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de Haan LR, van Golen RF, Heger M. Molecular Pathways Governing the Termination of Liver Regeneration. Pharmacol Rev 2024; 76:500-558. [PMID: 38697856 DOI: 10.1124/pharmrev.123.000955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 01/24/2024] [Accepted: 02/08/2024] [Indexed: 05/05/2024] Open
Abstract
The liver has the unique capacity to regenerate, and up to 70% of the liver can be removed without detrimental consequences to the organism. Liver regeneration is a complex process involving multiple signaling networks and organs. Liver regeneration proceeds through three phases: the initiation phase, the growth phase, and the termination phase. Termination of liver regeneration occurs when the liver reaches a liver-to-body weight that is required for homeostasis, the so-called "hepatostat." The initiation and growth phases have been the subject of many studies. The molecular pathways that govern the termination phase, however, remain to be fully elucidated. This review summarizes the pathways and molecules that signal the cessation of liver regrowth after partial hepatectomy and answers the question, "What factors drive the hepatostat?" SIGNIFICANCE STATEMENT: Unraveling the pathways underlying the cessation of liver regeneration enables the identification of druggable targets that will allow us to gain pharmacological control over liver regeneration. For these purposes, it would be useful to understand why the regenerative capacity of the liver is hampered under certain pathological circumstances so as to artificially modulate the regenerative processes (e.g., by blocking the cessation pathways) to improve clinical outcomes and safeguard the patient's life.
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Affiliation(s)
- Lianne R de Haan
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, China (L.R.d.H., M.H.); Department of Internal Medicine, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands (L.R.d.H.); Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands (R.F.v.G.); Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands (M.H.); and Membrane Biochemistry and Biophysics, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands (M.H.)
| | - Rowan F van Golen
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, China (L.R.d.H., M.H.); Department of Internal Medicine, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands (L.R.d.H.); Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands (R.F.v.G.); Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands (M.H.); and Membrane Biochemistry and Biophysics, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands (M.H.)
| | - Michal Heger
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, China (L.R.d.H., M.H.); Department of Internal Medicine, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands (L.R.d.H.); Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands (R.F.v.G.); Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands (M.H.); and Membrane Biochemistry and Biophysics, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands (M.H.)
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Ishihara M, Takahashi Y, Matsuo K, Nakamura A, Togo S, Tanaka K. Modification of ALPPS to avoid ischemia and congestion after stage 1: a case report. Surg Case Rep 2022; 8:137. [PMID: 35867313 PMCID: PMC9307701 DOI: 10.1186/s40792-022-01490-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 07/09/2022] [Indexed: 12/03/2022] Open
Abstract
Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been advocated for treating advanced liver tumors, but the devascularized ischemic area resulting from liver parenchymal division can become a nidus for sepsis. We present a patient who underwent ALPPS modified to avoid ischemia and congestion after liver partitioning during stage 1. Case presentation ALPPS was carried out for a patient with multiple bilobar liver metastases from rectosigmoid colon cancer. The 2-stage treatment included 3 partial resections within the left lateral section and parenchymal division at the umbilical fissure with right portal vein ligation as stage 1, followed by right trisectionectomy as stage 2. During parenchymal division at the umbilical fissure, Segment 4 portal pedicles and the middle hepatic vein had to be resected at their roots. To safely accomplish this, combined resection of Segment 4 and the drainage area of the middle hepatic vein was performed after parenchymal partition, aiming to avoid ischemia and congestion within the remnant liver. Successful stage 2 hepatectomy followed later. No ischemia or congestion occurred during stage 1 or 2. Conclusions During ALPPS, ischemia and congestion after stage 1 must be avoided to reduce morbidity and mortality. The modification described here should reduce likelihood of severe postoperative complications.
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Wen XD, Xiao L. Associating liver partition and portal vein ligation for staged hepatectomy in the treatment of colorectal cancer liver metastases. World J Gastrointest Surg 2021; 13:814-821. [PMID: 34512905 PMCID: PMC8394386 DOI: 10.4240/wjgs.v13.i8.814] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/24/2021] [Accepted: 07/13/2021] [Indexed: 02/06/2023] Open
Abstract
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.
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Affiliation(s)
- Xu-Dong Wen
- Department of Gastroenterology and Hepatology, Chengdu First People’s Hospital, Chengdu 610016, Sichuan Province, China
| | - Le Xiao
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
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Dixon M, Cruz J, Sarwani N, Gusani N. The Future Liver Remnant : Definition, Evaluation, and Management. Am Surg 2020; 87:276-286. [PMID: 32931301 DOI: 10.1177/0003134820951451] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
When considering patients for a major hepatectomy, one must carefully consider the volume of liver to be left behind and if additional procedures are necessary to augment its volume. This review considers the optimal volume of the future liver remnant (FLR) and analyzes the techniques of augmenting this volume, the various growth parameters to assess adequate growth of the FLR, as well as further management when there has been inadequate growth of the FLR.
