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.

Rescue associating liver partition and portal vein ligation for staged hepatectomy after portal embolization: Our experience and literature review

AIM To report a single-center experience in rescue associating liver partition and portal vein ligation for staged hepatectomy(ALPPS), after failure of previous portal embolization. We also performed a literature review.METHODS Between January 2014 and December 2015, every patient who underwent a rescue ALPPS procedure in Toulouse Rangueil University Hospital, France, was included. Every patient included had a project of major hepatectomy and a previous portal vein embolization(PVE) with insufficient future liver remnant to body weight ratio after the procedure. The ALPPS procedure was performed in two steps(ALPPS-1 and ALPPS-2), separated by an interval phase. ALPPS-2 was done within 7 to 9 d after ALPPS-1. To estimate the FLR, a computed tomography scan examination was performed 3 to 6 wk after the PVE procedure and 6 to 8 d after ALPPS-1. A transcystic stent was placed during ALPPS-1 and remained opened duringthe interval phase, in order to avoid biliary complications. Postoperative liver failure was defined using the 50-50 criteria. Postoperative complications were assessed according to the Dindo-Clavien Classification.RESULTS From January 2014 to December 2015, 7 patients underwent a rescue ALPPS procedure. Median FLR before PVE, ALPPS-1 and ALPPS-2 were respectively 263 cc(221-380), 450 cc(372-506), and 660 cc(575-776). Median FLR/BWR before PVE, ALPPS-1 and ALPPS-2 were respectively 0.4%(0.3-0.5), 0.6%(0.5-0.8), and 1%(0.8-1.2). Median volume growth of FLR was 69%(18-92) after PVE, and 45%(36-82) after ALPPS-1. The combination of PVE and ALPPS induced a growth of median initial FLR of +408 cc(254-513), leading to an increase of +149%(68-199). After ALPPS-2, 4 patients had stage Ⅰ-Ⅱ complications. Three patients had more severe complications(one stage Ⅲ, one stage Ⅳ and one death due to bowel perforation). Two patients suffered from postoperative liver failure according to the 50/50 criteria. None of our patients developed any biliary complication during the ALPPS procedure.CONCLUSION Rescue ALPPS may be an alternative after unsuccessful PVE and could allow previously unresectable patients to reach surgery. Biliary drainage seems to reduce biliary complications.

A study of the properties of hydrophobically associating water-soluble polymers used in drilling fluids

Hydrophobically associating water-soluble polymers (HPAP) have been synthesized from acrylamide(AM), acrylate (AA), 2-acrylamido-2-methyl propane sulfonic acid (AMPS) and hydrophobic monomer (AP) in aqueous solution by radical polymerization. New polymer drilling fluids are made up of HPAP, which is used as viscosifiers and encapsulation agents. Properties of this system are reported in this paper. Results indicate that this system has a high value of yield point to plastic viscosity (YP/PV≥0.7), high viscosity at a low-shear rate (LSRV≥30000mPa·s), excellent shear thinning behavior, good solid-carrying behavior, resistance to shear, good thermal stability (as high as 140℃) and salt resistance. The system has excellent behavior in high-density solution of NaCl and in calcium and magnesium rich saline solutions. Hence, HPAP also can be used in saltwater polymer drilling fluids.

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.

Associating liver partition and portal vein ligation for staged hepatectomy for extensive alveolar echinococcosis:First case report in the literature

Alveolar echinococcosis(AE) is a zoonotic disease that is caused by Echinococcus multilocularis that affects liver and a variety of organs and tissues. It differs from other echinococcal disease because it shows tumor like behavior in the affected organ and tissues. The treatment of choice is concomitant medical therapy and resection with negative margins. Nevertheless, resection with the intent of negative margins(R0) may lead to serious complications such as liver failure. In the present case report, we used Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy(ALPPS) procedure, which was defined in 2012 by Schnitzbauer et al, in a 28-year-old male patient to avoid complications of major liver resection in order to treat alveolar echinococcosis. Until now, we have not encountered any study using ALPPS procedure for the treatment of alveolar echinococcosis. In the present case report we aimed to show that ALPPS procedure can be safely performed for marginnegative resection of primary or recurrent AE that shows a tumor like behavior. It is our opinion that this procedure should be performed in centers that have expertise and sufficient technical capacity to perform liver transplantation and advanced liver surgery.

