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Orsso CE, Caretero A, Poltronieri TS, Arends J, de van der Schueren MA, Kiss N, Laviano A, Prado CM. Effects of high-protein supplementation during cancer therapy: a systematic review and meta-analysis. Am J Clin Nutr 2024; 120:1311-1324. [PMID: 39631998 PMCID: PMC11619795 DOI: 10.1016/j.ajcnut.2024.08.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 08/06/2024] [Accepted: 08/19/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Establishing the effectiveness of high-protein supplementation in reducing cancer-related side effects is crucial. OBJECTIVE The study aimed to assess the effectiveness and safety of high-protein supplementation on clinical outcomes of patients undergoing cancer therapy. METHODS Systematic searches were conducted on Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Cochrane Central Register of Controlled Trials, and Scopus from inception until July 2023. Randomized controlled trials administering supplements with ≥10 g protein/serving, given to 20+ adult patients undergoing cancer therapy were included. Random-effects meta-analyses were used to estimate the effects of high-protein supplementation on the primary outcomes of body weight and health-related quality of life (HRQoL). We employed a vote-counting approach based on effect direction for secondary outcomes (that is, body composition, muscle function, hospitalization, response to cancer therapy/toxicity, survival, and systemic inflammation). Risk-of-bias (ROB) was assessed. RESULTS Thirty-five studies involving 3701 patients with diverse cancer types were included. Patients who received high-protein supplementation lost less body weight than controls (mean difference = 1.45 kg; 95% CI: 0.42, 2.48 kg; P = 0.006; I2 = 80%). No differences in HRQoL were observed; all studies assessing HRQoL were rated as high ROB. A beneficial effect on muscle mass was found in 11 of 13 studies, although most had a high ROB due to assessment techniques. When considering higher quality studies, evidence of a beneficial effect was found in 5 of 5 studies for muscle strength, and 3 of 4 for hospitalization rate. Effects on other secondary outcomes were inconsistent or limited. No serious adverse effects were reported. CONCLUSIONS High-protein supplementation mitigates weight loss, improves muscle strength, and lowers hospitalization rates in patients undergoing cancer therapy. These positive clinical outcomes, along with a favorable safety profile, suggest that high-protein supplementation may be a valuable addition to medical practice. However, given the need for more robust trials and the high ROB observed in the existing studies, these conclusions should be interpreted with caution. This review was prospectively registered with PROSPERO under the registration number CRD42021237372.
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Affiliation(s)
- Camila E Orsso
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Anne Caretero
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Taiara Scopel Poltronieri
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada; Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Jann Arends
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
| | - Marian Ae de van der Schueren
- Department of Nutrition, Dietetics and Lifestyle, School of Allied Health, HAN University of Applied Sciences, Nijmegen, The Netherlands; Department of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands
| | - Nicole Kiss
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, VIC, Australia
| | - Alessandro Laviano
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Carla M Prado
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
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Zhang Y, Zhan L, Zhang L, Shi Q, Li L. Branched-Chain Amino Acids in Liver Diseases: Complexity and Controversy. Nutrients 2024; 16:1875. [PMID: 38931228 PMCID: PMC11206364 DOI: 10.3390/nu16121875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular signaling. The liver is a crucial site for BCAA metabolism, linking the changes in BCAA homeostasis with the pathogenesis of a variety of liver diseases and their complications. Peripheral circulating BCAA levels show complex trends in different liver diseases. This review delineates the alterations of BCAAs in conditions including non-alcoholic fatty liver disease, hepatocellular carcinoma, cirrhosis, hepatic encephalopathy, hepatitis C virus infection, and acute liver failure, as well as the potential mechanisms underlying these changes. A significant amount of clinical research has utilized BCAA supplements in the treatment of patients with cirrhosis and liver cancer. However, the efficacy of BCAA supplementation in clinical practice remains uncertain and controversial due to the heterogeneity of studies. This review delves into the complicated relationship between BCAAs and liver diseases and tries to untangle what role BCAAs play in the occurrence, development, and outcomes of liver diseases.
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Affiliation(s)
- Yaqi Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
| | - Luqi Zhan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
| | - Lingjian Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
- Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310024, China
| | - Qingmiao Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
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Na GH, Choi HJ, Chun JH, Choi Y, Park SE, Hong TH, You YK. Effects of Livact Granule on Liver Function Recovery After Donor Right Hemi-Hepatectomy. Transplant Proc 2024; 56:656-659. [PMID: 38350820 DOI: 10.1016/j.transproceed.2024.01.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/16/2024] [Indexed: 02/15/2024]
Abstract
BACKGROUND Living donor liver transplantation (LDLT) is currently widespread due to organ shortage. Because LDLT is a high-risk surgery for the donor, donor safety becomes an important issue. In adult LDLT, right lobe grafts are usually used, posing a greater risk to the donor than a left lobe. Reports have demonstrated that branched-chain amino acids help patients recover after hepatectomy. This study aimed to evaluate the effect of Livact granule on donor safety and recovery. METHODS From January 2016 to December 2021, LDLT was performed on 258 patients at our center. Among them, 148 were in the non-Livact group, and 110 were in the Livact group. Six of 110 patients in the Livact group stopped taking the granules due to nausea and vomiting, leaving 104 patients in the Livact group to be analyzed. Various preoperative and postoperative factors were evaluated to assess donor safety and recovery. RESULTS In the non-Livact group, the mean donor age was 35.8; in the Livact group, it was 40. There were no differences between the 2 groups in preoperative liver function tests and no difference in future liver remnant or steatosis. There was no difference in total bilirubin level between the 2 groups at 5 days postoperatively; however, in the Livact group, the prothrombin time international normalized ratio was lower, and albumin was higher. The days taken for total bilirubin to normalize were the same in both groups, but fewer days were needed for Livact to realize an international normalized ratio. More patients in the non-Livact group were discharged with the Jackson-Pratt drain because the drainage did not decrease. CONCLUSIONS In donor right hepatectomy patients, taking Livact granules and branched-chain amino acids helps donor recovery. For donor safety, administration of Livact granules during the perioperative period should be considered.
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Affiliation(s)
- Gun Hyung Na
- Department of Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Jin Ha Chun
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yoonyoung Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Eun Park
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Tae Ho Hong
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young Kyoung You
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Hsu YM, Kuan HC, Chen YA, Chiu CW, Chen PC, Tam KW. Effects of branched-chain amino acids supplementation on patients undergoing hepatic intervention: a meta-analysis of randomised controlled trials. Br J Nutr 2024; 131:276-285. [PMID: 37642137 DOI: 10.1017/s0007114523001885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/31/2023]
Abstract
The benefits of branched-chain amino acid (BCAA) administration after hepatic intervention in patients with liver diseases remain unclear. We conducted a systematic review and meta-analysis to evaluate the effects of BCAA on patients undergoing hepatectomy, trans-arterial embolisation and radiofrequency ablation. Relevant randomised controlled trials (RCT) were obtained from PubMed, EMBASE and Cochrane Library databases. A meta-analysis was performed to calculate the pooled effect size by using random-effects models. The primary outcomes were survival and tumour recurrence. The secondary outcomes were hospital stay, nutrition status, biochemistry profile, complication rate of liver treatment and adverse effect of BCAA supplementation. In total, eleven RCT involving 750 patients were included. Our meta-analysis showed no significant difference in the rates of tumour recurrence and overall survival between the BCAA and control groups. However, the pooled estimate showed that BCAA supplementation in patients undergoing hepatic intervention significantly increased serum albumin (mean difference (MD): 0·11 g/dl, 95 % CI: 0·02, 0·20; 5 RCT) at 6 months and cholinesterase level (MD: 50·00 U/L, 95 % CI: 21·08, 78·92; 1 RCT) at 12 months and reduced ascites incidence (risk ratio: 0·39, 95 % CI: 0·21, 0·71; 4 RCT) at 12 months compared with the control group. Additionally, BCAA administration significantly increased body weight at 6 months and 12 months and increased arm circumference at 12 months. In conclusion, BCAA supplementation significantly improved the liver function, reduced the incidence of ascites and increased body weight and arm circumference. Thus, BCAA supplementation may beneficial for selected patients undergoing liver intervention.
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Affiliation(s)
- Yan-Mei Hsu
- Department of Pharmacy, En Chu Kong Hospital, New Taipei City, Taiwan
| | - Hui-Chung Kuan
- Department of Medical Administration, En Chu Kong Hospital, New Taipei City, Taiwan
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Yu-An Chen
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ching-Wen Chiu
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Po-Cheng Chen
- Department of Urology, En Chu Kong Hospital, New Taipei City, Taiwan
| | - Ka-Wai Tam
- Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan
- Center for Evidence-Based Health Care, Shuang Ho Hospital, Taipei Medical University, New Taipei City23561, Taiwan
- Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
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Yap KY, Chi H, Ng S, Ng DHL, Shelat VG. Effect of perioperative branched chain amino acids supplementation in liver cancer patients undergoing surgical intervention: A systematic review. World J Gastrointest Surg 2023; 15:2596-2618. [PMID: 38111761 PMCID: PMC10725538 DOI: 10.4240/wjgs.v15.i11.2596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/15/2023] [Accepted: 10/23/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Branched chain amino acid (BCAA) supplementation has been associated with favourable outcomes in liver malignancies requiring definitive resection or liver transplantation. Currently, there are no updated systematic reviews evaluating the efficacy of perioperative BCAA supplementation in patients undergoing surgery for liver cancer. AIM To evaluate the efficacy of perioperative BCAA supplementation in patients undergoing surgery for liver cancer. METHODS A systematic review of randomized control trials and observational studies was conducted on PubMed, Embase, Cochrane Library, Scopus, and Web of Science to evaluate the effect of perioperative BCAA supplementation compared to standard in-hospital diet, in liver cancer patients undergoing surgery. Clinical outcomes were extracted, and a meta-analysis was performed on relevant outcomes. RESULTS 16 studies including 1389 patients were included. Perioperative BCAA administration was associated with reduced postoperative infection [risk ratio (RR) = 0.58 95% confidence intervals (CI): 0.39 to 0.84, P = 0.005] and ascites [RR = 0.57 (95%CI: 0.38 to 0.85), P = 0.005]. There was also a reduction in length of hospital stay (LOS) [weighted mean difference (WMD) = -3.03 d (95%CI: -5.49 to -0.57), P = 0.02] and increase in body weight [WMD = 1.98 kg (95%CI: 0.35 to 3.61, P = 0.02]. No significant differences were found in mortality, cancer recurrence and overall survival. No significant safety concerns were identified. CONCLUSION Perioperative BCAA administration is efficacious in reducing postoperative infection, ascites, LOS, and increases body weight in liver cancer patients undergoing surgical resection.
