|
1
|
Merath K, Tiwari A, Court C, Parikh A, Dillhoff M, Cloyd J, Ejaz A, Pawlik TM. Postoperative Liver Failure: Definitions, Risk factors, Prediction Models and Prevention Strategies. J Gastrointest Surg 2023; 27:2640-2649. [PMID: 37783906 DOI: 10.1007/s11605-023-05834-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 09/07/2023] [Indexed: 10/04/2023]
Abstract
BACKGROUND Liver resection is the treatment for a variety of benign and malignant conditions. Despite advances in preoperative selection, surgical technique, and perioperative management, post hepatectomy liver failure (PHLF) is still a leading cause of morbidity and mortality following liver resection. METHODS A review of the literature was performed utilizing MEDLINE/PubMed and Web of Science databases in May of 2023. The MESH terms "liver failure," "liver insufficiency," and "hepatic failure" in combination with "liver surgery," "liver resection," and "hepatectomy" were searched in the title and/or abstract. The references of relevant articles were reviewed to identify additional eligible publications. RESULTS PHLF can have devastating physiological consequences. In general, risk factors can be categorized as patient-related, primary liver function-related, or perioperative factors. Currently, no effective treatment options are available and the management of PHLF is largely supportive. Therefore, identifying risk factors and preventative strategies for PHLF is paramount. Ensuring an adequate future liver remnant is important to mitigate risk of PHLF. Dynamic liver function tests provide more objective assessment of liver function based on the metabolic capacity of the liver and have the advantage of easy administration, low cost, and easy reproducibility. CONCLUSION Given the absence of randomized data specifically related to the management of PHLF, current strategies are based on the principles of management of acute liver failure from any cause. In addition, goal-directed therapy for organ dysfunction, as well as identification and treatment of reversible factors in the postoperative period are critical.
Collapse
Affiliation(s)
- Katiuscha Merath
- Division of Surgical Oncology, University of Texas Health Science Center San Antonio MD Anderson Cancer Center, San Antonio, TX, USA
| | - Ankur Tiwari
- Division of Surgical Oncology, University of Texas Health Science Center San Antonio MD Anderson Cancer Center, San Antonio, TX, USA
| | - Colin Court
- Division of Surgical Oncology, University of Texas Health Science Center San Antonio MD Anderson Cancer Center, San Antonio, TX, USA
| | - Alexander Parikh
- Division of Surgical Oncology, University of Texas Health Science Center San Antonio MD Anderson Cancer Center, San Antonio, TX, USA
| | - Mary Dillhoff
- Department of Surgery, Division of Surgical Oncology, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12Th Ave., Suite 670, Columbus, OH, USA
| | - Jordan Cloyd
- Department of Surgery, Division of Surgical Oncology, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12Th Ave., Suite 670, Columbus, OH, USA
| | - Aslam Ejaz
- Department of Surgery, Division of Surgical Oncology, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12Th Ave., Suite 670, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12Th Ave., Suite 670, Columbus, OH, USA.
| |
Collapse
|
|
2
|
A Web-Based Prediction Model for Estimating the Probability of Post-hepatectomy Major Complications in Patients with Hepatocellular Carcinoma: A Multicenter Study from a Hepatitis B Virus-Endemic Area. J Gastrointest Surg 2022; 26:2082-2092. [PMID: 36038746 DOI: 10.1007/s11605-022-05435-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 07/23/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND The identification of patients at high risk of developing postoperative complications is important to improve surgical safety. We sought to develop an individualized tool to predict post-hepatectomy major complications in hepatitis B virus (HBV)-infected patients with hepatocellular carcinoma (HCC). METHODS A multicenter database of patients undergoing hepatectomy for HCC were analyzed; 2/3 and 1/3 of patients were assigned to the training and validation cohorts, respectively. Independent risks of postoperative 30-day major complications (Clavien-Dindo grades III-V) were identified and used to construct a web-based prediction model, which predictive accuracy was assessed using C-index and calibration curves, which was further validated by the validation cohort and compared with conventional scores. RESULTS Among 2762 patients, 391 (14.2%) developed major complications after hepatectomy. Diabetes mellitus, concurrent hepatitis C virus infection, HCC beyond the Milan criteria, cirrhosis, preoperative HBV-DNA level, albumin-bilirubin (ALBI), and aspartate transaminase to platelet ratio index (APRI) were identified as independent predictors of developing major complications, which were used to construct the online calculator ( http://www.asapcalculate.top/Cal11_en.html ). This model demonstrated good calibration and discrimination, with the C-indexes of 0.752 and 0.743 in the training and validation cohorts, respectively, which were significantly higher than those conventional scores (the training and validation cohorts: 0.565 ~ 0.650 and 0.568 ~ 0.614, all P < 0.001). CONCLUSIONS A web-based prediction model was developed to predict the probability of post-hepatectomy major complications in an individual HBV-infected patient with HCC. It can be used easily in the real-world clinical setting to help management-related decision-making and early warning, especially in areas with endemic HBV infection.
Collapse
|
|
3
|
Bharati SJ, Hoda W, Ratre BK. Critical Care of Hepatopancreatobiliary Surgery Patient. ONCO-CRITICAL CARE 2022:475-490. [DOI: 10.1007/978-981-16-9929-0_38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
4
|
Liu Y, Chen ZL, Yu XX, Liang YJ. Risk factors for hepatic insufficiency after major hepatectomy in non-cirrhotic patients. Asian J Surg 2021; 44:1324-1325. [PMID: 34548220 DOI: 10.1016/j.asjsur.2021.06.046] [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: 06/02/2021] [Accepted: 06/29/2021] [Indexed: 10/20/2022] Open
Abstract
It is very necessary for patients with liver cancer to reasonably apply the prediction method of liver failure after hepatectomy before liver surgery. Liver surgeons can benefit greatly from clinical activities.
Collapse
Affiliation(s)
- Yu Liu
- The First Affiliated Hospital of Harbin Medical University, HeiLongJiang, China
| | - Zheng-Liang Chen
- The First Affiliated Hospital of Harbin Medical University, HeiLongJiang, China
| | - Xing-Xin Yu
- The First Affiliated Hospital of Harbin Medical University, HeiLongJiang, China
| | - Ying-Jian Liang
- The First Affiliated Hospital of Harbin Medical University, HeiLongJiang, China.
| |
Collapse
|
|
5
|
Zhang XP, Chai ZT, Feng JK, Zhu HM, Zhang F, Hu YR, Zhong CQ, Chen ZH, Wang K, Shi J, Guo WX, Chen CS, Wu MC, Lau WY, Cheng SQ. Association of type 2 diabetes mellitus with incidences of microvascular invasion and survival outcomes in hepatitis B virus-related hepatocellular carcinoma after liver resection: A multicenter study. Eur J Surg Oncol 2021; 48:142-149. [PMID: 34452770 DOI: 10.1016/j.ejso.2021.08.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/26/2021] [Accepted: 08/09/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Microvascular invasion (MVI) adversely affects long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to examine the association between preoperative type 2 diabetes mellitus (T2DM) with incidences of MVI and prognosis in HBV-related HCC after liver resection (LR). MATERIAL AND METHODS Data of HBV-related HCC patients who underwent LR as an initial therapy from four hospitals in China were retrospectively collected. Clinicopathological factors associated with the incidence of MVI were identified using univariate and multivariate logistic regression analysis. The recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS Of 1473 patients who were included, 219 (14.9%) patients had T2DM. Preoperative T2DM, HBV DNA load, antiviral treatment, AFP level, varices, and tumor encapsulation were identified to be independent predictors of the incidence of MVI. Patients with HBV-related HCC and T2DM had a higher incidence of MVI (65.8%) than those without T2DM (55.4%) (P = 0.004). The RFS and OS were significantly worse in patients with T2DM than those without T2DM (median RFS: 11.1 vs 16.7 months; OS: 26.4 vs 42.6 months, both P < 0.001). Equivalent results were obtained in HCC patients with MVI who had or did not have T2DM (median RFS: 10.0 vs 15.9 months; OS: 24.5 vs 37.9 months, both P < 0.001). CONCLUSIONS Preoperative T2DM was an independent risk factor of incidence of MVI. Patients with HBV-related HCC and T2DM had worse prognosis than those without T2DM after LR.
Collapse
Affiliation(s)
- Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Zong-Tao Chai
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jin-Kai Feng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Hui-Min Zhu
- College of Basic Medical Sciences, Second Military Medical University, Shanghai, China
| | - Fan Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Binzhou Medical College, Shandong, China
| | - Yi-Ren Hu
- Department of General Surgery, Wenzhou People's Hospital, Zhejiang, China
| | - Cheng-Qian Zhong
- Department of Hepatobiliary Surgery, Longyan First Hospital, Affiliated to Fujian Medical University, Fujian, China
| | - Zhen-Hua Chen
- Department of General Surgery, Zhejiang Provincial Armed Police Corps Hospital, Zhejiang, China
| | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | | | - Meng-Chao Wu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wan Yee Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
| |
Collapse
|
|
6
|
Geh D, Manas DM, Reeves HL. Hepatocellular carcinoma in non-alcoholic fatty liver disease-a review of an emerging challenge facing clinicians. Hepatobiliary Surg Nutr 2021; 10:59-75. [PMID: 33575290 DOI: 10.21037/hbsn.2019.08.08] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 08/21/2019] [Indexed: 12/14/2022]
Abstract
Importance Non-alcoholic fatty liver disease (NAFLD) is a rapidly growing cause of chronic liver disease and is becoming a leading cause of hepatocellular carcinoma (HCC) in many developed countries. This presents major challenges for the surveillance, diagnosis and treatment of HCC. Objective To discuss the clinical challenges faced by clinicians in managing the rising number of NAFLD-HCC cases. Evidence Review MEDLINE, PubMed and Embase databases were searched using the keywords; NAFLD, HCC, surveillance, hepatectomy, liver transplantation, percutaneous ablation, transarterial chemoembolization (TACE), selective internal radiotherapy treatment (SIRT) and sorafenib. Relevant clinical studies were included. Findings Current HCC surveillance programmes are inadequate because they only screen for HCC in patients with cirrhosis, whereas in NAFLD a significant proportion of HCC develops in the absence of cirrhosis. Consequently NAFLD patients often present with a more advanced stage of HCC, with a poorer prognosis. NAFLD-HCC patients also tend to be older and to have more co-morbidities compared to HCC of other etiologies. This limits the use of curative treatments such as liver resection and orthotopic liver transplantation (OLT). Evidence suggests that although NAFLD-HCC patients who undergo liver resection or OLT have worse perioperative and short-term outcomes, overall long-term survival is comparable to HCC of other etiologies. This highlights the importance of careful patient selection, pre-habilitation and perioperative planning for NAFLD-HCC patients being considered for surgical treatment. Careful consideration is also important for non-surgical treatments, although the evidence supporting treatment selection is frequently lacking, as these patients tend to be poorly represented in clinical trials. Locoregional therapies such as percutaneous ablation and TACE may be less well tolerated and less effective in NAFLD patients with obesity or diabetes. The tyrosine kinase inhibitor sorafenib may also be less effective. Conclusions and Relevance This review highlights how international guidelines, for which NAFLD traditionally has made up a small part of the evidence base, may not be appropriate for all NAFLD-HCC patients. Future guidelines need to reflect the changing landscape of HCC, by making specific recommendations for the management of NAFLD-HCC.
