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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 -
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 -
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 -
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 -
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 -
International Journal of Surgery... Jan 2015Hepatic resection for malignancy is limited by the amount of liver parenchyma left behind. As a result, two-staged hepatectomy and portal vein occlusion (PVO) have... (Review)
Review
INTRODUCTION
Hepatic resection for malignancy is limited by the amount of liver parenchyma left behind. As a result, two-staged hepatectomy and portal vein occlusion (PVO) have become part of the treatment algorithm. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been recently described as a method to stimulate rapid and profound hypertrophy.
MATERIALS AND METHODS
A systematic review of the literature pertaining to ALPPS was undertaken. Peer-reviewed articles relating to portal vein ligation (PVL) and in situ split (ISS) of the parenchyma were included.
RESULTS
To date, ALPPS has been employed for a variety of primary and metastatic liver tumors. In early case series, the perioperative morbidity and mortality was unacceptably high. However with careful patient selection and improved technique, many centers have reported a 0% 90-day mortality. The benefits of ALPPS include hypertrophy of 61-93% over a median 9-14 days, 95-100% completion of the second stage, and high likelihood of R0 resection (86-100%).
DISCUSSION
ALPPS is only indicated when a two-stage hepatectomy is necessary and the future liver remnant (FLR) is deemed inadequate (<30%). Use in patients with poor functional status, or advanced age (>70 years) is cautioned. Discretion should be used when considering this in patients with pathology other than colorectal liver metastases (CRLM), especially hilar tumors requiring biliary reconstruction. Biliary ligation during the first stage and routine lymphadenectomy of the hepatoduodenal ligament should be avoided.
CONCLUSIONS
A consensus on the indications and contraindications for ALPPS and a standardized operative protocol are needed.
Topics: Hepatectomy; Humans; Hypertrophy; Ligation; Liver; Liver Neoplasms; Liver Regeneration; Patient Selection; Portal Vein; Vascular Surgical Procedures
PubMed: 25496851
DOI: 10.1016/j.ijsu.2014.12.008 -
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 -
World Journal of Surgical Oncology Dec 2017It is generally accepted that an insufficient future liver remnant is a major limitation of large-scale hepatectomy for patients with primary hepatocellular carcinoma.... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
It is generally accepted that an insufficient future liver remnant is a major limitation of large-scale hepatectomy for patients with primary hepatocellular carcinoma. Conventional two-stage hepatectomy (TSH) is commonly considered to accelerate future liver regeneration despite its low regeneration rate. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which is characterized by a rapid regeneration, has brought new opportunities.
METHODS
Relevant studies were identified by searching the selected databases up to September 2017. Then, a meta-analysis of regeneration efficiency, complication rate, R0 resection ratio, and short-term outcomes was performed.
RESULTS
Ten studies, comprising 719 patients, were included. The overall analysis showed that ALPPS was associated with a larger hyperplastic volume and a shorter time interval (P < 0.00001) than TSH. ALPPS also exhibited a higher completion rate for second-stage operations (odds ratio, OR 9.50; P < 0.0001) and a slightly higher rate of R0 resection (OR 1.90; P = 0.11). Interestingly, there was no significant difference in 90-day mortality between the two treatments (OR 1.44; P = 0.35).
CONCLUSIONS
These results indicate that compared with TSH, ALPPS possesses a stronger regenerative ability and better facilitates second-stage operations. However, the safety, patient outcomes, and patient selection for ALPPS require further study.
