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Impact of neoadjuvant chemotherapy on post-hepatectomy regeneration for patients with colorectal cancer liver metastasis - Systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:533-541. [PMID: 36631347 DOI: 10.1016/j.ejso.2022.12.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 12/18/2022] [Accepted: 12/30/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Today, there is still debate on the impact of neoadjuvant chemotherapy (NeoChem) on liver regeneration (LivReg). The objectives of this study were to assess the impact of NeoChem and its characteristics (addition of bevacizumab, number of cycles and time from end of NeoChem) on post-hepatectomy LivReg. MATERIAL & METHODS Studies reporting LivReg in patients submitted to liver resection were included. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases were searched. Only studies comparing NeoChem vs no chemotherapy or comparing chemotherapy characteristics from 1990 to present were included. Two researchers individually screened the identified records registered in a predesigned database. Primary outcome was future liver remnant regeneration rate (FLR3). Bias of the studies was evaluated with the ROBINS-I tool, and quality of evidence with the GRADE system. Data was presented as mean difference or standard mean difference. RESULTS Eight studies with a total of 681 patients were selected. Seven were retrospective and one prospective comparative cohort studies. In patients submitted to major hepatectomy, NeoChem did not have an impact on LivReg (MD 3.12, 95% CI -2,12-8.36, p 0,24). Adding bevacizumab to standard NeoChem was associated with better FLR3 (SMD 0.45, 95% CI 0.19-0.71, p 0.0006). DISCUSSION The main drawback of this review is the retrospective nature of the available studies. NeoChem does not have a negative impact on postoperative LivReg in patients submitted to liver resection. Regimens with bevacizumab seem to be associated with better postoperative LivReg rates when compared to standard NeoChem.
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Issues to be considered to address the future liver remnant prior to major hepatectomy. Surg Today 2020; 51:472-484. [PMID: 32894345 DOI: 10.1007/s00595-020-02088-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/08/2020] [Indexed: 02/08/2023]
Abstract
An accurate preoperative evaluation of the hepatic function and application of portal vein embolization in selected patients have helped improve the safety of major hepatectomy. In planning major hepatectomy, however, several issues remain to be addressed. The first is which cut-off values for serum total bilirubin level and prothrombin time should be used to define post-hepatectomy liver failure. Other issues include what minimum future liver remnant (FLR) volume is required; whether the total liver volume measured using computed tomography or the standard liver volume calculated based on the body surface area should be used to assess the adequacy of the FLR volume; whether there is a discrepancy between the FLR volume and function during the recovery period after portal vein embolization or hepatectomy; and how best the function of a specific FLR can be assessed. Various studies concerning these issues have been reported with controversial results. We should also be aware that different strategies and management are required for different types of liver damage, such as cirrhosis in hepatocellular carcinoma, cholangitis in biliary tract cancer, and chemotherapy-induced hepatic injury.
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Truant S, Baillet C, Gnemmi V, Fulbert M, Turpin A, Dardenne S, Leteurtre E, El Amrani M, Dharancy S, Dubuquoy L, Huglo D, Chesné C, Pruvot FR. The Impact of Modern Chemotherapy and Chemotherapy-Associated Liver Injuries (CALI) on Liver Function: Value of 99mTc-Labelled-Mebrofenin SPECT-Hepatobiliary Scintigraphy. Ann Surg Oncol 2020; 28:1959-1969. [PMID: 32833150 DOI: 10.1245/s10434-020-08988-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 04/16/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Chemotherapy is increasingly used before hepatic resection, with controversial impact regarding liver function. This study aimed to assess the capacity of 99mTc-labelled-mebrofenin SPECT-hepatobiliary scintigraphy (HBS) to predict liver dysfunction due to chemotherapy and/or chemotherapeutic-associated liver injuries (CALI), such as sinusoidal obstruction syndrome (SOS) and nonalcoholic steatohepatitis (NASH) activity score (NAS). METHODS From 2011 to 2015, all consecutive noncirrhotic patients scheduled for a major hepatectomy (≥ 3 segments) gave informed consent for preoperative SPECT-HBS allowing measurements of segmental liver function. As primary endpoint, HBS results were compared between patients with versus without (1) preoperative chemotherapy (≤ 3 months); and (2) CALI, mainly steatosis, NAS (Kleiner), or SOS (Rubbia-Brandt). Secondary endpoints were (1) other factors impairing function; and (2) impact of chemotherapy, and/or CALI on hepatocyte isolation outcome via liver tissues. RESULTS Among 115 patients, 55 (47.8%) received chemotherapy. Sixteen developed SOS and 35 NAS, with worse postoperative outcome. Overall, chemotherapy had no impact on liver function, except above 12 cycles. In patients with CALI, a steatosis ≥ 30% significantly compromised function, as well as NAS, especially grades 2-5. Conversely, SOS had no impact, although subjected to very low patients number with severe SOS. Other factors impairing function were diabetes, overweight/obesity, or fibrosis. Similarly, chemotherapy in 73 of 164 patients had no effect on hepatocytes isolation outcome; regarding CALI, steatosis ≥ 30% and NAS impaired the yield and/or viability of hepatocytes, but not SOS. CONCLUSIONS In this first large, prospective study, HBS appeared to be a valuable tool to select heavily treated patients at risk of liver dysfunction through steatosis or NAS.