Collapse
Affiliation(s)
- Daniel Geh
- Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Derek M Manas
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.,Hepatopancreatobiliary Multidisciplinary Team, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Helen L Reeves
- Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.,Hepatopancreatobiliary Multidisciplinary Team, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| |
Collapse
|
|
7
|
Sun LY, Zhu H, Diao YK, Xing H, Liang L, Li J, Zhou YH, Gu WM, Chen TH, Zeng YY, Pawlik TM, Lau WY, Li C, Shen F, Zhang CW, Yang T. A novel online calculator based on albumin-bilirubin and aspartate transaminase-to-platelet ratio index for predicting postoperative morbidity following hepatectomy for hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1591. [PMID: 33437790 PMCID: PMC7791207 DOI: 10.21037/atm-20-1421] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Email zhangchengwuzr@hotmail.com; Prof. Tian Yang, MD. Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai 200438, China. Email: yangtiandfgd@hotmail.com. Background Identifying patients at high risks of developing postoperative morbidity is important to improve perioperative outcomes. We sought to define the accuracy of two objective and non-invasive serological-based scores, i.e., albumin-bilirubin (ALBI) and aspartate transaminase-to-platelet ratio index (APRI), to predict postoperative morbidity among patients undergoing hepatectomy for hepatocellular carcinoma (HCC), and build up a personalized predictive tool for clinical practice. Methods Clinical data of patients who underwent hepatectomy for HCC at 8 hospitals from a multicenter database were retrospectively analyzed. The predictive accuracy of ALBI and APRI relative to 30-day overall and major morbidity were evaluated using area under the receiver operating characteristic curves (AUC). Based on multivariable logistic regression analyses, preoperative and postoperative nomogram models and consequent online calculators were constructed to predict overall and major morbidity, respectively. Results Among 2,301 patients, 725 (31.5%) experienced postoperative complications (major morbidity, 35.9%, 260/725). Multivariable analyses identified high ALBI grade (>−2.6) and APRI grade (>1.5) as independent risk factors associated with overall and major morbidity in both preoperative and postoperative prediction models. Two nomogram predictive models and corresponding online calculators that combined ALBI and APRI were subsequently constructed. The AUCs of the preoperative and postoperative models were 0.728 and 0.742 to predict overall morbidity, and 0.739 and 0.713 to predict major morbidity, respectively, which were much higher than those of Child-Pugh score and the model for end-stage liver disease (MELD). Using the bootstrap validation method, the resulting models were internally validated well. Conclusions Preoperative ALBI and APRI scores can predict postoperative morbidity following hepatectomy for HCC. An easy-to-use online calculator that combined ALBI and APRI was proposed for individually predicting the probabilities of postoperative overall and major morbidity before and immediately after surgery, so as to provide useful information to inform conversations about surgical risks.
Collapse
Affiliation(s)
- Li-Yang Sun
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Hong Zhu
- Department of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yong-Kang Diao
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Jie Li
- Department of Hepatobiliary Surgery, Fuyang People's Hospital, Fuyang, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Pu'er, China
| | - Wei-Min Gu
- The First Department of General Surgery, the Fourth Hospital of Harbin, Harbin, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Ziyang, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai, China.,Faculty of Medicine, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai, China
| | - Cheng-Wu Zhang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Tian Yang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.,Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai, China
| |
Collapse
|
|
8
|
Differential Survival Impact of Diabetes Mellitus on Hepatocellular Carcinoma: Role of Staging Determinants. Dig Dis Sci 2020; 65:3389-3402. [PMID: 31955286 DOI: 10.1007/s10620-020-06053-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 01/06/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) is common in patients with hepatocellular carcinoma (HCC) and may impact survival. Very few studies focused on the influence of DM in different clinical scenarios. We evaluated the prognostic impact of DM on HCC patients stratified by liver dysfunction, Milan criteria, and performance status defined in the Barcelona Clínic Liver Cancer staging parameters. METHODS A prospective dataset of 3573 HCC patients between 2002 and 2016 was retrospectively analyzed. The multivariate Cox proportional hazards model was used to identify independent prognostic predictors. The Kaplan-Meier method with a log-rank test was applied to compare the survival distributions between different patient groups. RESULTS Among all, DM was not an independent prognostic predictor in the Cox multivariate analysis (p = 0.1044). In the subgroup analysis, DM was not a significant prognostic predictor in Child-Turcotte-Pugh class A or class B/C patients. However, DM was associated with a decreased survival in patients within the Milan criteria (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.155-1.601, p = 0.0002) and in those with the performance status 0 (HR 1.213, 95% CI 1.055-1.394, p = 0.0067) in the multivariate Cox analysis, but not in those beyond the Milan criteria and poor performance status. CONCLUSIONS DM is highly prevalent in HCC patients and has a distinct survival impact. DM is an independent survival predictor among patients within the Milan criteria and good performance status. These high-risk patients should be closely monitored, and aggressive anticancer treatment should be considered.
Collapse
|
|
9
|
Shen J, Ni Z, Qian Y, Wang B, Zheng S. Clinical prediction score for superficial surgical site infections: Real-life data from a retrospective single-centre analysis of 812 hepatectomies. Int Wound J 2019; 17:16-20. [PMID: 31646746 DOI: 10.1111/iwj.13209] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Accepted: 07/27/2019] [Indexed: 11/30/2022] Open
Abstract
Superficial surgical site infections (SSIs) are one of the most common postoperative complications of hepatectomy for liver cancer. The objective of this study is to clarify the risk factors and determine a clinical prediction score for SSIs after partial hepatectomy for malignant tumour. A total of 812 consecutive patients were enrolled who underwent partial hepatectomy for liver malignant tumour from January 2017 to December 2017. Univariate and multivariate analyses were conducted to identify the risk factors for SSIs. Clinical prediction score was then constructed using coefficients of identified significant predictors. Risk stratification was then carried out by receiver operating characteristic curve analysis. Of all the 812 patients, SSIs were observed in 31 (3.82%) patients. A multivariate analysis identified four predictors as independent risk factors for SSIs, which were splenomegaly, perioperative blood transfusion, intensive care unit (ICU) admission, and low postoperative serum albumin concentration (<35 g/L). Clinical prediction score ranged from 0 to 4.6 with its discrimination concordance (C) statistic of 0.70 (95% confidence interval [CI] 0.59, 0.81). Risk stratification classified these patients into low, moderate, and high risk in SSIs. This risk score system may credibly stratify the risk of SSIs with relatively high sensitivity and specificity. Splenomegaly, history of blood transfusion, ICU admission, and postoperative serum albumin concentration less than 35 g/L could be used to predict SSIs with acceptable discrimination. This clinical risk score system may be useful in prediction of SSIs after hepatectomy for malignant tumours.
Collapse
Affiliation(s)
- Juwei Shen
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Zuowei Ni
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Yigang Qian
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Bei Wang
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| |
Collapse
|
|
10
|
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.
Collapse
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:
| |
Collapse
|
|
11
|
Comparison of twelve liver functional reserve models for outcome prediction in patients with hepatocellular carcinoma undergoing surgical resection. Sci Rep 2018; 8:4773. [PMID: 29555927 PMCID: PMC5859293 DOI: 10.1038/s41598-018-22923-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 02/23/2018] [Indexed: 02/08/2023] Open
Abstract
Various noninvasive liver functional reserve models have been proposed, but their prognostic ability in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to investigate the performance of twelve noninvasive liver reserve models in HCC patients undergoing surgical resection. A total of 645 patients undergoing resection were prospectively identified and retrospectively analyzed. Tumor recurrence, overall survival, and independent prognostic factors were evaluated by the Cox proportional hazards model. Of the twelve models, the King’s score showed the highest homogeneity and lowest corrected Akaike information criterion (AICc) value, suggesting a better predictive ability for tumor recurrence. In multivariate Cox analysis, we confirmed that King’s score, tumor size and serum alpha-fetoprotein level were independent predictors associated with recurrence. In survival prediction, albumin-bilirubin (ALBI) revealed the highest homogeneity and lowest value among twelve invasive models, indicating a better prognostic performance. In the Cox model, ALBI grade, tumor burden, alpha-fetoprotein, vascular invasion, diabetes mellitus and performance status were independent predictors linked with overall survival. In summary, the currently used liver function models have differential predictive ability for HCC patients undergoing surgical resection. The King’s score is a feasible tool to predict tumor recurrence, whereas ALBI grade is a more robust model for prognostic prediction.
Collapse
|
|
12
|
Yoshida N, Midorikawa Y, Higaki T, Nakayama H, Tsuji S, Matsuoka S, Ishihara H, Moriyama M, Takayama T. Diabetes mellitus not an unfavorable factor on the prognosis of hepatitis C virus-related hepatocellular carcinoma. Hepatol Res 2018; 48:28-35. [PMID: 28258663 DOI: 10.1111/hepr.12888] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Revised: 02/27/2017] [Accepted: 02/28/2017] [Indexed: 02/08/2023]
Abstract
AIM Diabetes mellitus (DM) is a potential risk factor for hepatocarcinogenesis, especially in patients with hepatitis C virus (HCV) infection. We aimed to elucidate whether DM influences the surgical outcomes of patients with hepatocellular carcinoma (HCC). METHODS Our patients were routinely controlled to keep urinary glucose excretion to less than 3.0 g/day before surgery, and the serum glucose level under 200 mg/dL after surgery. The surgical outcomes and postoperative complications of 112 patients with HCV-related HCC with DM (DM group) were compared to those of 112 propensity-matched patients without DM (non-DM group). RESULTS After a median follow-up of 3.2 years (range, 0.2-11.3 years), the median overall (5.2 years; 95% confidence interval, 3.8-6.5 years) and recurrence-free survival (2.2 years; 1.7-2.9 years) in the DM group were not significantly different from those (6.3 years; 5.4-7.1 years, P = 0.337; and 2.2 years; 1.7-3.6 years, P = 0.613) in the non-DM group. The independent factors related to overall survival were the background liver (hazard ratio, 2.06; 95% confidence interval, 1.27-3.39, P = 0.014) and tumor differentiation grade (2.07; 1.14-4.05, P = 0.015). Thirty-two patients (28.5%) in the DM group and 32 patients (28.5%) in the non-DM group had morbidities after operation, with no significant difference between the groups (P = 1.000). Furthermore, postoperative control status of DM did not affect the prognostic outcome. CONCLUSION Diabetes mellitus does not affect the surgical outcomes of patients with HCV-related HCC, and it is not an unfavorable factor when selecting candidates for liver resection of HCC.