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.

Dissolution Characteristics of Hydrophobically Associating Polyacrylamide in Stirred Tanks

Enhanced oil recovery(EOR)by means of polymer flooding is an important technology for the strategic development of offshore oilfields in China.Hydrophobically associating polyacrylamide(HAPAM)has been recently proposed as a new flooding agent.The solubility of HAPAM is low,which is the bottleneck for further improving the oil recovery through polymer flooding in offshore oilfield.Stirred tanks have been used on offshore platforms to enhance HAPAM dissolving.But there is little literature on the study of HAPAM dissolving characteristics in stirred tanks.In this paper,effects of temperature,salinity,stirring speed,impeller type and stirring method on the dissolution of HAPAM are reported.The experimental results manifest that the dissolving rate of HAPAM increases with temperature and stirring speed,but the viscosity of the polymer solution decreases.There is an optimal range of salinity for polymer dissolving.Combining the operation mode of up-pumping with varying stirring speed,hydrofoil impeller can accelerate the dissolution of HAPAM and maintain a high solution viscosity.

Rheological Properties of Hydrophobically Associating Polyacrylamide Solution

A temperature-resistant, salt-tolerant polyacrylamide, hydrophobically associating polymer （HAP）, was synthesized in the State Key Laboratory of Heavy Oil Processing. The rheological behavior of HAP solution was investigated by means of flow experiments in porous media and by using a HAAKE RS600 rheometer. The results of Nuclepore membrane filtration showed that filtration time increased sharply when the critical association concentration was reached. Shear rate had a greater impact on viscosity and shear stress with increasing HAP concentration. The HAP solution with a concentration of 100 mg/L （salinity 32,868 mg/L） exhibited negative thixotropy. However, at the same salinity the HAP solution showed thixotropy and its viscosity became greater when the polymer concentration increased to 1,500 mg/L. The flow experiments in cemented core samples indicated that the resistance factor and residual resistance factor of the HAP solution were 31.8 and 12 when polymer concentration and salinity were 1,500 mg/L, 32,868 mg/L at 85℃ respectively, which is favorable for flooding application. Such factors of partially hydrolyzed polyaerylamide 3530S were merely 3.14 and 1.71, so it could not be applied to polymer flooding in the oilfield with high temperature and high salinity.

maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model

AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, partial hepatecotmy(PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity.RESULTS Compared with PHx and sham groups, the proliferation of f LR was significantly higher in ALPPS group(P = 0.023 and 0.001 at second day, P = 0.034 and P < 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPSinduced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration.CONCLUSION Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage Ⅱ of ALPPS should be performed prudently in patients with marginally adequate f LR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration.

Current status of associating liver partition with portal vein ligation for staged hepatectomy: Comparison with two-stage hepatectomy and strategies for better outcomes

Since its introduction in 2012,associating liver partition with portal vein ligation for staged hepatectomy(ALPPS)has significantly expanded the pool of candidates for liver resection.It offers patients with insufficient liver function a chance of a cure.ALPPS is most controversial when its high morbidity and mortality is concerned.Operative mortality is usually a result of posthepatectomy liver failure and can be minimized with careful patient selection.Elderly patients have limited reserve for tolerating the demanding operation.Patients with colorectal liver metastasis have normal liver and are ideal candidates.ALPPS for cholangiocarcinoma is technically challenging and associated with fair outcomes.Patients with hepatocellular carcinoma have chronic liver disease and limited parenchymal hypertrophy.However,in selected patients with limited hepatic fibrosis satisfactory outcomes have been produced.During the inter-stage period,serum bilirubin and creatinine level and presence of surgical complication predict mortality after stage II.Kinetic growth rate and hepatobiliary scintigraphy also guide the decision whether to postpone or omit stage II surgery.The outcomes of ALPPS have been improved by a combination of technical modifications.In patients with challenging anatomy,partial ALPPS potentially reduces morbidity,but remnant hypertrophy may compare unfavorably to a complete split.When compared to conventional two-stage hepatectomy with portal vein embolization or portal vein ligation,ALPPS offers a higher resection rate for colorectal liver metastasis without increased morbidity or mortality.While ALPPS has obvious theoretical oncological advantages over two-stage hepatectomy,the long-term outcomes are yet to be determined.