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Affiliation(s)
- Kwan Yi Yap
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - HongHui Chi
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Sherryl Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Doris HL Ng
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore
| | - Vishal G Shelat
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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Rowley A, Adiamah A, Kushairi A, Lewis SJ, Lobo DN. The effect of post-discharge oral nutritional supplements on outcomes after gastrointestinal surgery: A systematic review and meta-analysis. Clin Nutr 2023; 42:1189-1201. [PMID: 37244753 DOI: 10.1016/j.clnu.2023.04.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 04/29/2023] [Indexed: 05/29/2023]
Abstract
BACKGROUND Malnutrition is a risk-factor for adverse postoperative outcomes. This systematic review and meta-analysis evaluated the impact of post-discharge oral nutritional supplements (ONS) on outcomes in patients undergoing gastrointestinal surgery. METHODS The Medline and Embase databases were searched for randomised clinical trials in patients undergoing gastrointestinal surgery who had received ONS for at least two weeks after discharge from hospital. The primary endpoint was weight change. Secondary endpoints included quality of life, total lymphocyte count, total serum protein and serum albumin. Analysis was performed using RevMan5.4 software. RESULTS Fourteen studies with 2480 participants (1249 ONS/1231 controls) were included. Pooling of results revealed that a reduction in postoperative weight loss in patients taking ONS, when compared with control: overall weighted mean difference (WMD) -1.69 kg, 95% CI -2.98 to -0.41, P = 0.01. Serum albumin concentration was increased in the ONS group: WMD = 1.06 g/L, 95% CI 0.04 to 2.07, P = 0.04. Haemoglobin was also increased: WMD = 2.91 g/L, 95% CI 0.58 to 5.25, P = 0.01. Total serum protein, total lymphocyte count, total cholesterol and quality of life did not differ between the groups. Patient compliance was relatively poor across the studies and there was variability in the composition of ONS, volume consumed and surgical procedures performed. CONCLUSIONS There was a reduction in postoperative weight loss and an improvement in some biochemical parameters in patients receiving ONS after gastrointestinal surgery. Future RCTs with more consistent methodologies are needed to investigate the efficacy of ONS after discharge from hospital following gastrointestinal surgery.
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Affiliation(s)
- Annabel Rowley
- Gastrointestinal Surgery, Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Alfred Adiamah
- Gastrointestinal Surgery, Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Anisa Kushairi
- Gastrointestinal Surgery, Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Stephen J Lewis
- Department of Gastroenterology, Derriford Hospital, Plymouth, United Kingdom
| | - Dileep N Lobo
- Gastrointestinal Surgery, Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK; MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
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Parsons HM, Forte ML, Abdi HI, Brandt S, Claussen AM, Wilt T, Klein M, Ester E, Landsteiner A, Shaukut A, Sibley SS, Slavin J, Sowerby C, Ng W, Butler M. Nutrition as prevention for improved cancer health outcomes: a systematic literature review. JNCI Cancer Spectr 2023; 7:pkad035. [PMID: 37212631 PMCID: PMC10290234 DOI: 10.1093/jncics/pkad035] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 04/27/2023] [Indexed: 05/23/2023] Open
Abstract
BACKGROUND Among adults with cancer, malnutrition is associated with decreased treatment completion, more treatment harms and use of health care, and worse short-term survival. To inform the National Institutes of Health Pathways to Prevention workshop, "Nutrition as Prevention for Improved Cancer Health Outcomes," this systematic review examined the evidence for the effectiveness of providing nutrition interventions before or during cancer therapy to improve outcomes of cancer treatment. METHODS We identified randomized controlled trials enrolling at least 50 participants published from 2000 through July 2022. We provide a detailed evidence map for included studies and grouped studies by broad intervention and cancer types. We conducted risk of bias (RoB) and qualitative descriptions of outcomes for intervention and cancer types with a larger volume of literature. RESULTS From 9798 unique references, 206 randomized controlled trials from 219 publications met the inclusion criteria. Studies primarily focused on nonvitamin or mineral dietary supplements, nutrition support, and route or timing of inpatient nutrition interventions for gastrointestinal or head and neck cancers. Most studies evaluated changes in body weight or composition, adverse events from cancer treatment, length of hospital stay, or quality of life. Few studies were conducted within the United States. Among intervention and cancer types with a high volume of literature (n = 114), 49% (n = 56) were assessed as high RoB. Higher-quality studies (low or medium RoB) reported mixed results on the effect of nutrition interventions across cancer and treatment-related outcomes. CONCLUSIONS Methodological limitations of nutrition intervention studies surrounding cancer treatment impair translation of findings into clinical practice or guidelines.
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Affiliation(s)
- Helen M Parsons
- Minnesota Evidence-Based Practice Center, Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Mary L Forte
- Minnesota Evidence-Based Practice Center, Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Hamdi I Abdi
- Minnesota Evidence-Based Practice Center, Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Sallee Brandt
- Minnesota Evidence-Based Practice Center, Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Amy M Claussen
- Minnesota Evidence-Based Practice Center, Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Timothy Wilt
- Minnesota Evidence-Based Practice Center, Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
- Minneapolis VA Center for Care Delivery and Outcomes Research, Minneapolis, MN, USA
- School of Medicine, University of Minnesota, Minneapolis, MN, USA
- Minneapolis VA Healthcare System, Minneapolis, MN, USA
| | - Mark Klein
- School of Medicine, University of Minnesota, Minneapolis, MN, USA
- Minneapolis VA Healthcare System, Minneapolis, MN, USA
| | | | - Adrienne Landsteiner
- Minneapolis VA Center for Care Delivery and Outcomes Research, Minneapolis, MN, USA
| | | | - Shalamar S Sibley
- School of Medicine, University of Minnesota, Minneapolis, MN, USA
- Minneapolis VA Healthcare System, Minneapolis, MN, USA
| | - Joanne Slavin
- Department of Food Science and Nutrition, College of Food, Agricultural and Natural Resource Sciences, St. Paul, MN, USA
| | - Catherine Sowerby
- Minneapolis VA Center for Care Delivery and Outcomes Research, Minneapolis, MN, USA
| | - Weiwen Ng
- Minnesota Evidence-Based Practice Center, Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Mary Butler
- Minnesota Evidence-Based Practice Center, Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
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Hayashi H, Shimizu A, Kubota K, Notake T, Masuo H, Yoshizawa T, Hosoda K, Sakai H, Yasukawa K, Soejima Y. Combination of sarcopenia and prognostic nutritional index to predict long-term outcomes in patients undergoing initial hepatectomy for hepatocellular carcinoma. Asian J Surg 2023; 46:816-823. [PMID: 35961897 DOI: 10.1016/j.asjsur.2022.07.122] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/20/2022] [Accepted: 07/26/2022] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE To determine if preoperative sarcopenia and prognostic nutritional index (PNI) could accurately predict the postoperative outcomes of patients with hepatocellular carcinoma (HCC) undergoing initial hepatectomy. METHODS Three hundred three patients who underwent curative hepatectomy for HCC between January 2010 and August 2021 were enrolled and their data were retrospectively analyzed. Sarcopenia was determined from computed tomography images obtained 3 weeks prior to surgery, and PNI was calculated from preoperative albumin and whole lymphocyte count data in receiver operating characteristic (ROC) curve analysis, with a cutoff value of 46.2 to categorize high and low groups. RESULTS One hundred six (35%) patients had sarcopenia prior to surgery. Kaplan-Meier analysis revealed that sarcopenia and low PNI were associated with significantly worse overall survival (OS) compared with no sarcopenia and high PNI, respectively (P = 0.023 and P = 0.035, respectively). In addition, patients with sarcopenia had worse OS than those without sarcopenia in the high and low PNI groups (P = 0.058 and P = 0.038, respectively). Sarcopenia (hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.00-2.76; P = 0.048) and PNI ≤46.2 (HR 1.96; 95% CI 1.17-3.27; P = 0.011) were independent prognostic factors on multivariate analysis, and combined sarcopenia and PNI had a higher AUC value (AUC = 0.722, P < 0.001) than either one alone in ROC analysis. CONCLUSION Combined sarcopenia and PNI as a prognostic marker can better predict the postoperative prognostic outcomes of HCC patients following hepatectomy than either sarcopenia or PNI alone.
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Affiliation(s)
- Hikaru Hayashi
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
| | - Akira Shimizu
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan.
| | - Koji Kubota
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
| | - Tsuyoshi Notake
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
| | - Hitoshi Masuo
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
| | - Takahiro Yoshizawa
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
| | - Kiyotaka Hosoda
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
| | - Hiroki Sakai
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
| | - Koya Yasukawa
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
| | - Yuji Soejima
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Japan
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Johnston HE, Takefala TG, Kelly JT, Keating SE, Coombes JS, Macdonald GA, Hickman IJ, Mayr HL. The Effect of Diet and Exercise Interventions on Body Composition in Liver Cirrhosis: A Systematic Review. Nutrients 2022; 14:nu14163365. [PMID: 36014871 PMCID: PMC9414099 DOI: 10.3390/nu14163365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/11/2022] [Accepted: 08/12/2022] [Indexed: 12/01/2022] Open
Abstract
Alterations in body composition, in particular sarcopenia and sarcopenic obesity, are complications of liver cirrhosis associated with adverse outcomes. This systematic review aimed to evaluate the effect of diet and/or exercise interventions on body composition (muscle or fat) in adults with cirrhosis. Five databases were searched from inception to November 2021. Controlled trials of diet and/or exercise reporting at least one body composition measure were included. Single-arm interventions were included if guideline-recommended measures were used (computed tomography/magnetic resonance imaging, dual-energy X-ray absorptiometry, bioelectrical impedance analysis, or ultrasound). A total of 22 controlled trials and 5 single-arm interventions were included. Study quality varied (moderate to high risk of bias), mainly due to lack of blinding. Generally, sample sizes were small (n = 6–120). Only one study targeted weight loss in an overweight population. When guideline-recommended measures of body composition were used, the largest improvements occurred with combined diet and exercise interventions. These mostly employed high protein diets with aerobic and or resistance exercises for at least 8 weeks. Benefits were also observed with supplementary branched-chain amino acids. While body composition in cirrhosis may improve with diet and exercise prescription, suitably powered RCTs of combined interventions, targeting overweight/obese populations, and using guideline-recommended body composition measures are needed to clarify if sarcopenia/sarcopenic obesity is modifiable in patients with cirrhosis.