Collapse
Affiliation(s)
- Naoki Yoshida
- Departments of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Yutaka Midorikawa
- Departments of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tokio Higaki
- Departments of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Hisashi Nakayama
- Departments of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Shingo Tsuji
- Genome Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo, Tokyo, Japan
| | - Shunichi Matsuoka
- Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Hisamitsu Ishihara
- Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo, Japan
| | - Mitsuhiko Moriyama
- Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Departments of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
13
|
Di Costanzo GG, Tortora R, Morisco F, Addario L, Guarino M, Cordone G, Falco L, Caporaso N. Impact of Diabetes on Outcomes of Sorafenib Therapy for Hepatocellular Carcinoma. Target Oncol 2017; 12:61-67. [PMID: 27503006 DOI: 10.1007/s11523-016-0454-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Patients with diabetes are at increased risk of developing hepatocellular carcinoma (HCC) and have a poorer prognosis as compared to non-diabetics when HCC occurs. Diabetics with non-HCC cancers are at higher risk of toxicity related to systemic therapy, but data on HCC are lacking. OBJECTIVE The aim of this study was to evaluate safety and effectiveness of sorafenib in HCC patients according to the presence/absence of diabetes. PATIENTS AND METHODS From October 2008 to June 2014, 313 patients with HCC treated with sorafenib were enrolled. The patients were staged according to the BCLC system. Treatment response was evaluated according to the mRECIST criteria. The main evaluated outcomes were the overall survival and the safety in the two groups. RESULTS Patients were divided in two groups: 80 diabetics (DIAB) and 233 nondiabetics (nDIAB). The median treatment duration was 4 months in DIAB and 3 months in nDIAB. Main adverse events occurred with comparable frequency in both groups, with the exception of rash, that was more frequent among DIAB than in nDIAB: 27.5 % vs 17.6 % (P = .047). The median overall survival was 9 months in nDIAB and 10 months in DIAB group (P = .535). Median time-to-progression (TTP) was longer the in DIAB than the nDIAB group (P = .038). CONCLUSIONS Sorafenib was as safe as effective in DIAB and in nDIAB patients. The longer TTP observed among DIAB than in nDIAB patients might suggest a better anticancer effect of sorafenib in patients with diabetes.
Collapse
Affiliation(s)
| | - Raffaella Tortora
- Department of Transplantation - Liver Unit, Cardarelli Hospital, Via A. Cardarelli 9, 80131, Naples, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery - Gastroenterology Unit, University of Naples "Federico II", Naples, Italy
| | - Luigi Addario
- Department of Transplantation - Liver Unit, Cardarelli Hospital, Via A. Cardarelli 9, 80131, Naples, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery - Gastroenterology Unit, University of Naples "Federico II", Naples, Italy
| | - Gabriella Cordone
- Department of Transplantation - Liver Unit, Cardarelli Hospital, Via A. Cardarelli 9, 80131, Naples, Italy
| | - Luigia Falco
- Department of Transplantation - Liver Unit, Cardarelli Hospital, Via A. Cardarelli 9, 80131, Naples, Italy
| | - Nicola Caporaso
- Department of Clinical Medicine and Surgery - Gastroenterology Unit, University of Naples "Federico II", Naples, Italy
| |
Collapse
|
|
14
|
Neethirajan SM, Rachapoodivenkata RR. Oral glucose tolerance test for preoperative assessment of liver function in liver resection. Ann Hepatobiliary Pancreat Surg 2017; 21:1-10. [PMID: 28317039 PMCID: PMC5353905 DOI: 10.14701/ahbps.2017.21.1.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 08/22/2016] [Accepted: 09/26/2016] [Indexed: 12/23/2022] Open
Abstract
BACKGROUNDS/AIMS We intended to determine the role of the Oral glucose tolerance test (OGTT), in addition to volumetry, in preoperative assessment of patients undergoing liver resection. METHODS This was a prospective study conducted at a tertiary care hospital, between February 2009 and February 2011. OGTT curve (parabolic/linear), linearity index (LI) and Parenchymal Hepatic Resection Rate (PHRR) were correlated with postoperative outcomes in terms of postoperative liver failure (PLF), by 50-50 criteria, morbidity, mortality and hospital stay. RESULTS Of the 33 patients included in the study, 23 (69.7%) patients underwent major liver resections. Hepatocellular carcinoma (30.3%) was the leading indication. The overall postoperative morbidity rate was 72.7%, but major complications occurred in 3 (9.1%) patients only. There was no 90-day mortality. The 50-50 criteria were met by 3 patients undergoing major resection. Significant correlation was noted between the linear OGTT curve and the overall hospital stay (12.1 days vs. 9.6 days in parabolic; p=0.04). Patients with linear OGTT met the 50-50 criteria more often (18%) than those having a parabolic curve (4.5%; p=0.25). Although the OGTT was more often linear with occurrence of morbidity (41.7% vs 11.1%), major morbidity (66.7% vs 30%) and PLF by 50-50 criteria (66.7% vs 30%), it was not statistically significant. The linearity index was marginally lower (0.9 vs 1.2) in the presence of major morbidity and PLF by 50-50 criteria. CONCLUSIONS Linear OGTT affects the PLF and major morbidity, therein impacting the hospital stay. OGTT LI and PHRR can help predict postoperative outcome for a given extent of liver resection.
Collapse
Affiliation(s)
- Saravanan Manickam Neethirajan
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | | |
Collapse
|
|
15
|
Li Q, Wang Y, Ma T, Lv Y, Wu R. Clinical outcomes of patients with and without diabetes mellitus after hepatectomy: A systematic review and meta-analysis. PLoS One 2017; 12:e0171129. [PMID: 28182632 PMCID: PMC5300262 DOI: 10.1371/journal.pone.0171129] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 01/15/2017] [Indexed: 12/24/2022] Open
Abstract
Background Clinical data regarding the influence of diabetes mellitus (DM) on the outcomes of patients undergoing hepatectomy are conflicting. To determine the impact of DM on the clinical outcomes of patients undergoing hepatectomy, we systematically reviewed published studies and carried out a meta-analysis. Methods A systematic literature search of Pubmed, Sciencedirect, Web of Science, and Chinese Biomedical Database was conducted from their inception through February 2, 2016. The combined relative risk (RR) or hazard ratio (HR) with 95% confidence intervals (95% CI) was calculated. Results A total of 16 observational studies with 15710 subjects were eligible for meta-analysis. The pooled results showed that DM significantly increased the risk of overall postoperative complications (RR 1.34; 95% CI 1.19–1.51; P<0.001), DM-associated complications (RR 1.8; 95% CI 1.29–2.53; P<0.001), liver failure (RR 2.21; 95% CI 1.3–3.76; P = 0.028) and post-operative infections (RR 1.59; 95% CI 1.01–2.5; P = 0.045). In addition, DM was also found to be significantly associated with unfavorable overall survival and disease free survival after liver resection. The pooled HR was 1.63 (95% CI 1.33–1.99; P<0.001) for overall survival and 1.55 (95% CI 1.07–2.25; P = 0.019) for disease free survival. Conclusion DM is associated with poor outcomes in patients undergoing hepatectomy. DM should be taken into account cautiously in the management of patients undergoing hepatectomy. Further prospective studies are warranted to explore effective interventions to improve the poor outcomes of diabetic patients undergoing hepatectomy.
Collapse
Affiliation(s)
- Qingshan Li
- Shaanxi Center for Regenerative Medicine and Surgical Engineering, Institute of Advanced Surgical Technology and Engineering, Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, China
| | - Yue Wang
- Shaanxi Center for Regenerative Medicine and Surgical Engineering, Institute of Advanced Surgical Technology and Engineering, Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, China
| | - Tao Ma
- Shaanxi Center for Regenerative Medicine and Surgical Engineering, Institute of Advanced Surgical Technology and Engineering, Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, China
| | - Yi Lv
- Shaanxi Center for Regenerative Medicine and Surgical Engineering, Institute of Advanced Surgical Technology and Engineering, Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, China
- * E-mail: (RW); (YL)
| | - Rongqian Wu
- Shaanxi Center for Regenerative Medicine and Surgical Engineering, Institute of Advanced Surgical Technology and Engineering, Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, China
- * E-mail: (RW); (YL)
| |
Collapse
|
|
16
|
Zhang Q, Deng YL, Liu C, Huang LH, Shang L, Chen XG, Wang LT, Du JZ, Wang Y, Wang PX, Zhang H, Shen ZY. Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation. World J Gastroenterol 2016; 22:9571-9585. [PMID: 27920478 PMCID: PMC5116601 DOI: 10.3748/wjg.v22.i43.9571] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2016] [Revised: 08/02/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine whether diabetes mellitus (DM) affects prognosis/recurrence after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent LT with antiviral prophylaxis. Patient data were obtained from the China Liver Transplant Registry (https://www.cltr.org/). To compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis.
RESULTS Univariate analysis of 1631 patients who underwent LT found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after LT between the two groups were significant (P = 0.041), but recurrence-free survival rates were not (P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years (P = 0.002), the presence of vascular invasion (P = 0.096), tumors ≤ 3 cm (P = 0.047), two to three tumor nodules (P = 0.007), Child-Pugh grade B (P = 0.018), and pre-LT alanine aminotransferase levels between 40 and 80 IU/L (P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/mL (P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM (P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after LT.
CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor LT outcomes. Prevention strategies for HCC patients with DM are recommended.
Collapse
|
|
17
|
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.
Collapse
|
|
18
|
Choi KS, Kim DS, Jung SW, Yu YD, Suh SO. Influence of metabolic and other clinicopathologic factors on the prognosis of patients with hepatocellular carcinoma undergoing hepatic resection. KOREAN JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 2015; 18:105-11. [PMID: 26155261 PMCID: PMC4492353 DOI: 10.14701/kjhbps.2014.18.4.105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Revised: 10/16/2014] [Accepted: 10/23/2014] [Indexed: 11/17/2022]
Abstract
Backgrounds/Aims The prognosis of hepatic resection for hepatocellular carcinoma (HCC) in patients with cirrhosis is worse than in those without cirrhosis. In Korea, the hepatitis B virus prevalence rate is higher than in other countries. Therefore, we investigated patients' clinicopathologic and metabolic factors that affect the postoperative outcomes of hepatic resection for HCC in our hospital in Korea. Methods From August 2000 to December 2012, 171 HCC patients underwent hepatic resections at our institution. Two operative mortality cases and two short-term follow up cases were excluded. Data was collected from a retrospective chart review. There were 133 males (79.6%) and 34 females (20.3%), with a mean age of 58.2±10.2 years (range, 22-81 years), and the relationship between clinicopathologic and metabolic factors and the prognosis of patients with HCC undergoing hepatic resection were evaluated by univariate and multivariate analysis. Results Hypertension, major surgery, perioperative transfusion, resection with radiofrequency ablation (RFA) or cryoablation, and resection margin were risk factors for overall survival, and hypertension, albumin, resection with RFA or cryoablation, perioperative transfusion, and tumor size were risk factors for disease-free survival. Conclusions We found that hypertension, perioperative transfusion, and resection with RFA or cryoablation were risk factors for both disease-free and overall survival after hepatic resection in HCC patients. Further study is required to clarify the influence of metabolic and other clinicopathologic factors on the prognosis of HCC.