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Affiliation(s)
- Matthew Dixon
- Division of Surgical Oncology, Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Jeffrey Cruz
- Division of Surgical Oncology, Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.,Department of Radiology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.,Department of Medicine, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Nabeel Sarwani
- Department of Radiology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Niraj Gusani
- Division of Surgical Oncology, Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.,Department of Medicine, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.,Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
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Uribe M, Uribe-Echevarría S, Mandiola C, Zapata MI, Riquelme F, Romanque P. Insight on ALPPS - Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy - mechanisms: activation of mTOR pathway. HPB (Oxford) 2018; 20:729-738. [PMID: 29571618 DOI: 10.1016/j.hpb.2018.02.636] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Revised: 02/21/2018] [Accepted: 02/24/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND ALPPS procedure has been introduced to increase the volume of future liver remnant. The mechanisms underlying the accelerated regeneration observed with ALPPS are unknown. It was hypothesized that AMPK/mTOR is activated as an integrating pathway for metabolic signals leading to proliferation and cell growth. Our aim was to analyze increase in liver volume, proliferation parameters and expression of AMPK/mTOR pathway-related molecules in patients undergoing ALPPS. METHODS A single center prospective study of patients undergoing ALPPS was performed from 2013 to 2015. Liver and serum samples, clinical laboratory results and CT-scan data were obtained. ELISA, Ki-67 immunostaining and qRT-PCR were performed in deportalized and remnant liver tissue in both stages of the procedure. RESULTS 11 patients were enrolled. Remnant liver volume increased 112 ± 63% (p < 0.05) in 9.1 ± 1.6 days. Proliferation-related cytokines IL-6, TNF-α, HGF and EGF significantly increased, while higher Ki-67 immunostaining and cyclin D expression were observed in remnant livers after ALPPS. mTOR, S6K1, 4E-BP1, TSC1 and TSC2 expression were significantly increased in remnant livers at second stage, while AMPK and Akt increased only in deportalized liver samples. CONCLUSION Rapid liver regeneration with ALPPS might be associated with hepatocyte proliferation induced by mTOR pathway activation.
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Affiliation(s)
- Mario Uribe
- Department of Surgery, Hospital del Salvador, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Sebastián Uribe-Echevarría
- Department of Surgery, Hospital del Salvador, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Carlos Mandiola
- Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - María I Zapata
- Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Francisco Riquelme
- Department of Surgery, Hospital del Salvador, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Pamela Romanque
- Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
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Ji R, Zuo S, Qiu S, Li P, Chan A, Sharr W, Lo CM. Combined associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) followed by left trisectionectomy and Whipple operation for PNET. Gland Surg 2018; 7:47-53. [PMID: 29629320 DOI: 10.21037/gs.2017.11.15] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Pancreatic neuroendocrine tumor (PNET) is slow-growing, and account only for 2% of all pancreatic primary tumors. Surgical resection is still the only curative treatment for PNET patients. Unfortunately, most of PNETs was found with unresectable multiple liver metastases and extrahepatic metastasis as their characteristics of non-functional and asymptomatic. With advances in liver surgery in these years, especially combined associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), provide a new curative surgical treatment for PNET with liver metastases patient. Here we report a PNET with multiple liver metastases case underwent ALPPS (followed by left trisectionectomy) and Whipple operation within one-stage.
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Affiliation(s)
- Ren Ji
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Shi Zuo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Siyuan Qiu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Ping Li
- Division of Pathology, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Albert Chan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - William Sharr
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Chung Mau Lo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
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Lau WY, Lai EC. Modifications of ALPPS - from complex to more complex or from complex to less complex operations. Hepatobiliary Pancreat Dis Int 2017; 16:346-352. [PMID: 28823363 DOI: 10.1016/s1499-3872(17)60034-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 05/12/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been developed to induce rapid liver hypertrophy to reduce the chance of post-hepatectomy liver failure in patients with borderline or insufficient future liver remnant. ALPPS is still in an early developmental stage and its techniques have not been standardized. This study aimed to review the technical modifications of the conventional ALPPS procedure. DATA SOURCES Studies were identified by searching MEDLINE and PubMed for articles published from January 2007 to December 2016 using the keywords "associating liver partition and portal vein ligation for staged hepatectomy" and "ALPPS". Additional articles were identified by a manual search of references from key articles. RESULTS There have been a lot of modifications of the conventional ALPPS. These are classified as: (1) modifications aiming to improve surgical results; (2) modifications aiming to expand surgical indications; (3) salvage ALPPS; (4) ALPPS using the minimally invasive approach. Some of these modifications have made the conventional ALPPS procedure to become even more complex, although there have also been other attempts to make the procedure less complex. The results of most of these modifications have been reported in small case series or case reports. We need better well-designed studies to establish the true roles of these modifications. However, it is interesting to see how this conventional ALPPS procedure has evolved since its introduction. CONCLUSIONS There is a trend for the use of minimally invasive procedure in the phase 1 or 2 of the conventional ALPPS procedure. Some of these modifications have expanded the use of ALPPS in patients who have been considered to have unresectable liver tumors. The long-term oncological outcomes of these modifications are still unknown.
