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Tamai K, Mizushima T, Wu X, Inoue A, Ota M, Yokoyama Y, Miyoshi N, Haraguchi N, Takahashi H, Nishimura J, Hata T, Matsuda C, Doki Y, Mori M, Yamamoto H. Photodynamic Therapy Using Indocyanine Green Loaded on Super Carbonate Apatite as Minimally Invasive Cancer Treatment. Mol Cancer Ther 2018; 17:1613-1622. [PMID: 29654066 DOI: 10.1158/1535-7163.mct-17-0788] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 12/26/2017] [Accepted: 04/06/2018] [Indexed: 11/16/2022]
Abstract
Minimally invasive treatment is getting more and more important in an aging society. The purpose of this study was to explore the possibility of ICG loaded on super carbonate apatite (sCA) nanoparticles as a novel photodynamic therapy (PDT) against cancers. Using colon cancer cells, ICG uptake and anti-tumor effects were examined between the treatments of ICG and sCA-ICG. Reactive oxygen species (ROS) production and temperature rise were also evaluated to explore the underlying mechanism. Atomic force microscopy revealed that the size of sCA-ICG ranged from 10 to 20 nm. In aqueous solution with 0.5% albumin, the temperature increase after laser irradiation was 27.1°C and 23.1°C in sCA-ICG and ICG, respectively (control DW: 5.7°C). A significant increase in ROS generation was noted in cell cultures treated with sCA-ICG plus irradiation compared with those treated with ICG plus irradiation (P < 0.01). Uptake of ICG in the tumor cells significantly increased in sCA-ICG compared with ICG in vitro and in vivo The fluorescence signals of ICG in the tumor, liver, and kidney faded away in both treatments by 24 hours. Finally, the HT29 tumors treated with sCA-ICG followed by irradiation exhibited drastic tumor growth retardation (P < 0.01), whereas irradiation of tumors after injection of ICG did not inhibit tumor growth. This study shows that sCA is a useful vehicle for ICG-based PDT. Quick withdrawal of ICG from normal organs is unique to sCA-ICG and contrasts with the other nanoparticles remaining in normal organs for a long time. Mol Cancer Ther; 17(7); 1613-22. ©2018 AACR.
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Affiliation(s)
- Koki Tamai
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Xin Wu
- Division of Health Sciences, Department of Molecular Pathology, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Akira Inoue
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Minori Ota
- Division of Health Sciences, Department of Molecular Pathology, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Yuhki Yokoyama
- Division of Health Sciences, Department of Molecular Pathology, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Norikatsu Miyoshi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Naotsugu Haraguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Hidekazu Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Junichi Nishimura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Taishi Hata
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Chu Matsuda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan
| | - Hirofumi Yamamoto
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita city, Osaka, Japan. .,Division of Health Sciences, Department of Molecular Pathology, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
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Schadde E, Hertl M, Breitenstein S, Beck-Schimmer B, Schläpfer M. Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure. J Vis Exp 2017. [PMID: 28829432 DOI: 10.3791/55895] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver metastases, the amount of liver tissue left behind after liver resection has become the main limiting factor of resectability of large or multiple liver tumors. A minimal amount of functional tissue is required to avoid the severe complication of post-hepatectomy liver failure, which has high morbidity and mortality. Inducing liver growth of the prospective remnant prior to resection has become more established in liver surgery, either in the form of portal vein embolization by interventional radiologists or in the form of portal vein ligation several weeks prior to resection. Recently, it was shown that liver regeneration is more extensive and rapid, when the parenchymal transection is added to portal vein ligation in a first stage and then, after only one week of waiting, resection performed in a second stage (Associating Liver Partition and Portal vein ligation for Staged hepatectomy = ALPPS). ALPPS has rapidly become popular across the world, but has been criticized for its high perioperative mortality. The mechanism of accelerated and extensive growth induced by this procedure has not been well understood. Animal models have been developed to explore both the physiological and molecular mechanisms of accelerated liver regeneration in ALPPS. This protocol presents a rat model that allows mechanistic exploration of accelerated regeneration.
