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Veterinary Surgery : VS Jul 2022To provide a systematic assessment of the efficacy of preoperative skin asepsis using chlorhexidine versus povidone-iodine based protocols for surgical site infection... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To provide a systematic assessment of the efficacy of preoperative skin asepsis using chlorhexidine versus povidone-iodine based protocols for surgical site infection (SSI) prevention in veterinary surgery.
STUDY DESIGN
Systematic meta-analytical review according to PRISMA-P guidelines.
SAMPLE POPULATION
Studies comparing preoperative skin asepsis protocols using chlorhexidine versus povidone-iodine in veterinary surgery identified by systematic search between 1990 and 2020.
METHODS
A search using MEDLINE/Pubmed, Web of Science and CAB Abstracts was performed, followed by secondary searches of Google Scholar, Proquest Dissertation and Theses, and relevant bibliographic articles. Primary and secondary outcome measures were the efficacy of skin asepsis protocols using chlorhexidine versus povidone-iodine on SSI incidence and skin bacterial colonization, respectively. A meta-analysis was performed with a random-effect model, with effect size calculated as risk ratio (RR) or mean standard deviation (MSD) with 95% CI. Statistical significance was set at P < .05.
RESULTS
Among 1067 publications that met the initial search criteria, 9 relevant studies were eligible for analysis. No difference in the incidence of postoperative SSI or skin bacterial colonization between preoperative asepsis protocols using chlorhexidine versus povidone-iodine was found. Insufficient information and detail were frequent among studies and precluded a clear assessment of bias.
CONCLUSION
This study showed that asepsis protocols using chlorhexidine were comparable to povidone-iodine in preventing postoperative SSI and reducing skin bacterial colonization.
CLINICAL SIGNIFICANCE
Given the limitations of the studies that were included in terms of both quality and quantity, more high-quality randomized controlled trials are needed to confirm these conclusions.
Topics: Animals; Anti-Infective Agents, Local; Asepsis; Chlorhexidine; Clinical Protocols; Ethanol; Meta-Analysis as Topic; Povidone-Iodine; Preoperative Care; Surgery, Veterinary; Surgical Wound Infection
PubMed: 35437786
DOI: 10.1111/vsu.13810 -
The Cochrane Database of Systematic... Jul 2019At the end of 2016, 145 countries reported to the World Health Organization (WHO) over 173,000 new cases of leprosy worldwide. In the past 20 years, over 16 million... (Review)
Review
BACKGROUND
At the end of 2016, 145 countries reported to the World Health Organization (WHO) over 173,000 new cases of leprosy worldwide. In the past 20 years, over 16 million people have been treated for leprosy globally. The condition's main complications are injuries and ulceration caused by sensory loss from nerve damage. In this review we explored interventions to prevent or treat secondary damage to the skin in people affected by leprosy (Hansen's disease). This is an update of a Cochrane Review published in 2008.
OBJECTIVES
To assess the effects of education, information, self-care programmes, dressings, skin care, footwear and other measures for preventing and healing secondary damage to the skin in persons affected by leprosy.
SEARCH METHODS
We updated our searches of the following databases up to July 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, and CINAHL. We also searched five trial registers, three grey literature databases, and the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs or quasi-RCTs or randomised cross-over trials involving anyone with leprosy and potential damage to peripheral nerves who was treated with any intervention designed to prevent damage, heal existing ulcers, and prevent development of new ulcers. Eligible comparisons were usual care, no interventions, or other interventions (e.g. other types of dressings or footwear).