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Affiliation(s)
- Wan Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
| | - Eric Ch Lai
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China
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Abstract
OBJECTIVE We describe a modified procedure associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) including portal pedicle preservation during parenchymal division, thus avoiding necrosis. BACKGROUND Although ALPPS recently has been advocated for treating advanced liver tumors, sepsis originating from the ischemic area produced by parenchymal division increases mortality, accounting for one-third of postoperative deaths. METHODS Our procedure differs from the original ALPPS technique by sparing portal pedicles at the transection plane, thus maintaining blood supply. The preserved pedicles are segment 4 (S4) in right lobectomy plus right portal vein ligation (PVL), S1 in extended right hepatectomy (extended to S1) plus right PVL, lateral portal pedicles of the right paramedian sector (RPS) in extended right lateral sectoriectomy plus lateral PVL, and both portal pedicles of the lateral RPS and S1 in extended right lateral sectoriectomy with S1 resection plus lateral PVL. RESULTS These procedures were performed in 5 patients. Morbidity rates at first- and second-stage operations were 0% and 80%, without mortality. Mean hypertrophy of the future liver remnant was 1.638 ± 0.384 a week after the first-stage procedure. CONCLUSIONS Our technique stimulates rapid hypertrophy and may improve safety in ALPPS.
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Modified ALPPS procedures: more safety through less invasive surgery. Langenbecks Arch Surg 2017; 402:563-574. [PMID: 28493147 DOI: 10.1007/s00423-017-1588-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE Although associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been advocated for treating advanced liver tumors, increased morbidity and mortality remain serious problems. Many modified procedures have been devised to improve patient safety, but some confusion persists as to benefits and risks. METHODS Modifications to ALPPS as originally reported were reviewed to clarify their contributions to safety and their clinical relevance. RESULTS A variety of modifications are explained and considered. Modifications mainly aim to reduce adhesions, prevent tumor spread, avoid devascularization during liver splitting, and reduce surgical severity. Such changes aiming to increase safety and reduce invasiveness are needed to avoid high morbidity and mortality rates with this innovative procedure. However, these modified procedures still require more meaningful statistical comparisons of outcome. CONCLUSIONS Prospective controlled studies are needed to confirm which modified procedures should be adopted in a standardized manner as an alternative to the original ALPPS. Further, we need to further explore mechanisms of liver regeneration, functional recovery, histopathologic changes of hepatocytes, and blood distribution during ALPPS simultaneously to developing and evaluating modifications of the procedure.
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Sanei B, Sheikhbahaei S, Sanei MH, Bahreini A, Jafari HR. Associating liver partition and portal vein ligation for staged hepatectomy: A surgical technique for liver resections. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2017; 22:52. [PMID: 28567071 PMCID: PMC5426088 DOI: 10.4103/jrms.jrms_829_16] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Revised: 01/02/2017] [Accepted: 01/29/2017] [Indexed: 12/27/2022]
Abstract
Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel surgical technique liver resection in traditionally nonresectable primary intrahepatic tumors or colorectal liver metastases. Materials and Methods: From June 2013 to March 2014, patients with primary tumor of liver or colorectal tumors with liver metastasis were selected to evaluate whether they met the initial criteria for ALPPS procedure. Results: Nine patients enrolled in the study with primary diagnoses of colon and rectosigmoid cancer, carcinoid tumor, gastrointestinal stromal tumor of small intestine, hepatocellular carcinoma, and pancreatic neuroendocrine tumor (PNET). Four candidates excluded from the study prior or during the first step operation due to fatty liver, hepatic fibrosis, peritoneal seeding, and multiple small intestine metastases. Five patients underwent two stages of ALPPS with the interval of about 1 week. Liver hypertrophy was 100% among our candidates after the initial step. One postoperative death happened because of massive pulmonary thromboembolism Recurrence of liver metastasis was seen in one patient. Hepatic failure Class B and A were observed in two patients which did not progress during follow-up period. One patient developed an enterocutaneous fistula. Discussion: We recommend to use 2 organ bags, one for wrapping right lobe and the other one for covering visceral organs and also do liver biopsy in suspicious cases of damaged liver parenchyma and laparoscopic exploration of abdomen for seeding and multiple metastases prior to laparotomy. Conclusion: As the procedure has not been well established and verified by oncologists yet, further studies are required to define the exact indications of ALPPS.