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Affiliation(s)
- Erik Schadde
- Institute of Physiology - Center for Integrative Human Physiology, University of Zurich; Department of Surgery, Rush University Medical Center; Department of Surgery, Cantonal Hospital Winterthur;
| | - Martin Hertl
- Department of Surgery, Rush University Medical Center
| | | | - Beatrice Beck-Schimmer
- Institute of Physiology - Center for Integrative Human Physiology, University of Zurich; Institute of Anesthesiology, University and University Hospital Zurich
| | - Martin Schläpfer
- Institute of Physiology - Center for Integrative Human Physiology, University of Zurich; Institute of Anesthesiology, University and University Hospital Zurich
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Lau WY, Lai EC, Lau SH. Associating liver partition and portal vein ligation for staged hepatectomy: the current role and development. Hepatobiliary Pancreat Dis Int 2017; 16:17-26. [PMID: 28119254 DOI: 10.1016/s1499-3872(16)60174-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been developed to induce rapid liver hypertrophy and reduce post-hepatectomy 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 MEDLINE 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". Additional 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% completion 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.
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Affiliation(s)
- Wan Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
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Sparrelid E, Jonas E, Tzortzakakis A, Dahlén U, Murquist G, Brismar T, Axelsson R, Isaksson B. Dynamic Evaluation of Liver Volume and Function in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy. J Gastrointest Surg 2017; 21:967-974. [PMID: 28283924 PMCID: PMC5443865 DOI: 10.1007/s11605-017-3389-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 02/20/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Despite a fast and potent growth of the future liver remnant (FLR), patients operated with associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are at risk of developing posthepatectomy liver failure. In this study, the relation between liver volume and function in ALPPS was studied using a multimodal assessment. METHODS Nine patients with colorectal liver metastases treated with neoadjuvant chemotherapy and operated with ALPPS were studied with hepatobiliary scintigraphy, computed tomography, indocyanine green clearance test, and serum liver function tests. A comparison between liver volume and function was conducted. RESULTS The preoperative FLR volume of 19.5% underestimated the preoperative FLR function of 25.3% (p = 0.011). The increase in FLR volume exceeded the increase in function at day 6 after stage 1 (FLR volume increase 56.7% versus FLR function increase 28.2%, p = 0.021), meaning that the increase in function was 50% of the increase in volume. After stage 2, functional increase exceeded the volume increase, resulting in similar values 28 days after stage 2. CONCLUSIONS In the inter-stage period of ALPPS, the high volume increase is not paralleled by a corresponding functional increase. This may in part explain the high morbidity and mortality rates associated with ALPPS. Functional assessment of the FLR is advised.
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Affiliation(s)
- Ernesto Sparrelid
- Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, 141 86, Stockholm, Sweden.
| | - Eduard Jonas
- Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, 141 86, Stockholm, Sweden
| | - Antonios Tzortzakakis
- Division of Radiology, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Ulrika Dahlén
- Department of Medical Physics, Karolinska University Hospital, Stockholm, Sweden
| | - Gustav Murquist
- Department of Medical Physics, Karolinska University Hospital, Stockholm, Sweden
| | - Torkel Brismar
- Division of Radiology, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Rimma Axelsson
- Division of Radiology, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Bengt Isaksson
- Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, 141 86, Stockholm, Sweden
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Xin Y, Liu T, Yang C. Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery. Int J Nanomedicine 2016; 11:5807-5821. [PMID: 27853366 PMCID: PMC5104302 DOI: 10.2147/ijn.s119999] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with promising future applications in cancer therapy.