DATA COLLECTION AND ANALYSIS
We adhered to standard methodological procedures expected by Cochrane. Primary outcomes were prevention of ulcer(s), healing of existing ulcer(s) and adverse events. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 14 trials (854 participants). Eleven studies reported on gender (men: 472, women: 157). Participant age varied from 18 to 74 years. Most participants had a single, mainly non-infected, wound on one foot, which had been there for less than a year. Only seven studies reported whole study duration (there was no follow-up post-treatment), which was on average six months (range: 1 to 12 months). The studies were conducted in Brazil, Ethiopia, Egypt, Indonesia, Mexico, South Korea, and India. Many 'Risk of bias' assessments were rated as unclear risk due to limited information. Six studies had high risk of bias in at least one domain, including selection and attrition bias.Thirteen studies evaluated different interventions for treating existing ulcers, one of them also evaluated prevention of new ulcers. One study aimed to prevent skin changes, such as cracking and fissures. Investigated interventions included: laser therapy, light-emitting diode (LED), zinc tape, intralesional pentoxifylline, pulsed magnetic fields, wax therapy, ketanserin, human amniotic membrane gel, phenytoin, plaster shoes, and footwear.We are uncertain about the following key results, as the certainty of evidence is very low. All time points were measured from baseline.Three studies compared zinc tape versus other interventions and reported results in favour of zinc tape. One study compared zinc tape versus magnesium sulphate: at one month the number of healed ulcers and reduction in mean ulcer area was higher with zinc tape (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.43 to 9.21, and mean difference (MD) -14.30 mm², 95% CI -26.51 to -2.09, respectively, 28 participants). Another study compared zinc tape and povidone iodine and found that even though there was a greater reduction in ulcer area after six weeks of treatment with zinc tape, there was no clear difference due to the wide 95% CI (MD 128.00 mm², 95% CI -110.01 to 366.01; 38 participants). The third study (90 participants) compared adhesive zinc tape with gauze soaked in Eusol, and found the healing time for deep ulcers was less compared to zinc tape: 17 days (95% CI 12 to 20) versus 30 days (95% CI 21 to 63). Adverse events were only collected in the study comparing zinc tape with gauze soaked in Eusol: there were no signs of skin sensitisation in either group at two months.Two studies compared topical phenytoin versus saline dressing and reported results in favour of phenytoin. One study reported a greater mean percentage reduction of ulcer area after four weeks with phenytoin 2% (MD 39.30%, 95% CI 25.82 to 52.78; 23 participants), and the other study reported a greater mean percentage reduction of ulcer volume (16.60%) after four weeks with phenytoin (95% CI 8.46 to 24.74; 100 participants). No adverse events were observed with either treatment during the four-month treatment period (2 studies, 123 participants). Prevention of ulcers was not evaluated in these nor the zinc studies, as the interventions were not for preventative use.Two studies compared protective footwear (with or without self-care) with either 1) polyvinyl chloride (PVC) boots, or 2) pulsed magnetic fields plus self-care and protective footwear. In the study comparing canvas shoes versus PVC boots, none of the 72 participants with scars at the start of the study developed new ulcers over one-year follow-up. Healing of ulcers was assessed in 38 participants from this study, but we are unclear if there is a difference between groups. In the study comparing pulsed magnetic fields (in addition to self-care and protective footwear) to only self-care and footwear in 33 participants, we are uncertain if the mean volume of ulcers at four to five weeks' follow-up was different between groups; this study did not evaluate the prevention of ulcers. Information for adverse events was only reported in the study comparing canvas shoes with PVC boots; the authors stated that the PVC boots could become hot in strong sunlight and possibly burn the feet.
AUTHORS' CONCLUSIONS
Based on the available evidence, we could not draw firm conclusions about the effects of the included interventions. The main evidence limitations were high or unclear risk of bias, including selection, performance, detection, and attrition bias; imprecision due to few participants in the studies; and indirectness from poor outcome measurement and inapplicable interventions. Future research should clearly report important outcomes, such as adverse events, and assess widely available interventions, which should include treatments aimed at prevention. These trials should ensure allocation concealment, blinding, and an adequate sample size.
PubMed: 31425632
DOI: 10.1002/14651858.CD012235.pub2 -
BJS Open Sep 2022A combination of chlorhexidine gluconate and alcohol (CHG-alcohol) is recommended for surgical skin preparation to prevent surgical site infection (SSI). Although more... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A combination of chlorhexidine gluconate and alcohol (CHG-alcohol) is recommended for surgical skin preparation to prevent surgical site infection (SSI). Although more than 1 per cent CHG-alcohol is recommended to prevent catheter-related bloodstream infections, there is no consensus regarding the concentration of the CHG compound for the prevention of SSI.