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Affiliation(s)
- Behnam Sanei
- Department of Liver Transplant and Hepatobiliary and Pancreatic Surgery, Isfahan, Iran.,Department of General Surgery, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Saba Sheikhbahaei
- Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Amin Bahreini
- Department of Liver Transplant and Hepatobiliary and Pancreatic Surgery, Ahvaz, Iran.,Department of General Surgery, Jundishapour University of Medical Sciences, Ahvaz, Iran
| | - Hamid Reza Jafari
- Department of General Surgery, Isfahan University of Medical Sciences, Isfahan, Iran
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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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Coimbra FJF, Ribeiro HSDC, Marques MC, Herman P, Chojniak R, Kalil AN, Wiermann EG, Cavallero SRDA, Coelho FF, Fernandes PHDS, Silvestrini AA, Almeida MFA, de Araújo ALE, Pitombo M, Teixeira HM, Waechter FL, Ferreira FG, Diniz AL, D'Ippolito G, D'Ippolito G, Begnami MDFDS, Prolla G, Balzan SMP, de Oliveira TB, Szultan LA, Lendoire J, Torres OJM. FIRST BRAZILIAN CONSENSUS ON MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 1: PRE-TREATMENT EVALUATION. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2016; 28:222-30. [PMID: 26734788 PMCID: PMC4755170 DOI: 10.1590/s0102-6720201500040002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 08/11/2015] [Indexed: 02/07/2023]
Abstract
Background : Liver metastases of colorectal cancer are frequent and potentially fatal event
in the evolution of patients with these tumors. Aim : In this module, was contextualized the clinical situations and parameterized
epidemiological data and results of the various treatment modalities established.
Method: Was realized deep discussion on detecting and staging metastatic colorectal
cancer, as well as employment of imaging methods in the evaluation of response to
instituted systemic therapy. Results : The next step was based on the definition of which patients would have their
metastases considered resectable and how to expand the amount of patients elegible
for modalities with curative intent. Conclusion : Were presented clinical, pathological and molecular prognostic factors,
validated to be taken into account in clinical practice.
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Affiliation(s)
| | | | | | - Paulo Herman
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
| | - Rubens Chojniak
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
| | | | | | | | | | | | | | | | | | - Marcos Pitombo
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
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Vennarecci G, Grazi GL, Sperduti I, Busi Rizzi E, Felli E, Antonini M, D'Offizi G, Ettorre GM. ALPPS for primary and secondary liver tumors. Int J Surg 2016; 30:38-44. [DOI: 10.1016/j.ijsu.2016.04.031] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 03/24/2016] [Accepted: 04/05/2016] [Indexed: 12/16/2022]
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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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15
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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 2016; 159:1058-1072. [PMID: 26747229 DOI: 10.1016/j.surg.2015.11.013] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [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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16
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Abstract
The nuances of determining resectability for liver tumors can be difficult to navigate, owing to the variety of primary and secondary malignancies involving the liver, the range of patient-specific factors to consider, and the hepatic anatomic and functional variability that seems inevitable. The basic principles, however, are simple;if surgery is deemed appropriate from an oncologic standpoint, the patient is in reasonably good health, and the tumor can be safely removed without compromising the integrity of the future remnant, nearly all patients will be candidates for resection.
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Affiliation(s)
- Cecilia G Ethun
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, Building C, 2nd Floor, Atlanta, GA 30322, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, Building C, 2nd Floor, Atlanta, GA 30322, USA.
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17
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Matsuo K, Murakami T, Kawaguchi D, Hiroshima Y, Koda K, Yamazaki K, Ishida Y, Tanaka K. Histologic features after surgery associating liver partition and portal vein ligation for staged hepatectomy versus those after hepatectomy with portal vein embolization. Surgery 2016; 159:1289-98. [PMID: 26775576 DOI: 10.1016/j.surg.2015.12.004] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 11/17/2015] [Accepted: 12/06/2015] [Indexed: 12/28/2022]
Abstract
OBJECTIVE We compared histologic findings in nonneoplastic portions of liver resected during surgery associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) with those from hepatectomy after portal vein embolization (PVE). SUMMARY BACKGROUND DATA Effects of congestion and ischemia in ALPPS on hepatocyte regeneration are incompletely understood, as are those on hepatocyte maturity. METHODS Specimens obtained from 8 patients treated with ALPPS and from 14 patients treated with hepatectomy after PVE were examined by light and electron microscopy. RESULTS Extrapolated kinetic growth of the future liver remnant (FLR) for ALPPS was 14.4 ± 4.8 mL/d, which was faster than for PVE (3.6 ± 2.2 mL/d; P < .001). Microscopically, the FLR showed greater hepatocyte cell density and smaller hepatocyte size in ALPPS than in PVE (P < .01 for each). Bright-appearing hepatocytes and sinusoidal narrowing were more frequent in ALPPS (50% and 50%) than in PVE (0% and 8.3%; P = .025 for each). In the deportalized ventral aspect of the anterior section, hepatocyte atrophy, hepatocyte degeneration or necrosis, sinusoidal dilation, fibrosis, and congestion were more frequent in ALPPS than in PVE (P = .001, P = .002, P < .001, and P < .001, respectively). Electron microscopy frequently showed vacant-appearing hepatocytic cytoplasm filled with glycogen granules in the FLR in ALPPS. Fewer cytoplasmic organelles and lipofuscin granules were observed in ALPPS than in PVE. CONCLUSION In the FLR, regenerative hepatocytes in ALPPS were morphologically immature compared with PVE. ALPPS should be performed with caution, considering limited functional increase in the FLR reflecting immaturity of the regenerative hepatocytes.
