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Hu Y, Du G, Li C, Wang R, Liu J, Wang Y, Dong J. EGFR-mediated crosstalk between vascular endothelial cells and hepatocytes promotes Piezo1-dependent liver regeneration. Genes Dis 2025; 12:101321. [PMID: 40083329 PMCID: PMC11904541 DOI: 10.1016/j.gendis.2024.101321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 03/08/2024] [Accepted: 03/31/2024] [Indexed: 03/16/2025] Open
Abstract
Hepatocyte proliferation is essential for recovering liver function after injury. In liver surgery, the mechanical stimulation induced by hemodynamic changes triggers vascular endothelial cells (VECs) to secrete large amounts of cytokines that enhance hepatocyte proliferation and play a pivotal role in liver regeneration (LR). Piezo1, a critical mechanosensory ion channel, can detect and convert mechanical forces into chemical signals, importing external stimuli into cells and triggering downstream biological effects. However, the precise role of Piezo1 in VECs, especially in terms of mediating LR, remains unclear. Here, we report on a potential mechanism by which early changes in hepatic portal hemodynamics activate Piezo1 in VECs to promote hepatocyte proliferation during the process of LR induced by portal vein ligation in rats. In this LR model, hepatocyte proliferation is mainly distributed in zone 1 and zone 2 of liver lobules at 24-48 h after surgery, while only a small number of Ki67-positive hepatocytes were observed in zone 3. Activation of Piezo1 promotes increased secretion of epiregulin and amphiregulin from VECs via the PKC/ERK1/2 axis, further activating epidermal growth factor receptor (EGFR) and ERK1/2 signals in hepatocytes and promoting proliferation. In the liver lobules, the expression of EGFR in hepatocytes of zone 1 and zone 2 is significantly higher than that in zone 3. The EGFR inhibitor gefitinib inhibits LR by suppressing the proliferation of hepatocytes in the middle zone. These data provide a theoretical basis for the regulation of LR through chemical signals mediated by mechanical stimulation.
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Affiliation(s)
- Yuelei Hu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing 102218, China
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Guifang Du
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing 102218, China
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Chao Li
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing 102218, China
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Rui Wang
- Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China
| | - Juan Liu
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing 102218, China
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Yunfang Wang
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing 102218, China
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
- Institute for Organ Transplant and Bionic Medicine, Tsinghua University, Beijing 100084, China
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China
| | - Jiahong Dong
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing 102218, China
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
- Institute for Organ Transplant and Bionic Medicine, Tsinghua University, Beijing 100084, China
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Ji YH, Son IW, Hong SB, Lee NK, Kim S, Seo HI, Noh BG. Functional Liver Imaging Score (FLIS) as imaging parameter for predicting post-hepatectomy complications in patients with liver cirrhosis. Acta Radiol 2025; 66:208-217. [PMID: 39726160 DOI: 10.1177/02841851241299088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
BackgroundLiver dysfunction has been reported as a risk factor for predicting complications after hepatectomy. In patients with liver cirrhosis (LC) who underwent hepatectomy, a Functional Liver Imaging Score (FLIS), derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI), has never been investigated as a predictor of clinically significant post-hepatectomy complications.PurposeTo evaluate whether FLIS can predict post-hepatectomy complications in patients with LC.Material and MethodsA retrospective review was conducted of patients with LC who underwent gadoxetic acid-enhanced MRI and hepatectomy. Univariable and multivariable logistic regression was used to identify clinicopathological and radiologic findings associated with the development of major complication (Clavien-Dindo classification [CDC] ≥ III). Receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of FLIS for predicting CDC ≥ III.ResultsOf the finally included 106 patients (77 men; mean age = 62.5 ± 8.3 years), 12 patients had a CDC ≥ III. Multivariable analysis showed that only FLIS independently predicted post-hepatectomy complications (odds ratio = 0.02; P = 0.01). ROC analysis suggested the FLIS ≤ 4 was the optimal cutoff for predicting CDC ≥ III (AUC value = 0.94; sensitivity = 91.67%; specificity = 95.74%; positive likelihood ratio = 21.54; and negative likelihood ratio = 0.09).ConclusionIn patients with LC, FLIS was an independent predictor of post-hepatectomy complications. FLIS showed excellent diagnostic performance in predicting post-hepatectomy complications.
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Affiliation(s)
- Yea Hee Ji
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Il Wan Son
- Department of Radiology, Busan Centum Hospital, Busan, Republic of Korea
| | - Seung Baek Hong
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Nam Kyung Lee
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Suk Kim
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Hyung Il Seo
- Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Byeong Gwan Noh
- Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
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Costa AC, Mazzotta A, Santa-Cruz F, Coelho FF, Tribillon E, Gayet B, Herman P, Soubrane O. Short-term outcomes of laparoscopic extended hepatectomy versus major hepatectomy: a single-center experience. HPB (Oxford) 2024; 26:818-825. [PMID: 38485564 DOI: 10.1016/j.hpb.2024.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 02/16/2024] [Accepted: 02/25/2024] [Indexed: 06/02/2024]
Abstract
INTRODUCTION Laparoscopic major hepatectomy (LMH) remains restricted to a few specialized centers and poses a challenge to surgeons performing laparoscopic resections. Laparoscopic extended resections are even more complex and rarely conducted. METHODS From a single-institution database, we compared the short-term outcomes of patients who underwent major and extended laparoscopic resections, stratifying the entire retrospective cohort into four groups: right hepatectomy, left hepatectomy, right extended hepatectomy, and left extended hepatectomy. Patient demographics, tumor characteristics, operative variables, and especially postoperative outcomes were evaluated. RESULTS 250 patients underwent major and extended laparoscopic liver resections, including 160 right, 31 right extended, 36 left, and 23 left extended laparoscopic hepatectomies. The most common indication for resection was colorectal liver metastases (64%). Laparoscopic extended hepatectomy (LEH) showed significantly longer operative time, more blood loss, need for Pringle maneuver, conversion to open surgery, higher rates of liver failure, postoperative ascites, and intra-abdominal hemorrhage, R1 margins and length of stay when compared with the LMH group. Mortality rates were similar between groups. Multivariate analysis revealed intraoperative blood transfusion (OR = 5.1[CI-95%: 1.15-6.79]; p = 0.02) as an independent predictor for major complications. CONCLUSIONS LEH showed to be feasible, however with higher blood loss and significantly associated to major complications.
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Affiliation(s)
- Adriano C Costa
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France; Department of Gastroenterology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, SP, Brazil.
| | - Alessandro Mazzotta
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
| | - Fernando Santa-Cruz
- Department of Gastroenterology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Fabricio F Coelho
- Department of Gastroenterology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Ecoline Tribillon
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
| | - Brice Gayet
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
| | - Paulo Herman
- Department of Gastroenterology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Olivier Soubrane
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
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Dou Z, Lu F, Hu J, Li B, Li X. CBX7 silencing promoted liver regeneration by interacting with BMI1 and activating the Nrf2/ARE signaling pathway. Sci Rep 2024; 14:11008. [PMID: 38744845 PMCID: PMC11094083 DOI: 10.1038/s41598-024-58248-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 03/27/2024] [Indexed: 05/16/2024] Open
Abstract
Multiple studies have shown knockdown of chromobox 7 (CBX7) promotes the regenerative capacity of various cells or tissues. We examined the effect of CBX7 on hepatocyte proliferation and liver regeneration after 2/3 hepatectomy in a mouse model. For in vitro experiments, NCTC 1469 and BNL CL.2 hepatocytes were co-transfected with siRNA-CBX7-1 (si-CBX7-1), siRNA-CBX7-2 (si-CBX7-2), pcDNA-CBX7, si-BMI1-1, si-BMI1-2, pcDNA-BMI1, or their negative control. For in vivo experiments, mice were injected intraperitoneally with lentivirus-packaged shRNA and shRNA CBX7 before hepatectomy. Our results showed that CBX7 was rapidly induced in the early stage of liver regeneration. CBX7 regulated hepatocyte proliferation, cell cycle, and apoptosis of NCTC 1469 and BNL CL.2 hepatocytes. CBX7 interacted with BMI1 and inhibited BMI1 expression in hepatocytes. Silencing BMI1 aggregated the inhibitory effect of CBX7 overexpression on hepatocyte viability and the promotion of apoptosis. Furthermore, silencing BMI1 enhanced the regulatory effect of CBX7 on Nrf2/ARE signaling in HGF-induced hepatocytes. In vivo, CBX7 silencing enhanced liver/body weight ratio in PH mice. CBX7 silencing promoted the Ki67-positive cell count and decreased the Tunel-positive cell count after hepatectomy, and also increased the expression of nuclear Nrf2, HO-1, and NQO-1. Our results suggest that CBX7 silencing may increase survival following hepatectomy by promoting liver regeneration.
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Affiliation(s)
- Zhimin Dou
- The First School of Clinical Medicine, Lanzhou University, No. 199, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China
- Department of Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Fei Lu
- The First School of Clinical Medicine, Lanzhou University, No. 199, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China
| | - Jinjing Hu
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, No. 1 Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China
| | - Bin Li
- Department of Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Xun Li
- The First School of Clinical Medicine, Lanzhou University, No. 199, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China.
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, No. 1 Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China.
- Department of General Surgery, The First Hospital of Lanzhou University, No. 1 Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China.
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Hu Y, Wang R, An N, Li C, Wang Q, Cao Y, Li C, Liu J, Wang Y. Unveiling the power of microenvironment in liver regeneration: an in-depth overview. Front Genet 2023; 14:1332190. [PMID: 38152656 PMCID: PMC10751322 DOI: 10.3389/fgene.2023.1332190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 11/29/2023] [Indexed: 12/29/2023] Open
Abstract
The liver serves as a vital regulatory hub for various physiological processes, including sugar, protein, and fat metabolism, coagulation regulation, immune system maintenance, hormone inactivation, urea metabolism, and water-electrolyte acid-base balance control. These functions rely on coordinated communication among different liver cell types, particularly within the liver's fundamental hepatic lobular structure. In the early stages of liver development, diverse liver cells differentiate from stem cells in a carefully orchestrated manner. Despite its susceptibility to damage, the liver possesses a remarkable regenerative capacity, with the hepatic lobule serving as a secure environment for cell division and proliferation during liver regeneration. This regenerative process depends on a complex microenvironment, involving liver resident cells, circulating cells, secreted cytokines, extracellular matrix, and biological forces. While hepatocytes proliferate under varying injury conditions, their sources may vary. It is well-established that hepatocytes with regenerative potential are distributed throughout the hepatic lobules. However, a comprehensive spatiotemporal model of liver regeneration remains elusive, despite recent advancements in genomics, lineage tracing, and microscopic imaging. This review summarizes the spatial distribution of cell gene expression within the regenerative microenvironment and its impact on liver regeneration patterns. It offers valuable insights into understanding the complex process of liver regeneration.
