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BMC Surgery Feb 2020Post-hepatectomy liver failure contributes significantly to postoperative mortality after liver resection. The prediction of the individual risk for liver failure is...
BACKGROUND
Post-hepatectomy liver failure contributes significantly to postoperative mortality after liver resection. The prediction of the individual risk for liver failure is challenging. This review aimed to provide an overview of cytokine and growth factor triggered signaling pathways involved in liver regeneration after resection.
METHODS
MEDLINE and Cochrane databases were searched without language restrictions for articles from the time of inception of the databases till March 2019. All studies with comparative data on the effect of cytokines and growth factors on liver regeneration in animals and humans were included.
RESULTS
Overall 3.353 articles comprising 40 studies involving 1.498 patients and 101 animal studies were identified and met the inclusion criteria. All included trials on humans were retrospective cohort/observational studies. There was substantial heterogeneity across all included studies with respect to the analyzed cytokines and growth factors and the described endpoints.
CONCLUSION
High-level evidence on serial measurements of growth factors and cytokines in blood samples used to predict liver regeneration after resection is still lacking. To address the heterogeneity of patients and potential markers, high throughput serial analyses may offer a method to predict an individual's regenerative potential in the future.
Topics: Animals; Biomarkers; Cytokines; Hepatectomy; Humans; Liver; Liver Regeneration; Postoperative Period
PubMed: 32050952
DOI: 10.1186/s12893-019-0664-8 -
World Journal of Surgical Oncology Dec 2022Several treatments induce liver hypertrophy for patients with liver malignancies but insufficient future liver remnant (FLR). Herein, the aim of this study is to compare... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of different options for liver regeneration of future liver remnant in patients with liver malignancies: a systematic review and network meta-analysis.
BACKGROUND
Several treatments induce liver hypertrophy for patients with liver malignancies but insufficient future liver remnant (FLR). Herein, the aim of this study is to compare the efficacy and safety of existing surgical techniques using network meta-analysis (NMA).
METHODS
We searched PubMed, Web of Science, and Cochrane Library from databases for abstracts and full-text articles published from database inception through Feb 2022. The primary outcome was the efficacy of different procedures, including standardized FLR (sFLR) increase, time to hepatectomy, resection rate, and R0 resection margin. The secondary outcome was the safety of different treatments, including the rate of Clavien-Dindo≥3a and 90-day mortality.
RESULTS
Twenty-seven studies, including three randomized controlled trials (RCTs), three prospective trials (PTs), and twenty-one retrospective trials (RTs), and a total number of 2075 patients were recruited in this study. NMA demonstrated that the Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) had much higher sFLR increase when compared to portal vein embolization (PVE) (55.25%, 95% CI 45.27-65.24%), or liver venous deprivation(LVD) (43.26%, 95% CI 22.05-64.47%), or two-stage hepatectomy (TSH) (30.53%, 95% CI 16.84-44.21%), or portal vein ligation (PVL) (58.42%, 95% CI 37.62-79.23%). ALPPS showed significantly shorter time to hepatectomy when compared to PVE (-32.79d, 95% CI -42.92-22.66), or LVD (-34.02d, 95% CI -47.85-20.20), or TSH (-22.85d, 95% CI -30.97-14.72), or PVL (-43.37d, 95% CI -64.11-22.62); ALPPS was considered as the highest resection rate when compared to TSH (OR=6.09; 95% CI 2.76-13.41), or PVL (OR =3.52; 95% CI 1.16-10.72), or PVE (OR =4.12; 95% CI 2.19-7.77). ALPPS had comparable resection rate with LVD (OR =2.20; 95% CI 0.83-5.86). There was no significant difference between them when considering the R0 marge rate. ALPPS had a higher Clavien-Dindo≥3a complication rate and 90-day mortality compared to other treatments, although there were no significant differences between different procedures.
CONCLUSIONS
ALPPS demonstrated a higher regeneration rate, shorter time to hepatectomy, and higher resection rate than PVL, PVE, or TSH. There was no significant difference between them when considering the R0 marge rate. However, ALPPS developed the trend of higher Clavien-Dindo≥3a complication rate and 90-day mortality compared to other treatments.