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Affiliation(s)
- Heidi E. Johnston
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Correspondence: ; Tel.: +61-7-3176-7938
| | - Tahnie G. Takefala
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
| | - Jaimon T. Kelly
- Centre for Online Health, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Centre for Health Services Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Shelley E. Keating
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Jeff S. Coombes
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Graeme A. Macdonald
- Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
| | - Ingrid J. Hickman
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Hannah L. Mayr
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Centre for Functioning and Health Research, Metro South Health, Brisbane, QLD 4102, Australia
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD 4226, Australia
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10
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Ogawa M, Satomi-Kobayashi S, Yoshida N, Komaki K, Izawa KP, Hamaguchi M, Inoue T, Sakai Y, Hirata KI, Okada K. Impact of Frailty on Postoperative Dysphagia in Patients Undergoing Elective Cardiovascular Surgery. JACC: ASIA 2022; 2:104-113. [PMID: 36340251 PMCID: PMC9627818 DOI: 10.1016/j.jacasi.2021.10.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 09/14/2021] [Accepted: 10/24/2021] [Indexed: 12/25/2022]
Abstract
Background Postextubation dysphagia (PED) is a serious postoperative complication following cardiovascular surgery that can lead to a worse prognosis. On the other hand, frailty is a prognostic factor in patients who undergo cardiac surgery. Objectives This study investigated the effect of frailty status on PED and impact of PED on postoperative complications. Methods This single-center retrospective cohort study included 644 consecutive patients who underwent elective cardiovascular surgery between May 1, 2014, and December 31, 2020; they were assigned to the PED or non-PED group based on postoperative swallowing status, and postoperative complications were investigated. Frailty status and physical functions, including walking speed, grip strength, Short Physical Performance Battery, and 6-minute walking distance, were preoperatively assessed; the frailty-status cutoff for predicting PED was determined from the receiver-operating characteristic curve. Results In this study cohort (mean age 67.7 years), the overall PED prevalence was 14.8%; preoperative frailty had a significantly higher prevalence in the PED group (50.0%) than in the non-PED group (20.3%; P < 0.001). PED correlated with a higher incidence of postoperative pneumonia and prolonged intensive care unit or hospital stay (P < 0.05 for all). After adjustment for confounders, multiple regression analysis revealed that preoperative frailty was independently associated with PED (P < 0.001). Conclusions PED occurred commonly after cardiovascular surgery and increased the risk of postoperative complications. Preoperative frailty was independently associated with PED. The 6-minute walking distance was the most powerful predictor of PED. Evaluation of preoperative frailty status is important for risk stratification and prevention of postoperative morbidity in patients undergoing surgery.
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Affiliation(s)
- Masato Ogawa
- Division of Rehabilitation Medicine, Kobe University Hospital, Kobe, Japan
- Department of Public Health, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - Seimi Satomi-Kobayashi
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- Address for correspondence: Dr Seimi Satomi-Kobayashi, Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
| | - Naofumi Yoshida
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kodai Komaki
- Division of Rehabilitation Medicine, Kobe University Hospital, Kobe, Japan
| | - Kazuhiro P. Izawa
- Department of Public Health, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - Mari Hamaguchi
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takeshi Inoue
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoshitada Sakai
- Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ken-ichi Hirata
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenji Okada
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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11
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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]
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12
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Jafari-Vayghan H, Moludi J, Saleh-Ghadimi S, Enamzadeh E, Seyed-Mohammadzad MH, Alizadeh M. Impact of Melatonin and Branched-Chain Amino Acids Cosupplementation on Quality of Life, Fatigue, and Nutritional Status in Cachectic Heart Failure Patients: A Randomized Controlled Trial. Am J Lifestyle Med 2022; 16:130-140. [PMID: 35185435 PMCID: PMC8848111 DOI: 10.1177/1559827619874044] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 08/14/2019] [Accepted: 08/15/2019] [Indexed: 01/23/2024] Open
Abstract
Background: Cardiac cachexia (CC) adversely affects the lifestyle of heart failure (HF) patients. The current study examined the impact of melatonin cosupplementation and branched-chain amino acids (BCAAs) on quality of life (QoL), fatigue, and nutritional status in cachectic HF patients. Methods: In this trial, 84 CC patients were randomized to melatonin, BCAAs, or coadministration (both) as intervention groups and a control group over 8 weeks. At baseline and postintervention, QoL, fatigue, and nutritional status were assessed. Results: After intervention, improvement in the overall and physical dimensions of QoL and appetite score were found to be statistically significant in the BCAAs (P < .001) and the melatonin+BCAAs (P < .001) groups compared with the placebo group. The emotional dimension score was significantly lower in the BCAAs group compared with the placebo group (P = .001). There was a statistically significant improvement in fatigue severity in all 3 intervention groups compared with the placebo group. The nutrition risk index (NRI) score increased significantly only in the melatonin group (P = .015), and there was no significant difference between the other groups (P = .804). Conclusions: Cosupplementation with BCAAs and melatonin improved QoL, fatigue status, and appetite in cachectic HF patients but did not affect NRI.
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Affiliation(s)
- Hamed Jafari-Vayghan
- Student Research Committee (HJ-V, JM), Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences (SS-G), Tabriz University of Medical Sciences, Tabriz, Iran
- Cardiovascular Research Center (EE), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science (MA), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Cardiology, Shohada Hospital, Urmia University of Medical Sciences, Urmia, Iran (MHS-M)
| | - Jalal Moludi
- Student Research Committee (HJ-V, JM), Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences (SS-G), Tabriz University of Medical Sciences, Tabriz, Iran
- Cardiovascular Research Center (EE), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science (MA), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Cardiology, Shohada Hospital, Urmia University of Medical Sciences, Urmia, Iran (MHS-M)
| | - Sevda Saleh-Ghadimi
- Student Research Committee (HJ-V, JM), Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences (SS-G), Tabriz University of Medical Sciences, Tabriz, Iran
- Cardiovascular Research Center (EE), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science (MA), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Cardiology, Shohada Hospital, Urmia University of Medical Sciences, Urmia, Iran (MHS-M)
| | - Elgar Enamzadeh
- Student Research Committee (HJ-V, JM), Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences (SS-G), Tabriz University of Medical Sciences, Tabriz, Iran
- Cardiovascular Research Center (EE), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science (MA), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Cardiology, Shohada Hospital, Urmia University of Medical Sciences, Urmia, Iran (MHS-M)
| | - Mir Hossein Seyed-Mohammadzad
- Student Research Committee (HJ-V, JM), Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences (SS-G), Tabriz University of Medical Sciences, Tabriz, Iran
- Cardiovascular Research Center (EE), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science (MA), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Cardiology, Shohada Hospital, Urmia University of Medical Sciences, Urmia, Iran (MHS-M)
| | - Mohammad Alizadeh
- Student Research Committee (HJ-V, JM), Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences (SS-G), Tabriz University of Medical Sciences, Tabriz, Iran
- Cardiovascular Research Center (EE), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science (MA), Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Cardiology, Shohada Hospital, Urmia University of Medical Sciences, Urmia, Iran (MHS-M)
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13
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Chen L, Chen X, Li G. Nutritional management after hepatopancreatobiliary surgery. Hepatobiliary Surg Nutr 2021; 10:273-275. [PMID: 33898576 DOI: 10.21037/hbsn-2021-10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Liming Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaowei Chen
- Department of Surgery, People's Hospital of Jingning She Autonomous County, Lishui, China
| | - Gu Li
- Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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14
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Zhang W, Zhang B, Chen XP. Adjuvant treatment strategy after curative resection for hepatocellular carcinoma. Front Med 2021; 15:155-169. [PMID: 33754281 DOI: 10.1007/s11684-021-0848-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 02/20/2021] [Indexed: 01/27/2023]
Abstract
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
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Affiliation(s)
- Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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15
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Cogo E, Elsayed M, Liang V, Cooley K, Guerin C, Psihogios A, Papadogianis P. Are Supplemental Branched-Chain Amino Acids Beneficial During the Oncological Peri-Operative Period: A Systematic Review and Meta-Analysis. Integr Cancer Ther 2021; 20:1534735421997551. [PMID: 33648360 PMCID: PMC7930658 DOI: 10.1177/1534735421997551] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are essential amino acids involved in immune responses, and may have roles in protein malnutrition and sarcopenia. Furthermore, certain liver diseases have been associated with a decreased Fischer's ratio (BCAAs to aromatic amino acids; phenylalanine, tyrosine, and tryptophan). We aimed to evaluate the safety and efficacy of BCAAs use in patients with cancer undergoing surgery. METHODS MEDLINE, Embase, and CENTRAL were searched (inception to July 24, 2020) for randomized controlled trials (RCTs) and comparative observational studies in English evaluating BCAAs (alone or in combinations) during the oncological peri-operative period. Study selection, data extraction, and quality appraisal were done in duplicate. RCT risk-of-bias was appraised using Cochrane Risk-of-Bias tool, and observational studies' quality assessment was conducted with Newcastle-Ottawa Scale. Meta-analyses were conducted when appropriate. RESULTS 20 articles were included comprising 13 RCTs and 6 observational cohort studies in 7 reports and 2019 total participants overall. Among 13 RCTs, 77% involved liver cancer. Methodological study quality scored substantial risk-of-bias across most RCTs. Meta-analysis of RCTs found a 38% decreased risk of post-operative infections in BCAAs group compared to controls (RR = 0.62; 95% CI = 0.44 to 0.87; P = .006; number of RCTs, k = 6; total sample size, N = 389; I2 = 0%). BCAAs were also found to be beneficial for ascites (RR = 0.55; 95% CI = 0.35 to 0.86; P = .008; k = 4; N = 296; I2 = 0%), body weight (MD = 3.24 kg; 95% CI = 0.44 to 6.04; P = .02; k = 3; N = 196; I2 = 24%), and hospitalization length (MD = -2.07 days; 95% CI = -3.97 to -0.17; P = .03; k = 5; N = 362; I2 = 59%). No differences were found between BCAAs and controls for mortality, recurrence, other post-operative complications (liver failure, edema, pleural effusion), blood loss, quality of life, ammonia level, and prothrombin time. No serious adverse events were related to BCAAs; however, serious adverse events were reported due to intravenous catheters. No safety concerns from observational studies were identified. CONCLUSIONS Branched-chain amino acids during the oncological surgical period demonstrated promise in reducing important post-operative morbidity from infections and ascites compared to controls. Blinded, placebo-controlled confirmatory trials of higher methodological quality are warranted, especially using oral, short-term BCAAs-enriched supplements within the context of recent ERAS programs. PROSPERO REGISTRATION CRD42018086168.
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Affiliation(s)
- Elise Cogo
- Canadian College of Naturopathic Medicine, Toronto, ON, Canada
| | - Mohamed Elsayed
- Canadian College of Naturopathic Medicine, Toronto, ON, Canada
| | - Vivian Liang
- Canadian College of Naturopathic Medicine, Toronto, ON, Canada
| | - Kieran Cooley
- Canadian College of Naturopathic Medicine, Toronto, ON, Canada.,University of Technology Sydney, Ultimo, Australia.,Pacific College of Health Sciences, San Diego, USA.,Southern Cross University, Lismore, Australia
| | | | - Athanasios Psihogios
- Canadian College of Naturopathic Medicine, Toronto, ON, Canada.,Ottawa Integrative Cancer Centre, Ottawa, ON, Canada
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16
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Abstract
Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.