METHODS
A systematic review and meta-analysis was performed. Four electronic databases were searched on 5 November 2020. SSI rates were compared between CHG-alcohol and povidone-iodine (PVP-I) according to the concentration of CHG (0.5 per cent, 2.0 per cent, 2.5 per cent, and 4.0 per cent).
RESULTS
In total, 106 of 2716 screened articles were retrieved for full-text review. The risk ratios (RRs) of SSI for 0.5 per cent (6 studies) and 2.0 per cent (4 studies) CHG-alcohol were significantly lower than those for PVP-I (RR = 0.71, 95 per cent confidence interval (c.i.) 0.52 to 0.97; RR = 0.52, 95 per cent c.i 0.31 to 0.86 respectively); however, no significant difference was observed in the compounds with a CHG concentration of more than 2.0 per cent.
CONCLUSIONS
This meta-analysis is the first study that clarifies the usefulness of an alcohol-based CHG solution with a 0.5 per cent or higher CHG concentration for surgical skin preparation to prevent SSI.
Topics: Anti-Infective Agents, Local; Chlorhexidine; Ethanol; Humans; Povidone-Iodine; Surgical Wound Infection
PubMed: 36124902
DOI: 10.1093/bjsopen/zrac111 -
BMC Musculoskeletal Disorders Aug 2022The greater likelihood of morbidity, mortality, length of hospital stays and poorer long-term outcomes as a result of surgical site infections secondary to spinal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The greater likelihood of morbidity, mortality, length of hospital stays and poorer long-term outcomes as a result of surgical site infections secondary to spinal surgery makes prophylactic measures an imperative focus. Therefore, the aim of this review was to evaluate the available research related to the efficacy of different intraoperative irrigation techniques used in spinal surgery for surgical site infection (SSI) prophylaxis.
METHODS
We performed a comprehensive search using Ovid Medline, EMBASE, Web of Science and the Cochrane library pertaining to this topic. Our meta-analysis was conducted according to PRISMA guidelines. The inclusion criteria consist of spine surgeries with intraoperative use of any wound irrigation technique, comparison groups with a different intraoperative irrigation technique or no irrigation, SSI identified with bacterial cultures or clinically in the postoperative period, reported SSI rates. Data extracted from eligible studies included, but was not limited to, SSI rates, irrigation technique and control technique. Exclusion criteria consist of articles with no human subjects, reviews, meta-analyses and case control studies and no details about SSI identification or rates. Pooled risk ratios were calculated. A meta-analysis was performed with a forest plot to determine risk estimates' heterogeneity with I index, Q-statistic, and p value under a random-effects model. Funnel plot was used to assess publication bias. All databases were last checked on January, 2022. PROBAST tool was used to assess both risk of bias and applicability concerns.
RESULTS
After reviewing 1494 titles and abstracts, 18 articles met inclusion criteria. They included three prospective randomized-controlled trials, 13 retrospective cohort studies, two prospective cohort studies. There were 54 (1.8%) cases of SSIs in the povidone-iodine irrigation group (N = 2944) compared to 159 (4.6%) in the control group (N = 3408). Using intraoperative povidone-iodine wound irrigation produced an absolute risk reduction of 2.8%. Overall risk ratio was 0.32 (95% CI 0.20-0.53, p < 0.00001). In a global analysis, study heterogeneity and synthesizing mostly retrospective data were primary limitations.
CONCLUSION
The most evidence exists for povidone-iodine and has Level 2 evidence supporting SSI reduction during spinal surgery. Other antiseptic solutions such as dilute chlorhexidine lack published evidence in this patient population which limits the ability to draw conclusions related to its use in spinal surgery.
LEVEL OF EVIDENCE
II - Systematic Review with Meta-Analysis.
Topics: Humans; Povidone-Iodine; Prospective Studies; Retrospective Studies; Surgical Wound Infection; Therapeutic Irrigation
PubMed: 36008858
DOI: 10.1186/s12891-022-05763-2 -
AJNR. American Journal of Neuroradiology Mar 2023Middle meningeal artery embolization is an emerging treatment option for chronic subdural hematomas. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Middle meningeal artery embolization is an emerging treatment option for chronic subdural hematomas.