Topics: Humans; Liver Regeneration; Network Meta-Analysis; Hepatectomy; Liver; Portal Vein; Liver Neoplasms; Ligation; Embolization, Therapeutic; Thyrotropin; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36527081
DOI: 10.1186/s12957-022-02867-w -
European Journal of Medical Research Jan 2021Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and... (Review)
Review
BACKGROUND
Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and Anderson, such models were created to understand liver regeneration mechanisms to improve outcomes in patients undergoing extensive liver resection for liver cancer or other underlying liver diseases.
METHODS
A systematic search was conducted using Pubmed, gathering publications up to January 2019, which engaged with the mouse model of extended liver resection as a method itself. The results of this search were filtered according to their language, novelty, and relevancy.
RESULTS
The Boolean search found 3741 articles on Pubmed, with 3130 publications remaining when filtered by language and the presence of a full text. In total, 21 of these publications examined the key themes of the animal model described. The mortality varied from 0 to 50% depending on the surgeon's experience and the resection method. The liver resection was mainly performed with classic sutures (14 out of 21 publications) and isoflurane was used for anaesthesia (10 out of 21 publications) in combination with analgesics (buprenorphine or ketamine/xylazine). The most used mouse strain was C57BL/6 (7 of 21 publications) which was on average 11 weeks old with a weight of 23 g.
CONCLUSION
Through the overview, laid out in the selected publications, this paper reviews the shift of the extended liver resection model from rat to the mouse, describes the state of the art in the experimental setting, and discusses the possible limitations and pitfalls. Clearly, the extended liver resection in mice is a reproducible, practical and easy to learn method.
Topics: Animals; Cell Proliferation; Disease Models, Animal; Hepatectomy; Humans; Liver; Liver Neoplasms; Liver Regeneration; Mice
PubMed: 33422147
DOI: 10.1186/s40001-020-00478-3 -
Scientific Reports Jul 2021The pathophysiology of post-hepatectomy liver failure is not entirely understood but is rooted in the disruption of normal hepatocyte regeneration and homeostasis.... (Meta-Analysis)
Meta-Analysis
The pathophysiology of post-hepatectomy liver failure is not entirely understood but is rooted in the disruption of normal hepatocyte regeneration and homeostasis. Current investigations of post-hepatectomy liver failure and regeneration are focused on evaluation of circulating hepatic function parameters (transaminases, cholestasis, and coagulation parameters), volumetry and hepatic hemodynamics. However, identification of biochemical factors associated with regeneration and post hepatectomy liver failure is crucial for understanding the pathophysiology and identification of patients at risk. The objective of the present systematic review was to identify circulating factors associated with liver regeneration and post hepatectomy liver failure in patients undergoing hepatectomy. The quantitative analysis was intended if studies provided sufficient data. Electronic databases (MEDLINE via PubMed, Web of Knowledge, Cochrane Library and WHO International Clinical Trials Registry Platform) were searched for publications on cell signaling factors in liver regeneration and post-hepatectomy liver failure following liver resection in clinical setting. No date restriction was given. No language restriction was used. Studies were assessed using MINORS. This study was registered at PROSPERO (CRD42020165384) prior to data extraction. In total 1953 publications were evaluated for titles and abstracts after exclusion of duplicates. Full texts of 167 studies were further evaluated for inclusion. 26 articles were included in the review and 6 publications were included in the meta-analyses. High levels of serum hyaluronic acid even preoperatively are associated with PHLF but especially increased levels early after resection are predictive of PHLF with high sensitivity and specificity. Postoperative elevation of HA to levels between 100 and 500 ng/ml is increased the risk for PHLF ([OR] = 246.28, 95% [CI]: 11.82 to 5131.83; p = 0.0004) Inteleukin-6 levels show contradicting result in association with organ dysfunction. HGF positively correlates with liver regeneration. Overall, due to heterogeneity, scarcity, observational study design and largely retrospective analysis, the certainty of evidence, assessed with GRADE, is very low. High levels of serum hyaluronic acid show a strong association with PHLF and increased levels after resection are predictive of PHLF with high sensitivity and specificity, even on POD1. Interleukin-6 levels need to be studied further due to contradictive results in association with organ dysfunction. For HGF, no quantitative analysis could be made. Yet, most studies find positive correlation between high HGF levels and regeneration. Prospective studies investigating HGF and other growth factors, hyaluronic acid and interleukins 1 and 6 in correlation with liver regeneration measured sequentially through e.g. volumetry, and liver function parameters, preferably expanding the analysis to include dynamic liver function tests, are needed to sufficiently illustrate the connection between biomolecule levels and clinical outcomes.