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17
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Ready-Made Oral Nutritional Supplements Improve Nutritional Outcomes and Reduce Health Care Use-A Randomised Trial in Older Malnourished People in Primary Care. Nutrients 2020; 12:nu12020517. [PMID: 32085537 PMCID: PMC7071441 DOI: 10.3390/nu12020517] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 02/12/2020] [Accepted: 02/14/2020] [Indexed: 11/22/2022] Open
Abstract
Large trials assessing oral nutritional supplements (ONS) and dietary advice (DA) in primary care are lacking. This study examined effects of ONS + DA versus DA on intake, weight, QoL, healthcare use and satisfaction in malnourished free-living older people. Three hundred and eight people (71.5 ± 10.7y) were randomised to receive ONS + DA (n154) or DA (n154) for 12 weeks. At baseline, 4, 8, 12 weeks, intake, weight, QoL, healthcare use and satisfaction were measured. ONS + DA group (mean daily intake ONS 480 kcal; 21 g protein; 80% compliance) had significantly greater total energy and protein intakes (+401 kcal/d, p < 0.001; +15 g/d, p < 0.001) and weight gain (+0.8 kg; p < 0.001) compared to DA. QoL improved in both groups over time with a significant improvement in index with ONS + DA (p = 0.009). Significantly more participants found ONS + DA made a difference for them (p = 0.011), but no differences were found between groups using Euroqol. Compared to DA, healthcare use reduced with ONS + DA, (HCP visits by 34%, emergency admissions 50%, LOS 62%). Acceptability of both interventions was high (ONS 96%, DA 95%), with significantly more participants satisfied with ONS (89%) than DA (73%) (p = 0.009). This trial in primary care indicates that ONS are acceptable, make a difference to patients, significantly improve intake and weight, and reduce health care use with potential savings.
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18
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Fan X, Chen G, Li Y, Shi Z, He L, Zhou D, Lin H. The Preoperative Prognostic Nutritional Index in Hepatocellular Carcinoma After Curative Hepatectomy: A Retrospective Cohort Study and Meta-Analysis. J INVEST SURG 2019; 34:826-833. [PMID: 31818159 DOI: 10.1080/08941939.2019.1698679] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
OBJECTIVE Conflicting results existed about the role of prognostic nutritional index (PNI) for hepatocellular carcinoma (HCC) patients who received curative hepatectomy. The aim of this study is to identify the predictive capacity of PNI for survival after hepatectomy. METHODS Preoperative PNI, neutrophil-to-lymphocyte ratio (NLR), tumor feature and clinical information of 187 patients with HCC from Sir Run Run Shaw hospital were evaluated. We also conducted a meta-analysis of seven cohort studies. RESULTS Our study showed that HCC patients with a low PNI of <45 had a poor recurrence-free survival (RFS) rate (hazard ratio [HR] 1.762, 95% confidence interval [CI] 1.066-2.911, p = 0.027, respectively). The 5-year OS and RFS rates of the high PNI (≥45) vs low PNI (<45) were 76.7% vs 50.1% (p = 0.001) and 47.0% vs 28.9% (p = 0.001), respectively. In HCC TNM I patients (n = 144), a low PNI remained an independent prognostic factor of OS and RFS (HR 2.305, 95% CI 1.008-5.268, p = 0.048; HR 2.122, 95% CI 1.149-3.920, p = 0.016). The 5-year OS and RFS rates of the high PNI vs low PNI were 81.3% vs 62.4% (p = 0.041) and 53.4% vs 45.6% (p = 0.013), respectively. In the pooled analysis, the data showed that a low PNI was significantly associated with poor OS and RFS (HR 2.27, 95% CI 1.03-4.07, p < 0.001 and HR 1.68, 95% CI 1.45-1.94, p < 0.001, respectively). CONCLUSIONS The preoperative PNI was an independent prognostic factor for OS and RFS rates in HCC patients who received hepatectomy.
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Affiliation(s)
- Xiaoxiao Fan
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine and Innovation Center for Minimally Invasive Technique and Device, Zhejiang University, Hangzhou, China
| | - Guoqiao Chen
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine and Innovation Center for Minimally Invasive Technique and Device, Zhejiang University, Hangzhou, China
| | - Yirun Li
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine and Innovation Center for Minimally Invasive Technique and Device, Zhejiang University, Hangzhou, China
| | - Zhaoqi Shi
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine and Innovation Center for Minimally Invasive Technique and Device, Zhejiang University, Hangzhou, China
| | - Lifeng He
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine and Innovation Center for Minimally Invasive Technique and Device, Zhejiang University, Hangzhou, China
| | - Daizhan Zhou
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine and Innovation Center for Minimally Invasive Technique and Device, Zhejiang University, Hangzhou, China.,Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Institute of Medical Genetics, Tongji University, Shanghai, China
| | - Hui Lin
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine and Innovation Center for Minimally Invasive Technique and Device, Zhejiang University, Hangzhou, China
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19
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Lu SD, Li L, Liang XM, Chen W, Chen FL, Fan LL, Ahir BK, Zhang WG, Zhong JH. Updates and advancements in the management of hepatocellular carcinoma patients after hepatectomy. Expert Rev Gastroenterol Hepatol 2019; 13:1077-1088. [PMID: 31648568 DOI: 10.1080/17474124.2019.1684898] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
Introduction: The 5-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection or local ablation is up to 70%. Adjuvant therapies to prevent HCC recurrence have been reported but are not currently recommended by EASL or AASLD guidelines. This review examined evidence from randomized controlled trials, meta-analyses and systematic reviews on the safety and efficacy of adjuvant therapies and chemotherapies in HCC patients after resection or local ablation.Areas covered: PubMed was searched through 15 June 2019. Available evidence was assessed based on the GRADE system.Expert commentary: Transarterial chemoembolization is the best adjuvant therapy for HCC patients at high risk of recurrence, antiviral therapy with nucleoside analogs is effective for preventing recurrence of HBV-related HCC, and interferon-α is effective for preventing recurrence of HCV-related HCC. Further studies are needed to clarify the efficacy of adjuvant immune checkpoint inhibitors. Adjuvant sorafenib appears to offer negligible clinical benefit and high risk of adverse effects.
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Affiliation(s)
- Shi-Dong Lu
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lin Li
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xin-Min Liang
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Wu Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Fu-Li Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Lang-Lin Fan
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Bhavesh K Ahir
- Section of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Wan-Guang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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20
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Okabayashi T, Sui K, Mastumoto T, Iwata J, Morita S, Iiyama T, Shimada Y. l-Carnitine Improves Postoperative Liver Function in Hepatectomized Patients. JPEN J Parenter Enteral Nutr 2019; 44:823-830. [PMID: 31599019 DOI: 10.1002/jpen.1720] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 08/05/2019] [Accepted: 09/13/2019] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND AIMS The effect of perioperative treatment with l-carnitine in hepatectomized patients is unclear. The objective of the current study is to evaluate the short-term outcomes after liver cancer surgery in patients treated with l-carnitine compared with nontreated patients. METHODS Patients with primary liver malignancies scheduled to undergo a hepatectomy were randomly assigned to receive either perioperative treatment with l-carnitine (carnitine group) or usual intake (control group). The primary endpoint of this study was the short-term outcome after liver surgery. RESULTS The study participants were randomly assigned into 2 groups: 106 patients in the control group and 102 patients in the perioperative l-carnitine supplementation group. The restoration of serum ammonia levels, prothrombin time, and peripheral neutrophil count at 3 days after the operation was significantly faster in the carnitine group than in the control group. Fewer patients in the carnitine group developed grade B posthepatic liver failure, according to the grading system of the International Study Group of Liver Surgery, than patients in the control group (20% vs 76%). The length of hospitalization was significantly shorter in patients in the carnitine group than in those in the control group. CONCLUSIONS We found that perioperative treatment with l-carnitine was significantly better than ordinary treatment in reducing postoperative serum ammonia levels, suggesting that l-carnitine may serve as a pivotal regulator of liver injury and repair and result in shorter postoperative hospitalization (ClinicalTrials.gov trial registration no. NCT03021876).
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Affiliation(s)
- Takehiro Okabayashi
- Department of Gastroenterological Surgery, Kōchi Health Sciences Center, Kōchi, Japan
| | - Kenta Sui
- Department of Gastroenterological Surgery, Kōchi Health Sciences Center, Kōchi, Japan
| | - Takatsugu Mastumoto
- Department of Gastroenterological Surgery, Kōchi Health Sciences Center, Kōchi, Japan
| | - Jun Iwata
- Department of Diagnostic Pathology, Kōchi Health Sciences Center, Kōchi, Japan
| | - Sojiro Morita
- Department of Radiology, Kōchi Health Sciences Center, Kōchi, Japan
| | - Tatsuo Iiyama
- Department of Biostatistics, National Center for Global Health and Medicine, Kōchi, Japan
| | - Yasuhiro Shimada
- Department of Clinical Oncology at Kōchi Health Sciences Center, Kōchi, Japan
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21
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McKay BP, Larder AL, Lam V. Pre-Operative vs. Peri-Operative Nutrition Supplementation in Hepatic Resection for Cancer: A Systematic Review. Nutr Cancer 2019; 71:179-198. [PMID: 30741015 DOI: 10.1080/01635581.2018.1560479] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Despite improvements in safety of hepatic resection post-operative complications occur in up to a half of patients. A systematic review was undertaken to compare the effect of pre-operative and peri-operative nutritional supplementation on post-operative outcomes in patients undergoing hepatic resection for malignancy. Included studies were identified through a search of PubMed (1966 to November 2016), Embase (1947 to November 2016) and the Cochrane Library (1993 to November 2016). Eleven studies involving a total of 725 patients were included in this systematic review. BCAA supplementation in the pre-operative and peri-operative period was reported to reduce the overall complication rate by 26.9% (P = 0.01) in one cohort study while pre-operative immunonutrition was shown to reduce post-operative ascites by 25.4% (P =0.012) in another cohort study without affecting the overall complication rate. Four further studies on enteral supplementation failed to show a benefit with regards to post-operative complications. Post-operative mortality was unaffected by pre-operative and peri-operative BCAA. Both pre-operative and peri-operative nutritional supplementation have shown promising results regarding the post-operative course of patients undergoing hepatic resection for malignancy. No randomized controlled study exists directly comparing pre-operative and peri-operative nutrition and this needs to be focused on in future research.
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Affiliation(s)
- Bartholomew P McKay
- a Department of Surgery , Royal Brisbane and Women's Hospital , Herston , Queensland , Australia.,b School of Medicine , University of Queensland , Herston , Queensland , Australia.,c Discipline of Surgery, School of Medicine , University of Sydney , Camperdown , NSW , Australia
| | - Annabel L Larder
- d School of Medicine , Griffith University , Southport , Queensland , Australia
| | - Vincent Lam
- c Discipline of Surgery, School of Medicine , University of Sydney , Camperdown , NSW , Australia.,e Department of Surgery , Westmead Hospital , New South Wales , Australia
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22
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Current therapies in alleviating liver disorders and cancers with a special focus on the potential of vitamin D. Nutr Metab (Lond) 2018; 15:13. [PMID: 29449867 PMCID: PMC5807831 DOI: 10.1186/s12986-018-0251-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 01/30/2018] [Indexed: 02/06/2023] Open
Abstract
Background Liver dysfunction is a topic of global concern with many advancing therapies being researched. Though vitamin D takes a center place, other therapies especially nutritional are also gaining ground. Vitamin D has gone beyond its role in skeletal disorders by showcasing its associations in other metabolic dysfunctions too. Result Epidemiological evidences show a correlation between the status of vitamin D and different forms of cancer. Vitamin D receptors and alterations in gene expression appear decisive in the development of chronic liver disorders. Nutritional status therefore plays a significant role in avoiding the complications related to liver dysfunctions, making it mandatory in maintaining vitamin D sufficiency in the body. Therapies with omega-3 fatty acids, antioxidants, amino acids, steroids also render benefits which could be further explored. Recent research on the progression of certain forms of liver cancer using vitamin D analogs like Seocalcitol EB 1089 has shown good promise. Conclusion The anti-inflammatory and immuno- regulatory properties of vitamin D makes its analogs, suitable candidates of better choice for the prevention and treatment of liver disorders and cancer.