PURPOSE
Our aim was to assess outcomes following middle meningeal artery embolization by different techniques, including in comparison with traditional surgical methods.
DATA SOURCES
We searched the literature databases from inception to March 2022.
DATA SELECTION
We selected studies reporting outcomes after middle meningeal artery embolization as a primary or adjunctive treatment for chronic subdural hematoma.
DATA ANALYSIS
We analyzed the risk of recurrence of chronic subdural hematoma, reoperation for recurrence or residual hematoma, complications, and radiologic and clinical outcomes using random effects modeling. Additional analyses were performed on the basis of whether middle meningeal artery embolization was used as the primary or adjunct treatment and by embolic agent type.
DATA SYNTHESIS
Twenty-two studies were included with 382 patients with middle meningeal artery embolization and 1373 surgical patients. The rate of subdural hematoma recurrence was 4.1%. Fifty (4.2%) patients underwent a reoperation for a recurrent or residual subdural hematoma. Thirty-six (2.6%) experienced postoperative complications. The rates of good radiologic and clinical outcomes were 83.1% and 73.3%, respectively. Middle meningeal artery embolization was significantly associated with decreased odds of subdural hematoma reoperation (OR = 0.48; 95% CI, 23.4-99.1; = .047) compared with surgery. The lowest rates of subdural hematoma radiologic recurrence, reoperation, and complications were observed among patients receiving embolization with Onyx, whereas good overall clinical outcome occurred most commonly with combined polyvinyl alcohol and coils.
LIMITATIONS
A limitation was the retrospective design of studies included.
CONCLUSIONS
Middle meningeal artery embolization is safe and effective, either as a primary or adjunctive treatment. Treatment using Onyx seems to yield lower rates of recurrence, rescue operation, and complications whereas particles and coils produce good overall clinical outcomes.
Topics: Humans; Hematoma, Subdural, Chronic; Meningeal Arteries; Retrospective Studies; Embolization, Therapeutic; Reoperation
PubMed: 36797028
DOI: 10.3174/ajnr.A7796 -
BioMed Research International 2022This study aimed to assess whether the third-generation PVAS was superior to percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) in treating patients... (Meta-Analysis)
Meta-Analysis
Therapeutic Efficacy of Third-Generation Percutaneous Vertebral Augmentation System (PVAS) in Osteoporotic Vertebral Compression Fractures (OVCFs): A Systematic Review and Meta-analysis.
PURPOSE
This study aimed to assess whether the third-generation PVAS was superior to percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) in treating patients with OVCFs.
METHODS
Databases, including Pubmed, Embase, and Cochrane library, were searched to identify relevant interventional and observational articles in vivo or in vitro comparing the third-generation PVAS to PVP/PKP in OVCFs patients. A meta-analysis was performed under the guidelines of the Cochrane Reviewer's Handbook.
RESULTS
11 in vivo articles involving 1035 patients with 1320 segments of diseased vertebral bodies and 8 in vitro studies enrolling 40 specimens with 202 vertebral bodies were identified. The vivo studies indicated no significant differences were found in visual analog scale (VAS), Oswestry Disability Index (ODI), operation time, or injected cement volume ( > 0.05). The third-generation PVAS was associated with significant improvement in vertebral height and Cobb angle ( < 0.05) and also with a significantly lower risk of cement leakages and new fractures ( < 0.05). The vitro studies suggest that the third-generation PVAS was associated with better anterior vertebral height (AVH) and kyphotic angle (KA) after deflation and cement. No significant differences were found in stiffness or failure load after cement between the two groups ( > 0.05).
CONCLUSION
Based on current evidence, although providing similar improvement in VAS and ODI, the third-generation PVAS may be superior to PVP/PKP in local kyphosis correction, vertebral height maintenance, and adverse events reduction. Further high-quality randomized studies are required to confirm these results.