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Affiliation(s)
- Stéphanie Truant
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France. .,CANTHER laboratory Cancer Heterogeneity, Plasticity and Resistance to Therapies UMR-S1277 INSERM, Team Mucins, Cancer and Drug Resistance, 59000, Lille, France.
| | - Clio Baillet
- Department of Nuclear Medicine, Univ. Lille, Lille, France
| | | | - Maxence Fulbert
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France
| | - Anthony Turpin
- Department of Medical Oncology, Univ. Lille, Lille, France
| | - Sabrina Dardenne
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France
| | | | - Mehdi El Amrani
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France.,CANTHER laboratory Cancer Heterogeneity, Plasticity and Resistance to Therapies UMR-S1277 INSERM, Team Mucins, Cancer and Drug Resistance, 59000, Lille, France
| | - Sébastien Dharancy
- Hepatology Unit, Univ. Lille, Lille, France.,LIRIC-Lille Inflammation Research International Center-U995, Univ. Lille, Inserm, CHU Lille, Lille, France
| | - Laurent Dubuquoy
- Hepatology Unit, Univ. Lille, Lille, France.,LIRIC-Lille Inflammation Research International Center-U995, Univ. Lille, Inserm, CHU Lille, Lille, France
| | - Damien Huglo
- Department of Nuclear Medicine, Univ. Lille, Lille, France
| | | | - François-René Pruvot
- Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France
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Truant S, Baillet C, Fulbert M, Olivier A, Sergent G, Turpin A, Boleslawski E, El Amrani M, Huglo D, Pruvot FR. Asymmetric kinetics of volume and function of the remnant liver after major hepatectomy as a key for postoperative outcome - A case-matched study. HPB (Oxford) 2020; 22:855-863. [PMID: 31669198 DOI: 10.1016/j.hpb.2019.10.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 08/22/2019] [Accepted: 10/01/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The kinetics of remnant liver (RL) function is unknown after major hepatectomy (MH), especially in case of post-hepatectomy liver failure (PHLF). This study investigated the change in RL function after MH using 99mTc-labelled-mebrofenin SPECT-scintigraphy and its correlation with RL volume and PHLF. METHODS From 2011 to 2015, 125 patients undergoing MH had volumetric assessment by CT and functional SPECT-scintigraphy preoperatively and at day 7 (POD7) and 1 month (1M). RL volume and function changes were compared in (i) overall population and (ii) 17 patients with vs. 42 without PHLF (ISGLS) matched on preoperative RL function. RESULTS Increase in RL function correlated poorly with volume increase at POD7 (r = 0.035, p = 0.43) and 1M (r = 0.394, p < 0.0001). Overall, function increase on POD7 (+38.8%) was lower than volume (+49.4%), but comparable at 1M (+78.8% vs. +73%). PHLF patients showed lower function increase on POD7 (+2.1% [-89%-77.8%] vs. +50% [-39%-218%]; p = 0.006). At 1M, 4 PHLF patients died with no function increase despite significant volumetric gain. CONCLUSIONS We first showed via sequential SPECT-scintigraphy that RL function increase after MH is slower than volume increase. A poor kinetic of function was correlated with PHLF as early as POD7, contrasting with substantial volume gain in PHLF patients.
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Affiliation(s)
- Stéphanie Truant
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France.
| | - Clio Baillet
- Department of Nuclear Medicine, CHU, Univ Nord de France, F-59000 Lille, France
| | - Maxence Fulbert
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France
| | - Anais Olivier
- Department of Nuclear Medicine, CHU, Univ Nord de France, F-59000 Lille, France
| | - Géraldine Sergent
- Department of Radiology, CHU, Univ Nord de France, F-59000 Lille, France
| | - Anthony Turpin
- Department of Medical Oncology, CHU, Univ Nord de France, F-59000 Lille, France
| | - Emmanuel Boleslawski
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France
| | - Mehdi El Amrani
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France
| | - Damien Huglo
- Department of Nuclear Medicine, CHU, Univ Nord de France, F-59000 Lille, France
| | - François-René Pruvot
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France
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Gong WF, Zhong JH, Lu Z, Zhang QM, Zhang ZY, Chen CZ, Liu X, Ma L, Zhang ZM, Xiang BD, Li LQ. Evaluation of liver regeneration and post-hepatectomy liver failure after hemihepatectomy in patients with hepatocellular carcinoma. Biosci Rep 2019; 39:BSR20190088. [PMID: 31383787 PMCID: PMC6706596 DOI: 10.1042/bsr20190088] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 07/03/2019] [Accepted: 07/30/2019] [Indexed: 02/06/2023] Open
Abstract
Aim: To explore clinical factors associated with extent of liver regeneration after hemihepatectomy to treat hepatocellular carcinoma (HCC).Methods: Future liver remnant volume (as a percentage of functional liver volume, %FLRV) and remnant liver volume were measured preoperatively and at 1, 5, 9, and 13 weeks postoperatively.Results: After hepatectomy, 1 of 125 patients (0.8%) died within 3 months, 13 (10.4%) experienced liver failure, and 99 (79.2%) experienced complications. %FLRV was able to predict liver failure with an area under the receiver operating characteristic curve of 0.900, and a cut-off value of 42.7% showed sensitivity of 85.7% and specificity of 88.6%. Postoperative median growth ratio was 21.3% at 1 week, 30.9% at 5 weeks, 34.6% at 9 weeks, and 37.1% at 13 weeks. Multivariate analysis identified three predictors associated with liver regeneration: FLRV < 601 cm3, %FLRV, and liver cirrhosis. At postoperative weeks (POWs) 1 and 5, liver function indicators were significantly better among patients showing high extent of regeneration than among those showing low extent, but these differences disappeared by POW 9.Conclusions: FLRV, %FLRV, and liver cirrhosis strongly influence extent of liver regeneration after hepatectomy. %FLRV values below 42.7% are associated with greater risk of post-hepatectomy liver failure.