Collapse
Affiliation(s)
- Kui Sun Choi
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Sung Won Jung
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Young-Dong Yu
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Sung Ock Suh
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| |
Collapse
|
|
19
|
Kaibori M, Ishizaki M, Iida H, Matsui K, Sakaguchi T, Inoue K, Mizuta T, Ide Y, Iwasaka J, Kimura Y, Hayashi F, Habu D, Kon M. Effect of Intramuscular Adipose Tissue Content on Prognosis in Patients Undergoing Hepatocellular Carcinoma Resection. J Gastrointest Surg 2015; 19:1315-23. [PMID: 25963482 DOI: 10.1007/s11605-015-2838-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Accepted: 04/23/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND It has recently been reported that myosteatosis, the infiltration of fat in skeletal muscle, is associated with insulin resistance and type 2 diabetes mellitus. The present study investigated the effect of skeletal muscle fat accumulation on short- and long-term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC) and aimed to identify prognostic factors. METHODS The records of 141 HCC patients who underwent hepatectomy were retrospectively reviewed. Clinicopathological and outcome data from 71 patients with high intramuscular adipose tissue content (IMAC) were compared with those from 70 patients with low IMAC. RESULTS The 5-year overall survival rate was 46% among patients with high IMAC and 75% among those with low IMAC. The 5-year disease-free survival rates in these groups were 18 and 38%, respectively. Multivariate analysis revealed that high IMAC was predictive of an unfavorable prognosis. High IMAC was significantly correlated with liver dysfunction, higher intraoperative blood loss, the need for blood transfusion, and comorbid diabetes mellitus. CONCLUSIONS Greater fat accumulation in skeletal muscle was predictive of worse overall survival after partial hepatectomy in patients with HCC, even with adjustment for other known predictors. The identification of patients with greater skeletal muscle fat accumulation before hepatectomy could permit early preventive strategies to maintain muscle quality and thus improve prognosis and patient selection for hepatectomy.
Collapse
Affiliation(s)
- Masaki Kaibori
- Department of Surgery, Hirakata Hospital, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1191, Japan,
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
20
|
Cauchy F, Belghiti J. A clinical perspective of the link between metabolic syndrome and hepatocellular carcinoma. J Hepatocell Carcinoma 2015; 2:19-27. [PMID: 27508191 PMCID: PMC4918280 DOI: 10.2147/jhc.s44521] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Metabolic syndrome (MS), which is defined as a constellation of clinico-biological features closely related to insulin-resistance has reached epidemic levels in Western Europe and Northern America. Non-alcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of MS. As its incidence parallels that of MS, NAFLD is currently becoming one of the most frequent chronic liver diseases in Western countries. On one hand, MS favors the development of hepatocellular carcinoma (HCC) either through NAFLD liver parenchymal alterations (steatosis; steatohepatitis; fibrosis), or in the absence of significant underlying liver parenchyma changes. In this setting, HCC are often diagnosed incidentally, tend to be larger than in patients developing HCC on cirrhosis and therefore frequently require major liver resections. On the other hand, MS patients are at increased risk of both liver-related postoperative complications and increased cardiorespiratory events leading to non-negligible mortality rates following liver surgery. These deleterious effects seem to be related to the existence of impaired liver function even in the absence of severe fibrosis but also higher cardiorespiratory sensitivity in a setting of MS/NAFLD. Hence, specific medical and surgical improvements in the perioperative management of these patients are required. These include complete preoperative cardiorespiratory work-up and the wide use of preoperative liver volume modulation. Finally, the long-term prognosis after curative surgery for MS-related HCC does not seem to be worse than for other HCC occurring on classical chronic liver diseases. This is probably related to less aggressive tumor behavior with lower micro vascular invasion and decreased rates of poorly differentiated lesions. In this setting, several medical therapies including metformin could be of value in the prevention of both occurrence and recurrence of HCC.
Collapse
Affiliation(s)
- François Cauchy
- HPB and Liver Transplantation Unit, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Jacques Belghiti
- HPB and Liver Transplantation Unit, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| |
Collapse
|
|
21
|
Masood MA, Zafar W, Yusuf MA. Is diabetes mellitus a poor prognostic factor for hepatocellular carcinoma? J Gastrointest Cancer 2014; 45:448-51. [PMID: 24961202 DOI: 10.1007/s12029-014-9631-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND There are scarce data regarding the impact of diabetes mellitus on the prognosis of hepatocellular carcinoma managed conservatively. The objective of this study was to compare the overall survival among diabetic and non-diabetic patients suffering from hepatocellular carcinoma and treated mainly by non-surgical means. METHODS We identified patients who underwent treatment for hepatocellular carcinoma over a period of 6.5 years at a single center in Lahore, Pakistan. Data regarding age, gender, morphology of tumor, size of tumor, Child-Pugh class, the Barcelona-Clínic Liver Cancer (BCLC) stage, treatment given, and outcome was retrieved from the medical records. Patients were classified as diabetic if there were at least two documented readings of fasting blood glucose level of more than 126 mg/dl or random blood glucose of more than 200 mg/dl or the patient was already diagnosed and on oral hypoglycemic agents or insulin. Statistical tests were applied to test for differences between diabetic and non-diabetic patients in terms of clinical features at presentation, treatments received, and disease outcomes. RESULTS A total of 282 patients were diagnosed as having hepatocellular carcinoma during the study period. Diabetic and non-diabetic patients were comparable in terms of the mean age at diagnosis of hepatocellular carcinoma, sex, whether the tumor was unifocal or multifocal, Child-Pugh class, BCLC stage, and infection with hepatitis B and/or C virus. Diabetic patients were significantly more likely to have initial alpha-feto protein levels lower than 200 IU/ml compared to non-diabetic patients. There was no difference among diabetic and non-diabetic patients in terms of the treatments they received or the outcomes. Non-diabetic and diabetic patients had a mean disease-free survival of 8.29 and 6.95 months, respectively, and overall survival of 15.48 and 15.36 months, respectively. Multivariate linear regression analyses, after adjusting for age and gender of the patient and the BCLC stage of the tumor among the subset of patients documented to have died during the follow-up period, showed that there was no significant difference between diabetic and non-diabetic patients in terms of overall survival. BCLC stage, however, was significantly associated with overall survival. CONCLUSION Diabetes mellitus has no prognostic significance in patients with hepatocellular carcinoma.
Collapse
|
|
22
|
Cauchy F, Fuks D, Zarzavadjian Le Bian A, Belghiti J, Costi R. Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The new scourges? World J Hepatol 2014; 6:306-14. [PMID: 24868324 PMCID: PMC4033288 DOI: 10.4254/wjh.v6.i5.306] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Revised: 01/01/2014] [Accepted: 01/17/2014] [Indexed: 02/06/2023] Open
Abstract
The aim of this topic highlight is to review relevant evidence regarding the influence of the metabolic syndrome (MS) and its associated liver manifestation, non-alcoholic fatty liver disease (NAFLD), on the development of liver cancer as well as their impact on the results of major liver surgery. MS and NAFLD, whose incidences are significantly increasing in Western countries, are leading to a changing profile of the patients undergoing liver surgery. A MEDLINE search was performed for relevant articles using the key words "metabolic syndrome", "liver resection", "liver transplantation", "non alcoholic fatty liver disease", "non-alcoholic steatohepatitis" and "liver cancer". On one hand, the MS favors the development of primary liver malignancies (hepatocellular carcinoma and cholangiocarcinoma) either through NAFLD liver parenchymal alterations (steatosis, steatohepatitis, fibrosis) or in the absence of significant underlying liver parenchyma changes. Also, the existence of NAFLD may have a specific impact on colorectal liver metastases recurrence. On the other hand, the postoperative period following partial liver resection and liver transplantation is at increased risk of both postoperative complications and mortality. These deleterious effects seem to be related to the existence of liver specific complications but also higher cardio-vascular sensitivity in a setting of MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of patients operated on with other types of underlying liver diseases. An increased rate of patients with MS/NAFLD referred to hepatobiliary units has to be expected. The higher operative risk observed in this subset of patients will require specific improvements in their perioperative management.
Collapse
Affiliation(s)
- François Cauchy
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| | - David Fuks
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| | - Alban Zarzavadjian Le Bian
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| | - Jacques Belghiti
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| | - Renato Costi
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| |
Collapse
|
|
23
|
Gao C, Fang L, Zhao HC, Li JT, Yao SK. Potential role of diabetes mellitus in the progression of cirrhosis to hepatocellular carcinoma: a cross-sectional case-control study from Chinese patients with HBV infection. Hepatobiliary Pancreat Dis Int 2013; 12:385-93. [PMID: 23924496 DOI: 10.1016/s1499-3872(13)60060-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Diabetes mellitus (DM) is regarded as a new risk factor for hepatocellular carcinoma (HCC), but few studies have focused on the potential role of DM in the progression of cirrhosis to HCC as well as in patients with simple HBV infection. METHODS A cohort of 1028 patients, treated at our hospital and with a hospital discharge diagnosis of HCC and/or cirrhosis, was screened. Among them, 558 were diagnosed with chronic HBV infection and 370 were analyzed statistically according to the diagnostic, inclusion and exclusion criteria. The demographic, clinical, metabolic, virological, biochemical, radiological and pathological features were analyzed and the multivariate logistic regression model was used to determine the potential role of DM. RESULTS In 248 cirrhotic patients, 76 were diabetic and their mean duration of DM was 4.6 years. In 122 HCC patients with cirrhosis, 25 were diabetic and their mean duration of DM was 4.4 years. Univariate analysis showed that compared with cirrhotic patients, the HCC patients had a higher percentage in males (P=0.001), a lower percentage in DM patients (P=0.039), a higher percentage in cigarette smokers (P=0.005), a higher percentage in patients with AFP>400 ng/mL (P<0.001), higher values of white blood cells (P<0.001), hemoglobin (P<0.001) and platelet (P<0.001), increased levels of ALT (P<0.001) and GGT (P<0.001), higher total bilirubin (P=0.018) and albumin levels (P<0.001), and a lower international normalized ratio (P<0.001). Multivariate logistic regression analysis showed that DM was an independent associated factor for HCC [odds ratio (OR)=0.376; 95% CI, 0.175-0.807; P=0.012]. Even after the HCC patients were restricted to those with decompensated cirrhosis and compared with decompensated cirrhotic patients, the similar result was observed (OR=0.192; 95% CI, 0.054-0.679; P=0.010). CONCLUSIONS DM is an independent factor in the progression of cirrhosis to HCC, but the role may be contrary to our current viewpoint. To clarify the causal relationship of DM and HCC, prospective and experimental studies are required.