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Affiliation(s)
- Yuelei Hu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, China
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Ruilin Wang
- Department of Cadre’s Wards Ultrasound Diagnostics, Ultrasound Diagnostic Center, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Ni An
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Chen Li
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- College of Life Science and Bioengineering, Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing, China
| | - Qi Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, China
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Yannan Cao
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, China
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Chao Li
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Juan Liu
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Yunfang Wang
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
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Ito T, Tanemura A, Kuramitsu T, Murase T, Kaluba B, Noguchi D, Fujii T, Yuge T, Maeda K, Hayasaki A, Gyoten K, Iizawa Y, Murata Y, Kuriyama N, Kishiwada M, Mizuno S. Spleen volume is a predictor of posthepatectomy liver failure and short-term mortality for hepatocellular carcinoma. Langenbecks Arch Surg 2023; 408:297. [PMID: 37548783 DOI: 10.1007/s00423-023-03025-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 07/20/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND The study aimed at retrospectively assessing the impact of spleen volume (SpV) on the development of posthepatectomy liver failure (PHLF) in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). METHODS 152 patients with primary HCC who underwent hepatectomy (sectionectomy or more) were classified into PHLF and non-PHLF groups, and then the relationship between PHLF and SpV was assessed. SpV (cm3) was obtained from preoperative CT and standardized based on the patient's body surface area (BSA, m2). RESULTS PHLF was observed in 39 (26%) of the 152 cases. SpV/BSA was significantly higher in the PHLF group, and the postoperative 1-year survival rate was significantly worse in the PHLF group than that in the non-PHLF group (p = 0.044). Multivariable analysis revealed SpV/BSA as a significant independent risk factor for PHLF. Using the cut-off value (160 cm3/m2), the 152 cases were divided into small SpV and large SpV groups. The incidence of PHLF was significantly higher in the large SpV group (p = 0.002), the liver failure-related mortality rate was also significantly higher in the large SpV group (p = 0.007), and the 1-year survival rate was significantly worse in the large SpV group (p = 0.035). CONCLUSION These results suggest SpV as a predictor of PHLF and short-term mortality in patients who underwent hepatectomy for HCC. Moreover, SpV measurement is a simple and potentially useful method for predicting PHLF in patients with HCC.
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Affiliation(s)
- Takahiro Ito
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
| | - Akihiro Tanemura
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Toru Kuramitsu
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Taichi Murase
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Benson Kaluba
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Daisuke Noguchi
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Tekehiro Fujii
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Takuya Yuge
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Koki Maeda
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Aoi Hayasaki
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Kazuyuki Gyoten
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Yusuke Iizawa
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Yasuhiro Murata
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Naohisa Kuriyama
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Masashi Kishiwada
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Shugo Mizuno
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
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Horisberger K, Rössler F, Oberkofler CE, Raptis D, Petrowsky H, Clavien PA. The value of intraoperative dynamic liver function test ICG in predicting postoperative complications in patients undergoing staged hepatectomy: a pilot study. Langenbecks Arch Surg 2023; 408:264. [PMID: 37403000 PMCID: PMC10319685 DOI: 10.1007/s00423-023-02983-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 06/13/2023] [Indexed: 07/06/2023]
Abstract
PURPOSE To assess the predictive value of intraoperative indocyanine green (ICG) test in patients undergoing staged hepatectomy. METHODS We analyzed intraoperative ICG measurements of future liver remnant (FLR), preoperative ICG, volumetry, and hepatobiliary scintigraphy in 15 patients undergoing associated liver partition and portal vein ligation for staged hepatectomy (ALPPS). Main endpoints were the correlation of intraoperative ICG values to postoperative complications (Comprehensive Complication Index (CCI®)) at discharge and 90 days after surgery, and to postoperative liver function. RESULTS Median intraoperative R15 (ICG retention rate at 15 min) correlated significantly with CCI® at discharge (p = 0.05) and with CCI® at 90 days (p = 0.0036). Preoperative ICG, volumetry, and scintigraphy did not correlate to postoperative outcome. ROC curve analysis revealed a cutoff value of 11.4 for the intraoperative R15 to predict major complications (Clavien-Dindo ≥ III) with 100% sensitivity and 63% specificity. No patient with R15 ≤ 11 developed major complications. CONCLUSION This pilot study suggests that intraoperative ICG clearance determines the functional capacity of the future liver remnant more accurately than preoperative tests. This may further reduce the number of postoperative liver failures, even if it means intraoperative abortion of hepatectomy in individual cases.
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Affiliation(s)
- Karoline Horisberger
- Swiss HPB Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland.
- Department of General, Visceral and Transplant Surgery, University Medical Center Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
| | - Fabian Rössler
- Swiss HPB Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Christian E Oberkofler
- Swiss HPB Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
- vivèvis AG - Visceral, Tumor and Robotic Surgery Clinic Hirslanden Zürich, Zurich, Switzerland
| | - Dimitri Raptis
- Organ Transplant Center of Excellence, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Henrik Petrowsky
- Swiss HPB Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Pierre-Alain Clavien
- Swiss HPB Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
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Zhang T, Li Q, Wei Y, Yao S, Yuan Y, Deng L, Wu D, Nie L, Wei X, Tang H, Song B. Preoperative evaluation of liver regeneration following hepatectomy in hepatocellular carcinoma using magnetic resonance elastography. Quant Imaging Med Surg 2022; 12:5433-5451. [PMID: 36465825 PMCID: PMC9703107 DOI: 10.21037/qims-22-306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 08/29/2022] [Indexed: 08/30/2023]
Abstract
BACKGROUND For patients with hepatocellular carcinoma (HCC) undergoing hepatectomy, insufficient remnant liver regenerative capacity can lead to liver failure. The aim of this study was to evaluate the potential role of magnetic resonance elastography (MRE) for the preoperative prediction of liver regeneration in patients with HCC after partial hepatectomy (PH). METHODS A total of 54 patients with HCC undergoing MRE prior to PH were retrospectively included. The total functional liver, volume of preoperative future liver remnant (LVpre), and volume of postoperative liver remnant (LVpost), respectively, were measured, and the regeneration index (RI) and parenchymal hepatic resection rate (PHRR) were manually calculated. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with a high RI, and receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the liver stiffness (LS) values. Patients were classified into three subgroups based on the value of PHRR: low PHRR (<30%), intermediate PHRR (30-50%), and high PHRR (>50%). Subsequently, Spearman correlation analysis was used to investigate the relationship between LS values and RI in the subgroups. RESULTS Multivariable analysis revealed a low LS value was associated with greater odds of a high RI [odds ratio (OR), 0.049; 95% confidence interval (CI): 0.002 to 0.980]. An optimal cutoff value of 3.30 kPa was used to divide all patients into a low RI group and a high RI group with an area under the curve (AUC) value of 0.882 (95% CI: 0.767 to 0.996). A significant negative relationship between RI and LS values (r=-0.799; P<0.001) was observed in the intermediate PHRR subgroup. CONCLUSIONS The LS values based on MRE may serve as a potential preoperative predictor of liver regeneration for patients with HCC undergoing PH.
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Affiliation(s)
- Tong Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Qian Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Wei
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Shan Yao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yuan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Liping Deng
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Dongbo Wu
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | | | | | - Hehan Tang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Sanya People’s Hospital, Sanya, China
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Sparrelid E, Olthof PB, Dasari BVM, Erdmann JI, Santol J, Starlinger P, Gilg S. Current evidence on posthepatectomy liver failure: comprehensive review. BJS Open 2022; 6:6840812. [PMID: 36415029 PMCID: PMC9681670 DOI: 10.1093/bjsopen/zrac142] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/21/2022] [Accepted: 10/03/2022] [Indexed: 11/24/2022] Open
Abstract
INTRODUCTION Despite important advances in many areas of hepatobiliary surgical practice during the past decades, posthepatectomy liver failure (PHLF) still represents an important clinical challenge for the hepatobiliary surgeon. The aim of this review is to present the current body of evidence regarding different aspects of PHLF. METHODS A literature review was conducted to identify relevant articles for each topic of PHLF covered in this review. The literature search was performed using Medical Subject Heading terms on PubMed for articles on PHLF in English until May 2022. RESULTS Uniform reporting on PHLF is lacking due to the use of various definitions in the literature. There is no consensus on optimal preoperative assessment before major hepatectomy to avoid PHLF, although many try to estimate future liver remnant function. Once PHLF occurs, there is still no effective treatment, except liver transplantation, where the reported experience is limited. DISCUSSION Strict adherence to one definition is advised when reporting data on PHLF. The use of the International Study Group of Liver Surgery criteria of PHLF is recommended. There is still no widespread established method for future liver remnant function assessment. Liver transplantation is currently the only effective way to treat severe, intractable PHLF, but for many indications, this treatment is not available in most countries.
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Affiliation(s)
- Ernesto Sparrelid
- Department of Clinical Science, Intervention and Technology, Division of Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Pim B Olthof
- Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.,Department of Surgery, Amsterdam UMC, Amsterdam, The Netherlands
| | - Bobby V M Dasari
- Department of HPB Surgery and Liver Transplantation, Queen Elizabeth Hospital, Birmingham, UK.,University of Birmingham, Birmingham, UK
| | - Joris I Erdmann
- Department of Surgery, Amsterdam UMC, Amsterdam, The Netherlands
| | - Jonas Santol
- Department of Surgery, HPB Center, Viennese Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria.,Department of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Patrick Starlinger
- Division of General Surgery, Department of Surgery, Medical University of Vienna, General Hospital of Vienna, Vienna, Austria.,Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, New York, USA
| | - Stefan Gilg
- Department of Clinical Science, Intervention and Technology, Division of Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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Anatomic resection versus radiofrequency ablation with an ablative margin ≥ 1.0 cm for solitary small hepatocellular carcinoma measuring ≤ 3 cm: Comparison of long-term outcomes using propensity score matching analysis. Eur J Radiol 2022; 155:110498. [PMID: 36049409 DOI: 10.1016/j.ejrad.2022.110498] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 07/17/2022] [Accepted: 08/20/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE To compare the long-term outcomes of anatomic resection (AR) and radiofrequency ablation (RFA) with an ablative margin (AM) of ≥ 1.0 cm as first-line treatment for solitary hepatocellular carcinoma measuring ≤ 3 cm. METHODS Two hundred and fifty-one patients who underwent AR (n = 156) or RFA (ablative margin ≥ 1.0 cm, n = 95) at any of 6 tertiary hospitals from 2009 to 2018 were enrolled. Propensity score matched analysis (PSM) were used to compare overall survival (OS), recurrence-free survival (RFS), and perioperative outcomes. Univariate and multivariate analyses were performed to identify prognostic factors associated with RFS and OS. RESULTS PSM created 67 patient-pairs. After 96 months of follow-up, RFA with an ablative margin ≥ 1.0 cm and AR showed comparable 1-year, 3-year, 5-year, and 8-year OS rates before (P = 0.580) and after (P = 0.640) PSM. However, RFS was better at 1, 3, 5, and 8 years after AR before (P = 0.0036) and after (P = 0.017) PSM. The operation time and postoperative hospital stay were significantly longer in the AR group than in the RFA group before and after PSM (P < 0.05). Multivariate analysis identified age and type of treatment to be independent prognostic factors for RFS and age and hepatitis C to be associated with OS. CONCLUSIONS Long-term OS was not significantly different between AR and RFA with an AM ≥ 1.0 cm in patients with a solitary hepatocellular carcinoma measuring ≤ 3 cm; but, RFS appeared to be better after AR than after RFA. However, RFA was associated with fewer perioperative complications and a shorter postoperative hospital stay.