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23
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Reconsideration of frailty in relation to surgical indication. Gen Thorac Cardiovasc Surg 2017; 66:201-213. [PMID: 29170898 DOI: 10.1007/s11748-017-0869-7] [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: 07/04/2017] [Accepted: 11/04/2017] [Indexed: 10/18/2022]
Abstract
Given that an increasing number of elderly patients are undergoing surgical procedures for a diversity of indications, the concept of frailty is currently being examined in more depth in clinical medicine. Established surgical risk scores designed to predict mortality are mainly focused on general demographic information and clinical factors; however, these do not account for the frailty condition. With vulnerability and low resiliency in the frail elderly, these conventional scores are unable to accurately predict postoperative outcomes including adverse complications, disability, the need for additional rehabilitation, and prolonged length of hospitalization. Over the last decade, it has been demonstrated that frailty is an independent risk factor of surgery and strongly associated with adverse postoperative outcomes and mortality. It is essential today that surgeons assimilate the concept of frailty and the relationship between frailty and surgical outcomes. A preoperative frailty assessment can assist in determining surgical indication and optimal perioperative management, ultimately impacting the postoperative functional state and quality of life. Here we review the validity of preoperative frailty assessments for surgical intervention, possible treatments for frailty, and indicate future directions in this field.
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24
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Kim JM, Sung MK. The Efficacy of Oral Nutritional Intervention in Malnourished Cancer Patients: a Systemic Review. Clin Nutr Res 2016; 5:219-236. [PMID: 27812512 PMCID: PMC5093220 DOI: 10.7762/cnr.2016.5.4.219] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 10/15/2016] [Accepted: 10/26/2016] [Indexed: 12/18/2022] Open
Abstract
Cancer is currently a leading cause of deaths worldwide and the number of new cases is growing rapidly in both, developed and developing countries. Nutritional management during and after cancer treatment affects treatment efficacy and patient quality of life (QOL). This review systemically examined the effect of oral nutritional interventions on nutritional and clinical outcomes in cancer patients. We especially focused on outcomes such as nutritional status indices, immune-associated biochemical markers, and QOL assessments to provide insights on the applicability of different outcomes. A total of 28 papers were selected for systematic review. The nutritional composition of oral nutritional supplements (ONS), outcome measures, and efficacy of the oral nutritional interventions were summarized and discussed. Most ONS contain 1 or more functional components in addition to basic nutrients. Each study used various outcome measures and significant efficacy was observed for a limited number of measures. Nutritional status indices, QOL measures, and the duration of hospital stay improved in about 40% of the studies. One or more markers of immune function and inflammatory responses were improved by ONS in 65% of the selected studies. These results suggest that appropriate use of ONS may be an ideal way to improve treatment efficacy; however, additional intervention trials are required to confirm these findings.
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Affiliation(s)
- Jin-Min Kim
- Department of Food and Nutrition, Sookmyung Women's University, Seoul 04310, Korea
| | - Mi-Kyung Sung
- Department of Food and Nutrition, Sookmyung Women's University, Seoul 04310, Korea
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25
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Kikuchi Y, Hiroshima Y, Matsuo K, Kawaguchi D, Murakami T, Yabushita Y, Endo I, Taguri M, Koda K, Tanaka K. A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma. Ann Surg Oncol 2016; 23:3727-3735. [PMID: 27338747 DOI: 10.1245/s10434-016-5348-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Indexed: 01/15/2023]
Abstract
BACKGROUND Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion. METHOD We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites. RESULTS Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group. CONCLUSION Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].
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Affiliation(s)
- Yutaro Kikuchi
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Yukihiko Hiroshima
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Kenichi Matsuo
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Daisuke Kawaguchi
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Takashi Murakami
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Yasuhiro Yabushita
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masataka Taguri
- Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Keiji Koda
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Kuniya Tanaka
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan. .,Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
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26
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Beppu T, Nitta H, Hayashi H, Imai K, Okabe H, Nakagawa S, Hashimoto D, Chikamoto A, Ishiko T, Yoshida M, Yamashita Y, Baba H. Effect of branched-chain amino acid supplementation on functional liver regeneration in patients undergoing portal vein embolization and sequential hepatectomy: a randomized controlled trial. J Gastroenterol 2015; 50:1197-205. [PMID: 25847401 DOI: 10.1007/s00535-015-1067-y] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 03/10/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Portal vein embolization (PVE) can decrease the resection ratio for major hepatectomy. (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy is useful for evaluating quantitative functional liver volume. Branched chain amino acids (BCAAs) modulate liver function and regeneration. We analyzed the effects of BCAAs, in terms of liver function and regeneration after PVE, in combination with major hepatectomy. METHODS This randomized controlled trial was conducted for patients receiving PVE through to complete hepatectomy from September, 2011 to June, 2013. BCAA granules were added two times a day to a conventional diet in the BCAA administration group (BCAA group). The primary end point was functional liver regeneration of the future remnant liver after PVE followed by hepatic resection. Functional liver regeneration was assessed by the liver uptake value obtained from (99m)Tc-GSA scintigraphy single-photon-emission computed tomography/computed tomography fusion images. The secondary end points were volumetric liver regeneration and changes in liver function and laboratory data. RESULTS A BCAA group (n = 13) and a non-BCAA group (control group; n = 15) were included. The primary end point was partially met: the liver uptake value significantly increased in the BCAA group compared with the control group 6 months after hepatic resection (266.7% vs 77.6%, P = 0.04) and marginally increased after PVE (43.8% vs 17.4%, P = 0.079). Following PVE, the increment of the uptake ratio of the liver to the liver plus heart at 15 min was significantly less in the BCAA group than in the control group (0.0 and 0.01, P = 0.023). CONCLUSIONS BCAA supplementation improved functional liver regeneration and function in patients undergoing PVE followed by major hepatic resection.
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Affiliation(s)
- Toru Beppu
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan.,Department of Multidisciplinary Treatment for Gastroenterological Cancer, Kumamoto University Hospital, Kumamoto, 860-8556, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Morikatsu Yoshida
- Department of Diagnostic Radiology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Yasuyuki Yamashita
- Department of Diagnostic Radiology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, chuo-Ku, Kumamoto, 860-8556, Japan.
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27
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Egger ME, Ohlendorf JM, Scoggins CR, McMasters KM, Martin RCG. Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series. HPB (Oxford) 2015; 17:839-45. [PMID: 26228262 PMCID: PMC4557660 DOI: 10.1111/hpb.12470] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 06/02/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature. METHODS Medline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis. RESULTS Fifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes. CONCLUSION Quality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery.
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Affiliation(s)
- Michael E Egger
- The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Joanna M Ohlendorf
- The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Charles R Scoggins
- The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Kelly M McMasters
- The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Robert C G Martin
- The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, Louisville, KY, USA
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28
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Ciacio O, Voron T, Pittau G, Lewin M, Vibert E, Adam R, Sa Cunha A, Cherqui D, Schielke A, Soubrane O, Scatton O, Salloum C, Azoulay D, Benoist S, Goyer P, Vaillant JC, Hannoun L, Boleslawski E, Agostini H, Samuel D, Castaing D. Interest of preoperative immunonutrition in liver resection for cancer: study protocol of the PROPILS trial, a multicenter randomized controlled phase IV trial. BMC Cancer 2014; 14:980. [PMID: 25523036 PMCID: PMC4302113 DOI: 10.1186/1471-2407-14-980] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Accepted: 11/26/2014] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Malnutrition is an independent risk factor of postoperative morbidity and mortality and it's observed in 20 to 50% of surgical patients. Preoperative interventions to optimize the nutritional status, reduce postoperative complications and enteral nutrition has proven to be superior to the parenteral one. Moreover, regardless of the nutritional status of the patient, surgery impairs the immunological response, thus increasing the risk of postoperative sepsis. Immunonutrition has been developed to improve the immunometabolic host response in perioperative period and it has been proven to reduce significantly postoperative infectious complications and length of hospital stay in patients undergoing elective gastrointestinal surgery for tumors. We hypothesize that a preoperative oral immunonutrition (ORAL IMPACT®) can reduce postoperative morbidity in liver resection for cancer. METHODS/DESIGN Prospective multicenter randomized placebo-controlled double-blind phase IV trial with two parallel treatment groups receiving either study product (ORAL IMPACT®) or control supplement (isocaloric isonitrogenous supplement--IMPACT CONTROL®) for 7 days before liver resection for cancer. A total of 400 patients will be enrolled. Patients will be stratified according to the type of hepatectomy, the presence of chronic liver disease and the investigator center. The main end-point is to evaluate in intention-to-treat analysis the overall 30-day morbidity. Secondary end-points are to assess the 30-day infectious and non-infectious morbidity, length of antibiotic treatment and hospital stay, modifications on total food intake, compliance to treatment, side-effects of immunonutrition, impact on liver regeneration and sarcopenia, and to perform a medico-economic analysis. DISCUSSION The overall morbidity rate after liver resection is 22% to 42%. Infectious post-operative complications (12% to 23%) increase the length of hospital stay and costs and are responsible for a quarter of 30-day mortality. Various methods have been advocated to decrease the rate of postoperative complications but there is no evidence to support or refute the use of any treatment and further trials are required. The effects of preoperative oral immunonutrition in non-cirrhotic patients undergoing liver resection for cancer are unknown. The present trial is designed to evaluate whether the administration of a short-term preoperative oral immunonutrition can reduce postoperative morbidity in non-cirrhotic patients undergoing liver resection for cancer. TRIAL REGISTRATION Clinicaltrial.gov: NCT02041871.
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Affiliation(s)
- Oriana Ciacio
- Centre Hépato-biliaire, Paul Brousse Hospital - APHP, 12-14 Avenue Paul Vaillant Couturier, 94800 Villejuif, France.