Collapse
Affiliation(s)
- Chun Gao
- Department of Gastroenterology, China-Japan Friendship Hospital, Ministry of Health, Beijing 100029, China
| | | | | | | | | |
Collapse
|
|
24
|
Okabayashi T, Kozuki A, Sumiyoshi T, Shima Y. Technical challenges and clinical outcomes of using a closed-loop glycemic control system in the hospital. J Diabetes Sci Technol 2013; 7:238-46. [PMID: 23439182 PMCID: PMC3692238 DOI: 10.1177/193229681300700129] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
According to large randomized trials, results suggest that maintaining normoglycemia postoperatively through tight glycemic control (TGC) and intensive insulin therapy (IIT) can improve surgical outcomes as well as reduce mortality and morbidity in critically ill patients. However, trials examining the effects of TGC have had conflicting results. Systematic reviews and meta-analyses have also led to differing conclusions. The main reason these clinical trials and meta-analyses show negative results for TGC is the high incidence of hypoglycemia induced by IIT. This could not be prevented because there is no reliable technique that can avoid this condition during IIT. The development of accurate, continuous blood glucose monitoring devices and closed-loop systems for computer-assisted blood glucose control in the intensive care unit (ICU) will probably help avoid hypoglycemia in these situations. The STG closed-loop glycemic control system was introduced to our department to be used and evaluated for strict serum glucose control with no hypoglycemic episodes during IIT in the surgical ICU, to reduce the workload of ICU nurses, and to decrease incidents related to the management of blood glucose levels according to manual conventional venous infusion insulin therapy. The goal of our team was to use the STG closed-loop glycemic control system for perioperative TGC in surgical patients to solve the complications of IIT and reduce risk of hypoglycemia. The challenge at our hospital demonstrated that the STG closed-loop glycemic control system can be expected to achieve TGC with no occurrence of hypoglycemia induced by IIT after surgery.
Collapse
Affiliation(s)
- Takehiro Okabayashi
- Department of Gastroenterological Surgery, Kochi Health Sciences Center, Kochi-City, Kochi, Japan.
| | | | | | | |
Collapse
|
|
25
|
Zarzavadjian Le Bian A, Costi R, Constantinides V, Smadja C. Metabolic disorders, non-alcoholic fatty liver disease and major liver resection: an underestimated perioperative risk. J Gastrointest Surg 2012; 16:2247-55. [PMID: 23054903 DOI: 10.1007/s11605-012-2044-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Accepted: 09/26/2012] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Despite increasing evidence of an association of metabolic syndrome and liver degeneration, little is known about the results of major hepatic resection in patients with metabolic disorders. Following the observation of some unexplained perioperative deaths following uncomplicated right hepatectomy in patients presenting metabolic disorders, we analyzed the perioperative mortality in such population. MATERIAL AND METHODS A retrospective analysis of immediate outcome was performed of patients undergoing right hepatectomy and affected by two or more metabolic disorders (diabetes mellitus, hypertension, dyslipidemia, obesity/overweight) without any other known cause of liver disease from January 2001 to May 2010. RESULTS Among 151 patients undergoing right hepatectomy, 30 patients presented two or more metabolic disorders. Perioperative mortality in this group reached 30 % (nine patients). In patients presenting MS (≥3 disorders), mortality reached 54 %. Univariate analysis identified four criteria associated with poor prognosis: MS, perioperative bleeding ≥1,000 mL, middle hepatic vein resection and primary hepatic malignancy. At multivariate analysis, middle hepatic vein resection and underlying primary hepatic malignancy resulted as being related to mortality. CONCLUSIONS Patients presenting with multiple metabolic disorders should be carefully evaluated before major liver resection, especially when the procedure is planned for hepatocellular carcinoma and when a middle hepatic vein resection is required.
Collapse
Affiliation(s)
- Alban Zarzavadjian Le Bian
- Service de Chirurgie Digestive, Hôpital Antoine Béclère, Clamart, Assistance Publique, Hôpitaux de Paris, Université Paris XI, France.
| | | | | | | |
Collapse
|
|
26
|
Diabetes, body mass index, and outcomes in hepatocellular carcinoma patients undergoing liver transplantation. Transplantation 2012; 94:539-43. [PMID: 22864187 DOI: 10.1097/tp.0b013e31825c58ea] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED For many cancers, features of the metabolic syndrome, such as diabetes and obesity, have been associated with both increased risk of cancer development and poor outcomes. METHODS We examined a large retrospective cohort of 342 consecutive patients who underwent liver transplantation for hepatocellular carcinoma between January 1999 and July 2010 at our institution. We evaluated the relationship between diabetes, obesity, hepatocellular carcinoma (HCC) recurrence, and overall survival. RESULTS We found that a body mass index (BMI) higher than 30 was an independent predictor of poor overall survival in a multivariable Cox model, approximately doubling the risk of death after transplantation. A BMI higher than 30 was also a predictor of recurrent HCC, although this was of borderline statistical significance (hazard ratio for recurrence, 1.9; 95% confidence interval, 0.9-4.1). We also found increased BMI to be an independent predictor of microvascular invasion within HCC tumors, lending a possible explanation to these results. Those with diabetes showed worsened overall survival compared with those without diabetes in univariate but not multivariable analysis, possibly related to longer wait times. CONCLUSIONS Our findings suggest a relationship between higher BMI, tumor vascular invasion, increased recurrence, and worsened overall survival. These findings may help explain why those with high BMI have worse outcomes from their cancers. A better understanding of the role of obesity and diabetes in patients with cancer should help develop better predictors of outcome and improved treatment options for patients with HCC.
Collapse
|
|
27
|
Influence of hepatic parenchymal histology on outcome following right hepatic trisectionectomy. J Gastrointest Surg 2012; 16:2064-73. [PMID: 22923210 DOI: 10.1007/s11605-012-2008-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2012] [Accepted: 08/14/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Histological abnormalities in the non-tumour-bearing liver (NTBL) may influence outcome following hepatectomy. Effects will be most pertinent following right trisectionectomy but have yet to be specifically examined in this context. This study aimed to investigate the influence of perioperative factors, including NTBL histology, on outcome following right trisectionectomy. METHODS Pathological review of the NTBL of 103 consecutive patients undergoing right trisectionectomy between January 2003 and December 2009 was performed using established criteria for steatosis, non-alcoholic steatohepatitis (NASH), sinusoidal injury (SI), fibrosis and cholestasis. Perioperative and pathological factors were correlated with post-operative outcome (morbidity, major morbidity, hepatic insufficiency and mortality). RESULTS Morbidity, hepatic insufficiency and major morbidity occurred in 37.9 %, 14.6 % and 22.3 % of cases, respectively. Ninety-day mortality rate was 5.8 %. NASH (P = 0.007) and perioperative blood transfusion (P = 0.001) were independently associated with hepatic insufficiency following trisectionectomy. NASH (P = 0.028), perioperative transfusion (P = 0.016), diabetes mellitus (P = 0.047) and coronary artery disease (P = 0.036) were independently associated with major morbidity. Steatosis, SI, fibrosis and cholestasis in the NTBL demonstrated no association with any adverse outcome. CONCLUSION NASH, but not steatosis or SI, is associated with adverse outcome following right trisectionectomy and caution must be exerted when considering major hepatectomy in patients with NASH.
Collapse
|
|
28
|
Wrighton LJ, O'Bosky KR, Namm JP, Senthil M. Postoperative management after hepatic resection. J Gastrointest Oncol 2012; 3:41-7. [PMID: 22811868 DOI: 10.3978/j.issn.2078-6891.2012.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2011] [Accepted: 01/12/2012] [Indexed: 12/18/2022] Open
Abstract
Hepatic resection has become the mainstay of treatment for both primary and certain secondary malignancies. Outcomes after hepatic resection have significantly improved with advances in surgical and anesthetic techniques and perioperative care. Metabolic and functional changes after hepatic resection are unique and cause significant challenges in management. In-depth understanding of hepatic physiology is essential to properly address the postoperative issues. Strategies implemented in the postoperative period to improve outcomes include adequate nutritional support, proper glycemic control, and interventions to reduce postoperative infectious complications among several others. This review article focuses on the major postoperative issues after hepatic resection and presents the current management.
Collapse
Affiliation(s)
- Lindsay J Wrighton
- Department of Surgery, Loma Linda University, Loma Linda, California, USA
| | | | | | | |
Collapse
|
|
29
|
Yang WS, Va P, Bray F, Gao S, Gao J, Li HL, Xiang YB. The role of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence and prognosis: a meta-analysis of prospective cohort studies. PLoS One 2011; 6:e27326. [PMID: 22205924 PMCID: PMC3244388 DOI: 10.1371/journal.pone.0027326] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Accepted: 10/13/2011] [Indexed: 12/17/2022] Open
Abstract
Background The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis. Methods We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models. Results The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15–2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39–2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13–1.48) risk of death from all-causes and 91% increased (95%CI: 1.41–2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12–3.33) compared with non-diabetic patients. Conclusion The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts.
Collapse
Affiliation(s)
- Wan-Shui Yang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
- State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Puthiery Va
- University of New England College of Osteopathic Medicine, Biddeford, Maine, United States of America
| | - Freddie Bray
- Section of Cancer Information, International Agency for Research on Cancer, Lyon, France
| | - Shan Gao
- State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing Gao
- State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hong-Lan Li
- State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yong-Bing Xiang
- State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- * E-mail:
| |
Collapse
|
|
30
|
Prognostic role of diabetes mellitus in hepatocellular carcinoma patients after curative treatments: a meta-analysis. Hepatobiliary Pancreat Dis Int 2011; 10:346-55. [PMID: 21813381 DOI: 10.1016/s1499-3872(11)60059-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The prognostic role of diabetes mellitus (DM) coexisting with hepatocellular carcinoma (HCC) remains controversial. To clarify its impact on survival in HCC patients after curative treatments, a meta-analysis was performed. DATA SOURCES Eligible studies were identified through multiple search strategies in the databases PubMed (MEDLINE), EMBASE, the Cochrane Library and ACP Journal Club between January 1950 and March 2010. Ten studies fulfilled the inclusion criteria, and data were aggregated comparing overall survival and recurrence-free survival in HCC patients according to DM status. RESULTS The pooled hazard ratios (HRs) estimate for overall survival was 1.34 (95% CI, 1.18-1.51; P<0.0001) and for recurrence-free survival was 1.48 (95% CI, 1.00-2.18; P<0.0001), showing a worse survival for HCC with coexisting DM. However, the patients with DM had a shorter survival time in HCV-related HCC (HR=1.71; 95% CI, 1.10-2.66; P=0.016), while HBV-related cases were not significantly different (HR=1.29; 95% CI, 0.69-2.40; P=0.182). Meanwhile, the coexistence of DM impaired overall survival in HCC patients with a small tumor burden (HR=1.63; 95% CI, 1.25-2.12; P<0.0001). CONCLUSION HCC patients with coexisting DM have a shorter survival time and a higher risk for tumor recurrence after curative treatments, while the precise value should be defined in more clinical trials with consistent methodology, especially prospective studies.