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11
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Cui B, Yang L, Zhao Y, Lu X, Song M, Liu C, Yang C. HOXA13 promotes liver regeneration through regulation of BMP-7. Biochem Biophys Res Commun 2022; 623:23-31. [PMID: 35868069 DOI: 10.1016/j.bbrc.2022.07.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/19/2022] [Accepted: 07/06/2022] [Indexed: 11/02/2022]
Abstract
In-depth knowledge of liver regeneration could facilitate the development of therapies for liver injury and liver failure. As a member of the homeobox superfamily, HOXA13 plays an important role in regulating tumorigenesis and development. However, the exact role of HOXA13 in liver regeneration remains unclear. In this study, we confirmed that HOXA13 promotes hepatocyte proliferation both in vivo and in vitro. HOXA13 was upregulated during liver regeneration, and its overexpression further accelerated hepatocyte proliferation and liver function recovery during liver regeneration. Furthermore, we found that HOXA13 promoted hepatocyte proliferation and liver regeneration by upregulating bone morphogenetic protein-7 (BMP-7) mRNA. These findings provide a new potential target for the treatment of liver failure.
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Affiliation(s)
- Beiyong Cui
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China
| | - Liu Yang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China
| | - Yingying Zhao
- Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250013, China
| | - Xiya Lu
- Department of Endoscopy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, PR China
| | - Meiyi Song
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
| | - Chang Liu
- Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China.
| | - Changqing Yang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
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12
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Papamichail M, Pizanias M, Heaton ND, M P, M P, Nd H. Minimizing the risk of small-for-size syndrome after liver surgery. Hepatobiliary Pancreat Dis Int 2022; 21:113-133. [PMID: 34961675 DOI: 10.1016/j.hbpd.2021.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant (FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-for-size syndrome (SFSS). DATA SOURCES This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specific modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. RESULTS Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. CONCLUSIONS With those techniques the indications of radical treatment for patients with liver tumors have significantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modification of interventions and the right timing of surgery.
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Affiliation(s)
- Michail Papamichail
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK.
| | - Michail Pizanias
- Department of General Surgery, Whittington Hospital, London N19 5NF, UK
| | - Nigel D Heaton
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Papamichail M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Pizanias M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Heaton Nd
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
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Kar I, Qayum K, Sofi J. Indications and Complications of Hepatic Resection Patients at Sher-I-Kashmir Institute of Medical Sciences: An Observational Study. Cureus 2021; 13:e19713. [PMID: 34934577 PMCID: PMC8684362 DOI: 10.7759/cureus.19713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/18/2021] [Indexed: 11/05/2022] Open
Abstract
Aim: This study aimed to determine the indications and demographic profile of hepatic resection at Sher-I-Kashmir Institute of Medical Sciences (SKIMS), the performed types of hepatic resection, as well as assess the details of the operation and perioperative complications of hepatic resection. Methods: This is a prospective, retrospective observational study. The retrospective study period was from January 2005 to August 2015 and the prospective study period was from 2015 till 2017. Prospective patients were clinically evaluated by medical history and clinical examination and also underwent various investigations. The patients were scored on Child-Pugh and American Society of Anesthesiology (ASA) scores for risk stratification and prepared for surgery, which included segmentectomy to major liver resection. The retrospective data were obtained from the Medical Records Department (MRD). Statistical analysis was done on SPSS software 25.0 version (Armonk, NY: IBM Corp.). Results: This study included 122 patients with a male to female ratio of 1:1.59. The patients' age was between 1 and 73 years. The patients' most common complaint was right upper quadrant abdominal pain. The main established clinical diagnosis was oriental cholangiohepatitis (OCH) (36.9%) followed by carcinoma of gallbladder (CaGB) which accounted for 37 cases (30.4%). Liver metastases including solitary masses and multiple lesions were 10 cases (8.2%). Fifty-five patients underwent left lateral segmentectomy (45.1%) and mostly for OCH. Standard wedge resection was done in 30.7% of cases and for all cases of CaGB. The mean blood loss was 146.5 ml. A total of 37 patients had complications. Wound infection was the most common complication, occurring in 10 patients (8.2%). Conclusion: Patients with hepatobiliary pathology, necessitating liver resection are now routinely admitted to the Department of Surgical Gastroenterology in SKIMS, Srinagar. Patients are carefully evaluated and operated with a confirmed definitive diagnosis. The overall surgical outcome does not differ from India's best centers.
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Bile duct ligation causes opposite impacts on the expression and function of BCRP and P-gp in rat brain partly via affecting membrane expression of ezrin/radixin/moesin proteins. Acta Pharmacol Sin 2021; 42:1942-1950. [PMID: 33558655 PMCID: PMC8563881 DOI: 10.1038/s41401-020-00602-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 12/18/2020] [Indexed: 02/08/2023]
Abstract
Breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) are co-located at blood-brain barrier (BBB) cells, preventing their substrates from entering brain. Accumulating evidence demonstrates that liver failure impairs P-gp and BCRP expression and function in the brain. In the current study, we investigated how liver failure influenced the expression and function of brain BCRP and P-gp in rats subjected to bile duct ligation (BDL). The function of BCRP, P-gp and BBB integrity was assessed using distribution of prazosin, rhodamine 123 and fluorescein, respectively. We showed that BDL significantly decreased BCRP function, but increased P-gp function without affecting BBB integrity. Furthermore, we found that BDL significantly downregulated the expression of membrane BCRP and upregulated the expression of membrane P-gp protein in the cortex and hippocampus. In human cerebral microvascular endothelial cells, NH4Cl plus unconjugated bilirubin significantly decreased BCRP function and expression of membrane BCRP protein, but upregulated P-gp function and expression of membrane P-gp protein. The decreased expression of membrane BCRP protein was linked to the decreased expression of membrane radixin protein, while the increased expression of membrane P-gp protein was related to the increased location of membrane ezrin protein. Silencing ezrin impaired membrane location of P-gp, whereas silencing radixin impaired membrane location of BCRP protein. BDL rats showed the increased expression of membrane ezrin protein and decreased expression of membrane radixin protein in the brain. We conclude that BDL causes opposite effects on the expression and function of brain BCRP and P-gp, attributing to the altered expression of membrane radixin and ezrin protein, respectively, due to hyperbilirubinemia and hyperammonemia.
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15
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Predictive value of combined computed tomography volumetry and magnetic resonance elastography for major complications after liver resection. Abdom Radiol (NY) 2021; 46:3193-3204. [PMID: 33683428 DOI: 10.1007/s00261-021-02991-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 02/01/2021] [Accepted: 02/11/2021] [Indexed: 12/21/2022]
Abstract
PURPOSE To retrospectively compare the predictive value of computed tomography volumetry (CTV), magnetic resonance elastography (MRE) of the liver, and their combination for major complications after liver resection. METHODS We enrolled 108 consecutive patients who underwent anatomical liver resection for liver tumors and preoperative contrast-enhanced CT and MRE. The future liver remnant (FLR) ratio was calculated by CTV, while the liver stiffness measurement (LSM) was obtained by MRE. FLR ratio alone, LSM alone, and combined FLR ratio and LSM were evaluated to predict major complications (Clavien-Dindo grade ≥ IIIa). Univariate and multivariate analyses of hepatic biochemical parameters and imaging data were performed to identify predictors of major complications. Receiver operating characteristic analyses of FLR ratio, LSM, and their combination were performed, and the sensitivity and specificity were calculated. RESULTS Twenty-two (20.4%) of the 108 patients experienced major complications. According to multiple regression analysis, the FLR ratio (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.91-0.99, p = 0.040) and LSM (OR 1.72, 95% CI 1.01-2.94, p = 0.047) were independent predictors of major complications. The combined FLR ratio and LSM were predictive of major complications, with an area under the curve (AUC) of 0.818, sensitivity of 68.2%, and specificity of 84.9%. The AUC and specificity for combined FLR ratio and LSM were larger than those for FLR ratio (AUC: 0.711, specificity: 80.2%) and LSM (AUC: 0.793, specificity: 80.2%). CONCLUSION Combined CTV and MRE analysis can improve the AUC and specificity for predicting major complications after anatomical liver resection.
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16
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Relationship between hepatic venous anatomy and hepatic venous blood loss during hepatectomy. Surg Today 2021; 51:1953-1968. [PMID: 34129114 DOI: 10.1007/s00595-021-02314-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 03/25/2021] [Indexed: 12/22/2022]
Abstract
PURPOSE Predicting increased blood loss based on anatomical intervascular relationships is essential in major hepatectomy. METHODS We assessed 63 consecutive patients undergoing anatomical hepatectomy exposing the hepatic vein (HV) trunk at two institutes. Correlations between anatomical alterations of the hepatic inferior vena cava (IVC), HV, hepatic IVC, or right atrium (RA) and the blood loss per standard weight (BLSW) or blood transfusion (n = 18) were analyzed. The results of IVC partial clamping (PC) were additionally examined. RESULTS The BLSW in type V-up anatomical morphology was significantly higher than that in straight type (p < 0.05). The parameters associated with an increased BLSW (> 13.5 mL/kg) were tumor size (> 4 cm), prothrombin activity (< 87%), CVP (> 7 mmHg), area of suprahepatic IVC (< 360 mm2), IVC-RA gap (> 28 mm), longitudinal angle of IVC (< 160°), and axial angle of the MHV (< 55°). A multivariate analysis revealed that a high IVC-RA gap was a significant independent risk factor (odds ratio; 4.32, p < 0.05). Among 25 patients undergoing IVC-PC, only three showed a remarkable decrease in hepatic venous bleeding. No other statistically significant differences in the surgical records were observed in most cases. CONCLUSION The IVC-RA gap might be a promising novel predictive parameter reflecting increased blood loss leading to blood transfusion in anatomical hepatectomy.