Topics: Carcinoma, Hepatocellular; Hepatectomy; Humans; Ligation; Liver; Liver Neoplasms; Liver Regeneration; Patient Selection; Portal Vein; Postoperative Complications; Prognosis; Treatment Outcome
PubMed: 29258518
DOI: 10.1186/s12957-017-1295-0 -
HPB : the Official Journal of the... Jan 2016Curative liver resection is the treatment of choice for both primary and secondary liver malignancies. However, an inadequate future liver remnant (FLR) frequently... (Review)
Review
BACKGROUND
Curative liver resection is the treatment of choice for both primary and secondary liver malignancies. However, an inadequate future liver remnant (FLR) frequently precludes successful surgery. Portal vein embolization is the gold-standard modality for inducing hypertrophy of the FLR. In recent times, unilobar Yttrium-90 selective internal radiation therapy (SIRT) has been reported to induce hypertrophy of the contralateral, untreated liver lobe. The aim of this study is to review the current literature reporting on contralateral liver hypertrophy induced by unilobar SIRT.
METHODS
A systematic review of the English-language literature between 2000 and 2014 was performed using the search terms "Yttrium 90" OR "selective internal radiation therapy" OR "radioembolization" AND "hypertrophy".
RESULTS
Seven studies, reporting on 312 patients, were included. Two hundred and eighty four patients (91.0%) received treatment to the right lobe. Two hundred and fifteen patients had hepatocellular carcinoma (HCC), 12 had intrahepatic cholangiocarcinoma, and 85 had liver metastases from mixed primaries. Y90 SIRT resulted in contralateral liver hypertrophy which ranged from 26 to 47% at 44 days-9 months. All studies were retrospective in nature, and heterogeneous, with substantial variations relative to pathology treated, underlying liver disease, dosage and delivery of Y90, number of treatment sessions and time to measurement of hypertrophy.
CONCLUSION
Unilobar Y90 SIRT results in significant hypertrophy of the contralateral liver lobe. The rate of hypertrophy seems to be slower than that achieved by other methods.
Topics: Embolization, Therapeutic; Hepatectomy; Humans; Hypertrophy; Liver; Liver Failure; Liver Neoplasms; Liver Regeneration; Organ Size; Radiopharmaceuticals; Risk Factors; Time Factors; Treatment Outcome; Yttrium Radioisotopes
PubMed: 26776845
DOI: 10.1016/j.hpb.2015.07.002 -
Bioscience Trends Oct 2015This meta-analysis aimed to review the regeneration rate of future liver remnant (FLR) and perioperative outcomes after associating liver partition and portal vein... (Comparative Study)
Comparative Study Meta-Analysis Review
A systematic review and meta-analysis of feasibility, safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) versus two-stage hepatectomy (TSH).
This meta-analysis aimed to review the regeneration rate of future liver remnant (FLR) and perioperative outcomes after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and two-stage hepatectomy (TSH). A web search was performed in "MEDLINE", "EMBASE", and "SCIENCE DIRECT" databases using both subject headings (MeSH) and truncated word to identify all the articles published that related to this topic. Pooled risk ratios were calculated for categorical variables and mean differences for continuous variables using the fixed-effects and random-effects models for meta-analysis. Three studies involved 282 patients, of whom 234 were in the TSH group and 48 in the ALPPS group. Morbidity was experienced in 56.3% patients in the ALPPS group and 36.1% in the TSH group. There was a statistical difference (RR = 1.08; Z = 3.24; 95% CI, p = 0.001). Second surgeries were performed successfully in 79.1% patients in the portal vein embolization (PVE) group and 100% in the ALPPS group. There was a statistical difference (Z = 2.48; 95% CI, p = 0.01). The mean regeneration rate of FLR in the ALPPS group was 56.4% compared with 52.8% in the TSH group. There was no statistical difference (95% CI, p = 0.34). So from the outcome of this meta-analysis, TSH had a similar remnant liver regeneration ability compared to ALPPS while the morbidity and mortality rates were relatively low. Cancer progression while waiting for the staged liver resection after portal vein embolization was a drawback for TSH.
Topics: Feasibility Studies; Hepatectomy; Humans; Ligation; Liver Neoplasms; Liver Regeneration; Portal Vein
PubMed: 26559020
DOI: 10.5582/bst.2015.01139