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29
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Jeng WJ, Lin CC, Chen WT, Sheen IS, Lin CY, Lin SM. Adjuvant therapy for hepatocellular carcinoma after curative treatment. Dig Dis 2014; 32:747-54. [PMID: 25376293 DOI: 10.1159/000368017] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy in the world. Although resection and various locoregional therapies can achieve eradication or complete ablation of small HCC, HCC recurrence after these therapies is still common. Although candidates for medical ablation usually exhibit compensated hepatic functional status, the frequent recurrence of HCC after successful ablation contributes to short survival. Therefore, attempts to prevent HCC recurrence are essential to prolong survival. Efforts in preventing HCC recurrence after curative therapies include prevention of early recurrence by improving liver immunity and eliminating microscopic tumor foci or micrometastases, and prevention of late recurrence by reducing the hepatitis activity and using antiviral therapies based on viral suppression/eradication. In HCC with vascular invasion, adjuvant transcatheter arterial chemoembolization should be considered to provide better control. Whether the adjuvant use of sorafenib may suppress microscopic tumor foci or micrometastases may be unveiled in the near future. This review article will update the algorithms, novel medication or study drugs in the prevention of HCC after curative therapies.
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Affiliation(s)
- Wen-Juei Jeng
- Division of Hepatology, Liver Research Unit, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taipei, Taiwan, ROC
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30
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Zhong JH, Zhong QL, Li LQ, Li H. Adjuvant and chemopreventive therapies for resectable hepatocellular carcinoma: a literature review. Tumour Biol 2014; 35:9459-9468. [PMID: 25119592 DOI: 10.1007/s13277-014-2443-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Accepted: 08/04/2014] [Indexed: 01/27/2023] Open
Abstract
The recurrence rate of hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR) is very high. Many clinical trials have explored the efficacy of several treatment modalities to prevent recurrence, including adjuvant and chemopreventive therapy, but they have often reported contradictory findings. As a result, most liver guidelines and liver seminars do not unequivocally endorse adjuvant or chemopreventive therapy for HCC patients after potentially curative HR. To examine the available evidence on this question, we comprehensively searched PubMed for controlled studies that included a supportive care or placebo control arm, and we used the GRADE system to classify and assess the results.
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Affiliation(s)
- Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, He Di Rd. #71, Nanning, 530021, People's Republic of China
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31
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Smith MD, McCall J, Plank L, Herbison GP, Soop M, Nygren J. Preoperative carbohydrate treatment for enhancing recovery after elective surgery. Cochrane Database Syst Rev 2014; 2014:CD009161. [PMID: 25121931 PMCID: PMC11060647 DOI: 10.1002/14651858.cd009161.pub2] [Citation(s) in RCA: 142] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Preoperative carbohydrate treatments have been widely adopted as part of enhanced recovery after surgery (ERAS) or fast-track surgery protocols. Although fast-track surgery protocols have been widely investigated and have been shown to be associated with improved postoperative outcomes, some individual constituents of these protocols, including preoperative carbohydrate treatment, have not been subject to such robust analysis. OBJECTIVES To assess the effects of preoperative carbohydrate treatment, compared with placebo or preoperative fasting, on postoperative recovery and insulin resistance in adult patients undergoing elective surgery. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 3), MEDLINE (January 1946 to March 2014), EMBASE (January 1947 to March 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1980 to March 2014) and Web of Science (January 1900 to March 2014) databases. We did not apply language restrictions in the literature search. We searched reference lists of relevant articles and contacted known authors in the field to identify unpublished data. SELECTION CRITERIA We included all randomized controlled trials of preoperative carbohydrate treatment compared with placebo or traditional preoperative fasting in adult study participants undergoing elective surgery. Treatment groups needed to receive at least 45 g of carbohydrates within four hours before surgery or anaesthesia start time. DATA COLLECTION AND ANALYSIS Data were abstracted independently by at least two review authors, with discrepancies resolved by consensus. Data were abstracted and documented pro forma and were entered into RevMan 5.2 for analysis. Quality assessment was performed independently by two review authors according to the standard methodological procedures expected by The Cochrane Collaboration. When available data were insufficient for quality assessment or data analysis, trial authors were contacted to request needed information. We collected trial data on complication rates and aspiration pneumonitis. MAIN RESULTS We included 27 trials involving 1976 participants Trials were conducted in Europe, China, Brazil, Canada and New Zealand and involved patients undergoing elective abdominal surgery (18), orthopaedic surgery (4), cardiac surgery (4) and thyroidectomy (1). Twelve studies were limited to participants with an American Society of Anaesthesiologists grade of I-II or I-III.A total of 17 trials contained at least one domain judged to be at high risk of bias, and only two studies were judged to be at low risk of bias across all domains. Of greatest concern was the risk of bias associated with inadequate blinding, as most of the outcomes assessed by this review were subjective. Only six trials were judged to be at low risk of bias because of blinding.In 19 trials including 1351 participants, preoperative carbohydrate treatment was associated with shortened length of hospital stay compared with placebo or fasting (by 0.30 days; 95% confidence interval (CI) 0.56 to 0.04; very low-quality evidence). No significant effect on length of stay was noted when preoperative carbohydrate treatment was compared with placebo (14 trials including 867 participants; mean difference -0.13 days; 95% CI -0.38 to 0.12). Based on two trials including 86 participants, preoperative carbohydrate treatment was also associated with shortened time to passage of flatus when compared with placebo or fasting (by 0.39 days; 95% CI 0.70 to 0.07), as well as increased postoperative peripheral insulin sensitivity (three trials including 41 participants; mean increase in glucose infusion rate measured by hyperinsulinaemic euglycaemic clamp of 0.76 mg/kg/min; 95% CI 0.24 to 1.29; high-quality evidence).As reported by 14 trials involving 913 participants, preoperative carbohydrate treatment was not associated with an increase or a decrease in the risk of postoperative complications compared with placebo or fasting (risk ratio of complications 0.98, 95% CI 0.86 to 1.11; low-quality evidence). Aspiration pneumonitis was not reported in any patients, regardless of treatment group allocation. AUTHORS' CONCLUSIONS Preoperative carbohydrate treatment was associated with a small reduction in length of hospital stay when compared with placebo or fasting in adult patients undergoing elective surgery. It was found that preoperative carbohydrate treatment did not increase or decrease postoperative complication rates when compared with placebo or fasting. Lack of adequate blinding in many studies may have contributed to observed treatment effects for these subjective outcomes, which are subject to possible biases.
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Affiliation(s)
- Mark D Smith
- Southland HospitalDepartment of General SurgeryKew RoadInvercargillNew Zealand9840
| | - John McCall
- Dunedin School of Medicine, University of OtagoDepartment of Surgical SciencesPO Box 913DunedinNew Zealand9054
| | - Lindsay Plank
- University of AucklandDepartment of SurgeryPrivate Bag 92019AucklandNew Zealand1142
| | - G Peter Herbison
- Dunedin School of Medicine, University of OtagoDepartment of Preventive & Social MedicinePO Box 913DunedinNew Zealand9054
| | - Mattias Soop
- Salford Royal NHS Foundation TrustDepartment of SurgeryStott LaneSalfordUK
| | - Jonas Nygren
- Institution of Clinical Sciences at Danderyds HospitalCentre for Gastrointestinal Disease, Ersta Hospital and Karolinska InstitutetStockholmSweden
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Sun Y, Yang Z, Tan H. Perioperative nutritional support and fluid therapy in patients with liver diseases. Hepatobiliary Surg Nutr 2014; 3:140-8. [PMID: 25019075 DOI: 10.3978/j.issn.2304-3881.2014.04.05] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Accepted: 03/31/2014] [Indexed: 12/13/2022]
Abstract
The prevalence of liver dysfunction and malnutrition is common among patients with obstructive jaundice or cirrhosis, the poor nutrition status in patients with indications for hepatic resection increases the risk of postoperative complications and/or mortality. Hepatic surgery significantly affects body's metabolism and environment. Therefore, it is very important for patients with liver diseases undergoing hepatic surgery to receive essential nutritional support and fluid therapy during perioperative period. There are several principles in nutritional support and fluid therapy that surgeons need to pay attention to, for example, time, nutritional approach, fluid volume, choice of fat emulsions and amino acids. Some issues, such as albumin and plasma application, choice of crystalloid and colloid, liver protective therapy, also need further attention.
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Affiliation(s)
- Yongliang Sun
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Zhiying Yang
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Haidong Tan
- Department of Hepatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
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Abstract
Hepatocellular carcinoma (HCC) is associated with poor prognosis and often recurs even after curative hepatic resection (HR) or radiofrequency ablation (RFA). In fact, recurrence is the most frequent cause of postoperative death in patients with HCC; it can arise through intrahepatic metastasis by the primary tumor or through the emergence of de novo tumors. Even though studies have examined numerous adjuvant therapies and chemotherapies for their ability to prevent recurrence, no consensus recommendations exist about their clinical application. To gain a comprehensive picture of clinical options, we identified 39 randomized controlled trials, involving 4113 participants, which explore the efficacy of adjuvant or chemotherapies to prevent HCC recurrence after potentially curative HR or RFA. The available evidence suggests a significant improvement in recurrence-free survival and overall survival when transarterial chemoembolization is used for patients who are at high risk for recurrence, lamivudine for patients with hepatitis B virus (HBV)-related HCC (>500 copies of HBV DNA/ml), and interferon-α for patients with hepatitis C virus (HCV)-infected HCC. In contrast, available evidence does not definitively establish clinical benefits of interferon-β for patients with HCV-related HCC, interferon-α for patients with HBV-related HCC, or any of the following therapies for patients with HCC: iodine-125 brachytherapy, autologous tumor vaccination, adoptive immunotherapy, or therapy involving acyclic retinoid, vitamin K2 analog, iodine-131-labeled lipiodol, sorafenib, heparanase inhibitor PI-88, or capecitabine. Though the findings of our review should be interpreted with caution because of clinical heterogeneity and small sample size in the included trials, they highlight gaps in the evidence base, and therefore, may guide future research.
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Affiliation(s)
- Jian-Hong Zhong
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University , Nanning 530021 , PR China
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34
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Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Iiyama T, Tokumaru T, Namikawa T, Sugimoto T, Takezaki Y, Maeda H, Kobayashi M, Hanazaki K. Extrahepatic stem cells mobilized from the bone marrow by the supplementation of branched-chain amino acids ameliorate liver regeneration in an animal model. J Gastroenterol Hepatol 2014; 29:870-877. [PMID: 24224518 DOI: 10.1111/jgh.12450] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/28/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS In recent years, bone marrow (BM)-derived stem cell repopulation of injured organs has been increasingly observed; however, the extent to which it occurs and its clinical relevance remain unclear. Here, we investigated on the potential of extrahepatic stem cells to become hepatocytes using the treatment of the oral supplementation of branched-chain amino acids (BCAA). METHODS In the first, Sprague-Dawley (SD) rats were administered BCAA to promote liver regeneration; in the second, syngenic liver transplantations using wild-type SD rats that do not express green fluorescent protein (GFP) as syngenic donors and GFP-transgenic SD rats as recipients to confirm that an extrahepatic source of cells (GFP(+)) could repopulate the transplanted (GFP(-)) liver were performed. RESULTS Treatment of the oral supplementation of BCAA for 2-3 weeks before transplantation to promote liver regeneration resulted in greater than 7 days graft volume, with extensive spotty conversion of a small wild-type graft to the recipient GFP(+) genotype. The treatment by oral supplementation of BCAA resulted in higher levels of CD34+SDF+c-kit+ stem cells in the blood and liver after liver transplantation. Liver repopulation could be achieved with hepatocytes that bone marrow-derived from stem cells proliferated. CONCLUSIONS We have identified extrahepatic stem cell migration from the BM to the injured liver as a mechanism underlying liver regeneration that supports hepatocyte proliferation in diseased liver. Our results suggested that BCAA is able to mobilize a population of BM-derived cells that contribute to hepatic regeneration.