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Affiliation(s)
- Wen-Feng Gong
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Zhan Lu
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Qiu-Ming Zhang
- General Medicine Department, The First People's Hospital of Qinzhou, Qinzhou, China
| | - Zhi-Yuan Zhang
- Hepatobiliary Surgery Department, The Fifth Affiliated Hospital of Guangxi Medical University, Guigang, China
| | - Chang-Zhi Chen
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Xu Liu
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Zhi-Ming Zhang
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Bang-De Xiang
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Le-Qun Li
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
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Valverde A, Ciria R, Caballero-Villarraso J, Aguilar-Melero P, Ferrín G, Ranchal I, Linares C, Herencia C, González-Rubio S, de la Mata M, Naranjo Á, Briceño J. Bevacizumab Allows Preservation of Liver Function and its Regenerative Capacity after Major Hepatectomy. Anticancer Agents Med Chem 2019; 19:1388-1398. [PMID: 31038079 DOI: 10.2174/1871520619666190417162409] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Revised: 02/25/2019] [Accepted: 03/26/2019] [Indexed: 02/01/2023]
Abstract
BACKGROUND Parallel to the safety of liver resections, new chemotherapy drugs have emerged for the control of liver metastases. However, there is unclear evidence about the combination of intensive BVZ-therapy and extended resections. The main aim was to analyse the impact of Bevacizumab (BVZ) in terms of liver safety and tolerability in two experimental models: a basal-toxicity situation and after major hepatectomy. METHODS Eighty male-Wistar rats were grouped as toxicity analysis (sham-operated rats-OS-) and regeneration after- surgery analysis (hepatectomy rats-H-). Eight further subgroups were created according to sacrifice (6- hours-6h- or 24-hours-24h-) and dose (μg) of BVZ (none, 100, 200, 400). Several measurements were performed, including biochemical serum samples, histopathological analysis, cytokines (IL-6, TNF-α, TGF-β), oxidative-stress (GSH/GSSG, ATP), lipid-peroxidation (TBARS) and epidermal and vascular endothelium growth-factors (EGF and VEGF). RESULTS In the toxicity analysis, safe results with BVZ were observed, with no significant differences among the groups. A trend towards a lower oxidative status was observed in the OS 6 h-100, -200 and -400 versus the OS 6 h-none group. Similar results were observed in the hepatectomy model, with stable oxidative-stress-index and IL-6, TNF- α, and TGF- β levels. Despite higher lipid peroxidation status, overall regeneration was preserved. As expected, VEGF was almost undetectable in BVZ-treated groups after resection, but not in the non-resection group. CONCLUSION It was concluded that liver status was not impaired by BVZ even at the high-dose. Similarly, liver regeneration after extended hepatectomy in BVZ-treated animals was well-preserved. Extended liver resections may be encouraged in BVZ-treated patients due to its excellent tolerability and good liver regeneration status.
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Affiliation(s)
- Amparo Valverde
- Unit of Hepatobiliary Surgery and Liver Transplantation, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain
| | - Rubén Ciria
- Unit of Hepatobiliary Surgery and Liver Transplantation, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain
| | - Javier Caballero-Villarraso
- Clinical Analyses Service & Department of Biochemistry and Molecular Biology, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain
| | | | - Gustavo Ferrín
- Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain
| | - Isidora Ranchal
- Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain
| | - Clara Linares
- Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain
| | - Carmen Herencia
- Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain
| | - Sandra González-Rubio
- Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain
| | - Manuel de la Mata
- Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain
| | - Álvaro Naranjo
- Unit of Hepatobiliary Surgery and Liver Transplantation, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain
| | - Javier Briceño
- Unit of Hepatobiliary Surgery and Liver Transplantation, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain
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Valdimarsson VT, Hellberg K, Brismar TB, Sparrelid E, Sturesson C. Repeat procedures for recurrent colorectal liver metastases: analysis of long-term liver regeneration and outcome. Cancer Manag Res 2019; 11:2617-2622. [PMID: 31118767 PMCID: PMC6497974 DOI: 10.2147/cmar.s191653] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Accepted: 01/21/2019] [Indexed: 12/31/2022] Open
Abstract
Background and aim: Repeat hepatectomy is increasingly performed for the management of recurrent colorectal liver metastases (CRLM). The aim of this study was to evaluate long-term functional liver volume (FLV) after a second hepatic procedure and to measure survival outcome. Methods: In this retrospective cohort study, patients treated for recurrent CRLM in the years 2005-2015 at two liver centers were included. Total FLV was calculated before the first procedure and before and after the second procedure. Overall survival was calculated. Results: Eighty-two patients were identified. The median follow-up was 53 (40-71) months from the first procedure. The median interval between first and second procedure was 13 (8-22) months. The initial FLV was 1584 (1313-1927) mL. The FLV was 1438 (1204-1896) mL after the first procedure and 1470 (1172-1699) mL after the second procedure (P<0.001). After the second procedure, a total of ten patients (12%) had a residual liver volume of less than 75% of the initial liver volume. The 5-year overall survival was 37 (26-54)% after the second procedure. Conclusion: Small changes in FLV were found after two hepatic procedures but with considerable inter-individual variation. Patients selected for a repeated hepatic procedure for recurrent CRLM had an acceptable survival.