Topics: Clinical Trials as Topic; Cytokines; Female; Hepatectomy; Humans; Intercellular Signaling Peptides and Proteins; Liver; Liver Failure; Liver Function Tests; Liver Regeneration; Male; Risk Factors
PubMed: 34215781
DOI: 10.1038/s41598-021-92888-4 -
European Surgical Research. Europaische... 2011METHODS/AIMS: Despite improved preoperative evaluation, surgical techniques and perioperative intensive care, some patients still experience postoperative liver failure... (Review)
Review
UNLABELLED
METHODS/AIMS: Despite improved preoperative evaluation, surgical techniques and perioperative intensive care, some patients still experience postoperative liver failure in part due to insufficient regeneration. The aim of this review is to give the reader a historical synopsis of the major trends in animal research on liver regeneration from the early experiments in 1877 up to modern investigation. A major focus is placed on the translational value of experimental surgery.
METHODS
A systematic review of the English literature published in Medline was undertaken with the search words 'pig, porcine, dog, canine, liver regeneration, experimental'.
RESULTS
The evolution of the various models tentatively explaining the process of liver regeneration is described.
CONCLUSIONS
We conclude by emphasizing the importance of large-animal surgical research on liver regeneration as it offers a more integrated, systemic biological understanding of this complex process. Furthermore, in our opinion, a closer collaboration between the hepatologist, liver surgeon/transplant surgeon and the laboratory scientist may advance clinically relevant research in liver regeneration.
Topics: Animals; Energy Metabolism; Hemodynamics; Humans; Intercellular Signaling Peptides and Proteins; Liver; Liver Circulation; Liver Regeneration; Models, Animal; Oxygen
PubMed: 21135558
DOI: 10.1159/000321361 -
Cureus Apr 2022The incidence of liver disease increases throughout the years due to many lifestyle factors; thus, the only definite treatment available for chronic liver disease is a... (Review)
Review
The incidence of liver disease increases throughout the years due to many lifestyle factors; thus, the only definite treatment available for chronic liver disease is a liver transplant. However, the liver has a natural ability to repair itself and regenerate its hepatic tissue from stem cells. It is hypothesized that by inducing the liver with specific growth factors and cytokines such as interleukin 6 (IL-6) compared to general growth factors like growth differentiation factor 15 (GDF-15), it can regenerate, decreasing the need for liver transplant procedures. MEDLINE, the Journal of Hepatology, and Google Scholar were used to find articles. Various studies, including epidemiological studies dated from the year 2000 and greater, were used for the introduction. The results used only randomized control trials, experimental studies, and primary articles published since 2000. This compared the results of manipulating variables to determine the effects of hepatic regeneration by either specific hepatocyte growth factors or general growth factors like GDF-15. A total of 10 collected studies showed increased levels of gene expression and function, improved gross morphology, and histological appearance of the liver when induced by cytokines and specific growth factors versus general growth factors. Overall, the hypothesis was proven. The effects of GDF-15 were not significant compared to the effects of hepatocyte-specific growth factors and cytokines like IL-6 because they have two different effects on the liver after liver injury. Future studies should investigate this topic on the human hepatic regenerative ability, plus compare the effects of general growth factors like GDF-15 and specific hepatocyte growth factors and cytokines such as IL-6 in human liver tissue.
PubMed: 35651436
DOI: 10.7759/cureus.24539 -
HPB : the Official Journal of the... Mar 2022Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has expanded and spearheaded development in hepatobiliary surgery. Monosegment-ALPPS... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has expanded and spearheaded development in hepatobiliary surgery. Monosegment-ALPPS tests liver regeneration limits and may present as the last feasible curative treatment option.
METHODS
Electronic databases (MEDLINE, Web of Science, Google Scholar, Cochrane Library and WHO International Clinical Trials Registry Platform) were searched for publications on mono-ALPPS using a predefined strategy without date or language restrictions. Individual patient data was extracted and analyzed.