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Affiliation(s)
- Takehiro Okabayashi
- Department of Surgery, Kochi Medical School, Kochi, Japan; Department of Biostatistics, Kochi Medical School, Kochi, Japan
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35
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Tajiri K, Shimizu Y. Branched-chain amino acids in liver diseases. World J Gastroenterol 2013; 19:7620-7629. [PMID: 24282351 PMCID: PMC3837260 DOI: 10.3748/wjg.v19.i43.7620] [Citation(s) in RCA: 127] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Revised: 08/12/2013] [Accepted: 09/15/2013] [Indexed: 02/06/2023] Open
Abstract
Branched chain amino acids (BCAAs) have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro, and are essential for lymphocyte proliferation and dendritic cell maturation. In patients with advanced chronic liver disease, BCAA concentrations are low, whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high, conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients. Based on these basic observations, patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines, with positive effects.
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Meng J, Zhong J, Zhang H, Zhong W, Huang Z, Jin Y, Xu J. Pre-, peri-, and postoperative oral administration of branched-chain amino acids for primary liver cancer patients for hepatic resection: a systematic review. Nutr Cancer 2013; 66:517-522. [PMID: 24033366 DOI: 10.1080/01635581.2013.780628] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Pre-, peri-, and postoperative oral administration of branched-chain amino acids (BCAA) to patients with primary liver cancer (PLC) during hepatic resection (HR) remains controversial. The aim of this systematic review was to evaluate the efficacy and safety of this practice. Seven literature databases were systematically searched for randomized controlled trials (RCTs) that reported pre-, peri-, and postoperative oral administration of BCAA for PLC patients during HR. Three RCTs were included in a meta-analysis in which risk ratios (RRs) and 95% confidence intervals (95% CIs) were calculated. The 2 groups showed similar recurrence rates (RR = 1.03, 95% CI 0.78 to 1.36) and similar overall survival (RR = 0.91, 95% CI 0.71 to 1.18). Adverse events related to oral administration of BCAA were more than the control group, including nausea, vomiting, diarrhea, abdominal distension, abdominal pain, and hypertension. However, all adverse reactions disappeared after symptomatic treatment. The available evidence suggests that although pre-, peri-, and postoperative oral BCAA for patients with PLC is safe, it is of questionable clinical value. More RCTs are warranted to explore this question definitively.
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Affiliation(s)
- Jianyuan Meng
- a Department of Hepatobiliary Surgery , The First Affiliated Hospital of Guangxi Medical University, Nanning, China, and Department of Hepatobiliary Surgery, The Seventh Affiliated Hospital of Guangxi Medical University , Wuzhou , China
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37
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Kawaguchi T, Taniguchi E, Sata M. Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis. Nutr Clin Pract 2013; 28:580-8. [PMID: 23945292 DOI: 10.1177/0884533613496432] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Branched-chain amino acids (BCAAs) constituting of valine, leucine, and isoleucine act as both substrates of proteins and as key regulators for various nutrient metabolisms. Patients with liver cirrhosis frequently lack sufficient BCAAs and therefore suffer from various metabolic disorders. Hepatic encephalopathy (HE) is a severe metabolic disorder with neurologic manifestations such as flapping tremors and coma in patients with liver cirrhosis. In addition, a mild form of HE known as minimal HE (MHE) is an important social issue because it occurs in up to 80% of patients with chronic liver disease and affects prognosis and activities of daily living, possibly resulting in falls and motor vehicle accidents. Although HE/MHE can be caused by various pathological conditions, including in an accumulation of mercaptans, short-chain fatty acids, and alterations in the gut flora, hyperammonemia has also been implicated in an important pathogenesis of HE/MHE. Besides urea cycle of liver, ammonia can be detoxified in the skeletal muscles by the amidation process for glutamine synthesis using BCAAs. Thus, BCAA supplementation may enhance detoxification of ammonia in skeletal muscle and may be a possible therapeutic strategy for HE/MHE. In this review, we summarize the clinical impacts of BCAA supplementation on HE/MHE and discuss possible mechanisms for a BCAA-induced improvement of HE/MHE. Furthermore, we present some modifications of oral BCAA therapy for improvement of efficacy in HE treatment. We also briefly describe pleiotropic benefits of BCAAs on life-threatening events and overall prognosis in patients with liver cirrhosis.
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Affiliation(s)
- Takumi Kawaguchi
- Takumi Kawaguchi, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
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Ichikawa K, Okabayashi T, Maeda H, Namikawa T, Iiyama T, Sugimoto T, Kobayashi M, Mimura T, Hanazaki K. Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study. Surg Today 2013; 43:720-726. [PMID: 22890582 DOI: 10.1007/s00595-012-0288-4] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Accepted: 04/09/2012] [Indexed: 02/06/2023]
Abstract
PURPOSES The long-term outcomes of branched-chain amino acids (BCAA) administration after hepatic resection in patients with hepatocellular carcinoma (HCC) remain unclear. This study assessed the effect of oral supplementation with BCAA on the development of liver tumorigenesis after hepatic resection in HCC patients. METHODS Fifty-six patients were randomly assigned to receive either BCAA supplementation (Livact group, n = 26) or a conventional diet (Control group, n = 30). Twenty-six patients in the BCAA group were treated orally for 2 weeks before and 6 months after hepatic resection. Postoperative tumor recurrence was continuously evaluated in all patients by measuring various clinical parameters. RESULTS There was no significant difference in the overall survival rate between the two patient groups; however, the recurrence rate at 30 months after surgery was significantly better in the Livact group in comparison to the Control group. Interestingly, the tumor markers, such as AFP and PIVKA-II, significantly decreased at 36 months after liver resection in the Livact group in comparison to the Control group. CONCLUSIONS Oral supplementation of BCAA reduces early recurrence after hepatic resection in patients with HCC. This treatment regimen offers potential benefits for clinical use in such patients, even in cases with a well-preserved preoperative liver function.
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Affiliation(s)
- Kengo Ichikawa
- Regenerative Medicine Group, Department of Surgery, Center for Innovative and Translational Medicine, Kochi Medical School, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan
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39
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A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery. Clin Nutr 2013. [DOI: 10.1016/j.clnu.2012.10.011] [Citation(s) in RCA: 230] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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40
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Ichikawa K, Okabayashi T, Shima Y, Iiyama T, Takezaki Y, Munekage M, Namikawa T, Sugimoto T, Kobayashi M, Mimura T, Hanazaki K. Branched-chain amino acid-enriched nutrients stimulate antioxidant DNA repair in a rat model of liver injury induced by carbon tetrachloride. Mol Biol Rep 2012; 39:10803-10810. [PMID: 23053977 DOI: 10.1007/s11033-012-1974-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Accepted: 10/01/2012] [Indexed: 02/08/2023]
Abstract
Oxidative stress (OS) plays an important role in the progression of chronic liver disease including organ injury and hypoalbuminemia. Long-term oral supplementation with branched-chain amino acids (BCAAs) can inhibit liver dysfunction but their role in the prevention of liver fibrosis and injury to the liver is unclear. The aim of this study was to assess how BCAAs preserve liver function from OS. To investigate how BCAAs specifically prevent OS, we evaluated the effect of oral supplementation with BCAAs on OS using a rat liver cirrhosis model. Liver cirrhosis was induced in ten male Sprague-Dawley rats by administering carbon tetrachloride for 12 weeks. Five of the ten carbon tetrachloride-treated rats were assigned to a control group and five to a BCAA group. BCAA-supplementation significantly preserved plasma albumin concentrations and significantly inhibited the occurrence of organ injury as determined by blood chemistry analysis. Hepatic expression of OGG1 mRNA was increased in the BCAA group compared to the control group. In the BCAA group, increased hepatic levels of OGG1 protein were found by western blot. On the other hand, the number of 8-OHdG-positive cells was significantly higher in liver sections taken 1 month after carbon tetrachloride treatment. Furthermore, OGG1-positive cells were significantly increased in the hepatocytes around the central vein. BCAA was found to reduce OS, which could possibly lead to a decrease in the occurrence of hypoalbuminemia and organ injury. Our results indicate that BCAA-enriched nutrients stimulate antioxidant DNA repair in a rat model of liver injury induced by carbon tetrachloride.
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Affiliation(s)
- Kengo Ichikawa
- Regenerative Medicine Group, Center for Innovative and Translational Medicine, Department of Surgery at Kochi Medical School, Kochi University, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan
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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.
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Affiliation(s)
- Lindsay J Wrighton
- Department of Surgery, Loma Linda University, Loma Linda, California, USA
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42
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Masuda T, Shirabe K, Yoshiya S, Matono R, Morita K, Hashimoto N, Ikegami T, Yoshizumi T, Baba H, Maehara Y. Nutrition support and infections associated with hepatic resection and liver transplantation in patients with chronic liver disease. JPEN J Parenter Enteral Nutr 2012; 37:318-26. [PMID: 22898793 DOI: 10.1177/0148607112456041] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Malnutrition is common in liver cirrhotic patients who will undergo liver resection or liver transplantation. A precise evaluation of their nutrition status is thus difficult because of the presence of ascites and the edema caused by their impaired protein synthesis. Both perioperative enteral and parenteral nutrition have benefits in reducing the morbidity and mortality of liver surgery, and in general, oral nutrition supplements are recommended. Branched-chain amino acids (BCAAs) promote protein and glycogen synthesis and regulate immune system function. Synbiotics, a combination of pro- and prebiotics, is reported to enhance immune responses. Oral nutrition support with BCAAs, synbiotics, and an immune-enhancing diet have a beneficial effect on preventing the perioperative infections associated with hepatic resection or liver transplantation.