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Affiliation(s)
- Yu Xin
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Tie Liu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Chenlong Yang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
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Cai YL, Song PP, Tang W, Cheng NS. An updated systematic review of the evolution of ALPPS and evaluation of its advantages and disadvantages in accordance with current evidence. Medicine (Baltimore) 2016; 95:e3941. [PMID: 27311006 PMCID: PMC4998492 DOI: 10.1097/md.0000000000003941] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The main obstacle to achieving an R0 resection after a major hepatectomy is inability to preserve an adequate future liver remnant (FLR) to avoid postoperative liver failure (PLF). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel technique for resecting tumors that were previously considered unresectable, and this technique results in a vast increase in the volume of the FLR in a short period of time. However, this technique continues to provoke heated debate because of its high mortality and morbidity.The evolution of ALPPS and its advantages and disadvantages have been systematically reviewed and evaluated in accordance with current evidence. Electronic databases (PubMed and Medline) were searched for potentially relevant articles from January 2007 to January 2016.ALPPS has evolved into various modified forms. Some of these modified techniques have reduced the difficulty of the procedure and enhanced its safety. Current evidence indicates that the advantages of ALPPS are rapid hypertrophy of the FLR, the feasibility of the procedure, and a higher rate of R0 resection in comparison to other techniques. However, ALPPS is associated with worse major complications, more deaths, and early tumor recurrence.Hepatobiliary surgeons should carefully consider whether to perform ALPPS. Some modified forms of ALPPS have reduced the mortality and morbidity of the procedure, but they cannot be recommended over the original procedure currently. Portal vein embolization (PVE) is still the procedure of choice for patients with a tumor-free FLR, and ALPPS could be used as a salvage procedure when PVE fails. More persuasive evidence needs to be assembled to determine whether ALPPS or two-stage hepatectomy (TSH) is better for patients with a tumor involving the FLR. Evidence with regard to long-term oncological outcomes is still limited. More meticulous comparative studies and studies of the 5-year survival rate of ALPPS could ultimately help to determine the usefulness of ALPPS. Indications and patient selection for the procedure need to be determined.
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Affiliation(s)
- Yu-Long Cai
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Pei-Pei Song
- Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa-shi, Chiba, Japan
| | - Wei Tang
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Nan-Sheng Cheng
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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Donati M, Basile F, Oldhafer KJ. Present status and future perspectives of ALPPS (associating liver partition and portal vein ligation for staged hepatectomy). Future Oncol 2016; 11:2255-8. [PMID: 26260803 DOI: 10.2217/fon.15.145] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
First International Consensus Meeting, Hamburg, Germany, 27-28 February 2015 More than 160 participants took part in the conference for 2 days. A total of 58 world renown experts on ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) were invited from all over the world. The faculty was divided into many different subgroups that were in contact during the 2-3 months before the conference analyzing all the most important aspects of this technique and summarizing it in a common structured work to be presented during the congress, giving final recommendations in the form of bulleted point statements. The aim was to gain a solid basis of preliminary agreement on many controversial aspects of ALPPS. A poster area was also organized with 35 posters reporting mostly mono-institutional experiences on single aspects of the technique from all five continents.
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Affiliation(s)
- Marcello Donati
- Department of Surgery & Medico-Surgical Specialties, General & Oncologic Surgery Unit, Vittorio-Emanuele University Hospital of Catania, University of Catania, Via Plebiscito 628, 95122, Catania, Italy.,Semmelweiss University of Budapest, Asklepios Campus Hamburg, Hamburg, Germany
| | - Francesco Basile
- Department of Surgery & Medico-Surgical Specialties, General & Oncologic Surgery Unit, Vittorio-Emanuele University Hospital of Catania, University of Catania, Via Plebiscito 628, 95122, Catania, Italy
| | - Karl J Oldhafer
- Semmelweiss University of Budapest, Asklepios Campus Hamburg, Hamburg, Germany.,Department of General & Abdominal Surgery, Asklepios Barmbek Hospital, Hamburg, Germany