Topics: Acrylic Resins; Bone Cements; Fractures, Compression; Humans; Kyphoplasty; Kyphosis; Osteoporotic Fractures; Retrospective Studies; Spinal Fractures; Treatment Outcome; Vertebroplasty
PubMed: 35578725
DOI: 10.1155/2022/9637831 -
Value in Health : the Journal of the... Apr 2021Gastrointestinal (GI) bleeding is a common medical emergency associated with significant mortality. Transcatheter arterial embolization first was introduced by Rosch... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Gastrointestinal (GI) bleeding is a common medical emergency associated with significant mortality. Transcatheter arterial embolization first was introduced by Rosch et al as an alternative to surgery for upper GI bleeding. The clinical success in patients with GI bleeding treated with transcatheter arterial embolization previously has been reported. However, there are no cost-effectiveness analyses reported to date. Here we report cost-effectiveness analysis of N-butyl 2-cyanoacrylate glue (NBCA) and ethylene-vinyl alcohol copolymer (Onyx) versus coil (gold standard) for treatment of GI bleeding from a healthcare payer perspective.
METHODS
Fixed-effects modeling with a generalized linear mixed method was used in NBCA and coil intervention arms to determine the pooled probabilities of clinical success and mortality with complications with their confidence intervals, while the Clopper-Pearson model was used for Onyx to determine the same parameters. Models were provided by the "Meta-Analysis with R" software package. A decision tree was built for cost-effectiveness analysis, and Microsoft Excel was used for probabilistic sensitivity analysis. The cost-effective option was determined based on the incremental cost-effectiveness ratio and scatter plots of incremental cost versus incremental quality-adjusted life-years.
RESULTS
Comparing scatter plots and incremental cost-effectiveness ratio results, -$1024 and -$1349 per quality-adjusted life-year for Onyx and N-butyl 2-cyanoacrylate glue, respectively, Onyx was the least expensive and most effective intervention.
CONCLUSION
Onyx was the dominant strategy regardless of threshold values. Our analyses provide a framework for researchers to predict the target clinical effectiveness for early-stage TAE interventions and guide resource allocation decisions.
Topics: Arteries; Catheterization; Cost-Benefit Analysis; Decision Trees; Embolization, Therapeutic; Enbucrilate; Gastrointestinal Hemorrhage; Humans; Monte Carlo Method; Polyvinyls
PubMed: 33840425
DOI: 10.1016/j.jval.2020.10.027 -
European Journal of Vascular and... Aug 2021This study aimed to develop and internally validate risk prediction models for predicting groin wound surgical site infections (SSIs) following arterial intervention and... (Comparative Study)
Comparative Study
Groin Wound Infection after Vascular Exposure (GIVE) Risk Prediction Models: Development, Internal Validation, and Comparison with Existing Risk Prediction Models Identified in a Systematic Literature Review.
OBJECTIVE
This study aimed to develop and internally validate risk prediction models for predicting groin wound surgical site infections (SSIs) following arterial intervention and to evaluate the utility of existing risk prediction models for this outcome.
METHODS
Data from the Groin wound Infection after Vascular Exposure (GIVE) multicentre cohort study were used. The GIVE study prospectively enrolled 1 039 consecutive patients undergoing an arterial procedure through 1 339 groin incisions. An overall SSI rate of 8.6% per groin incision, and a deep/organ space SSI rate of 3.8%, were reported. Eight independent predictors of all SSIs, and four independent predictors of deep/organ space SSIs were included in the development and internal validation of two risk prediction models. A systematic search of the literature was conducted to identify relevant risk prediction models for their evaluation.
RESULTS
The "GIVE SSI risk prediction model" ("GIVE SSI model") and the "GIVE deep/organ space SSI risk prediction model" ("deep SSI model") had adequate discrimination (C statistic 0.735 and 0.720, respectively). Three other groin incision SSI risk prediction models were identified; both GIVE risk prediction models significantly outperformed these other risk models in this cohort (C statistic 0.618 - 0.629; p < .050 for inferior discrimination in all cases).
CONCLUSION
Two models were created and internally validated that performed acceptably in predicting "all" and "deep" groin SSIs, outperforming current existing risk prediction models in this cohort. Future studies should aim to externally validate the GIVE models.