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Affiliation(s)
- Kenichi Matsuo
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Takashi Murakami
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Daisuke Kawaguchi
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Yukihiko Hiroshima
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Keiji Koda
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Kazuto Yamazaki
- Division of Diagnostic Pathology, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Yasuo Ishida
- Division of Diagnostic Pathology, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Kuniya Tanaka
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.
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18
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Truant S, Pruvot FR. Is there still a room to improve the safety of ALPPS procedure? A new technical note. Eur J Surg Oncol 2015; 41:1554-5. [DOI: 10.1016/j.ejso.2015.08.151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Accepted: 08/13/2015] [Indexed: 11/27/2022] Open
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20
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Mei Y, Peng CJ, Li WN, Li XX, Xie WT, Shu DJ, Zhang JG. Surgical treatment of hilar cholangiocarcinoma: New advances. Shijie Huaren Xiaohua Zazhi 2015; 23:2907-2912. [DOI: 10.11569/wcjd.v23.i18.2907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hilar cholangiocarcinoma, a malignant tumor that occurs in the left and right hepatic duct, is the most common form of bile duct carcinoma. Early diagnosis of hilar cholangiocarcinoma is difficult, and the majority of patients are diagnosed in advanced stages. Therefore, surgery for this malignancy is difficult, has high risk, and is associated with a poor prognosis. In recent years, with the development of imaging technology and extended radical surgery, the preoperative diagnosis and surgical treatment of hilar cholangiocarcinoma have been improved. However, hilar cholangiocarcinoma still has a low cure rate, high complication rate, and poor prognosis. Therefore, we should strengthen the research on the susceptible factors and biological characteristics of hilar cholangiocarcinoma, and improve early diagnosis. Currently, although there has been no unified standard for the resectability of the tumor, surgery combined with partial hepatectomy is strongly recommended in patients without surgical contraindication. This paper reviews the recent progress in surgical treatment of hilar cholangiocarcinoma.
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Schadde E, Ardiles V, Slankamenac K, Tschuor C, Sergeant G, Amacker N, Baumgart J, Croome K, Hernandez-Alejandro R, Lang H, de Santibaňes E, Clavien PA. 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. World J Surg 2015; 38:1510-9. [PMID: 24748319 DOI: 10.1007/s00268-014-2513-3] [Citation(s) in RCA: 209] [Impact Index Per Article: 20.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Portal vein occlusion to increase the size of the future liver remnant (FLR) is well established, using portal vein ligation (PVL) or embolization (PVE) followed by resection 4-8 weeks later. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL and complete parenchymal transection, followed by hepatectomy within 1-2 weeks. ALPPS has been recently introduced but remains controversial. We compare the ability of ALPPS versus PVE or PVL for complete tumor resection. METHODS A retrospective review of all patients undergoing ALPPS or conventional staged hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and 2012 was performed. Patients with primary liver tumors and liver metastases were included. Primary endpoint was complete tumor resection. Secondary endpoints include 90-day mortality, complications, FLR increase, time to resection, and tumor recurrence. RESULTS Forty-eight patients with ALPPS were compared with 83 patients with conventional-staged hepatectomies. Eighty-three percent (40/48 patients) of ALPPS patients achieved complete resection compared with 66 % (55/83 patients) in PVE/PVL (odds ratio 3.34, p = 0.027). Ninety-day mortality in ALPPS and PVE/PVL was 15 and 6 %, respectively (p = 0.2). Extrapolated growth rate was 11 times higher in ALPPS (34.8 cc/day; interquartile range (IQR) 26-49) compared with PVE/PVL (3 cc/day; IQR2-6; p = 0.001). Tumor recurrence at 1 year was 54 versus 52 % for ALPPS and PVE/PVL, respectively (p = 0.7). CONCLUSIONS This study provides evidence that ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors at the cost of a high mortality. The technique is promising but should currently not be used outside of studies and registries.
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Affiliation(s)
- Erik Schadde
- Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
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22
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The ALPPS procedure: a surgical option for hepatocellular carcinoma with major vascular invasion. World J Surg 2015; 38:1498-503. [PMID: 24146197 DOI: 10.1007/s00268-013-2296-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) tends to have a particular invasiveness toward the portal vein (PV) branches and hepatic veins. This situation can hamper major surgical resection with a risk of postoperative liver failure due to the small future liver remnant (FLR) in cirrhotic livers. These patients are then usually directed to palliative treatments with poor results. The associating liver partition and PV ligation (PVL) in staged hepatectomy (ALPPS) strategy is one of the main surgical innovations in recent years in the field of liver surgical oncology. The ALPPS approach could allow surgical resection in patients with HCC and associated major vascular invasion. METHODS Among 1,143 liver resection performed in our center, the ALPPS approach was employed in order to induce rapid hypertrophy of the left FLR in patients with HCC and associated major vascular invasion. This strategy consists of combining the in situ splitting of the liver along the main portal scissura or on the right side of the falciform ligament and PVL in a strategy of staged hepatectomy. RESULTS In our experience the ALPPS approach allowed us to achieve a sufficient FLR in two cases of HCC with major vascular invasion, in which the classic two-stage strategy could not be applied. In both cases the patients could undergo major hepatectomies without mortality. CONCLUSIONS This novel strategy could expand the number of patients undergoing major liver resections that were previously considered non-resectable because of the risk of liver decompensation for an insufficient FLR.