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Edmondson MJ, Sodergren MH, Pucher PH, Darzi A, Li J, Petrowsky H, Campos RR, Serrablo A, Jiao LR. Variations and adaptations of associated liver partition and portal vein ligation for staged hepatectomy (ALPPS): Many routes to the summit. Surgery 2015; 159:1058-72. [PMID: 26747229 DOI: 10.1016/j.surg.2015.11.013] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 10/19/2015] [Accepted: 11/11/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Our aim was to review variations from the originally described associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure and relevant clinical outcomes. METHODS A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (ie, PRISMA) guidelines. A search of PubMed and Google Scholar was conducted until March 2015. Inclusion criteria were any publications reporting technical variations and descriptions of ALPPS. Exclusion criteria were insufficient technical description, data repeated elsewhere, or data that could not be accessed in English. RESULTS Initial search results returned 790 results; 46 studies were included in the final qualitative analysis. There were several alternatives described to the first stage of complete parenchymal split. Variations included partial ALPPS (partial split; hypertrophy of future liver remnant [FLR] 80-90%), radiofrequency-assisted liver partition and portal vein ligation (mean FLR hypertrophy 62%), laparoscopic microwave ablation and portal vein ligation (FLR hypertrophy 78-90%), associating liver tourniquet and portal ligation for staged hepatectomy (median FLR hypertrophy 61%), and sequential associating liver tourniquet and portal ligation for staged hepatectomy (FLR hypertrophy 77%) with a potential decrease in morbidity particularly after stage I. We analyzed several other variations, including considerations for segment IV, operative maneuvers, use of laparoscopy, identification of biliary complications, and liver containment. CONCLUSION The current literature demonstrates a large variability in techniques of ALPPS that limits meaningful statistical comparisons of outcomes. Not physically splitting the liver at the first stage may decrease morbidity; however, randomized controlled trials are needed to determine benefits in technical variations.
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Affiliation(s)
- Matthew J Edmondson
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Mikael H Sodergren
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
| | - Philip H Pucher
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Ara Darzi
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Jun Li
- Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Henrik Petrowsky
- Swiss HPB and Transplant Center, University Hospital Zurich, Zurich, Switzerland
| | - Ricardo Robles Campos
- Department of General Surgery, Liver Transplant Unit, Virgen De La Arrixaca University Hospital, Murcia, Spain
| | | | - Long R Jiao
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
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Associating liver partition and portal vein ligation for staged hepatectomy offers high oncological feasibility with adequate patient safety: a prospective study at a single center. Ann Surg 2015; 261:723-32. [PMID: 25493362 DOI: 10.1097/sla.0000000000001046] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To determine the safety, feasibility, and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in a single high-volume hepatobiliary center. BACKGROUND The ALPPS approach allows achieving resectability of liver malignancies by a rapid and large future liver remnant (FLR) hypertrophy. However, this proposal has been associated with high morbidity and mortality rates. METHODS This was a single-cohort, prospective, observational study [NCT02164292]. Between June 2011 and April 2014, patients with liver malignancies considered unresectable due to an insufficient FLR who underwent ALPPS were included. RESULTS Thirty patients were treated. Median age was 58.6 years (range = 35-81) and 19 patients were males (63%). In a median of 6 days (range = 4-67), the median FLR hypertrophy was 89.7% (range = 21-287). Twenty-nine patients completed the second stage (97% feasibility). Morbidity according to the Dindo-Clavien classification was 53% (grade ≥IIIa 43% and grade ≥IIIb 31%). The mortality rate was 6.6%. Total parenchymal transection was identified as an independent risk factor for complications (P = 0.049). There was not significant difference in terms of FLR hypertrophy between total or partial parenchymal transection (P = 0.45). Median hospital stay was 16 days (range = 11-62). The overall and disease-free survival at 1 year was 78% and 67% and at 2 years was 63% and 40%, respectively. CONCLUSIONS This prospective study on the largest reported single-center experience shows that ALPPS has acceptable morbidity and mortality, together with a high oncological feasibility and hypertrophic efficacy. Partial parenchymal transection seems to reduce morbidity without negatively impacting FLR hypertrophy.
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Hasselgren K, Sandström P, Björnsson B. Role of associating liver partition and portal vein ligation for staged hepatectomy in colorectal liver metastases: A review. World J Gastroenterol 2015; 21:4491-4498. [PMID: 25914457 PMCID: PMC4402295 DOI: 10.3748/wjg.v21.i15.4491] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 02/11/2015] [Accepted: 03/12/2015] [Indexed: 02/07/2023] Open
Abstract
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 to decrease 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.
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