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Affiliation(s)
- Valentinus T Valdimarsson
- Department of Clinical Sciences Lund, Surgery, Lund University, Skane University Hospital, Lund, Sweden
| | - Katarina Hellberg
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Torkel B Brismar
- Division of Radiology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Ernesto Sparrelid
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Christian Sturesson
- Department of Clinical Sciences Lund, Surgery, Lund University, Skane University Hospital, Lund, Sweden
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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Yamaguchi T, Kokudo T, Akamatsu N, Kaneko J, Arita J, Sakamoto Y, Kokudo N, Hasegawa K. Liver Regeneration is Preserved After At Least Four Repeated Liver Resections for Hepatocellular Carcinoma. World J Surg 2018; 42:4070-4080. [PMID: 29947985 DOI: 10.1007/s00268-018-4714-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Repeated resection is known to prolong survival, with an acceptable morbidity rate, in patients with hepatocellular carcinoma. However, little is known about the effect of repeated liver resection on postoperative liver regeneration and liver function. The aim of this study is to determine the impact of repeated liver resections on the postoperative liver regeneration rate and liver function. METHODS A total of 71 patients, who had undergone more than three liver resections for hepatocellular carcinoma between May 2001 and December 2013 at a tertiary care hospital in Japan, were included in the analysis. Among them, CT-volumetric data for the first, second, third, and fourth or more resections were available for 36, 49, 53, and 24 patients. We analyzed the regeneration index (RI) defined as the postoperative TLV/preoperative TLV × 100 was calculated after each operation to measure the degree of regeneration. Liver function was evaluated using the indocyanine green retention rate at 15 min (ICG-R15). RESULTS No significant differences in RI were observed among the first, second, and third or more liver resection groups. No significant difference in the ICG R15 value was seen between the first liver resection group and the second or more liver resection group (P = 0.75). However, a significant difference in the RI was observed when the 1 segmentectomy or less liver resection group (median [range] RI 98.1 [72.9-119.9]) was compared with the 2 or more segmentectomy group (median [range] RI 90.5 [62.6-113.6]) (P = 0.005). CONCLUSION The regeneration process is maintained after as many as four repeated resections. Patients with sustained liver function can safely undergo repeated liver resections for recurrences of HCC.
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Affiliation(s)
- Takamune Yamaguchi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan.
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
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Preoperative Chemotherapy on Functional Liver Regeneration for Colorectal Liver Metastases Assessed With 99mTc-GSA SPECT/CT Imaging. Int Surg 2018. [DOI: 10.9738/intsurg-d-16-00209.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective:
To investigate the functional liver regeneration after chemotherapy and liver resection for colorectal liver metastases (CRLM).
Background/Purpose:
Preoperative chemotherapy followed by liver resection for CRLM has been increasing; however, its negative impact on liver regeneration remains unknown.
Methods:
From January 2009 to December 2013, we enrolled 40 selected patients who underwent major hepatectomy without viral hepatitis and severe liver fibrosis. CRLM patients with preoperative chemotherapy (CT-CRLM group, n = 12) and patients without preoperative chemotherapy (control group, n = 28) were evaluated. Liver volume (LV) and functional liver volume (FLV) was assessed using Tc-99m–labeled galactosyl human serum albumin (99mTc-GSA) scintigraphy, single-photon emission computed tomography (SPECT), CT-fused images. Preoperative, future remnant liver, and post 1-month values were compared.
Results:
Median course of preoperative chemotherapy was 8 (range: 6–16). Preoperative background factors were almost identical including resection rate and functional resection rate. In the CT-CRLM group and in the control group, the percentage increases in LV were 39.3% ± 29.0% and 23.2% ± 23.5% (P = 0.037), and FLV were 79.4% ± 43.1% and 57.0% ± 33.4% (P = 0.417), respectively; absolute differences in LV were 216.2 ± 155.7 cm3 and 148.7 ± 134.7 cm3 (P = 0.086) and FLV were 19.4% ± 8.5%/m2 and 17.4% ± 7.9%/m2 (P = 0.235), respectively. We found no obvious tendency for negative influence on liver functional regeneration by the preoperative regimens for CRLM.
Conclusions:
Several courses of preoperative chemotherapy may not affect functional liver regeneration for CRLM patients after major hepatectomy.
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Ozawa Y, Tamura T, Owada Y, Shimizu Y, Kemmochi A, Hisakura K, Matsuzaka T, Shimano H, Isoda H, Ohkohchi N. Evaluation of safety for hepatectomy in a novel mouse model with nonalcoholic-steatohepatitis. World J Gastroenterol 2018; 24:1622-1631. [PMID: 29686469 PMCID: PMC5910545 DOI: 10.3748/wjg.v24.i15.1622] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 03/16/2018] [Accepted: 03/25/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether the liver resection volume in a newly developed nonalcoholic steatohepatitis (NASH) model influences surgical outcome.
METHODS For establishment of a NASH model, mice were fed a high-fat diet for 4 wk, administered CCl4 for the last 2 wk, and administered T0901317 for the last 5 d. We divided these mice into two groups: A 30% partial hepatectomy (PH) of NASH liver group and a 70% PH of NASH liver group. In addition, a 70% PH of normal liver group served as the control. Each group was evaluated for survival rate, regeneration, apoptosis, necrosis and DNA expression after PH.
RESULTS In the 70% PH of NASH group, the survival rate was significantly decreased compared with that in the control and 30% PH of NASH groups (P < 0.01). 10 of 32 mice in the NASH 70% PH group died within 48 h after PH. Serum aspartate aminotransferase (AST) levels and total bilirubin (T-Bil) in the NASH 70% PH group were significantly higher than the levels in the other two groups (AST: P < 0.05, T-Bil: P < 0.01). In both PH of NASH groups, signaling proteins involved in regeneration were expressed at lower levels than those in the control group (P < 0.01). The 70% PH of NASH group also exhibited a lower number of Ki-67-positive cells and higher rates of apoptosis and necrosis than the NASH 30% PH group (P < 0.01). In addition, DNA microarray assays showed differences in gene expression associated with cell cycle arrest and apoptosis.
CONCLUSION The function of the residual liver is impaired in fatty liver compared to normal liver. A larger residual volume is required to maintain liver functions in mice with NASH.