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Affiliation(s)
- Toshiro Masuda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Abstract
BACKGROUND Weight loss and muscle wasting are commonly found in patients with end-stage liver disease. Since there is an association between malnutrition and poor clinical outcome, such patients (or those at risk of becoming malnourished) are often given parenteral nutrition, enteral nutrition, or oral nutritional supplements. These interventions have costs and adverse effects, so it is important to prove that their use results in improved morbidity or mortality, or both. OBJECTIVES To assess the beneficial and harmful effects of parenteral nutrition, enteral nutrition, and oral nutritional supplements on the mortality and morbidity of patients with underlying liver disease. SEARCH METHODS The following computerised databases were searched: the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, and Science Citation Index Expanded (January 2012). In addition, reference lists of identified trials and review articles and Clinicaltrials.gov were searched. Trials identified in a previous systematic handsearch of Index Medicus were also considered. Handsearches of a number of medical journals, including abstracts from annual meetings, were done. Experts in the field and manufacturers of nutrient formulations were contacted for potential references. SELECTION CRITERIA Randomised clinical trials (parallel or cross-over design) comparing groups of patients with any underlying liver disease who received, or did not receive, enteral or parenteral nutrition or oral nutritional supplements were identified without restriction on date, language, or publication status. Six categories of trials were separately considered: medical or surgical patients receiving parenteral nutrition, enteral nutrition, or supplements. DATA COLLECTION AND ANALYSIS The following data were sought in each report: date of publication; geographical location; inclusion and exclusion criteria; the type of nutritional support and constitution of the nutrient formulation; duration of treatment; any nutrition provided to the controls; other interventions provided to the patients; number, sex, age of the study participants; hospital or outpatient status; underlying liver disease; risks of bias (sequence generation, allocation concealment, blinding, incomplete outcome reporting, intention-to-treat analysis, selective outcome reporting, others (vested interests, baseline imbalance, early stopping)); mortality; hepatic morbidity (development or resolution of ascites or hepatic encephalopathy, occurrence of gastrointestinal bleeding); quality of life scores; adverse events; infections; lengths of stay in the hospital or intensive care unit; costs; serum bilirubin; postoperative complications (surgical trials only); and nutritional outcomes (nitrogen balance, anthropometric measurements, body weight). The primary outcomes of this review were mortality, hepatic morbidity, quality of life, and adverse events. Data were extracted in duplicate; differences were resolved by consensus.Data for each outcome were combined in a meta-analysis (RevMan 5.1). Estimates were reported using risk ratios or mean differences, along with the 95% confidence intervals (CI). Both fixed-effect and random-effects models were employed; fixed-effect models were reported unless one model, but not the other, found a significant difference (in which case both were reported). Heterogeneity was assessed by the Chi(2) test and I(2) statistic. Subgroup analyses were planned to assess specific liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma), acute or chronic liver diseases, and trials employing standard or branched-chain amino acid formulations (for the hepatic encephalopathy outcomes). Sensitivity analyses were planned to compare trials at low and high risk of bias and trials reported as full papers. The following exploratory analyses were undertaken: 1) medical and surgical trials were combined for each nutritional intervention; 2) intention-to-treat analyses in which missing dichotomous data were imputed as best- and worst-case scenarios; 3) all trials were combined to assess mortality; 4) effects were estimated by absolute risk reductions. MAIN RESULTS Thirty-seven trials were identified; only one was at low risk of bias. Most of the analyses failed to find any significant differences. The significant findings that were found were the following: 1) icteric medical patients receiving parenteral nutrition had a reduced serum bilirubin (mean difference (MD) -2.86 mg%, 95% CI -3.82 mg% to -1.89 mg%, 3 trials) and better nitrogen balance (MD 3.60 g/day, 95% CI 0.86 g/day to 6.34 g/day, 1 trial); 2) surgical patients receiving parenteral nutrition had a reduced incidence of postoperative ascites only in the fixed-effect model (RR 0.65, 95% CI 0.48 to 0.87, 2 trials, I(2) = 70%) and one trial demonstrated a reduction in postoperative complications, especially infections (pneumonia in particular); 3) enteral nutrition may have improved nitrogen balance in medical patients (although a combination of the three trials was not possible); 4) one surgical trial of enteral nutrition found a reduction in postoperative complications; and 5) oral nutritional supplements had several effects in medical patients (reduced occurrence of ascites (RR 0.57, 95% CI 0.37 to 0.88, 3 trials), possibly (significant differences only seen in the fixed-effect model) reduced rates of infection (RR 0.49, 95% CI 0.24 to 0.99, 3 trials, I(2) = 14%), and improved resolution of hepatic encephalopathy (RR 3.75, 95% CI 1.15 to 12.18, 2 trials, I(2) = 79%). While there was no overall effect of the supplements on mortality in medical patients, the one low risk of bias trial found an increased risk of death in the recipients of the supplements. Three trials of supplements in surgical patients failed to show any significant differences. No new information was derived from the various subgroup or sensitivity analyses. The exploratory analyses were also unrevealing except for a logical conundrum. There was no difference in mortality when all of the trials were combined, but the trials of parenteral nutrition found that those recipients had better survival (RR 0.53, 95% CI 0.29 to 0.98, 10 trials). Either the former observation represents a type II error or the latter one a type I error. AUTHORS' CONCLUSIONS The data do not compellingly justify the routine use of parenteral nutrition, enteral nutrition, or oral nutritional supplements in patients with liver disease. The fact that all but one of these trials were at high risks of bias even casts doubt on the few benefits that were demonstrated. Data from well-designed and executed randomised trials that include an untreated control group are needed before any such recommendation can be made. Future trials have to be powered adequately to see small, but clinically important, differences.
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Koretz RL, Avenell A, Lipman TO. Nutritional support for liver disease. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2012. [PMID: 22592729 DOI: 10.1002/14651858.cd008344] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Weight loss and muscle wasting are commonly found in patients with end-stage liver disease. Since there is an association between malnutrition and poor clinical outcome, such patients (or those at risk of becoming malnourished) are often given parenteral nutrition, enteral nutrition, or oral nutritional supplements. These interventions have costs and adverse effects, so it is important to prove that their use results in improved morbidity or mortality, or both. OBJECTIVES To assess the beneficial and harmful effects of parenteral nutrition, enteral nutrition, and oral nutritional supplements on the mortality and morbidity of patients with underlying liver disease. SEARCH METHODS The following computerised databases were searched: the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, and Science Citation Index Expanded (January 2012). In addition, reference lists of identified trials and review articles and Clinicaltrials.gov were searched. Trials identified in a previous systematic handsearch of Index Medicus were also considered. Handsearches of a number of medical journals, including abstracts from annual meetings, were done. Experts in the field and manufacturers of nutrient formulations were contacted for potential references. SELECTION CRITERIA Randomised clinical trials (parallel or cross-over design) comparing groups of patients with any underlying liver disease who received, or did not receive, enteral or parenteral nutrition or oral nutritional supplements were identified without restriction on date, language, or publication status. Six categories of trials were separately considered: medical or surgical patients receiving parenteral nutrition, enteral nutrition, or supplements. DATA COLLECTION AND ANALYSIS The following data were sought in each report: date of publication; geographical location; inclusion and exclusion criteria; the type of nutritional support and constitution of the nutrient formulation; duration of treatment; any nutrition provided to the controls; other interventions provided to the patients; number, sex, age of the study participants; hospital or outpatient status; underlying liver disease; risks of bias (sequence generation, allocation concealment, blinding, incomplete outcome reporting, intention-to-treat analysis, selective outcome reporting, others (vested interests, baseline imbalance, early stopping)); mortality; hepatic morbidity (development or resolution of ascites or hepatic encephalopathy, occurrence of gastrointestinal bleeding); quality of life scores; adverse events; infections; lengths of stay in the hospital or intensive care unit; costs; serum bilirubin; postoperative complications (surgical trials only); and nutritional outcomes (nitrogen balance, anthropometric measurements, body weight). The primary outcomes of this review were mortality, hepatic morbidity, quality of life, and adverse events. Data were extracted in duplicate; differences were resolved by consensus.Data for each outcome were combined in a meta-analysis (RevMan 5.1). Estimates were reported using risk ratios or mean differences, along with the 95% confidence intervals (CI). Both fixed-effect and random-effects models were employed; fixed-effect models were reported unless one model, but not the other, found a significant difference (in which case both were reported). Heterogeneity was assessed by the Chi(2) test and I(2) statistic. Subgroup analyses were planned to assess specific liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma), acute or chronic liver diseases, and trials employing standard or branched-chain amino acid formulations (for the hepatic encephalopathy outcomes). Sensitivity analyses were planned to compare trials at low and high risk of bias and trials reported as full papers. The following exploratory analyses were undertaken: 1) medical and surgical trials were combined for each nutritional intervention; 2) intention-to-treat analyses in which missing dichotomous data were imputed as best- and worst-case scenarios; 3) all trials were combined to assess mortality; 4) effects were estimated by absolute risk reductions. MAIN RESULTS Thirty-seven trials were identified; only one was at low risk of bias. Most of the analyses failed to find any significant differences. The significant findings that were found were the following: 1) icteric medical patients receiving parenteral nutrition had a reduced serum bilirubin (mean difference (MD) -2.86 mg%, 95% CI -3.82 mg% to -1.89 mg%, 3 trials) and better nitrogen balance (MD 3.60 g/day, 95% CI 0.86 g/day to 6.34 g/day, 1 trial); 2) surgical patients receiving parenteral nutrition had a reduced incidence of postoperative ascites only in the fixed-effect model (RR 0.65, 95% CI 0.48 to 0.87, 2 trials, I(2) = 70%) and one trial demonstrated a reduction in postoperative complications, especially infections (pneumonia in particular); 3) enteral nutrition may have improved nitrogen balance in medical patients (although a combination of the three trials was not possible); 4) one surgical trial of enteral nutrition found a reduction in postoperative complications; and 5) oral nutritional supplements had several effects in medical patients (reduced occurrence of ascites (RR 0.57, 95% CI 0.37 to 0.88, 3 trials), possibly (significant differences only seen in the fixed-effect model) reduced rates of infection (RR 0.49, 95% CI 0.24 to 0.99, 3 trials, I(2) = 14%), and improved resolution of hepatic encephalopathy (RR 3.75, 95% CI 1.15 to 12.18, 2 trials, I(2) = 79%). While there was no overall effect of the supplements on mortality in medical patients, the one low risk of bias trial found an increased risk of death in the recipients of the supplements. Three trials of supplements in surgical patients failed to show any significant differences. No new information was derived from the various subgroup or sensitivity analyses. The exploratory analyses were also unrevealing except for a logical conundrum. There was no difference in mortality when all of the trials were combined, but the trials of parenteral nutrition found that those recipients had better survival (RR 0.53, 95% CI 0.29 to 0.98, 10 trials). Either the former observation represents a type II error or the latter one a type I error. AUTHORS' CONCLUSIONS The data do not compellingly justify the routine use of parenteral nutrition, enteral nutrition, or oral nutritional supplements in patients with liver disease. The fact that all but one of these trials were at high risks of bias even casts doubt on the few benefits that were demonstrated. Data from well-designed and executed randomised trials that include an untreated control group are needed before any such recommendation can be made. Future trials have to be powered adequately to see small, but clinically important, differences.
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Abstract
Albeit a very large number of experiments have assessed the impact of various substrates on liver regeneration after partial hepatectomy, a limited number of clinical studies have evaluated artificial nutrition in liver resection patients. This is a peculiar topic because many patients do not need artificial nutrition, while several patients need it because of malnutrition and/or prolonged inability to feeding caused by complications. The optimal nutritional regimen to support liver regeneration, within other postoperative problems or complications, is not yet exactly defined. This short review addresses relevant aspects and potential developments in the issue of postoperative parenteral nutrition after liver resection.
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