pawlik TM.Current management of colorectal hepatic metastasis[J].Expert Rev Gastroenterol Hepatol，2009，3（2）：131-144.

[2]Clavien PA，Petrow sky H，DeOlivera M L，et al.Strategies for safer liver surgery and partial liver transplantation[J].N Eng J Med，2007，356（15）：1545-1559.

[3]Pawlik TM，Schulick RD，Choti MA.Expanding criteria for resectability of colorectal liver metastases[J].Oncologist，2008，13（1）：51-64.

[4]Garcea G，Ong SL，Maddern GJ.Predicting liver failure following major hepatectomy[J].Dig Liver Dis，2009，41（11）：798-806.

[5]Tanaka K，Shimada H，Matsuo K，et al.Remnant liver regeneration after two-stage hepatectomy for multiple bilobar colorectal metastases[J].Eur JSurg Oncol，2007，33（3）：329-335.

[6]Tucker ON，Heaton N.The“small for size”liver syndrome[J]. Curr Opin CritCare，2005，11（2）：150-155.

[7]Earl TM，Chapman WC.Conventional surgical treatment of hepatocellular carcinoma[J].Clin Liver Dis，2011，15（2）：353-370.

[8]Truant S，Oberlin O，SergentG，et al.Remnant liver volume to body weight ratio＞or=0.5%：a new cut-off to estimate postoperative risks after extended resection in noncirrhotic liver [J].JAm Coll Surg，2007，204（1）：22-33.

[9]M adoff DC，Abdalla EK，Gupta S，et al.Transhepatic ipsilateral right portal vein embolization extended to segment Ⅳ ：improving hypertrophy and resection outcomes with spherical particles and coils[J].JVasc Interv Radiol，2005，16 （2 Pt1）：215-225.

[10]Makuuchi M，Thai BL，Takayasu K，et al.Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma：a preliminary report[J].Surgery，1990，107 （5）：521-527.

[11]Nagino M，Kamiya J，Kanai M，et al.Right trisegment portal vein embolization for biliary tract carcinoma：technique and clinicalutility[J].Surgery，2000，127（2）：155-160.

[12]Ribero D，Abdalla，EK，Madoff，DC，et al.Portal vein embolization before major hepatectomy and its effects on regeneration，resectability and outcome[J].Br JSurg，2007，94 （11）：1386-1394.

[13]Shindoh J，Truty MJ，A loia TA，et al.Kinetic grow th rate after portal vein embolization predicts posthepatectomy outcomes：toward zero liver-related mortality in patients with colorectal liver metastases and small future liver remnant[J].JAm Coll Surg，2013，216（2）：201-209.

[14]Jaeck D，Oussoultzoglou E，Rosso E，et al.A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal livermetastases[J].Ann Surg，2004，240（6）：1037-1051.

[15]Adam R，LaurentA，Azoulay D，etal.Two-stage hepatectomy：a planned strategy to treat irresectable liver tumors[J].Ann Surg，2000，232（6）：777-785.

[16]Abulkhir A，Limongelli P，Healey AJ，etal.Preoperative portal vein embolization formajor liver resection：ameta-analysis[J]. Ann Surg，2008，247（1）：49-57.

[17]Schnitzbauer AA，Lang SA，Goessmann H，et al.Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings[J].Ann Surg，2012，255（3）：405-414.

[18]Schadde E，Ardiles V，Slankamenac K，et al.ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors compared with conventional-staged hepatectomies：results of a multicenter analysis[J].World J Surg，2014，38（6）：1510-1519.

[19]Shindoh J，Vauthey JN，Zimmitti G，et al.Analysis of the efficacy of portal vein embolization for patients with extensive liver malignancy and very low future liver remnant volume，including a comparison with the associating liver partition with portal vein ligation for staged hepatectomy approach[J].JAm Coll Surg，2013，217（1）：126-134.

[20]Figueras J，Belghiti J.The ALPPS approach：should we sacrifice basic therapeutic rules in the name of innovation?[J]. World JSurg，2014，38（6）：1520-1521.

[21]Jeroen DJ，Kim MO.Liver regeneration：mechanisms and clinical relevance，Chapter 5-Blumgart’s Surgery of the Liver，Biliary tract and Pancreas（Fifth Edition）[M].Philadelphia：Elsevier，2012：87-101.