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23
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Bertens KA, Hawel J, Lung K, Buac S, Pineda-Solis K, Hernandez-Alejandro R. ALPPS: challenging the concept of unresectability--a systematic review. Int J Surg 2014; 13:280-287. [PMID: 25496851 DOI: 10.1016/j.ijsu.2014.12.008] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2014] [Accepted: 12/07/2014] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hepatic resection for malignancy is limited by the amount of liver parenchyma left behind. As a result, two-staged hepatectomy and portal vein occlusion (PVO) have become part of the treatment algorithm. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been recently described as a method to stimulate rapid and profound hypertrophy. MATERIALS AND METHODS A systematic review of the literature pertaining to ALPPS was undertaken. Peer-reviewed articles relating to portal vein ligation (PVL) and in situ split (ISS) of the parenchyma were included. RESULTS To date, ALPPS has been employed for a variety of primary and metastatic liver tumors. In early case series, the perioperative morbidity and mortality was unacceptably high. However with careful patient selection and improved technique, many centers have reported a 0% 90-day mortality. The benefits of ALPPS include hypertrophy of 61-93% over a median 9-14 days, 95-100% completion of the second stage, and high likelihood of R0 resection (86-100%). DISCUSSION ALPPS is only indicated when a two-stage hepatectomy is necessary and the future liver remnant (FLR) is deemed inadequate (<30%). Use in patients with poor functional status, or advanced age (>70 years) is cautioned. Discretion should be used when considering this in patients with pathology other than colorectal liver metastases (CRLM), especially hilar tumors requiring biliary reconstruction. Biliary ligation during the first stage and routine lymphadenectomy of the hepatoduodenal ligament should be avoided. CONCLUSIONS A consensus on the indications and contraindications for ALPPS and a standardized operative protocol are needed.
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Affiliation(s)
- Kimberly A Bertens
- Department of Surgery, Schulich School of Medicine & Dentistry, University of Western Ontario, 339 Windermere Road, London, ON, Canada N6A 5A5
| | - Jeffrey Hawel
- Department of Surgery, Schulich School of Medicine & Dentistry, University of Western Ontario, 339 Windermere Road, London, ON, Canada N6A 5A5
| | - Kalvin Lung
- Department of Surgery, Schulich School of Medicine & Dentistry, University of Western Ontario, 339 Windermere Road, London, ON, Canada N6A 5A5
| | - Suzana Buac
- Department of Surgery, Schulich School of Medicine & Dentistry, University of Western Ontario, 339 Windermere Road, London, ON, Canada N6A 5A5
| | - Karen Pineda-Solis
- Department of Surgery, Schulich School of Medicine & Dentistry, University of Western Ontario, 339 Windermere Road, London, ON, Canada N6A 5A5; Multi-Organ Transplant Program, London Health Sciences Centre, 339 Windermere Road, London, ON, Canada N6A 5A5
| | - Roberto Hernandez-Alejandro
- Department of Surgery, Schulich School of Medicine & Dentistry, University of Western Ontario, 339 Windermere Road, London, ON, Canada N6A 5A5; Multi-Organ Transplant Program, London Health Sciences Centre, 339 Windermere Road, London, ON, Canada N6A 5A5.
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24
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Rescue ALPPS: Intraoperative Conversion to ALPPS during Synchronous Resection of Rectal Cancer and Liver Metastasis. Case Rep Surg 2014; 2014:487852. [PMID: 25506458 PMCID: PMC4259134 DOI: 10.1155/2014/487852] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 11/10/2014] [Indexed: 12/14/2022] Open
Abstract
Future liver remnant (FLR) is the most important deciding factor in planning for liver resection. Portal vein embolization (PVE) was first introduced in the 1980s to induce liver hypertrophy, enabling removal of multiple/bilobar tumors. PVE was later combined with sequential hepatectomies with the aim of allowing the liver remnant to hypertrophy (15–20%) between procedures. However, the interval between the two procedures (3–8 weeks) put patients at risk for disease progression. With portal vein ligation alone or when combined with sequential hepatectomy, there is also a risk for inadequate liver hypertrophy because of intrahepatic portal collaterals leading to a high (19–30%) dropout rate. The ALPPS procedure (associating liver partition and portal vein ligation for staged hepatectomy) was recently developed as a feasible means to perform extensive/bilobar liver resections. It produces rapid, enormous hypertrophy of the remnant, making previously unresectable lesions resectable. Indications for ALPPS include any extensive liver resection with inadequate FLR. Here we present a novel indication for ALPPS as a rescue when inadequate FLR was faced intraoperatively, during a simultaneous resection of rectal primary and liver metastasis.