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Affiliation(s)
- Yusuke Ozawa
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Takafumi Tamura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Yohei Owada
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Yoshio Shimizu
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Akira Kemmochi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Katsuji Hisakura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Takashi Matsuzaka
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Hitoshi Shimano
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Hiroko Isoda
- Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
| | - Nobuhiro Ohkohchi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
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11
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Chakedis J, Squires MH, Beal EW, Hughes T, Lewis H, Paredes A, Al-Mansour M, Sun S, Cloyd JM, Pawlik TM. Update on current problems in colorectal liver metastasis. Curr Probl Surg 2017; 54:554-602. [PMID: 29198365 DOI: 10.1067/j.cpsurg.2017.10.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Jeffrey Chakedis
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Malcolm H Squires
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Eliza W Beal
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Tasha Hughes
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Heather Lewis
- University of Colorado Health System, Fort Collins, CO
| | - Anghela Paredes
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Mazen Al-Mansour
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Steven Sun
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Jordan M Cloyd
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Timothy M Pawlik
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH.
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12
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Margonis GA, Buettner S, Andreatos N, Sasaki K, Pour MZ, Deshwar A, Wang J, Ghasebeh MA, Damaskos C, Rezaee N, Pawlik TM, Wolfgang CL, Kamel IR, Weiss MJ. Preoperative bevacizumab and volumetric recovery after resection of colorectal liver metastases. J Surg Oncol 2017; 116:1150-1158. [DOI: 10.1002/jso.24769] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 06/26/2017] [Indexed: 12/14/2022]
Affiliation(s)
| | - Stefan Buettner
- Department of Surgery; The Johns Hopkins Hospital; Baltimore Maryland
| | | | - Kazunari Sasaki
- Department of Surgery; The Johns Hopkins Hospital; Baltimore Maryland
| | | | - Ammar Deshwar
- Department of Surgery; The Johns Hopkins Hospital; Baltimore Maryland
| | - Jane Wang
- Department of Surgery; The Johns Hopkins Hospital; Baltimore Maryland
| | | | - Christos Damaskos
- Second Department of Propaedeutic Surgery; Laiko Hospital; University of Athens; Athens Greece
| | - Neda Rezaee
- Department of Surgery; The Johns Hopkins Hospital; Baltimore Maryland
| | - Timothy M. Pawlik
- Department of Surgery; The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center; Columbus Ohio
| | | | - Ihab R. Kamel
- Department of Radiology; The Johns Hopkins Hospital; Baltimore Maryland
| | - Matthew J. Weiss
- Department of Surgery; The Johns Hopkins Hospital; Baltimore Maryland
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13
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Duwe G, Knitter S, Pesthy S, Beierle AS, Bahra M, Schmelzle M, Schmuck RB, Lohneis P, Raschzok N, Öllinger R, Sinn M, Struecker B, Sauer IM, Pratschke J, Andreou A. Hepatotoxicity following systemic therapy for colorectal liver metastases and the impact of chemotherapy-associated liver injury on outcomes after curative liver resection. Eur J Surg Oncol 2017; 43:1668-1681. [PMID: 28599872 DOI: 10.1016/j.ejso.2017.05.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Revised: 05/05/2017] [Accepted: 05/08/2017] [Indexed: 02/08/2023] Open
Abstract
Patients with colorectal liver metastases (CLM) have remarkably benefited from the advances in medical multimodal treatment and surgical techniques over the last two decades leading to significant improvements in long-term survival. More patients are currently undergoing liver resection following neoadjuvant chemotherapy, which has been increasingly established within the framework of curative-indented treatment strategies. However, the use of several cytotoxic agents has been linked to specific liver injuries that not only impair the ability of liver tissue to regenerate but also decrease long-term survival. One of the most common agents included in modern chemotherapy regimens is oxaliplatin, which is considered to induce a parenchymal damage of the liver primarily involving the sinusoids defined as sinusoidal obstruction syndrome (SOS). Administration of bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has been reported to improve response of CLM to chemotherapy in clinical studies, concomitantly protecting the liver from the development of SOS. In this review, we aim to summarize current data on multimodal treatment concepts for CLM, give an in-depth overview of liver damage caused by cytostatic agents focusing on oxaliplatin-induced SOS, and evaluate the role of bevacizumab to improve clinical outcomes of patients with CLM and to protect the liver from the development of SOS.
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Affiliation(s)
- G Duwe
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - S Knitter
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - S Pesthy
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - A S Beierle
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - M Bahra
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - M Schmelzle
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - R B Schmuck
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - P Lohneis
- Institute of Pathology, Charité - Universitätsmedizin Berlin, Germany
| | - N Raschzok
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - R Öllinger
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - M Sinn
- Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Germany
| | - B Struecker
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - I M Sauer
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - J Pratschke
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - A Andreou
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany; Berlin School of Integrative Oncology, Charité - Universitätsmedizin Berlin, Germany.
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14
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Hasselgren K, Malagò M, Vyas S, Campos RR, Brusadin R, Linecker M, Petrowsky H, Clavien PA, Machado MA, Hernandez-Alejandro R, Wanis K, Valter L, Sandström P, Björnsson B. Neoadjuvant chemotherapy does not affect future liver remnant growth and outcomes of associating liver partition and portal vein ligation for staged hepatectomy. Surgery 2017; 161:1255-1265. [PMID: 28081953 DOI: 10.1016/j.surg.2016.11.033] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 11/09/2016] [Accepted: 11/30/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND The only potentially curative treatment for patients with colorectal liver metastases is hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy has emerged as a method of treatment for patients with inadequate future liver remnant. One concern about associating liver partition and portal vein ligation for staged hepatectomy is that preoperative chemotherapy may negatively affect the volume increase of the future liver remnant and outcomes. METHODS This study from the International Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Registry (NCT01924741) includes 442 patients with colorectal liver metastases registered from 2012-2016. Future liver remnant hypertrophy (absolute increase, percent increase, and kinetic growth rate) and clinical outcome were analyzed retrospectively in relation to type and amount of chemotherapy. The analyzed groups included patients with no chemotherapy, 1 regimen of chemotherapy, >1 regimen, and a group that received monoclonal antibodies in addition to chemotherapy. RESULTS Ninety percent of the patients received neoadjuvant oncologic therapy including 42% with 1 regimen of chemotherapy, 44% with monoclonal antibodies, and 4% with >1 regimen. Future liver remnant increased between 74-92% with the largest increase in the group with 1 regimen of chemotherapy. The increase in milliliters was between 241 mL (>1 regimen) and 306 mL (1 regimen). Kinetic growth rate was between 14-18% per week and was greatest for the group with 1 regimen of chemotherapy. No statistical significance was found between the groups with any of the measurements of future liver remnant hypertrophy. CONCLUSION Neoadjuvant chemotherapy, including monoclonal antibodies, does not negatively affect future liver remnant growth. Patients with colorectal liver metastases who might be potential candidates for associating liver partition and portal vein ligation for staged hepatectomy should be considered for neoadjuvant chemotherapy.