RESULTS
237 publications were identified. 19 patients were identified to have undergone mono-ALPPS. Primarily, mono-ALPPS has been utilized as curative treatment for CRLM (17 of 19 cases). Successful mono-ALPPS was possible in FLR above 8% SLV. All patients received either chemotherapy alone or in combination with radiotherapy prior to surgery. 8 of 19 patients experienced PHLF grade A or B. There was no in-hospital mortality described. Recurrent disease has occurred in 7 of 19 patients and 3 have died during follow-up.
CONCLUSION
Mono-ALPPS is an experimental procedure that provides a reasonably safe opportunity to curatively treat extensive liver malignancies in patients with FLR as low as 8% SLV. PHLF is the most prevalent complication in mono-ALPPS. Mono-ALPPS should be evaluated in a multicentral study setting.
Topics: Hepatectomy; Humans; Ligation; Liver; Liver Neoplasms; Liver Regeneration; Portal Vein; Treatment Outcome
PubMed: 34330644
DOI: 10.1016/j.hpb.2021.06.427 -
Theranostics 2022In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes... (Review)
Review
In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes including cell proliferation, immune regulation, angiogenesis and tissue repair, have emerged as one of the most attractive nanotherapeutics for regenerative medicine. Herein we provide a systematic review of the latest progress of EVs for regenerative applications. Firstly, we will briefly introduce the biogenesis, function and isolation technology of EVs. Then, the underlying therapeutic mechanisms of the native unmodified EVs and engineering strategies of the modified EVs as regenerative entities will be discussed. Subsequently, the main focus will be placed on the tissue repair and regeneration applications of EVs on various organs including brain, heart, bone and cartilage, liver and kidney, as well as skin. More importantly, current clinical trials of EVs for regenerative medicine will also be briefly highlighted. Finally, the future challenges and insightful perspectives of the currently developed EV-based nanotherapeutics in biomedicine will be discussed. In short, the bioactive EV-based nanotherapeutics have opened new horizons for biologists, chemists, nanoscientists, pharmacists, as well as clinicians, making possible powerful tools and therapies for regenerative medicine.
Topics: Extracellular Vesicles; Kidney; Nanoparticles; Regenerative Medicine; Wound Healing
PubMed: 35836815
DOI: 10.7150/thno.72812 -
HPB : the Official Journal of the... May 2014Major hepatic resection is now performed frequently and with relative safety, but is accompanied by significant pathophysiological changes. The aim of this review is to... (Review)
Review
OBJECTIVES
Major hepatic resection is now performed frequently and with relative safety, but is accompanied by significant pathophysiological changes. The aim of this review is to describe these changes along with interventions that may help reduce the risk for adverse outcomes after major hepatic resection.
METHODS
The MEDLINE, EMBASE and CENTRAL databases were searched for relevant literature published from January 2000 to December 2011. Broad subject headings were 'hepatectomy/', 'liver function/', 'liver failure/' and 'physiology/'.
RESULTS
Predictable changes in blood biochemistry and coagulation occur following major hepatic resection and alterations from the expected path indicate a complicated course. Susceptibility to sepsis, functional renal impairment, and altered energy metabolism are important sequelae of post-resection liver failure.
CONCLUSIONS
The pathophysiology of post-resection liver failure is difficult to reverse and thus strategies aimed at prevention are key to reducing morbidity and mortality after liver surgery.
Topics: Animals; Blood Coagulation; Energy Metabolism; Hepatectomy; Humans; Liver; Liver Failure; Liver Regeneration; Risk Factors; Treatment Outcome
PubMed: 23991862
DOI: 10.1111/hpb.12164 -
Annals of Hepatology 2015Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that... (Meta-Analysis)
Meta-Analysis Review
Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that granulocyte-colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G-CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G-CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable.
Topics: Acute-On-Chronic Liver Failure; Cause of Death; Chi-Square Distribution; Disease Progression; Filgrastim; Humans; Multiple Organ Failure; Odds Ratio; Risk Assessment; Risk Factors; Severity of Illness Index; Survival Analysis; Time Factors; Treatment Outcome
PubMed: 26256891
DOI: No ID Found