Collapse
|
|
31
|
Francés DE, Ronco MT, Ingaramo PI, Monti JA, Pisani GB, Parody JP, Pellegrino JM, Carrillo MC, Martín-Sanz P, Carnovale CE. Role of reactive oxygen species in the early stages of liver regeneration in streptozotocin-induced diabetic rats. Free Radic Res 2011; 45:1143-53. [PMID: 21740310 DOI: 10.3109/10715762.2011.602345] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Diabetes mellitus is a risk factor for prognosis after liver resection. In previous work, we found a pro-apoptotic state in the diabetic rat liver. In this work, this was also observed 1 hour post-partial hepatectomy (PH) and resulted in a deficient regenerative response 24 hours post-PH. Treatment with insulin and/or Desferoxamine (DES) (iron chelator) or Tempol (TEM) (free radicals scavenger) was effective in preventing the liver reactive oxygen species (ROS) production induced by diabetic state. High levels of ROS play a role in hepatic lipid peroxidation in diabetes before and after PH, and lead to increased pro-apoptotic events, which contribute to a reduced regenerative response. This becomes of relevance for the potential use of antioxidants/free radical scavengers plus insulin for improvement of post-surgical recovery of diabetic patients subjected to a PH.
Collapse
Affiliation(s)
- Daniel E Francés
- Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario, Argentina
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Gao C, Zhao HC, Li JT, Yao SK. Diabetes mellitus and hepatocellular carcinoma: Comparison of Chinese patients with and without HBV-related cirrhosis. World J Gastroenterol 2010; 16:4467-75. [PMID: 20845516 PMCID: PMC2941072 DOI: 10.3748/wjg.v16.i35.4467] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the role of diabetes mellitus (DM) and other associated factors in Chinese hepatocellular carcinoma (HCC) patients with cirrhosis, compared with those HCC patients without cirrhosis, in the single setting of hepatitis B virus (HBV) infection, after other known concomitant diseases were excluded.
METHODS: A total of 482 patients, treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period January 2003 to June 2009, and with a hospital discharge diagnosis of HCC, were included. Demographic, clinical, laboratory, metabolic and instrumental features were analyzed.
RESULTS: Of the total, 310 patients were diagnosed with HBV infection and, following the inclusion and exclusion criteria, 224 were analyzed, including 122 patients (54.5%) with cirrhosis (the case group) and 102 patients without cirrhosis (the control group). Twenty-seven patients (12.1%) were diabetic, including 19 in the case group and 8 in the control group (19/122 = 15.6% vs 8/102 = 7.8%, P = 0.077). Thirty-one possible relevant parameters were compared by univariate analysis, and 9 variables were selected for multivariable analysis, including DM (P = 0.077), past history of HBV infection (P = 0.005), total bilirubin (P < 0.001), albumin level (P < 0.001), international normalized ratio (INR) (P < 0.001), alanine aminotransferase (P = 0.050), platelet (P < 0.001), total cholesterol (P = 0.047), and LDL cholesterol (P = 0.002) levels. Diabetes showed a statistical difference by multivariable analysis [odds ratio (OR) 4.88, 95% confidence interval (CI): 1.08-21.99, P = 0.039], although no significant difference was found in univariate analysis. In addition, three cirrhosis-related parameters remained statistically different, including INR (OR 117.14, 95% CI: 4.19-3272.28, P = 0.005), albumin (OR 0.89, 95% CI: 0.80-0.99, P = 0.027), and platelet count (OR 0.992, 95% CI: 0.987-0.999, P = 0.002).
CONCLUSION: Besides the three cirrhosis-related parameters, DM was found to be the sole independent factor associated with HCC in patients with HBV-related cirrhosis, compared with those without cirrhosis.
Collapse
|
|
33
|
Mann CD, Palser T, Briggs CD, Cameron I, Rees M, Buckles J, Berry DP. A review of factors predicting perioperative death and early outcome in hepatopancreaticobiliary cancer surgery. HPB (Oxford) 2010; 12:380-8. [PMID: 20662788 PMCID: PMC3028578 DOI: 10.1111/j.1477-2574.2010.00179.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES In the context of comparisons of surgical outcomes, risk adjustment is the retrospective adjustment of a provider's or a surgeon's results for case mix and/or hospital volume. It allows accurate, meaningful inter-provider comparison. It is therefore an essential component of any audit and quality improvement process. The aim of this study was to review the literature to identify those factors known to affect prognosis in hepatobiliary and pancreatic cancer surgery. METHODS PubMed was used to identify studies assessing risk in patients undergoing resection surgery, rather than bypass surgery, for hepatobiliary and pancreatic cancer. RESULTS In total, 63 and 68 papers, pertaining to 24 609 and 63 654 patients who underwent hepatic or pancreatic resection for malignancy, respectively, were identified. Overall, 22 generic preoperative factors predicting outcome on multivariate analysis, including demographics, blood results, preoperative biliary drainage and co-morbidities, were identified, with tumour characteristics proving disease-specific factors. Operative duration, transfusion, operative extent, vascular resection and additional intra-abdominal procedures were also found to be predictive of early outcome. CONCLUSIONS The development of a risk adjustment model will allow for the identification of those factors with most influence on early outcome and will thus identify potential targets for preoperative optimization and allow for the development of a multicentre risk prediction model.
Collapse
Affiliation(s)
- Chris D Mann
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester General HospitalLeicester, UK
| | - Tom Palser
- Clinical Effectiveness Unit, Royal College of Surgeons of EnglandLondon, UK
| | - Chris D Briggs
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester General HospitalLeicester, UK
| | - Iain Cameron
- Department of Hepatobiliary and Pancreatic Surgery, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Myrrdin Rees
- Department of Surgery, Basingstoke and North Hampshire NHS Foundation TrustBasingstoke, Hampshire, UK
| | - John Buckles
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth HospitalBirmingham, UK
| | - David P Berry
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester General HospitalLeicester, UK
| |
Collapse
|
|
34
|
Okabayashi T, Maeda H, Sun ZL, Montgomery RA, Nishimori I, Hanazaki K. Perioperative insulin therapy using a closed-loop artificial endocrine pancreas after hepatic resection. World J Gastroenterol 2009; 15:4116-21. [PMID: 19725143 PMCID: PMC2738805 DOI: 10.3748/wjg.15.4116] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulation of liver metabolism and immune function, impairing postoperative recovery. Current evidence suggests that maintaining normoglycemia postoperatively improves surgical outcome and reduces the mortality and morbidity of critically ill patients. On the basis of these observations, several large randomized controlled studies were designed to evaluate the benefit of postoperative tight glycemic control with intensive insulin therapy. However, intensive insulin therapy carries the risk of hypoglycemia, which is linked to serious neurological events. Recently, we demonstrated that perioperative tight glycemic control in surgical patients could be achieved safely using a closed-loop glycemic control system and that this decreased both the incidence of infection at the site of the surgical incision, without the appearance of hypoglycemia, and actual hospital costs. Here, we review the benefits and requirements of perioperative intensive insulin therapy using a closed-loop artificial endocrine pancreas system in hepatectomized patients. This novel intensive insulin therapy is safe and effectively improves surgical outcome after hepatic resection.
Collapse
|
|
35
|
Okabayashi T, Nishimori I, Yamashita K, Sugimoto T, Yatabe T, Maeda H, Kobayashi M, Hanazaki K. Risk factors and predictors for surgical site infection after hepatic resection. J Hosp Infect 2009; 73:47-53. [PMID: 19640610 DOI: 10.1016/j.jhin.2009.04.022] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2008] [Accepted: 04/23/2009] [Indexed: 12/12/2022]
Abstract
Strict control of blood glucose levels with insulin in a surgical intensive care unit reduces postoperative morbidity and mortality. The aim of this study was to identify risk factors and the predictors for the prevention of surgical site infection (SSI) in a consecutive series of hepatectomised cases in a single institution. The association between SSI and various clinical parameters was investigated in 152 patients who underwent hepatic resection at Kochi Medical School from January 2000 through March 2007. The incidence of SSI in these patients was 14.5%. Multivariate analysis identified four independent parameters correlating with the occurrence of SSI: (i) body mass index >23.6 kg/m(2); (ii) estimated blood volume loss >810 mL; (iii) presence of postoperative bile leakage of organ/space SSI; and (iv) use of the sliding scale method for postoperative glucose control. There was no observed SSI after liver resection in the group whose postoperative blood glucose levels were controlled by an artificial pancreas. This study reveals that lack of postoperative glycaemic control is associated with a significantly higher incidence of postoperative infectious complications and longer hospitalisation. Obesity and the level of intraoperative estimated blood loss and bile leakage after hepatic resection are also risk factors with predictive value for SSI. Artificial pancreas is a safe and beneficial device to perform postoperative strict glycaemic control without hypoglycaemia for patients who undergo hepatic resection for liver diseases.