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Affiliation(s)
- Kristina Hasselgren
- Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Massimo Malagò
- Department of Hepatopancreaticobiliary Surgery and Liver Transplantation, Division of Surgical and Interventional Sciences, University College London, Royal Free Hospital, London, United Kingdom
| | - Soumil Vyas
- Department of Hepatopancreaticobiliary Surgery and Liver Transplantation, Division of Surgical and Interventional Sciences, University College London, Royal Free Hospital, London, United Kingdom
| | - Ricardo Robles Campos
- Department of General Surgery, Liver Transplant Unit, Virgen De La Arrixaca University Hospital, Murcia, Spain
| | - Roberto Brusadin
- Department of General Surgery, Liver Transplant Unit, Virgen De La Arrixaca University Hospital, Murcia, Spain
| | - Michael Linecker
- Department of Surgery and Transplantation, Swiss Hepatopancreaticobiliary and Transplant Center Zürich, University Hospital Zürich, Zürich, Switzerland
| | - Henrik Petrowsky
- Department of Surgery and Transplantation, Swiss Hepatopancreaticobiliary and Transplant Center Zürich, University Hospital Zürich, Zürich, Switzerland
| | - Pierre Alain Clavien
- Department of Surgery and Transplantation, Swiss Hepatopancreaticobiliary and Transplant Center Zürich, University Hospital Zürich, Zürich, Switzerland
| | | | | | - Kerollos Wanis
- Department of Surgery, Western University, London, Ontario, Canada
| | - Lars Valter
- Research and Development Unit in Local Healthcare, Linköping University, Linköping, Sweden
| | - Per Sandström
- Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Bergthor Björnsson
- Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
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15
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Sasaki K, Margonis GA, Andreatos N, Wilson A, Weiss M, Wolfgang C, Sergentanis TN, Polychronidis G, He J, Pawlik TM. Prognostic impact of margin status in liver resections for colorectal metastases after bevacizumab. Br J Surg 2017; 104:926-935. [PMID: 28266705 DOI: 10.1002/bjs.10510] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Revised: 01/13/2017] [Accepted: 01/16/2017] [Indexed: 01/09/2023]
Abstract
BACKGROUND Margin status with resection of colorectal liver metastasis (CRLM) was an important prognostic factor in the years before the introduction of biological chemotherapy. This study examined outcomes following CRLM resection in patients who received neoadjuvant chemotherapy with or without the monoclonal antiangiogenic antibody bevacizumab. METHODS Patients who underwent surgery for CRLM at the Johns Hopkins Hospital between 2000 and 2015 were identified from an institutional database. Data regarding surgical margin status, preoperative bevacizumab administration and overall survival (OS) were assessed using multivariable analyses. RESULTS Of 630 patients who underwent CRLM resection, 417 (66·2 per cent) received neoadjuvant chemotherapy with (214, 34·0 per cent) or without (203, 32·2 per cent) bevacizumab. The remaining 213 (33·8 per cent) did not receive neoadjuvant chemotherapy. Univariable analysis found that positive margins were associated with worse 5-year OS than R0 resection (36·2 versus 54·9 per cent; P = 0·005). After dichotomizing by the receipt of preoperative bevacizumab versus chemotherapy alone, the prognostic value of pathological margin persisted among patients who did not receive preoperative bevacizumab (5-year OS 53·0 versus 37 per cent after R0 versus R1 resection; P = 0·010). OS was not significantly associated with margin status in bevacizumab-treated patients (5-year OS 46·8 versus 33 per cent after R0 versus R1 resection; P = 0·081), in whom 5-year survival was slightly worse (presumably reflecting more advanced disease) than among patients treated with cytotoxic agents alone. Pathological margin status was not significantly associated with 5-year OS in patients with a complete or near-complete response to chemotherapy and bevacizumab (43 versus 30 per cent after R0 versus R1 resection; P = 0·917), but this may be due to a type II error. CONCLUSION The impact of margin status varied according to the receipt of bevacizumab. Bevacizumab may have a role to play in improving outcomes among patients with more advanced disease.