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25
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Eshkenazy R, Dreznik Y, Lahat E, Zakai BB, Zendel A, Ariche A. Small for size liver remnant following resection: prevention and management. Hepatobiliary Surg Nutr 2014; 3:303-12. [PMID: 25392842 DOI: 10.3978/j.issn.2304-3881.2014.09.08] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 09/09/2014] [Indexed: 12/11/2022]
Abstract
In the latest decades an important change was registered in liver surgery, however the management of liver cirrhosis or small size hepatic remnant still remains a challenge. Currently post-hepatectomy liver failure (PLF) is the major cause of death after liver resection often associated with sepsis and ischemia-reperfusion injury (IRI). ''Small-for-size'' syndrome (SFSS) and PFL have similar mechanism presenting reduction of liver mass and portal hyper flow beyond a certain threshold. Few methods are described to prevent both syndromes, in the preoperative, perioperative and postoperative stages. Additionally to portal vein embolization (PVE), radiological examinations (mainly CT and/or MRI), and more recently 3D computed tomography are fundamental to quantify the liver volume (LV) at a preoperative stage. During surgery, in order to limit parenchymal damage and optimize regenerative capacity, some hepatoprotective measures may be employed, among them: intermittent portal clamping and hypothermic liver preservation. Regarding the treatment, since PLF is a quite complex disease, it is required a multi-disciplinary approach, where it management must be undertaken in conjunction with critical care, hepatology, microbiology and radiology services. The size of the liver cannot be considered the main variable in the development of liver dysfunction after extended hepatectomies. Additional characteristics should be taken into account, such as: the future liver remnant; the portal blood flow and pressure and the exploration of the potential effects of regeneration preconditioning are all promising strategies that could help to expand the indications and increase the safety of liver surgery.
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Affiliation(s)
- Rony Eshkenazy
- 1 Department of HPB Surgery, 2 Department of Surgery B, 3 Department of Surgery C, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Yael Dreznik
- 1 Department of HPB Surgery, 2 Department of Surgery B, 3 Department of Surgery C, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Eylon Lahat
- 1 Department of HPB Surgery, 2 Department of Surgery B, 3 Department of Surgery C, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Barak Bar Zakai
- 1 Department of HPB Surgery, 2 Department of Surgery B, 3 Department of Surgery C, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Alex Zendel
- 1 Department of HPB Surgery, 2 Department of Surgery B, 3 Department of Surgery C, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Arie Ariche
- 1 Department of HPB Surgery, 2 Department of Surgery B, 3 Department of Surgery C, Chaim Sheba Medical Center, Tel-Hashomer, Israel
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26
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Vennarecci G, Laurenzi A, Levi Sandri GB, Busi Rizzi E, Cristofaro M, Montalbano M, Piselli P, Andreoli A, D'Offizi G, Ettorre GM. The ALPPS procedure for hepatocellular carcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2014; 40:982-988. [PMID: 24767805 DOI: 10.1016/j.ejso.2014.04.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 03/31/2014] [Accepted: 04/01/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND The main limiting factor to major hepatic resections is the amount of the future liver remnant (FLR). Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a procedure which induces a rapid hypertrophy of the FLR in patients with non-resectable liver tumours. METHODS ALPPS is a surgical technique of in-situ splitting of the liver along the main portal scissura or the right side of the falciform ligament, in association with portal vein ligation in order to induce a rapid hypertrophy of the left FLR. RESULTS The median FLR volume increase was 18.7% within one week after the first step and 38.6% after the second step. At the first step the median operating time was 300 min, blood transfusions were not required in any case, median blood loss was 150 cc. At the second step median operating time was 180 min, median blood loss was 50 cc, none of the patients required intra-operative blood. All patients are alive at a median follow up of 9 months. CONCLUSIONS This novel strategy seems to be feasible even in the context of a cirrhotic liver, and demonstrates the capacity to reach a sufficient FLR within a shorter interval of time.
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Affiliation(s)
- G Vennarecci
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy.