Topics: Aged; Anti-Infective Agents, Local; Area Under Curve; Blood Vessel Prosthesis; Chlorhexidine; Endovascular Procedures; Female; Groin; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Observational Studies as Topic; Povidone-Iodine; Probability; ROC Curve; Regression Analysis; Risk Assessment; Risk Factors; Surgical Wound Infection
PubMed: 34246547
DOI: 10.1016/j.ejvs.2021.05.009 -
Journal of Vascular Surgery Sep 2021The long-term success of endovascular aneurysm repair (EVAR) is limited by complications, most importantly endoleaks. In case of (persistent) type I endoleak (T1EL),...
OBJECTIVE
The long-term success of endovascular aneurysm repair (EVAR) is limited by complications, most importantly endoleaks. In case of (persistent) type I endoleak (T1EL), secondary intervention is indicated to prevent secondary aneurysm rupture. Different treatment options are suggested for T1ELs, such as endo anchors, (fenestrated) cuffs, embolization, or open conversion. Currently, the treatment of T1EL with liquid embolic agents is available; however, results are not yet addressed. This review presents the safety and efficacy of embolization with liquid embolic agents for treatment of T1ELs after EVAR.
METHODS
A systematic literature search was performed for all studies reporting the use of liquid embolic agents as monotherapy for treatment of T1ELs after EVAR. Patient numbers, technical success (successful delivery of liquid embolics in the T1EL) and clinical success (absence of aneurysm related death, endoleak recurrence or additional interventions during follow-up) were examined.
RESULTS
Of 1604 articles, 10 studies met the selection criteria, including 194 patients treated with liquid embolics; 73.2% of the patients were male with a median age of 71 years. The overall technical success was 97.9%. Clinical success was 87.6%. Because the median follow-up was only 13.0 months (range, 1-89 months), data on long-term success are almost absent. Four cases (2.1%) of secondary aneurysm rupture after embolization owing to endoleak recurrence were reported. All ruptures occurred in aneurysms exceeding initial treatment diameter of 70 mm.
CONCLUSIONS
Initial technical success after liquid embolization for T1EL is high, although long-term clinical success rates are lacking. Within this review, the risk of secondary rupture is comparable with untreated T1EL at 2% with a median follow-up of 13 months, regardless of the initial success of embolization. In general, no decrease in secondary aneurysm rupture after embolization of T1EL after EVAR is demonstrated, although the results of late embolization are debated.
Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis Implantation; Dimethyl Sulfoxide; Embolization, Therapeutic; Enbucrilate; Endoleak; Endovascular Procedures; Female; Humans; Male; Polyvinyls; Risk Assessment; Risk Factors; Thrombin; Time Factors; Treatment Outcome
PubMed: 33940072
DOI: 10.1016/j.jvs.2021.03.061 -
Cardiovascular and Interventional... Sep 2021This systematic review was conducted to determine factors that are associated with the degree of hypertrophy of the future liver remnant following portal vein...
This systematic review was conducted to determine factors that are associated with the degree of hypertrophy of the future liver remnant following portal vein embolization. An extensive search on September 15, 2020, and subsequent literature screening resulted in the inclusion of forty-eight articles with 3368 patients in qualitative analysis, of which 18 studies were included in quantitative synthesis. Meta-analyses based on a limited number of studies showed an increase in hypertrophy response when additional embolization of segment 4 was performed (pooled difference of medians = - 3.47, 95% CI - 5.51 to - 1.43) and the use of N-butyl cyanoacrylate for portal vein embolization induced more hypertrophy than polyvinyl alcohol (pooled standardized mean difference (SMD) = 0.60, 95% CI 0.30 to 0.91). There was no indication of a difference in degree of hypertrophy between patients who received neo-adjuvant chemotherapy and those who did not receive pre-procedural systemic therapy(pooled SMD = - 0.37, 95% CI - 1.35 to 0.61), or between male and female patients (pooled SMD = 0.19, 95% CI - 0.12 to 0.50).The study was registered in the International Prospective Register of Systematic Reviews on April 28, 2020 (CRD42020175708).
Topics: Embolization, Therapeutic; Hepatectomy; Humans; Hypertrophy; Liver; Liver Neoplasms; Portal Vein; Retrospective Studies
PubMed: 34142192
DOI: 10.1007/s00270-021-02877-3