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Comment on"Preoperative Single-Dose Methylprednisolone Prevents Surgical Site Infections After Major Liver Resection: A Randomized Controlled Trial.": Preoperative single-dose methylprednisolone prevents surgical site infections or protects the hepatic function. Ann Surg 2021; 274:e906-e907. [PMID: 33938496 DOI: 10.1097/sla.0000000000004926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Lee DH, Lee ES, Bae JS, Lee JY, Han JK, Yi NJ, Lee KW, Suh KS, Kim H, Lee KB, Choi BI. 2D shear wave elastography is better than transient elastography in predicting post-hepatectomy complication after resection. Eur Radiol 2021; 31:5802-5811. [PMID: 33459859 DOI: 10.1007/s00330-020-07662-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 12/11/2020] [Accepted: 12/21/2020] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Both transient elastography (TE) and 2D shear wave elastography (SWE) are accurate methods to evaluate liver fibrosis. We aimed to evaluate the diagnostic performance of 2D-SWE in predicting post-hepatectomy complication and to compare it with TE. METHODS We prospectively enrolled 125 patients with liver tumors. Liver stiffness (LS) (kilopascal [kPa]) was measured using both TE and 2D-SWE before surgery. All post-operative complication was evaluated using the comprehensive complication index (CCI), and CCI ≥ 26.2 was defined as severe complication. Logistic regression analysis was performed to identify predictive factors for severe complication. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of TE/2D-SWE in detecting liver fibrosis and severe complication. RESULTS Severe complication developed in 18 patients. The median LS in patients with severe complication was significantly higher for both 2D-SWE (11.4 kPa vs. 7.0 kPa, p < 0.001) and TE (8.9 kPa vs. 6.2 kPa, p = 0.009). LS obtained from 2D-SWE was a significant factor correlated with severe complication (odds ratio: 1.27 per kPa [1.10-1.46], p = 0.001). The diagnostic performance of 2D-SWE was significantly higher than that of TE in detecting both ≥F3 (p = 0.024) and F4 (p = 0.048). The area under the curve of 2D-SWE to predict severe complication was 0.854, significantly higher than 0.692 of TE (p = 0.004). The optimal cut-off LS from 2D-SWE to predict severe complication was 8.6 kPa, with sensitivity of 88.9% (16/18) and specificity of 73.8% (79/107). CONCLUSION LS obtained from 2D-SWE was a significant predictive factor for severe complication, and 2D-SWE showed significantly a better diagnostic performance than TE in detecting liver fibrosis and severe complication. KEY POINTS • The diagnostic performance of 2D-SWE was significantly higher than that of TE in detecting both ≥ F3 (AUC: 0.853 vs. 0.779, p = 0.024) and F4 (AUC: 0.929 vs. 0.872, p = 0.048). • Liver stiffness value obtained from 2D-SWE was a significant factor correlated with the development of severe complication defined as CCI ≥ 26.2 after hepatic resection for liver tumors (odds ratio: 1.27 per kPa [1.10-1.46], p = 0.001). • 2D-SWE provided significantly a better diagnostic performance in predicting severe complication after hepatic resection than TE (AUC for 2D-SWE: 0.853 vs. AUC for TE: 0.692, p = 0.004).
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Affiliation(s)
- Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 03080, South Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, South Korea
| | - Eun Sun Lee
- Department of Radiology, Chung-Ang University Hospital, Seoul, South Korea.,Department of Radiology, Chung-Ang University College of Medicine, Seoul, South Korea
| | - Jae Seok Bae
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 03080, South Korea
| | - Jae Young Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 03080, South Korea. .,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, South Korea. .,Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea.
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 03080, South Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, South Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyung Bun Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea
| | - Byung Ihn Choi
- Department of Radiology, Chung-Ang University Hospital, Seoul, South Korea
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Bae JS, Lee DH, Yoo J, Yi NJ, Lee KW, Suh KS, Kim H, Lee KB. Association between spleen volume and the post-hepatectomy liver failure and overall survival of patients with hepatocellular carcinoma after resection. Eur Radiol 2020; 31:2461-2471. [PMID: 33026503 DOI: 10.1007/s00330-020-07313-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 08/05/2020] [Accepted: 09/17/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Post-hepatectomy liver failure (PHLF) can occur as a major complication after hepatic resection (HR) in patients with hepatocellular carcinoma (HCC) and negatively affects the prognosis. We aimed to retrospectively assess whether the spleen volume (SV) measured from preoperative CT images would be associated with the development of PHLF and overall survival (OS) after HR in patients with HCC. METHODS We enrolled 317 consecutive patients with very early/early stage HCC who underwent a preoperative CT and HR between January 2010 and December 2016. The SV was obtained from preoperative CT images using semi-automated volumetric software and was divided by body surface area to yield SVBSA. Receiver operating characteristic (ROC) curves and logistic regression analyses were performed to identify factors affecting the development of PHLF. The Cox proportional hazard model was used to identify prognostic factors for OS. RESULTS PHLF was observed in 72 patients (22.7% [72/317]). SVBSA was associated with the development of PHLF (odds ratio, 2.321; 95% CI, 1.347-4.001; p = 0.002) with the area under the ROC curve of 0.663 using the cutoff value of 107.5 cm3 (p < 0.001). SVBSA was also an influencing factor for OS (hazard ratio, 3.935; 95% CI 1.520-10.184; p = 0.005), with the optimal cutoff of 146 cm3. The 5-year OS rate was higher in 245 patients with a SVBSA ≤ 146 cm3 than in 72 patients with a SVBSA > 146 cm3 (95.0% vs. 78.7%, p < 0.001). CONCLUSIONS In patients with HCC, a larger SVBSA was associated with a higher rate of PHLF and worse OS after HR. The SVBSA may be useful in selecting good surgical candidates. KEY POINTS • A significantly higher spleen volume divided by body surface area was observed in patients who experienced post-hepatectomy liver failure than in patients who did not (148 cm3 vs. 112 cm3, p < 0.001). • The area under the receiver operating characteristic curve of spleen volume divided by body surface area to predict the development of post-hepatectomy liver failure was 0.663 (p < 0.001). • Spleen volume divided by body surface area was a significant influencing factor for overall survival (hazard ratio, 3.935; 95% CI, 1.520-10.184; p < 0.001), with the optimal cutoff of 146 cm3.
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Affiliation(s)
- Jae Seok Bae
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. .,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
| | - Jeongin Yoo
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Kyung Bun Lee
- Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
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Lorente S, Hautefeuille M, Sanchez-Cedillo A. The liver, a functionalized vascular structure. Sci Rep 2020; 10:16194. [PMID: 33004881 PMCID: PMC7531010 DOI: 10.1038/s41598-020-73208-8] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 09/10/2020] [Indexed: 12/26/2022] Open
Abstract
The liver is not only the largest organ in the body but also the one playing one of the most important role in the human metabolism as it is in charge of transforming toxic substances in the body. Understanding the way its blood vasculature works is key. In this work we show that the challenge of predicting the hepatic multi-scale vascular network can be met thanks to the constructal law of design evolution. The work unveils the structure of the liver blood flow architecture as a combination of superimposed tree-shaped networks and porous system. We demonstrate that the dendritic nature of the hepatic artery, portal vein and hepatic vein can be predicted, together with their geometrical features (diameter ratio, duct length ratio) as the entire blood flow architectures follow the principle of equipartition of imperfections. At the smallest scale, the shape of the liver elemental systems-the lobules-is discovered, while their permeability is also predicted. The theory is compared with good agreement to anatomical data from the literature.
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Affiliation(s)
- Sylvie Lorente
- Department of Mechanical Engineering, Villanova University, Villanova, PA, 19085, USA.
| | - Mathieu Hautefeuille
- Departamento de Física, Facultad de Ciencias, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, CP04510, Coyoacán, Ciudad de México, Mexico
| | - Aczel Sanchez-Cedillo
- Centro Médico 20 de Noviembre, ISSSTE,, Félix Cuevas 540, Del Valle Sur, Benito Juárez, CP03100, Ciudad de México, Mexico
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21
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Konishi T, Yoshidome H, Shimizu H, Yoshitomi H, Furukawa K, Takayashiki T, Kuboki S, Takano S, Miyazaki M, Ohtsuka M. Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases. World J Surg Oncol 2020; 18:139. [PMID: 32576191 PMCID: PMC7313099 DOI: 10.1186/s12957-020-01918-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 06/15/2020] [Indexed: 11/13/2022] Open
Abstract
Background Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection. Methods We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed. Results A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration. Conclusions Splenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.
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Affiliation(s)
- Takanori Konishi
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Hiroyuki Yoshidome
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan. .,Department of Surgery, Oami Municipal Hospital, 884-1 Tomida, Oami-Shirasato-shi, Chiba, 299-3221, Japan.
| | - Hiroaki Shimizu
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Hideyuki Yoshitomi
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Katsunori Furukawa
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Tsukasa Takayashiki
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Satoshi Kuboki
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Shigetsugu Takano
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Masaru Miyazaki
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan.,Surgery and Digestive Disease Center, International University of Health and Welfare, Mita Hospital, 1-4-3 Mita, Minato-Ku, Tokyo, 108-8329, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
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22
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Surgical resection for liver cancer during the COVID-19 outbreak. Updates Surg 2020; 72:305-307. [PMID: 32436017 PMCID: PMC7239351 DOI: 10.1007/s13304-020-00799-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 05/11/2020] [Indexed: 12/18/2022]
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23
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Stevens CL, Reid JL, Babidge WJ, Maddern GJ. Peer review of mortality after hepatectomy in Australia. HPB (Oxford) 2020; 22:611-621. [PMID: 31558369 DOI: 10.1016/j.hpb.2019.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/27/2019] [Accepted: 09/02/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The data within the Australian and New Zealand Audit of Surgical Mortality (ANZASM) provides a unique opportunity to consider the contributing factors to perioperative deaths as determined by peer review. Consideration of the factors contributing to mortality after hepatectomy can provide greater insight into how deaths can be prevented. The objective of this study was to determine the reasons for patient deaths post-hepatectomy in Australia. METHODS ANZASM data from 1 January 2010 to 30 Jun 2017 was reviewed and all deaths following hepatectomy were selected for analysis. Assessors determinations of whether management could have been improved were reviewed, and then classified into groups of significant clinical events using thematic analysis with a data driven approach. RESULTS The study included 88 deaths reported to ANZASM after hepatectomy. The assessors questioned the decision to operate in 23/88 (25%) patients with a further nine (10%) patients insufficiently investigated prior to resection. ANZASM assessors determined that there was a delay in recognising a significant complication in 16/88 (18%) patients. CONCLUSION Multi-disciplinary decision making is strongly recommended when deciding which patients to treat with hepatic resection. Optimal care post-hepatectomy includes early recognition of complications and enactment of an adequate rescue plan.
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Affiliation(s)
- Claire L Stevens
- Discipline of Surgery, University of Adelaide, The Queen Elizabeth Hospital, Australia.
| | - Jessica L Reid
- Discipline of Surgery, University of Adelaide, The Queen Elizabeth Hospital, Australia
| | - Wendy J Babidge
- Discipline of Surgery, University of Adelaide, Australian and New Zealand Audit of Surgical Mortality, Royal Australasian College of Surgeons, Australia
| | - Guy J Maddern
- Discipline of Surgery, University of Adelaide, The Queen Elizabeth Hospital, Australia
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Kim JY, Choi D, Kim J, Kim YM, Lim H, Sung JM, Lee MK, Choung YJ, Chang JH, Jeong MA. Co-administration of erythropoietin and iron complex improves late-phase liver regeneration. BMB Rep 2020. [PMID: 31401982 PMCID: PMC7118350 DOI: 10.5483/bmbrep.2020.53.3.160] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Erythropoietin and iron have individually shown beneficial effects on early-phase liver regeneration following partial hepatectomy (PHx); however, there are limited data on the combined effect on late-phase liver regeneration after PHx. Here we examined combined effects of recombinant human erythropoietin (rhEPO, 3,000 IU/kg) and iron isomaltoside (IIM, 40 mg/kg) on late-phase liver regeneration following PHx and investigated the possible underlying mechanism. Rats administrated with rhEPO showed significantly higher liver mass restoration, interleukin-6 (IL-6, a hepatocyte mitogen) levels, and Ki-67-positive hepatocytes on day 7 after PHx than saline-treated controls. These beneficial effects were further enhanced on days 7 and 14 by co-treatment with IIM. This combination also significantly improved liver function indices, such as increased albumin production and decreased bilirubin levels, but did not alter serum levels of toxic parameters, such as aspartate transaminase and alanine transaminase. This study demonstrates that the combination of rhEPO and IIM synergistically improves late-phase liver regeneration and function after PHx, probably by promoting IL-6-mediated hepatocyte proliferation without adverse effects. Thus, this combination treatment can be a potential therapeutic strategy for patients undergoing resection for hepatic malignancies.