[22]Zhang GQ，Zhang ZW，Lau WY，et al.Associating liver partition and portal vein ligation for staged hepatectomy （ALPPS）：A new strategy to increase resectability in liver surgery[J].Int JSurg，2014，12（5）：437-441.

[23]Aussilhou B，Lesurtel M，Sauvanet A，et al.Right portal vein ligation is as efficient as portal vein embolization to induce hypertrophy of the left liver remnant[J].JGastrointest Surg，2008，12（2）：297-303.

[24]Broering DC，Hillert C，K rupski G，et al. Portal vein embolization vs.portal vein ligation for induction of hypertrophy of the future liver remnant[J].JGastrointest Surg. 2002，6（6）：905-913.

[25]Capussotti L，Muratore A，Baracchi F，etal.Portalvein ligation as an efficient method of increasing the future liver remnant volume in the surgical treatment of colorectal metastases[J]. Arch Surg，2008，143（10）：978-982.

[26]Hemming AW，Reed AI，Howard RJ，et al.Preoperative portal vein embolization for extended hepatectomy[J].Ann Surg，2003，237（5）：686-693.

[27]Madd of DC，Hicks ME，Abdalla EK，et al.Portal vein embolization with polyvinyl alcohol particles and coils in preparation for major liver resection for hepatobiliary malignancy：safety and effectiveness—Study in 26 patients[J]. Radiology，2003，227（1）：251-260.

[28]Lelpo B，Caruso R，Ferri V，et al.ALPPS procedure：our experience and state of the art[J].Hepatogastroenterology，2013，60（128）：2069-2075.

[29]Lelpo B，Quijano Y，Vicente E. Pearls and pitfalls on ALPPS procedure：new complications in a new technique [J]. Updat Surg，2014，66（2）：159-161.

[30]Robinson SM， Wilson CH， Burt AD， et al. Chemotherapy-associated liver injury in patients with colorectal liver metastases：a systematic review and meta-analysis[J].Ann Surg Oncol，2012，19（13）：4287-4299.

[31]Asencio JM，Vaquero J，Olmedilla L，et al.“Small-for-flow”syndrome：shifting the“size”paradigm[J].M ed Hypotheses，2013，80（5）：573-577.

[32]Adam R，Miller R，Pitombo M，et al.Two-stage hepatectomy approach for initially unresectable colorectal hepaticmetastases [J].Surg Oncol ClinNAm，2007，16（3）：525-536.

[33]Brouquet A，Abdalla EK，Kopetz S，et al.High survival rate after two-stage resection of advanced colorectal liver metastases：response-based selection and complete resection defineoutcome[J].JClin Oncol，2011，29（8）：1083-1090.

[34]Narita M，Oussoultzoglou E，Jaeck D，et al. Two-stage hepatectomy for multiple bilobar colorectal liver metastases [J]. Br J Surg，2011，98（10）：1463-1475.

[35]Pamecha V，Nedjat-Shokouhi B，Gurusamy K，et al. Prospective evaluation of two-stage hepatectomy combined with selective portal vein embolisation and systemic chemotherapy for patients with unresectable bilobar colorectal livermetastases[J].Dig Surg，2008，25（5）：387-393.

[36]Aussilhou B，Dokmak S，Faivre S，et al.Preoperative liver hypertrophy induced by portal flow occlusion before major hepatic resection for colorectal metastases can be impaired by bevacizumab[J].Ann Surg Oncol，2009，16（6）：1553-1559.

[37]Kianmanesh R，Sauvanet A，Hentic O，et al.Two-step surgery for synchronous bilobar liver metastases from digestive endocrine tumors：a safe approach for radical resection[J].Ann Surg，2008，247（4）：659-665.

[38]Scatton O，Katsanos G，Soubrane O.Two-stage hepatectomy：tape it and hang it，while you can[J].World JSurg，2012，36 （7）：1647-1650.

[39]Torres OJ，Fernandes Ede S，Oliveira CV，et al.Associating liver partition and portal vein ligation for staged hepatectomy （ALPPS）：the Brazilian experience[J].Arq Bras Cir Dig，2013，26（1）：40-43.

[40]Sala S，Ardiles V，Ulla M，et al.Our initial experience with ALPPS technique：encouraging results[J].Updates Surg，2012，64（3）：167-172.

[41]De Santibañes E，A lvarez FA，Ardiles V.How to avoid postoperative liver failure：a novel method[J].World J Surg，2012，36（1）：125-128.