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Affiliation(s)
- K Sasaki
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - G A Margonis
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - N Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - A Wilson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - M Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - C Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - T N Sergentanis
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - G Polychronidis
- Department of General, Abdominal and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - J He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - T M Pawlik
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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16
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Use of Bevacizumab in the Management of Potentially Resectable Colorectal Liver Metastases: Safety, Pathologic Assessment and Benefit. CURRENT COLORECTAL CANCER REPORTS 2016. [DOI: 10.1007/s11888-016-0326-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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17
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Russolillo N, Langella S, Perotti S, Lo Tesoriere R, Forchino F, Ferrero A. Preoperative assessment of chemotherapeutic associated liver injury based on indocyanine green retention test. Int J Surg 2016; 31:80-5. [DOI: 10.1016/j.ijsu.2016.05.065] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 04/27/2016] [Accepted: 05/28/2016] [Indexed: 01/22/2023]
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18
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van Riel WG, van Golen RF, Reiniers MJ, Heger M, van Gulik TM. How much ischemia can the liver tolerate during resection? Hepatobiliary Surg Nutr 2016; 5:58-71. [PMID: 26904558 DOI: 10.3978/j.issn.2304-3881.2015.07.05] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The use of vascular inflow occlusion (VIO, also known as the Pringle maneuver) during liver surgery prevents severe blood loss and the need for blood transfusion. The most commonly used technique for VIO entails clamping of the portal triad, which simultaneously occludes the proper hepatic artery and portal vein. Although VIO is an effective technique to reduce intraoperative blood loss, it also inevitably inflicts hepatic ischemia/reperfusion (I/R) injury as a side effect. I/R injury induces formation of reactive oxygen species that cause oxidative stress and cell death, ultimately leading to a sterile inflammatory response that causes hepatocellular damage and liver dysfunction that can result in acute liver failure in most severe cases. Since the duration of ischemia correlates positively with the severity of liver injury, there is a need to find the balance between preventing severe blood loss and inducing liver damage through the use of VIO. Although research on the maximum duration of hepatic ischemia has intensified since the beginning of the 1980s, there still is no consensus on the tolerable upper limit. Based on the available literature, it is concluded that intermittent and continuous VIO can both be used safely when ischemia times do not exceed 120 min. However, intermittent VIO should be the preferred technique in cases that require >120 min duration of ischemia.
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Affiliation(s)
- Wouter G van Riel
- Department of Surgery, Surgical Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Rowan F van Golen
- Department of Surgery, Surgical Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Megan J Reiniers
- Department of Surgery, Surgical Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Michal Heger
- Department of Surgery, Surgical Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Surgical Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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19
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Impact of Bevacizumab on parenchymal damage and functional recovery of the liver in patients with colorectal liver metastases. BMC Cancer 2016; 16:84. [PMID: 26864935 PMCID: PMC4750178 DOI: 10.1186/s12885-016-2095-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2015] [Accepted: 01/28/2016] [Indexed: 01/04/2023] Open
Abstract
Background Little is known about the safety of the anti-VEGF antibody bevacizumab in patients undergoing resection for colorectal liver metastases (CLM). This meta-analysis evaluates the impact of bevacizumab on parenchymal damage and functional recovery in patients undergoing resection for CLM. Methods The Medline, Embase and Cochrane Library were systematically searched for studies on preoperative chemotherapy with and without bevacizumab prior to resection of CLM. Studies that reported histological and/or clinical outcomes were eligible for inclusion. Meta-analyses were performed using a random effects model. Results A total of 18 studies with a total sample size of 2430 patients (1050 patients with bevacizumab) were found. Meta-analyses showed a significant reduction in sinusoidal obstruction syndrome (SOS) (Odds ratio 0.50 [95 % confidence interval 0.37, 0.67]; p < 0.001; I2 = 0 %) and hepatic fibrosis (0.61 [0.4, 0.86]; p = 0.004; I2 = 7 %) after preoperative chemotherapy with bevacizumab. The reduced incidence of posthepatectomy liver failure in patients with bevacizumab treatment just failed to reach statistical significance (0.61 [0.34, 1.07]; p = 0.08 I2 = 6 %). While there was no difference in perioperative morbidity and mortality, the incidence of wound complications was significantly increased in patients who received bevacizumab (1.81 [1.12, 2.91]; p = 0.02 I2 = 4 %). Conclusions The combination of bevacizumab with cytotoxic chemotherapy is safe but increases the incidence of wound complications after resection of CLM. The reduction of SOS and hepatic fibrosis warrant further investigation and may explain the inverse association of bevacizumab administration and posthepatectomy liver failure. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2095-6) contains supplementary material, which is available to authorized users.
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20
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Konda B, Shum H, Rajdev L. Anti-angiogenic agents in metastatic colorectal cancer. World J Gastrointest Oncol 2015; 7:71-86. [PMID: 26191351 PMCID: PMC4501927 DOI: 10.4251/wjgo.v7.i7.71] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 05/13/2015] [Accepted: 06/01/2015] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer (CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various anti-angiogenic agents in patients with metastatic CRC (mCRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in mCRC patients. Despite the discovery of several promising anti-angiogenic agents, mCRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients.
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21
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Desurmont T, Skrypek N, Duhamel A, Jonckheere N, Millet G, Leteurtre E, Gosset P, Duchene B, Ramdane N, Hebbar M, Van Seuningen I, Pruvot FR, Huet G, Truant S. Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival. Cancer Sci 2015; 106:262-9. [PMID: 25580640 PMCID: PMC4376434 DOI: 10.1111/cas.12603] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 12/18/2014] [Accepted: 12/24/2014] [Indexed: 12/21/2022] Open
Abstract
Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients’ outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02–50.92) vs 0.55 (0.07–3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00–7.85) vs 0.15 (0.01–7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities.