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Affiliation(s)
- Ji-Yoon Kim
- Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul 04763, Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University Hospital, Seoul 04763, Korea
| | - Joohwan Kim
- Department of Molecular and Cellular Biochemistry, Kangwon National University, School of Medicine, Chuncheon 24341, Korea
| | - Young-Myeong Kim
- Department of Molecular and Cellular Biochemistry, Kangwon National University, School of Medicine, Chuncheon 24341, Korea
| | - Hyunyoung Lim
- Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul 04763, Korea
| | - Jeong Min Sung
- Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul 04763, Korea
| | - Min Kyu Lee
- Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul 04763, Korea
| | - Yoo Jin Choung
- Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul 04763, Korea
| | - Ji Hee Chang
- Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul 04763, Korea
| | - Mi Ae Jeong
- Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul 04763, Korea
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Hamada T, Hidaka M, Takatsuki M, Sakai Y, Yu H, Natsuda K, Ono S, Adachi T, Soyama A, Eguchi S. The Relationship Between Lymphangiogenesis and Liver Regeneration After Partial Hepatectomy in Cholestatic Mice. Lymphat Res Biol 2020; 18:322-328. [PMID: 32069131 DOI: 10.1089/lrb.2019.0068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background: The mechanisms of lymphangiogenesis in the cholestatic liver after partial hepatectomy (PH) remain unclear. We aimed to demonstrate the relationship between lymphangiogenesis and liver regeneration after partial hepatectomy in the cholestatic liver. Methods and Results: C57BL/6 mice were subjected to 70% partial hepatectomy only (PH group, n = 20) and 70% partial hepatectomy with temporary common bile duct (BD) obstruction by clipping (BD+PH group, n = 20). Five mice per group were sacrificed at 1, 3, 5, and 7 days after the procedure. The liver function was examined by blood tests, and the liver regeneration rate was assessed by body weight and liver weight. Immunohistochemical staining of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) showed liver lymphangiogenesis. The gene expression of lymphangiogenesis-associated factors (e.g., vascular endothelial growth factor receptor-3 [VEGFR-3]) was examined by a real-time polymerase chain reaction. The liver function in the BD+PH group was worse than that in the PH group on postoperative day 1 (POD1) (aspartate aminotransferase: 6528 ± 1641 U/L vs. 2741 ± 368 U/L, p < 0.05, alanine aminotransferase: 4160 ± 1255 U/L vs. 2315 ± 357 U/L, total bilirubin: 1.36 ± 1.16 mg/dL vs. 0.09 ± 0.01 mg/dL), and the liver regeneration rate in the BD+PH group was worse on POD7 (4.57% vs. 5.91%, p < 0.05). The LYVE-1 expression in Glisson's capsule peaked on POD5 and POD7 in the PH and BD+PH groups, respectively. The peak gene expression of VEGFR-3 in the BD+PH group was delayed in comparison with the PH group. Conclusions: Lymphangiogenesis after partial hepatectomy in the cholestatic liver was suggested to be delayed due to impaired liver regeneration and the late expression of VEGFR-3.
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Affiliation(s)
- Takashi Hamada
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Mitsuhisa Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Yusuke Sakai
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Haung Yu
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Koji Natsuda
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Shinichiro Ono
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Tomohiko Adachi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan
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Chan J, Bradshaw L, Houli N, Weinberg L, Perini MV, Fink M, Muralidharan V, Starkey G, Jones R, Wang BZ, Christophi C, Nikfarjam M. Outcomes of central hepatectomy versus extended hepatectomy. Hepatobiliary Pancreat Dis Int 2019; 18:249-254. [PMID: 30987899 DOI: 10.1016/j.hbpd.2019.03.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Accepted: 03/12/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Central hepatectomy (CH) is more difficult than extended hepatectomy (EH) and is associated with greater morbidity. In this modern era of liver management with aims to prevent post-hepatectomy liver failure (PHLF), there is a need to assess outcomes of CH as a parenchyma-sparing procedure for centrally located liver tumors. METHODS A total of 178 major liver resections performed by specialist surgeons from two Australian tertiary institutions between June 2009 and March 2017 were reviewed. Eleven patients had CH and 24 had EH over this study period. Indications and perioperative outcomes were compared between the groups. RESULTS The main indication for performing CH was colorectal liver metastases. There was no perioperative mortality in the CH group and four (16.7%) in the EH group (P = 0.285). No group differences were found in median operative time [CH vs. EH: 450 min (290-840) vs. 523 min (310-860), P = 0.328], intraoperative blood loss [850 mL (400-1500) vs. 650 mL (100-2000), P = 0.746] or patients requiring intraoperative blood transfusion [1 (9.1%) vs. 7 (30.4%), P = 0.227]. There was a trend towards fewer hepatectomy-specific complications in the CH group [3 (27.3%) vs. 13 (54.2%), P = 0.167], including PHLF (CH vs. EH: 0 vs. 29.2%, P = 0.072). Median length of stay was similar between groups [CH vs. EH: 9 days (5-23) vs. 12 days (4-85), P = 0.244]. CONCLUSIONS CH has equivalent postoperative outcomes to EH. There is a trend towards fewer hepatectomy-specific complications, including PHLF. In appropriate patients, CH may be considered as a safe parenchyma-sparing alternative to EH.
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Affiliation(s)
- Jenny Chan
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Luke Bradshaw
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia; Department of Surgery, University of Melbourne, Northern Health, Epping, Victoria, Australia
| | - Nezor Houli
- Department of Surgery, University of Melbourne, Northern Health, Epping, Victoria, Australia
| | - Laurence Weinberg
- Department of Anaesthesia, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Marcos V Perini
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Michael Fink
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Vijayaragavan Muralidharan
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Graham Starkey
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Robert Jones
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Bao Zhong Wang
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Christopher Christophi
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia
| | - Mehrdad Nikfarjam
- Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia.
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Mosharaf-Dehkordi M. A fully coupled porous media and channels flow approach for simulation of blood and bile flow through the liver lobules. Comput Methods Biomech Biomed Engin 2019; 22:901-915. [PMID: 31124725 DOI: 10.1080/10255842.2019.1601180] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Two dimensional, steady state, and incompressible blood and bile flows through the liver lobules are numerically simulated. Two different geometric models A and B are proposed to study the effects of lobule structure on the fluid flow behaviour. In Model A, the lobule tissue is represented as a hexagonal shape porous medium with a set of flow channels at its vertices accounting for the hepatic artery, portal and central veins along with bile ductules. Model B is a channelized porous medium constructed by adding a set of flow channels, representing the bile canaliculies and lobule sinusoids, to Model A. The bile and blood flow through the lobule is simulated by the finite element approach, based on the Darcy/Brinkman equations in the lobule tissue and the Navier-Stokes (or Stokes) equations in the flow channels. In Model B, a transmission factor on the boundaries of the bile canaliculies is introduced to connect the bile and blood flows. First, a single regular lobule is utilized to exhibit the fluid flow pattern through the liver lobule represented by proposed geometric models. Then, the model is extended to a group of liver lobules to demonstrate the flow through a liver slice represented by irregular lobules. Numerical results indicate that the Darcy and Brinkman equations provide nearly the same solutions for Model A and similar solutions with a little difference for Model B. It is shown that the existence of sinusoids and bile canaliculies inside the liver lobules has noticeable effects on its fluid flow pattern, in terms of pressure and velocity fields.
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Affiliation(s)
- Mehdi Mosharaf-Dehkordi
- a Department of Mechanical Engineering, Faculty of Engineering , University of Isfahan , Isfahan , Iran
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28
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Hasanin AS, Mahmoud FM, Soliman HM. Factors affecting acid base status during hepatectomy in cirrhotic patients. EGYPTIAN JOURNAL OF ANAESTHESIA 2019. [DOI: 10.1016/j.egja.2013.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Ashraf S. Hasanin
- Department of Anesthesia & ICU, National Liver Institute, Menoufia University, Egypt
| | - Fatma M.A. Mahmoud
- Department of Anesthesia & ICU, National Liver Institute, Menoufia University, Egypt
| | - Hossam M. Soliman
- Department of Hepatobiliary Surgery & Liver Transplantation, National Liver Institute, Menoufia University, Egypt
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Taman HI, Elhefnawy E. Hepatic Protective Effect of Dexmedetomidine after Partial Hepatectomy Surgery: A Prospective Controlled Study. Anesth Essays Res 2019; 13:132-137. [PMID: 31031493 PMCID: PMC6444966 DOI: 10.4103/aer.aer_106_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Background: Inflow occlusion of the portal triad is a common blood loss-reducing method during hepatectomy which may induce ischemic-reperfusion injury of the remaining parts of the liver. Dexmedetomidine is used for reducing ischemic-reperfusion injury in hepatectomy. Aim: The aim of this study was to assess the protective effect of dexmedetomidine on liver after partial hepatectomy using inflow occlusion. Setting and Design: This prospective controlled, double-blinded, randomized study included any patients of either sex with age between 20 and 70 years, those in physical status American Society of Anesthesiologists Classes I and II, and those who were planned for partial hepatectomy. Patients and Methods: Patients with elective hepatectomy were randomized into dexmedetomidine group, which received dexmedetomidine at 0.3 mg/kg/h, and control group, which received a placebo. Statistical Analysis: Statistical analysis was performed using IBM SPSS software version 18. Data were tested using Kolmogorov–Smirnov test, independent t-test or Mann–Whitney U-test, and Chi-square or Fisher's exact test. The statistical significance was considered at P < 0.05. Results: Serum albumin, aspartate aminotransferase, alanine aminotransferase, prothrombin time were higher in control group in comparison to dexmedetomidine group. Hypotension duration was lower in control group in comparison to dexmedetomidine group. Vasoconstrictor usage, amount of blood loss, and colloid, crystalloid, and blood given to patients were higher in control group in comparison to the study group. Conclusions: Dexmedetomidine can protect the liver during hepatic resection surgery with inflow occlusion with decreasing blood loss and need for blood transfusion.