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.

Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy

AIM To highlight the potential mechanisms of regeneration in the Associating Liver Partition and Portal vein ligation for Stage hepatectomy models(clinical and experimental) that could unlock the myth behind the extraordinary capability of the liver for regeneration,which would help in designing new therapeutic options for the regenerative drive in difficult setup,such as chronic liver diseases. Associating Liver Partition and Portal vein ligation for Stage hepatectomy has been recently advocated to induce rapid future liver remnant hypertrophy that significantly shortens the time for the second stage hepatectomy. The introduction of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in the surgical armamentarium of therapeutic tools for liver surgeons represented a real breakthrough in the history of liver surgery. METHODS A comprehensive literature review of Associating Liver Partition and Portal vein ligation for Stage hepatectomy and its utility in liver regeneration is performed. RESULTS Liver regeneration after Associating Liver Partition and Portal vein ligation for Stage hepatectomy is a combination of portal flow changes and parenchymal transection that generate a systematic response inducing hepatocyte proliferation and remodeling. CONCLUSION Associating Liver Partition and Portal vein ligation for Stage hepatectomy represents a real breakthrough in the history of liver surgery because it offers rapid liver regeneration potential that facilitate resection of liver tumors that were previously though unresectable. The jury is still out though in terms of safety,efficacy and oncological outcomes. As far as Associating Liver Partition and Portal vein ligation for Stage hepatectomy-induced liver regeneration is concerned,further research on the field should focus on the role of nonparenchymal cells in liver regeneration as well as on the effect of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in liver regeneration in the setup of parenchymal liver disease.

Correlation of ^1H NMR Chemical Shift for Aqueous Solutions by Statistical Associating Fluid Theory Association Model

1H NMR chemical shifts of binary aqueous mixtures of acylamide, alcohol, dimethyl sulphoxide (DMSO), and acetone are correlated by statistical associating fluid theory (SAFT) association model. The comparison between SAPT association model and Wilson equation shows that the former is better for dealing with aqueous solutions. Finally, the specialties of both models are discussed.

Synthesis and Solution Properties of Hydrophobic Associating Polymers

Acrylamide/2-acrylamido alkane sulfonic acid hydrophobic associating copolymers were synthesized by micellar copolymerization. Effects of hydrophobe content, polymer concentration, salinity and surfactant on rheological behavior of copolymers were investigated and the conformation of polymers in solution was studied by means of environmental scanning electronic microscopy and dynamic light scattering. The experimental results showed that in the dilute regime the hydrophobic parts could interact intramolecularly, while in the regime where the polymer concentration was higher than the critical association concentration, intermolecular hydrophobic association became predominant. Within the limit of the solubility, the critical association concentration of the polymer decreased with the increase of the salinity. The experimental results of the solution conformation indicated the presence of the three-dimensional network structure in deionized water and the size of the mesh in the network varied with the polymer concentration. In NaCl solution, above the critical association concentration, an increase in polymer concentration enhanced the intermolecular association and also enlarged the hydrodynamic radius. It would result in the improvement of the thickening power of polymers.