Collapse
Affiliation(s)
- T Okabayashi
- Department of Surgery, Kochi Medical School, Kochi, Japan.
| | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Okabayashi T, Nishimori I, Yamashita K, Sugimoto T, Namikawa T, Maeda H, Yatabe T, Hanazaki K. Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: a randomized clinical trial using an artificial pancreas. Amino Acids 2009; 38:901-7. [PMID: 19399583 DOI: 10.1007/s00726-009-0297-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2008] [Accepted: 04/09/2009] [Indexed: 02/05/2023]
Affiliation(s)
- Takehiro Okabayashi
- Department of Surgery, Kochi Medical School, Kohasu-Okocho, Nankoku-City, Kochi 783-8505, Japan.
| | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Liu C, Wang X, Chen Z, Zhang L, Wu Y, Zhang Y. Hepatic ischemia-reperfusion induces insulin resistance via down-regulation during the early steps in insulin signaling in rats. Transplant Proc 2009; 40:3330-4. [PMID: 19100383 DOI: 10.1016/j.transproceed.2008.07.143] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2008] [Accepted: 07/07/2008] [Indexed: 12/27/2022]
Abstract
BACKGROUND The effects of hepatic ischemia-reperfusion (I/R) on insulin signaling remain unclear. We observed changes in insulin secretion and signal protein expression during the early steps in insulin signaling after hepatic I/R in rats. MATERIALS AND METHODS Eighty healthy Wistar rats were randomly divided into an I/R group and a control (C) group. After we exposed the hepatic hilum, ischemia was induced by clamping the hepatic artery and portal vein for 30 minutes and then the liver was reperfused for 2 hours in the I/R group; a show procedure was done in the C group. Blood samples were obtained after exposure of the hepatic hilum (T1) and 2 hours after reperfusion in the I/R group (T2) and 2.5 hours after T1 in the C group (T2). We measured glucose and insulin plasma concentrations. We determined the expressions of insulin signaling proteins, including insulin receptor (IR) beta unit (IR beta), IR substrate 1 (IRS-1), IRS-2, and P85 in phosphatidylinositol 3-kinase (PI3K) and tyrosine phosphorylation of these proteins in liver and skeletal muscle. RESULTS Plasma glucose concentrations increased in both groups at T2 (P < .01) and were higher in the I/R group (P < .01). Insulin concentrations in the I/R group did not change significantly at T2. Insulin concentrations at T2 were higher than those at T1 in the C group (P < .05). Expressions of insulin signal proteins showed no significant difference between the 2 groups; however, tyrosine phosphorylation of IR beta, IRS-1, IRS-2, and the interactions between IRS-1 in skeletal muscle or IRS-2 in liver and PI3K were significantly lower in the I/R group than the C group. CONCLUSION Hepatic I/R inhibited insulin secretion and induced insulin resistance via down-regulation during the early steps in insulin signaling in rats.
Collapse
Affiliation(s)
- C Liu
- First Affiliated Hospital of Nanjing Medical University, The Liver Transplantation Center, Nanjing, Jiangsu, China.
| | | | | | | | | | | |
Collapse
|
|
38
|
Lonardo A, Loria P. Article Commentary: Insulin Resistance, Type 2 Diabetes and Chronic Liver Disease. A Deadly Trio. CLINICAL MEDICINE. ENDOCRINOLOGY AND DIABETES 2009; 2:CMED.S3518. [DOI: 10.4137/cmed.s3518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
In this commentary to the paper by Donadon V. et al (Clinical Medicine: Endocrinology and Diabetes. 2009;2:25–33.) the association and significance of insulin resistance with chronic liver disease are shortly reviewed and the molecular mechanisms underlying the diabetogenic and oncogenic potentials of advanced liver disease are summarized. Literature studies demonstrate that hepatocellular carcinoma (HCC) can be part of the natural history of NASH. HCCs in patients with features of metabolic syndrome as the only risk factor for liver disease have distinct morphological characteristics and mainly occur in the absence of significant fibrosis in the background liver. Moreover, data indicate that the presence of diabetes carries an approximately three to four-fold increased risk of HCC and such a risk is strongly increased by concurrent viral infections. Finally, the relationship between insulin resistance, steatosis and diabetes in NAFLD and HCV infection will be commented, along with the directions for future studies.
Collapse
Affiliation(s)
- Amedeo Lonardo
- University of Modena and Reggio Emilia Department of Internal Medicine, Endocrinology, Geriatrics Nuovo Ospedale Sant'Agostino Estense di Baggiovara, Baggiovara, Modena, Italy
| | - Paola Loria
- University of Modena and Reggio Emilia Department of Internal Medicine, Endocrinology, Geriatrics Nuovo Ospedale Sant'Agostino Estense di Baggiovara, Baggiovara, Modena, Italy
| |
Collapse
|
|
39
|
Assessment of liver function for successful hepatectomy in patients with hepatocellular carcinoma with impaired hepatic function. ACTA ACUST UNITED AC 2008; 15:596-602. [PMID: 18987929 DOI: 10.1007/s00534-007-1326-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2007] [Accepted: 11/27/2007] [Indexed: 12/22/2022]
Abstract
BACKGROUND/PURPOSE This study aimed to construct a formula for assessing liver function in order to prevent post-hepatectomy liver failure. METHODS A formula was constructed by analyzing data from 28 patients with hepatocellular carcinoma (HCC) with liver cirrhosis operated on between 1981 and 1984. Next, we evaluated the validity of this formula in 207 hepatectomy patients operated on from 1985 to 1999. For 145 hepatectomy patients operated on from 2000 to 2006, this formula was calculated before surgery in order to assess their risk of hepatectomy. RESULTS The formula for liver functional evaluation, constructed from preoperative hepatic function parameters, was: liver failure score = 164.8 - 0.58 x Alb - 1.07 x HPT + 0.062 x GOT - 685 x K. ICG - 3.57 x OGTT. LI + 0.074 x RW, where Alb is albumin (g/dl); HPT, hepaplastin test (%); GOT, glutamate oxaloacetate transaminase (U/l); K. ICG, K value of indocyanine green clearance test; OGTT. LI, 60-min/120-min glucose level in 75-g oral glucose tolerance test. linearity index of OGTT; and RW, weight of resected liver (g). We decided that a score below 25 would be safe for hepatectomy. CONCLUSIONS The mortality rate decreased from 3.9% in 1985--1999 to 1.3% in 2000--2006. This finding allows us to conclude that the formula is valid for assessing the risk of post-hepatectomy liver failure.
Collapse
|
|
40
|
Continuous post-operative blood glucose monitoring and control using a closed-loop system in patients undergoing hepatic resection. Dig Dis Sci 2008; 53:1405-10. [PMID: 17934862 DOI: 10.1007/s10620-007-0010-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2007] [Accepted: 08/28/2007] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND AIMS Hyperglycemia induced by surgical stress often causes the dysregulation of liver metabolism and immune function resulting in impaired post-operative recovery. The aim of this study was to evaluate the usefulness of a closed-loop system providing continuous monitoring and strict control of post-operative blood glucose in patients after hepatic resection. PATIENTS AND METHODS A total of 19 patients who underwent hepatic resection for primary liver tumor between August and December 2006 were enrolled in the study. Following surgery, blood glucose was continuously monitored by the STG-22 closed-loop system. Glucose levels were controlled using either a manual injection of insulin according to the commonly used sliding scale (manual insulin group, n = 9) or a programmed infusion of insulin determined by the control algorithm of the STG-22 (programmed insulin group, n = 10). The total amount of insulin used in the first 16 h following hepatic resection in the two groups was measured. RESULTS In the manual insulin group, post-operative blood glucose rose initially and reached a plateau of approximately 250 mg/dl between 4 h and 7 h post-hepatectomy and then returned towards normal levels by 16 h. In the programmed insulin group, blood glucose was steadily lowered, reaching the target zone (90-110 mg/dl) by 12 h post-surgery. The total amount of insulin administered per patient during the first 16 h post-surgery was significantly higher in the programmed insulin group (183 +/- 188 IU) than in the manual insulin group (8 +/- 7 IU; P < 0.001). No hypoglycemia was observed in either group. CONCLUSIONS Post-operative hyperglycemia was observed for up to 16 h in hepatectomized patients. In this post-operative hyperglycemic state, the STG-22 closed-loop system safely and quickly achieved glycemic control, indicating its clinical value in the post-operative management of hepatectomized patients.
Collapse
|
|
41
|
Kita Y, Mizukoshi E, Takamura T, Sakurai M, Takata Y, Arai K, Yamashita T, Nakamoto Y, Kaneko S. Impact of diabetes mellitus on prognosis of patients infected with hepatitis C virus. Metabolism 2007; 56:1682-8. [PMID: 17998021 DOI: 10.1016/j.metabol.2007.07.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2006] [Accepted: 07/10/2007] [Indexed: 12/29/2022]
Abstract
Diabetes is a risk factor for the progression of liver fibrosis and development of hepatocellular carcinoma in chronic hepatitis C. However, the impact of diabetes on the long-term prognosis and the synergistic interactions of various host factors for diabetes to the progression of liver fibrosis are unknown. In the present study, we examined the host factors associated with the progression of hepatitis C in 68 patients with a posttransfusion hepatitis (PTH) and analyzed the relationships. Multivariate analysis showed that age of PTH, being male, and type 2 diabetes mellitus were risk factors for the progression of liver fibrosis. By the Kaplan-Meier method, the cirrhosis-free survival rates after the onset of PTH were significantly lower in the diabetic group than in the nondiabetic group (P < .01). Diabetes also had a great impact on the long-term prognosis of chronic hepatitis C by reducing the time from PTH to the occurrence of hepatocellular carcinoma (P < .01) and to liver-related death (P < .05). Coexistence of obesity (body mass index > or =25 kg/m(2)) or hypertriglyceridemia (> or =150 mg/dL) with diabetes had a synergistic effect on liver fibrosis progression in patients with chronic hepatitis C. Thus, the treatment of diabetes, obesity, and hypertriglyceridemia may hold the key to improving the prognosis of chronic hepatitis.
Collapse
Affiliation(s)
- Yuki Kita
- Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Wang T, Shankar K, Ronis MJ, Mehendale HM. Mechanisms and outcomes of drug- and toxicant-induced liver toxicity in diabetes. Crit Rev Toxicol 2007; 37:413-59. [PMID: 17612954 DOI: 10.1080/10408440701215100] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Increase dincidences of hepatotoxicity have been observed in diabetic patients receiving drug therapies. Neither the mechanisms nor the predisposing factors underlying hepatotoxicity in diabetics are clearly understood. Animal studies designed to examine the mechanisms of diabetes-modulated hepatotoxicity have traditionally focused only on bioactivation/detoxification of drugs and toxicants. It is becoming clear that once injury is initiated, additional events determine the final outcome of liver injury. Foremost among them are two leading mechanisms: first, biochemical mechanisms that lead to progression or regression of injury; and second, whether or not timely and adequate liver tissue repair occurs to mitigate injury and restore liver function. The liver has a remarkable ability to repair and restore its structure and function after physical or chemical-induced damage. The dynamic interaction between biotransformation-based liver injury and compensatory tissue repair plays a pivotal role in determining the ultimate outcome of hepatotoxicity initiated by drugs or toxicants. In this review, mechanisms underlying altered hepatotoxicity in diabetes with emphasis on both altered bioactivation and liver tissue repair are discussed. Animal models of both marked sensitivity (diabetic rats) and equally marked protection (diabetic mice) from drug-induced hepatotoxicity are described. These examples represent a remarkable species difference. Availability of the rodent diabetic models offers a unique opportunity to uncover mechanisms of clinical interest in averting human diabetic sensitivity to drug-induced hepatotoxicities. While the rat diabetic models appear to be suitable, the diabetic mouse models might not be suitable in preclinical testing for potential hepatotoxic effects of drugs or toxicants, because regardless of type 1 or type2 diabetes, mice are resistant to acute drug-or toxicant-induced toxicities.