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Affiliation(s)
- Hani I Taman
- Department of Anesthesia and Surgical Intensive Care, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Emad Elhefnawy
- Department of Anesthesia and Surgical Intensive Care, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Abstract
Liver resection is an important clinical intervention to treat liver disease. Following liver resection, patients exhibit a wide range of outcomes including normal recovery, suppressed recovery, or liver failure, depending on the regenerative capacity of the remnant liver. The objective of this work is to study the distinct patient outcomes post hepatectomy and determine the processes that are accountable for liver failure. Our model based approach shows that cell death is one of the important processes but not the sole controlling process responsible for liver failure. Additionally, our simulations showed wide variation in the timescale of liver failure that is consistent with the clinically observed timescales of post hepatectomy liver failure scenarios. Liver failure can take place either instantaneously or after a certain delay. We analyzed a virtual patient cohort and concluded that remnant liver fraction is a key regulator of the timescale of liver failure, with higher remnant liver fraction leading to longer time delay prior to failure. Our results suggest that, for a given remnant liver fraction, modulating a combination of cell death controlling parameters and metabolic load may help shift the clinical outcome away from post hepatectomy liver failure towards normal recovery.
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31
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Chan J, Perini M, Fink M, Nikfarjam M. The outcomes of central hepatectomy versus extended hepatectomy: a systematic review and meta-analysis. HPB (Oxford) 2018; 20:487-496. [PMID: 29439847 DOI: 10.1016/j.hpb.2017.12.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2017] [Revised: 12/07/2017] [Accepted: 12/19/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Central hepatectomy (CH) is a relatively uncommon liver resection technique. It is generally perceived as a more complex operation than extended hepatectomies (EH), with potentially higher associated morbidity. The outcomes of CH compared with EH is not well defined and there is a need to reassess. METHODS A systematic literature search was conducted in PubMed, MEDLINE, EMBASE and Web of Science according to PRISMA guidelines for studies on the treatment of liver tumours with CH published from 1972 until February 2017. Outcomes of patients undergoing CH were assessed and compared to those undergoing EH. RESULTS 18 publications including 1380 CH were included for analysis. Mortality rates after CH ranged from 0 to 9%. There were 20 (1.4%) deaths after CH and the most common cause of death was post-hepatectomy liver failure (PHLF). Morbidity rates varied between 12 and 61% and 316 (23%) post-operative events were reported. Analysis of five comparative studies showed similar mortality between CH and EH groups (OR: 0.64, 95% CI = 0.24-1.70, p = 0.37). There were significantly fewer overall post-operative complications in the CH group (OR: 0.38, 95% CI = 0.28-0.51, p < 0.001) and reduced PHLF was found in the CH group compared to EH (OR: 0.53, 95% CI = 0.29-0.98, p = 0.04). The rates of post-hepatectomy biliary complications were similar between groups (OR: 0.98, 95% CI = 0.51-1.88, p = 0.96). Mean length of stay (days) was shorter in the CH group (MD: -2.67, 95% CI = -4.93 to -0.41, p = 0.02). CONCLUSION CH appears to have similar post-operative mortality rates compared to EH but is associated with fewer post-operative complications, including PHLF and shorter overall length of stay.
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Affiliation(s)
- Jenny Chan
- University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia
| | - Marcos Perini
- University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia
| | - Michael Fink
- University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia
| | - Mehrdad Nikfarjam
- University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia.
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Athanasiou A, Spartalis E, Hennessy M, Spartalis M, Pikoulis E. Comment on "Establishing a Porcine Model of Small for Size Syndrome following Liver Resection". Can J Gastroenterol Hepatol 2018; 2018:4915817. [PMID: 29951472 PMCID: PMC5987303 DOI: 10.1155/2018/4915817] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Accepted: 01/31/2018] [Indexed: 01/01/2023] Open
Affiliation(s)
- Antonios Athanasiou
- Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Eleftherios Spartalis
- Laboratory of Experimental Surgery and Surgical Research, University of Athens, Medical School, Ag. Thoma 15B, 11527 Athens, Greece
| | - Mairead Hennessy
- Department of Surgery, Mercy University Hospital, Grenville Place, Cork, Ireland
| | - Michael Spartalis
- Laboratory of Experimental Surgery and Surgical Research, University of Athens, Medical School, Ag. Thoma 15B, 11527 Athens, Greece
| | - Emmanouil Pikoulis
- First Surgery Department, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Rahnemai-Azar AA, Cloyd JM, Weber SM, Dillhoff M, Schmidt C, Winslow ER, Pawlik TM. Update on Liver Failure Following Hepatic Resection: Strategies for Prediction and Avoidance of Post-operative Liver Insufficiency. J Clin Transl Hepatol 2018; 6:97-104. [PMID: 29577036 PMCID: PMC5863005 DOI: 10.14218/jcth.2017.00060] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Revised: 10/22/2017] [Accepted: 10/23/2017] [Indexed: 01/27/2023] Open
Abstract
Liver resection is increasingly used for a variety of benign and malignant conditions. Despite advances in preoperative selection, surgical technique and perioperative management, posthepatectomy liver failure (PHLF) is still a leading cause of morbidity and mortality following liver resection. Given the devastating physiological consequences of PHLF and the lack of effective treatment options, identifying risk factors and preventative strategies for PHLF is paramount. In the past, a major limitation to conducting high quality research on risk factors and prevention strategies for PHLF has been the absence of a standardized definition. In this article, we describe relevant definitions for PHLF, discuss risk factors and prediction models, and review advances in liver assessment tools and PHLF prevention strategies.
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Affiliation(s)
- Amir A. Rahnemai-Azar
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin Hospital, Madison, WI, USA
| | - Jordan M. Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Sharon M. Weber
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin Hospital, Madison, WI, USA
| | - Mary Dillhoff
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Carl Schmidt
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Emily R. Winslow
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin Hospital, Madison, WI, USA
| | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- *Correspondence to: Timothy M. Pawlik, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Department of Surgery, Wexner Medical Center, Ohio State University, 395 W. 12 Ave., Suite 670, Columbus, OH 43210, USA. Tel: +1-614 293 8701, Fax: +1-614 293 4063, E-mail:
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Truant S, El Amrani M, Skrzypczyk C, Boleslawski E, Sergent G, Hebbar M, Dharancy S, Pruvot FR. Factors associated with fatal liver failure after extended hepatectomy. HPB (Oxford) 2017; 19:682-687. [PMID: 28465090 DOI: 10.1016/j.hpb.2017.04.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 04/05/2017] [Accepted: 04/09/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Posthepatectomy liver failure (PHLF) is the leading cause of posthepatectomy mortality. This study aimed to revisit the etiology and pattern of PHLF and its role in posthepatectomy morbidity and mortality. METHODS The pattern and etiology of PHLF and subsequent morbidity and mortality were analysed in the subgroup of patients without cirrhosis undergoing an extended hepatectomy (≥4 segments) over a 5 year period. PHLF was defined using ISGLS criteria and/or 50-50 and/or peak serum bilirubin >7 mg/dl. RESULTS Among 285 included patients (median age 62 [20-89]), 81 (28%) developed PHLF with higher rates of major complications (38%) and mortality (27%) than patients without PHLF (13% and 2%, respectively; p < 0.001). Twenty-six patients (9%) died, 22 of whom had PHLF. Of these 22 patients, only 4 patients died from complications purely-attributed to PHLF. All the remaining 18 patients had additional peri-operative factors that contributed to the mortality of which severe vascular events were the most common. CONCLUSION PHLF is associated with higher rates of morbidity and mortality following extended resection. The etiology of PHLF is multifactorial with vascular events being common precipitant. The multifactorial origin of PHLF may explain the low predictive value of current clinical risk scores.
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Ironside N, Bell R, Bartlett A, McCall J, Powell J, Pandanaboyana S. Systematic review of perioperative and survival outcomes of liver resections with and without preoperative portal vein embolization for colorectal metastases. HPB (Oxford) 2017; 19:559-566. [PMID: 28438427 DOI: 10.1016/j.hpb.2017.03.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 02/14/2017] [Accepted: 03/01/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this systematic review was to evaluate perioperative and long term outcomes in patients who underwent PVE prior to liver resection for colorectal liver metastases. METHODS A systematic search of PubMed, MEDLINE, Embase and the Cochrane library was performed in accordance with PRISMA guidelines. Studies including patients who underwent liver resection with and without PVE (N-PVE) were included. RESULTS Thirteen studies including 1345 were included of which 539 patients had PVE and 806 had N-PVE. Eight studies reported that from a total of 450 patients who underwent PVE, 136 (30%) did not proceed to liver resection. In 114 (84%) patients this was due to disease progression. The postoperative morbidity was 42% (n = 151) after PVE and 10% (n = 35) developed postoperative liver failure after liver resection. Median overall survival, reported in all studies, was 38.9 months and 45.6 months respectively, following resection with PVE and N-PVE. The median disease free survival, reported in eight studies, was 15.7 (PVE) and 21.4 (N-PVE) months respectively. CONCLUSION Following PVE 70% of patients proceed to liver resection, with a 10% risk of postoperative liver failure. Tumour progression after PVE was the predominant reason for not proceeding to liver resection.
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Affiliation(s)
- Natasha Ironside
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Richard Bell
- Department of Hepatobiliary Surgery, St James Hospital, Leeds, UK
| | - Adam Bartlett
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Hepatobiliary Surgery, Auckland City Hospital, Auckland, New Zealand
| | - John McCall
- Department of Hepatobiliary Surgery, Auckland City Hospital, Auckland, New Zealand
| | - James Powell
- Department of Hepatobiliary Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Sanjay Pandanaboyana
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Hepatobiliary Surgery, Auckland City Hospital, Auckland, New Zealand.
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Laser speckle contrast imaging and Oxygen to See for assessing microcirculatory liver blood flow changes following different volumes of hepatectomy. Microvasc Res 2017; 110:14-23. [DOI: 10.1016/j.mvr.2016.11.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Revised: 11/04/2016] [Accepted: 11/07/2016] [Indexed: 12/14/2022]
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Andreatos N, Amini N, Gani F, Margonis GA, Sasaki K, Thompson VM, Bentrem DJ, Hall BL, Pitt HA, Wilson A, Pawlik TM. Albumin-Bilirubin Score: Predicting Short-Term Outcomes Including Bile Leak and Post-hepatectomy Liver Failure Following Hepatic Resection. J Gastrointest Surg 2017; 21:238-248. [PMID: 27619809 DOI: 10.1007/s11605-016-3246-4] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Accepted: 08/10/2016] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Post-operative bile leak (BL) and post hepatectomy liver failure (PHLF) are the major potential sources of morbidity among patients undergoing liver resection. We sought to define the incidence of BL and PHLF among a large cohort of patients, as well as examine the prognostic impact of model for end-stage liver disease (MELD) and albumin-bilirubin (ALBI) scores to predict these short-term outcomes. MATERIALS AND METHODS Patients who underwent a hepatectomy between January 1, 2014 and December 31, 2014 were identified using the National Surgical Quality Improvement Program (NSQIP) liver-targeted database. Risk factors for BL and PHLF were identified using multivariable logistic regression. RESULTS Among the 3064 patients identified, median age was 60 years (IQR 50-68). Most patients underwent surgery (78.9 %) for malignant lesions. Post-operatively, 250 (8.5 %) patients experienced a BL while PHLF occurred in 149 cases (4.9 %). Both MELD (MELD <10 4.9 %; MELD ≥10, 10 %; P = 0.001) and ALBI (grade 1, 4.0 %; grade 2, 7.2 %; grade 3, 10.0 %; P = 0.001) were associated with PHLF occurrence, while only ALBI predicted PHLF severity (P = 0.008). Moreover, ALBI was associated with BL (grade 1, 7.1 %; grade 2, 11.5 %; grade 3, 14.0 %; P < 0.001), whereas MELD was not (MELD <10, 8.4 %; MELD ≥10, 11.2 %; P = 0.13). On multivariable analysis, ALBI grade 2/3 was associated with PHLF (OR 1.57, 95 % CI 1.08-2.27; P = 0.02), PHLF severity (OR 3.06, 95 % CI 1.50-6.23; P = 0.003), and the development of a BL (OR 1.35, 95 % CI 1.02-1.80; P = 0.04). CONCLUSION The ALBI score was associated with short-term post-operative outcomes following hepatic resection and represents a useful pre-operative risk-assessment tool to identify patients at risk for adverse post-operative outcomes.