SYNTHESIS AND CHARACTERIZATION OF A NOVEL FLUORINE-CONTAINING HYDROPHOBICALLY ASSOCIATING POLYMER

In this article, the synthesis and characterization of a novel fluoromonomer and its copolymer with acrylamide is reported. 2-perfluoroamyl-4-hydroxylquinoline 2 was synthesized from ethyl 2, 2-dihydroperfluoroheptanoate in high yields. The monomer 4 was then synthesized from 2 in two steps readily in high yields. Synthesis and characterization of copolymers of acrylamide (AM) and the fluoromonomer were investigated. The composition and intrinsic viscosity of these copolymers were studied. It was found that the rheological properties of aqueous solutions of polyacrylamide were modified significantly when a small proportion of the fluoromonomer 4 was incorporated on investigating the viscosity-concentration profiles, pseudoplasticity of these solutions and the effect of the presence of surfactant. These results could be explained by the hydrophobic association of the fluorocarbon segments in the aqueous solutions of these copolymers.

HYDROPHOBICALLY ASSOCIATING POLYACRYLAMIDES MODIFIED BY A NOVEL SELF-ASSOCIATIVE CATIONIC MONOMER

A series of hydrophobically associating polyacrylamides modified by small amounts （〈 3 mol%） of a self- associative cationic monomer 4-（2-（acryloyloxy） ethoxy） benzyl tri-ethyl ammonium bromide （AEBA） as hydrophobe were synthesized by radical copolymerization in aqueous solutions without external surfactants. The resulting eopolymers containing a multiblock structure exhibited a high tendency for hydrophobic association and a high thickening capacity. Solution properties and aggregation structures were investigated by viscometry and fluorescence technique. The high viscosity enhancement was found as the polymer concentration beyond a critical value c＊ and strongly depended on the copolymer microstructures. The number and length of hydrophobic microblocks within the copolymer backbones could be controlled by changing the AEBA concentration in copolymerization system. Addition of salt induced more hydrophobic association and viscosity enhancement. The synthesis method used was simple and environmentally friendly without any external surfactant contamination in comparison with the conventional micellar copolymerization.

The effect of betaine surfactants on the association behavior of associating polymer

The interfacial properties and rheological behavior of surfactant/polymer complex systems were measured to investigate the association behavior of the associating polymer.Compared with the pure surfactant solution,there are two inflection points in the surface tension curve for the surfactant/polymer complex systems.The two inflection points are dependent on the surfactant type and polymer concentration.The effect of surfactant on the rheological behavior of polymer can be divided into two aspects.First,the addition of short-chain betaine surfactant is detrimental to the viscosity of polymer solution due to the electrostatic shielding effect.Second,long-chain betaine surfactant also reduces the viscosity of polymer solutions at low concentrations.However,when the concentration of the long-chain betaine surfactant is relatively high,the long-chain betaine surfactant could form worm-like micelles that promote the intermolecular association and thus increase the number of associating junctions,thereby resulting in the augmentation of viscosity.So it is necessary to apply the long-chain betaine surfactant to build the polymer/surfactant flooding system.The interaction model between surfactant and polymer is proposed,which is different from the traditional‘Three-Region Model’.

Arterial ischemia in the deportalized liver following associating liver partition and portal vein ligation for staged hepatectomy

Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) is a novel 2-stage technique intended to induce rapid growth of the future liver remnant(FLR). Initial reports of a 12% mortality rate have sparked debate regarding the safety of the procedure. A 64 years old male was planned for a rightsided hemi-hepatectomy due to colorectal cancer liver metastases. Intra-operatively it was decided to convert to an ALPPS due to unexpectedly small segments 2-4. Post-operative serum laboratory tests indicated an acute liver failure and radiological imaging showed no sign of arterial blood flow to the right hemi-liver. A computed tomography examination on post-operative day 3 revealed that the FLR had increased from 290 to 690 m L in 3 d(138% growth). In the following days serum values gradually improved and stage 2 was carried out on post-operative day 7. The rest of the hospital stay was uneventful and the patient made a full recovery. ALPPS is a fascinating advancement in liver surgery. Despite severe post-operative complications, in properly selected cases it provides successful outcomes that other modalities of treatment cannot offer.

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.