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Affiliation(s)
- Thibault Desurmont
- Inserm, U837, Team-5 (Mucins, Epithelial Differentiation, and Carcinogenesis), Jean-Pierre Aubert Research Centre, Université Lille, France; Department of Digestive and Visceral Surgery, GHICL, Saint-Vincent de Paul Hospital, Lille, France
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22
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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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Morine Y, Shimada M, Utsunomiya T. Evaluation and management of hepatic injury induced by oxaliplatin-based chemotherapy in patients with hepatic resection for colorectal liver metastasis. Hepatol Res 2014; 44:59-69. [PMID: 23551330 DOI: 10.1111/hepr.12107] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2013] [Revised: 02/19/2013] [Accepted: 02/24/2013] [Indexed: 12/23/2022]
Abstract
Patients with colorectal liver metastasis (CRLM) can be cured with surgical resection. Recent advances in systemic chemotherapy, including molecular target agents, can be used to introduce "conversion surgery" and achieve R0 resection even in patients with initially unresectable CRLM. Furthermore, neoadjuvant chemotherapy also tries to be applied in patients with resectable CRLM to maximize the remnant liver and reduce the residual micrometastasis before surgery. The development of chemotherapy-induced hepatic injuries is increasingly being recognized, including sinusoidal obstructive syndrome (SOS), steatosis, steatohepatitis and biliary sclerosis. Especially, oxaliplatin (L-OHP)-based chemotherapy in clinical settings appears to be primarily associated with SOS. Various reports have tried to demonstrate the rationale of the correlation between L-OHP-based chemotherapy and SOS for the following hepatic surgery. While we can recognize that this pathophysiological disadvantage leads to hepatic dysfunction and the increasing postoperative morbidity, the essential part of this problem including clinical disadvantage, onset mechanism, evaluation systems, and targeted agents for prevention and treatment of SOS continue to be unclear. In this review, we summarize the current experience with hepatic injury induced by L-OHP-based chemotherapy, focusing on SOS-based on clinical and experimental data, in order to assist in the resolution of these identified factors. Finally, the need for reliable methods to identify the risk of SOS, to evaluate SOS status and to predict the safety of surgical treatment in patients with chemotherapy prior to surgery will be emphasized.
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Affiliation(s)
- Yuji Morine
- Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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Salamander-derived, human-optimized nAG protein suppresses collagen synthesis and increases collagen degradation in primary human fibroblasts. BIOMED RESEARCH INTERNATIONAL 2013; 2013:384091. [PMID: 24288677 PMCID: PMC3833026 DOI: 10.1155/2013/384091] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Revised: 09/15/2013] [Accepted: 09/19/2013] [Indexed: 11/18/2022]
Abstract
Unlike humans, salamanders regrow their amputated limbs. Regeneration depends on the presence of regenerating axons which upregulate the expression of newt anterior gradient (nAG) protein. We had the hypothesis that nAG might have an inhibitory effect on collagen production since excessive collagen production results in scarring, which is a major enemy to regeneration. nAG gene was designed, synthesized, and cloned. The cloned vector was then transfected into primary human fibroblasts. The results showed that the expression of nAG protein in primary human fibroblast cells suppresses the expression of collagen I and III, with or without TGF- β 1 stimulation. This suppression is due to a dual effect of nAG both by decreasing collagen synthesis and by increasing collagen degradation. Furthermore, nAG had an inhibitory effect on proliferation of transfected fibroblasts. It was concluded that nAG suppresses collagen through multiple effects.
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Okabe H, Beppu T, Nakagawa S, Yoshida M, Hayashi H, Masuda T, Imai K, Mima K, Kuroki H, Nitta H, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Yamashita Y, Baba H. Percentage of future liver remnant volume before portal vein embolization influences the degree of liver regeneration after hepatectomy. J Gastrointest Surg 2013; 17:1447-51. [PMID: 23715651 DOI: 10.1007/s11605-013-2237-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Accepted: 05/13/2013] [Indexed: 01/31/2023]
Abstract
BACKGROUND Clinical determinants of liver regeneration induced by portal vein embolization (PVE) and hepatectomy remain unclear. The aims of this study were to investigate how liver regeneration occurs after PVE followed by hepatectomy and to determine which factors strongly promote liver regeneration. METHODS Thirty-six patients who underwent both preoperative PVE and major hepatectomy were enrolled in this study. Percentage of future liver remnant volume before PVE (%FLR-pre) was compared with the remnant liver volume after PVE (%FLR-post-PVE) and on postoperative day 7 after hepatic resection (%FLR-post-HR). Clinical indicators contributing to liver regeneration induced by both PVE and hepatectomy were examined by logistic regression analysis. RESULTS PVE and hepatectomy caused a two-step regeneration. FLR-pre, FLR-post-PVE, and FLR-post-HR were 448, 579, and 761 cm(3), respectively. The %FLR-pre was significantly associated with liver regeneration induced by both PVE and hepatectomy (r = 0.63, p < 0.0001). Multiple regression analysis showed that only %FLR-pre was independently correlated with posthepatectomy liver regeneration (p = 0.027, odds ratio = 13.8). CONCLUSION After PVE and the subsequent hepatectomy, liver regeneration was accomplished in a two-step manner. Liver regeneration was strongly influenced by the %FLR-pre.
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Affiliation(s)
- Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto, 860-8556, Japan
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McWhirter D, Kitteringham N, Jones RP, Malik H, Park K, Palmer D. Chemotherapy induced hepatotoxicity in metastatic colorectal cancer: a review of mechanisms and outcomes. Crit Rev Oncol Hematol 2013; 88:404-15. [PMID: 23786843 DOI: 10.1016/j.critrevonc.2013.05.011] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2012] [Revised: 05/23/2013] [Accepted: 05/23/2013] [Indexed: 01/22/2023] Open
Abstract
Colorectal cancer remains one of the most common cancers worldwide. The treatment of metastatic disease has advanced considerably in the past 10 years both in terms of surgical technique and development of novel chemotherapeutic agents. The widespread use of multiple chemotherapeutic agents has lead to recognition of distinct patterns of hepatotoxicity associated with specific drugs. These side-effects have potential implications for both the patient and medical professional, but the underlying mechanisms involved in these conditions remains poorly understood. This review explores the mechanisms of action of the commonly used chemotherapeutic agents and the potential mechanisms for their hepatotoxicity. It is important that all medical professionals involved in the management of metastatic colorectal cancer understand the problems of hepatotoxicity and the impact they have on the patient.
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Affiliation(s)
- Derek McWhirter
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, L69 3GE, United Kingdom; North Western Hepatobiliary Unit, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, United Kingdom.
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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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