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Affiliation(s)
- Nikolaos Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Neda Amini
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Faiz Gani
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Georgios A Margonis
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Kazunari Sasaki
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Vanessa M Thompson
- National Surgical Quality Improvement Program, American College of Surgeons, Chicago, IL, USA
| | - David J Bentrem
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Bruce L Hall
- Department of Surgery, Washington University School of Medicine at St. Louis, St. Louis, MO, USA
| | - Henry A Pitt
- Department of Surgery, Temple University Health System, Philadelphia, PA, USA
| | - Ana Wilson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M Pawlik
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. .,Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research Wexner Medical Center at The Ohio State University, 395 W. 12th Avenue, Suite 670, Columbus, OH, 43210, USA.
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Al-Alem F, Mattar RE, Fadl OA, Alsharabi A, Al-Saif F, Hassanain M. Morbidity and mortality and predictors of outcome following hepatectomy at a Saudi tertiary care center. Ann Saudi Med 2016; 36:414-421. [PMID: 27920414 PMCID: PMC6074202 DOI: 10.5144/0256-4947.2016.414] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Hepatic resection is a major surgical procedure. Data on outcomes of hepatectomy in Saudi Arabia are scarce. OBJECTIVE To measure morbidity and mortality and assess predictors of outcome after hepatectomy. DESIGN Descriptive study. SETTING Tertiary care center in Saudi Arabia with well established hepatobiliary surgery unit. PATIENTS AND METHODS All patients undergoing liver resection in our institute during 2006-2014. Data were analyzed by Kaplan-Meier survival analysis. MAIN OUTCOMES MEASURE(S) Postoperative morbidity and 90-day mortality. Secondary outcomes were risk factors associated with increased morbidity and mortality. RESULTS Data on 77 resections were collected; 56 patients (72.7%) had a malignant etiology, mainly colorectal liver metastases and hepatocellular carcinoma (45.5% and 14.3% respectively). Complications developed following 30 resections (39.0%), with the majority being Clavien grades I-III. In the univariate analysis, predicting factors were the total bilirubin level preoperatively, operative time, extent of resection (i.e., major resection), use of epidural anesthesia, and postoperative liver dysfunction. In the multivariate analysis, the Schindl liver dysfunction score showed the strongest correlation with the development of complications (P=.006). The 90-day postoperative mortality was 5.2% (4/77 patients); 3 patients fulfilled the 50:50 liver dysfunction criteria. Significant predictors were concurrent intra-abdominal surgery, postoperative liver dysfunction, and multiple complications. CONCLUSION Factors that predicted development of complications were elevated total bilirubin level preoperatively, operative time, extent of the resection, use of epidural anesthesia and a postoperative need for blood transfusion. Liver resection is a safe and feasible option at our center. LIMITATIONS The small number of indications for resection and consequent reduction in variety of risk factors limited ability to make inferences. Additionally, only a handful of cases were performed laparoscopically.
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Affiliation(s)
| | | | | | | | | | - Mazen Hassanain
- Dr. Mazen Hassanain, Department of General Surgery,, College of Medicine,, King Saud University,, Riyadh 11466, Saudi Arabia, Department of Oncology,, McGill University, Montreal,, Quebec, Canada, , ORCID: http://orcid.org/0000- 0002-2441-5142
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Voskanyan SE, Naidyonov EV, Artemyev AI, Zabezhinsky DA, Rudakov VS, Zhurbin AS, Bashkov AN, Grigorieva OO. [Comparative results of use liver protecting drugs for prophylaxis of the liver failure after extensive resections of the liver]. Khirurgiia (Mosk) 2016:71-75. [PMID: 27723699 DOI: 10.17116/hirurgia2016971-75] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
After 100 extensive resections of a liver for excision of metastasises of a colorectal cancer, the different drugs protecting a liver were used for prophylaxis of a liver failure. MATERIAL AND METHODS Patients were distributed on 2 equivalent groups. Patients of the first group received Ademetionin in a dosage 400 mg 2 times a day within 7 days. Patients of the second group received Remaxol in a dosage 400 ml within 7 days once a day. RESULTS Frequency of cases of an acute liver failure in the first group of patients was 38%, in the second group of patients - 20% (p<0.05). Patients of the second group had milder course of an acute liver failure (by criteria of ISGLS, 2011) in comparison with patients of the first group. Postoperative bed - days in the first group of patients lasted 13 (11-15) days, in the second group of patients - 11 (10-13) days (p<0.05). There was no postoperative lethality.
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Affiliation(s)
- S E Voskanyan
- State Research Center of the Russian Federation - Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
| | - E V Naidyonov
- State Research Center of the Russian Federation - Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
| | - A I Artemyev
- State Research Center of the Russian Federation - Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
| | - D A Zabezhinsky
- State Research Center of the Russian Federation - Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
| | - V S Rudakov
- State Research Center of the Russian Federation - Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
| | - A S Zhurbin
- State Research Center of the Russian Federation - Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
| | - A N Bashkov
- State Research Center of the Russian Federation - Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
| | - O O Grigorieva
- State Research Center of the Russian Federation - Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
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Chen Z, Kuang Q, Lao XJ, Yang J, Huang W, Zhou D. Differentiation of UC-MSCs into hepatocyte-like cells in partially hepatectomized model rats. Exp Ther Med 2016; 12:1775-1779. [PMID: 27602090 PMCID: PMC4998204 DOI: 10.3892/etm.2016.3543] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 07/25/2016] [Indexed: 12/18/2022] Open
Abstract
The aim of the study was to investigate the possibility of human umbilical cord mesenchymal stem cells (UC-MSCs) surviving and differentiating into hepatocyte-like cells in partially hepatectomized model rats. MSCs were isolated from human umbilical cord and cultured with collagenase digestion. Cell surface markers were detected and fifth generation UC-MSCs were labeled with PKH26. The partially hepatectomized model rats were injected with the labeled human umbilical cord MSCs and transplanted through the portal vein. The survival of the labeled cells, in differentiation conditions and the expression of hepatic marker albumin were observed at post-transplantation 1, 2 and 3 weeks under a fluorescence microscope. It was found that the human umbilical cord MSCs could be cultured and amplified in vitro. Following transplantation to the partially hepatectomized liver of the model rat, the cells survived and expresses the hepatic marker albumin in vivo. After being labeled with PKH26, the cells were visualized as red fluorescence under a fluorescence microscope. In the frozen sections of the liver, the marked cells scattered around and most of them expressed albumin with green fluorescence under the fluorescence microscope. In conclusion, the transplanted human umbilical cord MSCs survived and differentiated into hepatocyte-like cells. The human umbilical cord MSCs may therefore be a main source of hepatocytes in transplantation.
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Affiliation(s)
- Zheng Chen
- Department of General Surgery, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Qiaoting Kuang
- Department of General Surgery, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Xue-Jun Lao
- Department of General Surgery, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Jie Yang
- Department of General Surgery, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Weidong Huang
- Department of General Surgery, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Dong Zhou
- Department of General Surgery, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
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Impact of Perioperative Phosphorus and Glucose Levels on Liver Regeneration and Long-term Outcomes after Major Liver Resection. J Gastrointest Surg 2016; 20:1305-16. [PMID: 27121234 DOI: 10.1007/s11605-016-3147-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 03/31/2016] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The impact of phosphorus as well as glycemic alterations on liver regeneration has not been directly examined. We sought to determine the impact of phosphorus and glucose on liver regeneration after major hepatectomy. METHODS Early and late liver regeneration index was defined as the relative increase of liver volume (RLV) within 2[(RLV2m-RLVp)/RLVp] and 7 months[(RLV7m-RLVp)/RLVp] following surgery. The association of perioperative metabolic factors, liver regeneration, and outcomes was assessed. RESULTS On postoperative day 2, 50 (52.6 %) patients had a low phosphorus level (≤2.4 mg/dl), while 45 (47.4 %) had a normal/high phosphorus level (>2.4 mg/dl). Despite comparable clinicopathologic characteristics (all P > 0.05) and RLV/TLV at surgery (P = 0.84), regeneration index within 2 months was lower in the normal/high phosphorus group (P = 0.01) with these patients having increased risk for postoperative liver failure (P = 0.01). The inhibition of liver regeneration persisted at 7 months (P = 0.007) and was associated with a worse survival (P = 0.02). Preoperative hypoglycemia was associated only with a lower early regeneration index (P = 0.02). CONCLUSIONS Normal/high phosphorus was associated with inhibition of early and late liver regeneration, as well as with an increased risk of liver failure and worse long-term outcomes. Immediate preoperative hypoglycemia was associated with a lower early volumetric gain. Metabolic factors may represent early indicators of liver failure that could identify patients at increased risk for worse outcomes.
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Cannistrà M, Grande R, Ruggiero M, Novello M, Zullo A, Bonaiuto E, Vaccarisi S, Cavallari G, Serra R, Nardo B. Resection of hepatocellular carcinoma in elderly patients and the role of energy balance. Int J Surg 2016; 33 Suppl 1:S119-25. [PMID: 27353847 DOI: 10.1016/j.ijsu.2016.06.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Progressive functional impairment with age has a significant impact on perioperative risk management. Chronic liver diseases induce a strong oxidative stress; in the elderly, in particular, impaired elimination of free radicals leads to insufficient DNA repair. The events associated with a weak response to growth factors after hepatectomy leads to a decline in liver regeneration. Hypercholesterolemia is highly prevalent in the elderly, which may alter the coenzyme Q10 (CoQ) levels and in turn the cellular energy balance. This condition is commonly treated with statins. The aim of this study is to investigate the role of preoperative cellular energy balance in predicting hepatocellular carcinoma (HCC) postresection outcomes. MATERIALS AND METHODS In a 5-year period (2009-2013), elderly patients with hypercholesterolemia, cardiovascular disease, and diabetes mellitus, undergoing HCC resection, were recruited and grouped by age (<75 and ≥ 75 years old). All patients were previously treated with statins. The risk factors associated with hospital morbidity/mortality and prolonged length of stay (LOS) were evaluated. RESULTS Forty-five elderly patients were recruited and grouped according to their treatment: Group 1 (n = 23) was treated with statins alone (control group), whereas Group 2 (n = 22) was treated with statins and a CoQ analogue, 3 weeks from the surgery and at least a month later (experimental group). The majority of our patients were treated with atorvastatin [n = 28 (53.84%)] and the minority with simvastatin [n = 17 (32.69%)], 20 mg/day, for at least 3 years before the surgery. Perioperative mortality was observed in one patient of Group 1 (4.3%). Morbidities were noted in 13 patients of Group 1 (56.5%) and four patients of Group 2 (18.2%). The control group showed delayed functional recovery, muscle weakness, increased infection rate, and pleural effusion due to prolonged bed rest (hospital stay 13 days (7-19) vs. 8.5 days (5-12)), compared with the experimental group. The overall survival at 5 years was similar for both groups (n = 10 patients (43%) in Group 1 vs. n = 10 patients (45%) in Group 2). CONCLUSION In the elderly population, survival is closely linked to postoperative morbidity and mortality. In our study, prolonged LOS was found to be related to delayed bioenergetic recovery. When limited, risk factors such as infections, neutropenia, and red blood cell transfusions could lower LOS and mortality of elderly patients with HCC. Higher age was associated with greater postoperative morbidity and successful hospital stay.