[42]De Santibañes E，Clavien PA.Playing Play-Doh to prevent postoperative liver failure：the"ALPPS"approach[J].Ann Surg，2012，255（3）：415-417.

[43]Torres OJ，Moraes-Junior JM，Lima e Lima NC，et al. Associating liver partition and portal vein ligation for staged hepatectomy（ALPPS）：a new approach in liver resections[J]. Arq BrasCir Dig，2012，25（4）：290-292. [44]Wilms C，Mueller L，Lenk C，et al.Comparative study of portal vein embolization versus portal vein ligation for induction of hypertrophy of the future liver remnant using a mini-pigmodel[J].Ann Surg，2008，247（5）：825-834.

[45]Riehle KJ，Dan YY，Campbell JS，et al.New concepts in liver regeneration[J].J Gastroenterol Hepatol，2011，26（Suppl 1）：203-212.

[46]Li J，Girotti P，Königsrainer I，et al.ALPPS in right trisectionectomy：a safe procedure to avoid postoperative liver failure?[J].J Gastrointest Surg，2013，17（5）：956-961.

[47]Alvarez FA，Ardiles V，Sanchez Claria R，et al.Associating liver partition and portal vein ligation for staged hepatectomy （ALPPS）：tipsand tricks[J].J Gastrointest Surg，2013，17（4）：814-821.

[48]Machado MA，Makdissi FF，Surjan RC.ALPPS procedure with theuseof pneumoperitoneum[J].Ann Surg Oncol，2013，20（5）：1491-1493.

[49]Dokmak S，Belghiti J.Which limits to the“ALPPS”approach? [J].Ann Surg，2012，256（3）：e6.

[50]de Santibañes E，Alvarez FA，Ardiles V.How to avoid postoperative liver failure：a novel method[J].World J Surg，2012，36（1）：125-128.

[51]Vennarecci G，Laurenzi A，Levi Sandri GB，et al.The ALPPS procedure for hepatocellular carcinoma[J].Eur JSurg Oncol，2014，40（8）：982-988.

[52]Machado MA，Makdissi FF，Surjan RC.ALPPS procedure with the use of pneumoperitoneum[J].Ann Surg Oncol，2013，20（5）：1491-1493.

[53]Machado MA，Makdissi FF，Surjan RC.Totally laparoscopic ALPPS is feasible and may be worthwhile[J].Ann Surg，2012，256（3）：e13.

[54]Conrad C，Shivathirthan N，Camerlo A，et al.Laparoscopic portal vein ligation with in situ liver split for failed portal vein embolization[J].Ann Surg，2012，256（3）：e14-e15.

[55]Vyas S，Markar S，Partelli S，etal.Portal vein embolization and ligation for extended hepatectomy[J].Indian J Surg Oncol，2014，5（1）：30-42.

联合肝脏离断和门静脉结扎的二步肝切除术：突破了肝可切除与不可切除的界线

穆罕默德·马赫布·哈桑1，马俊永2，闫振林2
1.达卡三军联合医院，孟加拉国；2.第二军医大学东方肝胆外科医院肝外四科，上海 200438

肝功能衰竭仍是导致患者肝切除术后死亡的主要因素。残余肝脏体积（future liver remnant，FLR）不足是肝切除术的一个主要阻碍。肝切除术的安全标志是术后肝功能临界状态和足够的残余肝脏体积。联合肝脏离断和门静脉结扎的二步肝切除术（associated liver partition and portalvein ligation for staged hepatectomy，ALPPS）是一种创新性的手术方式，可用于残余肝脏体积不足本不能耐受扩大肝切除术的患者，待FLR增生足以耐受扩大肝切除术的水平。本文综述ALPPS的建立及其与传统方法在提高残余肝脏体积方面的对比。本文对ALPPS及其它方法促使肝脏增生的病理生理学机制进行了详细讨论，并通过相关文献对其结果和预后进行综述。

门静脉栓塞；二期肝切除术；联合肝脏离断和门静脉结扎的二步肝切除术；残余肝脏体积

R615

A

2095-378X（2016）03-0201-08

2016-04-05）

穆罕默德.马赫布.哈桑（1972—），男，外科高级专家，研究普通外科学

闫振林，电子信箱：zhenlinyan@sohu.com

10.3969/j.issn.2095-378X.2016.03.017