Collapse
Affiliation(s)
- T Wang
- Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71209, USA
| | | | | | | |
Collapse
|
|
43
|
Kawai T, Yokoyama Y, Nagino M, Kitagawa T, Nimura Y. Is there any effect of renal failure on the hepatic regeneration capacity following partial hepatectomy in rats? Biochem Biophys Res Commun 2007; 352:311-6. [PMID: 17126297 DOI: 10.1016/j.bbrc.2006.11.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2006] [Accepted: 11/03/2006] [Indexed: 10/23/2022]
Abstract
The effects of renal dysfunction on liver regeneration capacity have not been fully elucidated before, although many patients with renal failure are subjected to hepatectomy due to hepatobiliary diseases. In this study, we sought to determine the effects of renal dysfunction on the hepatic regeneration capacity using rat chronic renal failure model. After establishing chronic renal failure (CRF group) by semi-total renal resection, the rats were subjected to 70% partial hepatectomy (PHx). Rats without renal failure were used as control (Sham group). The hepatic regeneration rate, histology of the liver, clearance of indocyanine green into the bile, and the expression of hepatic regeneration-associated genes in the liver were evaluated. The hepatic regeneration rate was lower in CRF group as compared to Sham group on day 1 after PHx. Mitotic index evaluated by histologic examination on day 1 after PHx was also significantly lower in CRF group. However, no difference in these indices was observed on day 2 and 7 between Sham and CRF. Indocyanine green clearance rate was almost identical between Sham and CRF on day 7 following PHx. The baseline expressions of the hepatic regeneration-associated genes, such as IL-6, TNF-alpha, HGF, c-fos, and c-jun, in the liver of CRF were significantly lower than those of Sham. However, the rate of upregulation of these genes was not significantly different between Sham and CRF. These results clearly demonstrate that the renal dysfunction, although initially delays the onset, does not suppress the total hepatic regeneration capacity following partial hepatectomy. The function of the regenerated liver on day 7 after PHx also was not different. Our results provide a possibility that the hepatectomy can be indicated even for the patient with a chronic renal failure.
Collapse
Affiliation(s)
- Toru Kawai
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | | | | | | | | |
Collapse
|
|
44
|
Moscatiello S, Manini R, Marchesini G. Diabetes and liver disease: an ominous association. Nutr Metab Cardiovasc Dis 2007; 17:63-70. [PMID: 17164082 DOI: 10.1016/j.numecd.2006.08.004] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2006] [Accepted: 08/24/2006] [Indexed: 02/08/2023]
Abstract
Diabetes mellitus and advanced liver disease are associated with each other more frequently than expected by chance, and such an association carries a significant risk of morbidity and mortality. A metabolic pathway leading to advanced liver disease via fatty liver and steatohepatitis has been demonstrated, further supporting the possibility that cirrhosis may be a late complication of diabetes. In addition, an interaction between hepatitis C virus (HCV) and insulin resistance increases the overall prevalence of associated diseases, through largely unidentified mechanisms. Extensive prospective monitoring of non-alcoholic fatty liver disease cases, analysis of insulin signaling in HCV-infected patients using molecular biology techniques, and intervention studies, will help to clarify the mechanisms of action of the possible clinical strategies, the predictive value of biochemical, histological, and clinical markers, and the effectiveness of treatments available.
Collapse
Affiliation(s)
- Simona Moscatiello
- Unit of Metabolic Diseases, Alma Mater Studiorum University, Policlinico S. Orsola, Via Massarenti 9, I-40138 Bologna, Italy
| | | | | |
Collapse
|
|
45
|
Sigal SH, Stanca CM, Kontorinis N, Bodian C, Ryan E. Diabetes mellitus is associated with hepatic encephalopathy in patients with HCV cirrhosis. Am J Gastroenterol 2006; 101:1490-6. [PMID: 16863551 DOI: 10.1111/j.1572-0241.2006.00649.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES An increased ammonia level of gut bacterial origin is an important mediator in the pathogenesis of hepatic encephalopathy (HE), and constipation is a frequent precipitant of hepatic coma. Because diabetes mellitus (DM) may be associated with delayed gastrointestinal transit, we speculated that its presence in patients with HCV-related cirrhosis would predispose to and exacerbate HE. METHODS Sixty-five patients (50 men, 15 women) with HCV-related cirrhosis attending a liver transplantation clinic were assessed for severity of liver disease and presence of DM in a cross-sectional study. A modified Child-Pugh score that excluded HE was calculated. Frequency and severity of HE (absent, mild, and severe) in diabetic and nondiabetic patients were assessed. Clinical severity of cirrhosis and results of neuropsychometric testing in diabetic and nondiabetic patients with mild and severe HE were compared. RESULTS Fifty-four patients (83%) had HE (33 mild, 21 severe). Twenty patients (31%) had DM. HE was present in 19 (95%) patients with diabetes and 35 (78%) patients without diabetes (p = 0.087). Severity of HE was greater in diabetic (35% mild, 60% severe) than in nondiabetic patients (58% mild, 20% severe) (p = 0.007). In both the mild and severe HE categories, severity of liver disease in diabetic patients was otherwise milder than in the nondiabetic patients. CONCLUSIONS Diabetic patients with HCV cirrhosis have more severe HE. Diabetic patients have severe HE at earlier stages of biochemical decompensation and portal hypertension compared with nondiabetic patients.
Collapse
Affiliation(s)
- Samuel H Sigal
- Center for Liver Disease and Transplantation, New York Weill Cornell Medical Center, New York 10021, USA
| | | | | | | | | |
Collapse
|
|
46
|
Affiliation(s)
- Ellen C Ebert
- Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, New Brunswick, USA
| |
Collapse
|
|
47
|
Uno K, Suginoshita Y, Kakimi K, Moriyasu F, Hirosaki M, Shirakawa T, Kishida T. Impairment of IFN-alpha production capacity in patients with hepatitis C virus and the risk of the development of hepatocellular carcinoma. World J Gastroenterol 2006; 11:7330-4. [PMID: 16437637 PMCID: PMC4725153 DOI: 10.3748/wjg.v11.i46.7330] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the utility of interferon (IFN)-alpha production capacity in patients with hepatitis C virus (HCV) infection for the measurement of immuno-surveillance potential and for the early detection of hepatocellular carcinoma (HCC) by investigating the Sendai virus (HVJ) stimulated IFN-alpha production capacity of patients with HCV infection. METHODS HVJ stimulated IFN-alpha production was determined in a large number of patients with HCV infection and the development of HCC was monitored for 3 years in patients with liver cirrhosis (LC). RESULTS IFN-alpha production capacity decreases gradually with the progression of liver disease from chronic hepatitis (CH) to HCC. A significant correlation between the duration of HCV infection and impaired IFN-alpha production capacity was observed. IFN-alpha production in patients who developed HCC within 3 years was significantly lower than that of patients who remained in LC without developing HCC. CONCLUSION Measurement of IFN-alpha production in LC patients may be useful for the early detection of HCC.
Collapse
Affiliation(s)
- Kazuko Uno
- Louis Pasteur Center for Medical Research, 103-5 Tanaka-monzen-cho, Sakyo-ku, Kyoto 606, Japan.
| | | | | | | | | | | | | |
Collapse
|
|
48
|
Abstract
Diabetes mellitus is a growing health concern in our society. In addition to the well-known cardiovascular, renal, and ophthalmologic complications of diabetes, liver-related complications occur commonly and are often underrecognized. The ensuing article will review the relationship between diabetes mellitus and two common liver diseases: chronic hepatitis C and nonalcoholic fatty liver disease. The association with diabetes and cirrhosis, acute liver failure, hepatocellular carcinoma, and outcomes following orthotopic liver transplantation will also be discussed.
Collapse
Affiliation(s)
- Stephen A Harrison
- Department of Hepatology, Brooke Army Medical Center, Fort Sam, Houston, TX, USA.
| |
Collapse
|
|
49
|
Huang YH, Wu JC, Chen CH, Chang TT, Lee PC, Chau GY, Lui WY, Chang FY, Lee SD. Comparison of recurrence after hepatic resection in patients with hepatitis B vs. hepatitis C-related small hepatocellular carcinoma in hepatitis B virus endemic area. Liver Int 2005; 25:236-41. [PMID: 15780044 DOI: 10.1111/j.1478-3231.2005.01081.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are two important factors in the development of hepatocellular carcinoma (HCC). The carcinogenic mechanism of HBV and HCV is considered to be different. It is interesting to compare the recurrence after hepatic resection in patients with small HCC who were infected with HBV or HCV. METHODS From 1991 to 1995, 145 patients who were positive for hepatitis B surface antigen (HBsAg) or antibody to HCV (anti-HCV) and diagnosed as small HCC (< or =3 cm) in three medical centers in Taiwan were evaluated in this study. All patients underwent hepatic resection. Among them, 83 (57.2%) were infected by HBV, 51 (35.2%) were infected by HCV, and 11 (7.6%) had dual HBV and HCV infection. RESULTS Anti-HCV+ HCCs were associated with older age, lower serum albumin, higher alanine transaminase (ALT) level and multi-nodular tumors during diagnosis. During the follow-up, 92 (63.4%) patients developed tumor recurrence. Anti-HCV + HCC had a higher cumulated recurrence rate than HBsAg+ HCC (72.4% vs 53.6 % at 5 year, P = 0.032). In multivariate analysis, the presence of vascular invasion and lower serum albumin levels (<3.9 g/dl) were the determinants for tumor recurrence. CONCLUSIONS HCV infection, as compared with HBV infection, had a higher cumulated recurrence after hepatic resection in patients with small HCC. Low serum albumin level was significantly associated with recurrence among these patients.
Collapse
Affiliation(s)
- Yi-Hsiang Huang
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Abstract
The association of metabolic disorders with liver disease is receiving increasing attention in the gastroenterological community. Cohort studies have shown that advanced liver disease may stem from metabolic disorders, via fatty liver, non-alcoholic steatohepatitis, cryptogenic cirrhosis, and eventually hepatocellular carcinoma. In both obesity and diabetes, deaths from cirrhosis are higher than expected, mainly in subjects with no or moderate alcohol consumption, but high rates of fatty liver disease have been associated with all features of the metabolic syndrome. Also the risk of hepatocellular carcinoma is higher than normal, being dependent on body mass index (BMI) in obesity, and independent of age, BMI, gender and race in diabetes. Finally, metabolic liver disease may interact with hepatitis C virus infection, increasing the risk of steatosis and liver disease progression, as well as reducing the chances of an effective antiviral treatment. There is evidence that treatments aimed at reducing insulin resistance are also effective in improving liver histology. Although cardiovascular disease remains the major cause of increased morbidity and excess mortality in metabolic disorders, the risk of progressive liver disease should no longer be underestimated, being a threat to millions of people at risk in the present epidemics of obesity and diabetes, and therapeutic strategies need to be tested.
Collapse
Affiliation(s)
- Giulio Marchesini
- Unit of Metabolic Diseases, Alma Mater Studiorum University, Bologna, and San Giovanni Battista Hospital, Turin, Italy.
| | | | | |
Collapse
|