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Affiliation(s)
- Marco Cannistrà
- Department of Surgery, Annunziata Hospital of Cosenza, Cosenza, Italy.
| | - Raffaele Grande
- Department of Medical and Surgical Sciences, University of Catanzaro, Italy.
| | - Michele Ruggiero
- Department of Medical and Surgical Sciences, University of Catanzaro, Italy.
| | - Matteo Novello
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Italy.
| | - Alessandra Zullo
- Department of Medical and Surgical Sciences, University of Catanzaro, Italy.
| | | | | | - Giuseppe Cavallari
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Italy.
| | - Raffaele Serra
- Department of Medical and Surgical Sciences, University of Catanzaro, Italy.
| | - Bruno Nardo
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Italy.
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Takahashi K, Kurokawa T, Oshiro Y, Fukunaga K, Sakashita S, Ohkohchi N. Postoperative Decrease in Platelet Counts Is Associated with Delayed Liver Function Recovery and Complications after Partial Hepatectomy. TOHOKU J EXP MED 2016; 239:47-55. [PMID: 27181573 DOI: 10.1620/tjem.239.47] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Peripheral platelet counts decrease after partial hepatectomy; however, the implications of this phenomenon are unclear. We assessed if the observed decrease in platelet counts was associated with postoperative liver function and morbidity (complications grade ≤ II according to the Clavien-Dindo classification). We enrolled 216 consecutive patients who underwent partial hepatectomy for primary liver cancers, metastatic liver cancers, benign tumors, and donor hepatectomy. We classified patients as either low or high platelet percentage (postoperative platelet count/preoperative platelet count) using the optimal cutoff value calculated by a receiver operating characteristic (ROC) curve analysis, and analyzed risk factors for delayed liver functional recovery and morbidity after hepatectomy. Delayed liver function recovery and morbidity were significantly correlated with the lowest value of platelet percentage based on ROC analysis. Using a cutoff value of 60% acquired by ROC analysis, univariate and multivariate analysis determined that postoperative lowest platelet percentage ≤ 60% was identified as an independent risk factor of delayed liver function recovery (odds ratio (OR) 6.85; P < 0.01) and morbidity (OR, 4.90; P < 0.01). Furthermore, patients with the lowest platelet percentage ≤ 60% had decreased postoperative prothrombin time ratio and serum albumin level and increased serum bilirubin level when compared with patients with platelet percentage ≥ 61%. A greater than 40% decrease in platelet count after partial hepatectomy was an independent risk factor for delayed liver function recovery and postoperative morbidity. In conclusion, the decrease in platelet counts is an early marker to predict the liver function recovery and complications after hepatectomy.
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Affiliation(s)
- Kazuhiro Takahashi
- Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Department of Surgery, University of Tsukuba
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Encapsulated Whole Bone Marrow Cells Improve Survival in Wistar Rats after 90% Partial Hepatectomy. Stem Cells Int 2015; 2016:4831524. [PMID: 26649048 PMCID: PMC4663362 DOI: 10.1155/2016/4831524] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Revised: 01/18/2015] [Accepted: 01/28/2015] [Indexed: 12/16/2022] Open
Abstract
Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-β-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.
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3D T1 relaxometry pre and post gadoxetic acid injection for the assessment of liver cirrhosis and liver function. Magn Reson Imaging 2015; 33:1075-1082. [DOI: 10.1016/j.mri.2015.06.013] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 06/09/2015] [Accepted: 06/20/2015] [Indexed: 02/06/2023]
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Defining Post Hepatectomy Liver Insufficiency: Where do We stand? J Gastrointest Surg 2015; 19:2079-92. [PMID: 26063080 DOI: 10.1007/s11605-015-2872-6] [Citation(s) in RCA: 81] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 06/02/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND Post-hepatectomy liver failure (PHLF) is a major source of morbidity and mortality in patients undergoing liver resection. The aim of this review is to summarize the recent literature available on PHLF including its definition, predictive factors, preoperative risk assessment, severity grading, preventative measures, and management strategies. METHODS A systematic literature search was carried out with the search engines PubMed, Medline, and Cochrane Database using the keywords related to "liver failure", "posthepatectomy", and "hepatic resection". RESULTS Liver resection is a curative treatment of liver tumors. However, it leads to concurrent death and regeneration of the remaining hepatocytes. Factors related to the patient, liver parenchyma and the extent of surgery can inhibit regeneration leading to PHLF. CONCLUSION Given its resistance to treatment and the high postoperative mortality associated with PHLF, great effort has been put in to both accurately identify patients at high risk and to develop strategies that can help prevent its occurrence.
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Effect of the Human Amniotic Membrane on Liver Regeneration in Rats. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2015; 2015:706186. [PMID: 26457000 PMCID: PMC4589631 DOI: 10.1155/2015/706186] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Accepted: 09/07/2015] [Indexed: 12/14/2022]
Abstract
Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations.
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mTOR-Dependent Suppression of Remnant Liver Regeneration in Liver Failure After Massive Liver Resection in Rats. Dig Dis Sci 2015; 60:2718-29. [PMID: 25956703 DOI: 10.1007/s10620-015-3676-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Accepted: 04/17/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Massive hepatectomy often leads to fatal liver failure because of a small remnant liver volume. The aim of this study was to investigate the potential mechanisms leading to liver failure. METHODS Sprague-Dawley rats had performed a sham operation, 85 % partial hepatectomy (PH) or 90 % PH, and all had free access to water with or without supplemented glucose. Liver function and survival were evaluated. Liver parenchymal injury was assessed by evaluating hepatic pathology, blood biochemistry, and apoptotic and necrotic alterations. The regeneration response was assessed by the weight gain of the remnant liver, hepatocyte proliferation markers, and regeneration-related molecules. RESULTS The 90 % hepatectomy resulted in a significantly lower survival rate and impaired liver function; however, no significant more serious liver parenchymal injuries were detected. TNF-α, HGF, myc and IL-6 were either similarly expressed or overexpressed; however, the increase in remnant liver weight, mitotic index, and the presence of Ki-67 and PCNA were significantly lower in the 90 %-hepatectomized rats. mTOR, p70S6K and 4EBP1 were not activated in the remnant liver after a 90 % hepatectomy as obviously as those after an 85 % hepatectomy, which was concomitant with the higher expression of phospho-AMPK and a lower intrahepatic ATP level. Glucose treatment significantly improved the survival rate of 90 %-hepatectomized rats. CONCLUSIONS Suppression of remnant liver regeneration was observed in the 90 % PH and contributed to fatal liver failure. This suppressed liver regenerative capacity was related to the inhibited activation of mTOR signaling.
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von Heesen M, Dold S, Müller S, Scheuer C, Kollmar O, Schilling MK, Menger MD, Moussavian MR. Cilostazol improves hepatic blood perfusion, microcirculation, and liver regeneration after major hepatectomy in rats. Liver Transpl 2015; 21:792-800. [PMID: 25772848 DOI: 10.1002/lt.24114] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Revised: 02/09/2015] [Accepted: 03/01/2015] [Indexed: 12/19/2022]
Abstract
Major hepatectomy or small-for-size liver transplantation may result in postoperative liver failure. So far, no treatment is available to improve liver regeneration. Herein, we studied whether cilostazol, a selective phosphodiesterase III inhibitor, is capable of improving liver regeneration after major hepatectomy. Sprague-Dawley rats (n = 74) were treated with cilostazol (5 mg/kg daily) or a glucose solution and underwent either 70% liver resection or a sham operation. Before and after surgery, hepatic arterial and portal venous blood flow and hepatic microvascular perfusion were analyzed. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, western blotting, and bile excretion analysis. Cilostazol significantly increased hepatic blood flow and microcirculation before and after hepatectomy in comparison with sham-operated controls. This was associated with an elevation of hepatic vascular endothelial growth factor expression, an increase of hepatocellular proliferation, and an acceleration of liver regeneration. Furthermore, cilostazol protected the tissue of the remnant liver as indicated by an attenuation of hepatocellular disintegration. In conclusion, cilostazol increases hepatic blood perfusion, microcirculation, and liver regeneration after a major hepatectomy. Thus, cilostazol may represent a novel strategy to reduce the rate of liver failure after both extended hepatectomy and small-for-size liver transplantation.
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Affiliation(s)
| | - Stefan Dold
- Department of General, Visceral, Vascular, and Paediatric Surgery
| | - Simon Müller
- Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
| | - Claudia Scheuer
- Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
| | - Otto Kollmar
- Department of General, Visceral, Vascular, and Paediatric Surgery
| | | | - Michael D Menger
- Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
| | - Mohammed R Moussavian
- Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
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Assessment of Liver Remnant Using ICG Clearance Intraoperatively during Vascular Exclusion: Early Experience with the ALIIVE Technique. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2015; 2015:757052. [PMID: 26106254 PMCID: PMC4461766 DOI: 10.1155/2015/757052] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 05/11/2015] [Indexed: 12/11/2022]
Abstract
Background. The most significant risk following major hepatectomy is postoperative liver insufficiency. Current preoperative assessment of the future liver remnant relies upon assumptions which may not be valid in the setting of advanced resection strategies. This paper reports the feasibility of the ALIIVE technique which assesses the liver remnant with ICG clearance intraoperatively during vascular exclusion. Methods. 10 patients undergoing planned major liver resection (hemihepatectomy or greater) were recruited. Routine preoperative assessment included CT and standardized volumetry. ICG clearance was measured noninvasively using a finger spectrophotometer at various time points including following parenchymal transection during inflow and outflow occlusion before vascular division, the ALIIVE step. Results. There were one case of mortality and three cases of posthepatectomy liver failure. The patient who died had the lowest ALIIVE ICG clearance (7.1%/min versus 14.4 ± 4.9). Routine preoperative CT and standardized volumetry did not predict outcome. Discussion/Conclusion. The novel ALIIVE technique is feasible and assesses actual future liver remnant function before the point of no return during major hepatectomy. This technique may be useful as a check step to offer a margin of safety to prevent posthepatectomy liver failure and death. Further confirmatory studies are required to determine a safety cutoff level.
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