| | - A Laurenzi
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| | - G B Levi Sandri
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| | - E Busi Rizzi
- Division of Radiology, S. Camillo Hospital, Rome, Lazio, Italy
| | - M Cristofaro
- Division of Radiology, S. Camillo Hospital, Rome, Lazio, Italy
| | - M Montalbano
- Hepatology and Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | - P Piselli
- Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | - A Andreoli
- Hepatology, S. Camillo Hospital, Rome, Lazio, Italy
| | - G D'Offizi
- Hepatology and Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | - G M Ettorre
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
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27
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Oldhafer KJ, Donati M, Jenner RM, Stang A, Stavrou GA. ALPPS for patients with colorectal liver metastases: effective liver hypertrophy, but early tumor recurrence. World J Surg 2014; 38:1504-1509. [PMID: 24326456 DOI: 10.1007/s00268-013-2401-2] [Citation(s) in RCA: 113] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a promising method to increase resectability rates of liver tumors. Little has been published about oncological results so far. This report describes clinical evidence regarding a possible effect of ALPPS on tumor recurrence. METHODS Ten ALPPS procedures were performed for otherwise non-resectable colorectal liver metastases. Seven of these ten patients had a follow-up of at least 3 months and were analyzed for tumor recurrence. RESULTS Six of these seven patients had tumor recurrence to the liver. Three of seven patients presented with lung metastases, occurring earlier than liver metastases in two of three cases. One patient with a follow-up of 3 months had no visible recurrent disease, but increasing carcinoembryonic antigen levels. CONCLUSIONS The patient group operable only through ALPPS is at high risk for recurrence and early tumor progression. Still, this new method is the only chance for an oncological treatment strategy including a surgical approach and possibly better outcome.
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Affiliation(s)
- Karl J Oldhafer
- Division of General and Abdominal Surgery, Department of Surgery, Asklepios Hospital Barmbek, Ruebenkamp 220, 22291, Hamburg, Germany,
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28
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Ratti F, Cipriani F, Gagliano A, Catena M, Paganelli M, Aldrighetti L. Defining indications to ALPPS procedure: technical aspects and open issues. Updates Surg 2013; 66:41-9. [PMID: 24343420 DOI: 10.1007/s13304-013-0243-y] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Accepted: 11/30/2013] [Indexed: 12/12/2022]
Abstract
The limit to surgical treatment of patients with hepatic tumors is represented by the proportion of residual hepatic parenchyma at the end of surgery (FLR, future liver remnant) that provides an estimation of the risk of postoperative liver failure. Recently, a new two-stage technique has been developed with the acronym (ALPPS) associating liver partitioning and portal vein ligation for staged hepatectomy with the aim of obtaining a more rapid and effective increase in FLR, even though indications are not clear yet. Between January and December 2012, eight patients were candidates to ALPPS at the Hepatobiliary Surgery Unit of San Raffaele Hospital, Milan. The first three patients (Series 1) underwent right trisectionectomy and were affected by tumors infiltrating biliary confluence, while the others (Series 2) were candidates to right hepatectomy for colorectal liver metastases. Two patients were then excluded from Series 2 because intraoperative finding of irresectable disease. Intra- and postoperative outcome was evaluated with the aim of defining indications to ALPPS. All patients reached an adequate FLR after a median of 7.5 days from the first procedure (rate of program completion 100 %). In Series 1 two patients developed complications related to bile leakage from the raw surface of the liver to be resected and septic events secondary to ischemic necrosis of the liver segment IV. One patient died following multi-organ failure secondary to sepsis. In Series 2 postoperative course was uneventful in all the patients, and in particular no patient showed disease progression between the two procedures or signs of postoperative liver failure. ALPPS approach was initially considered suitable for patients affected by Klatskin tumors who require, despite a small tumor volume, extended hepatectomies associated with surgery of the biliary tract: the analysis of this first series of patients has led to a re-evaluation of the indication to this strategy, as a consequence of encountered criticisms. Actually only a subset of patients affected by colorectal liver metastases are candidates to ALPPS.
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Affiliation(s)
- Francesca Ratti
- General Surgery Department, Hepatobiliary Surgery Unit, IRCCS H San Raffaele, Via Olgettina 60, 20132, Milan, Italy,
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Donati M, Stavrou GA, Oldhafer KJ. Current position of ALPPS in the surgical landscape of CRLM treatment proposals. World J Gastroenterol 2013; 19:6548-6554. [PMID: 24151380 PMCID: PMC3801367 DOI: 10.3748/wjg.v19.i39.6548] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Revised: 07/21/2013] [Accepted: 08/17/2013] [Indexed: 02/06/2023] Open
Abstract
The Authors summarize problems, criticisms but also advantages and indications regarding the recent surgical proposal of associating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) for the surgical management of colorectal liver metastases. Looking at published data, the technique, when compared with other traditional and well established methods such as PVL/portal vein embolisation (PVE), seems to give real advantages in terms of volumetric gain of future liver remnant. However, major concerns are raised in the literature and some questions remain unanswered, preliminary experiences seem to be promising. The method has been adopted all over the world over the last 2 years, even if oncological long-term results remain unknown, and benefit for patients is questionable. No prospective studies comparing traditional methods (PVE, PVL or classical 2 staged hepatectomy) with ALPPS are available to date. Technical reinterpretations of the original method were also proposed in order to enhance feasability and increase safety of the technique. More data about morbidity and mortality are also expected. The real role of ALPPS is, to date, still to be established. Large clinical studies, even if, for ethical reasons, in well selected cohorts of patients, are expected to better define the indications for this new surgical strategy.
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Affiliation(s)
- Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan,
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Alvarez FA, Ardiles V, de Santibañes E. The ALPPS Approach for the Management of Colorectal Carcinoma Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2013. [DOI: 10.1007/s11888-013-0159-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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