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Frontiers in Oncology 2022Functional liver imaging can identify functional liver distribution heterogeneity and integrate it into radiotherapy planning. The feasibility and clinical benefit of...
BACKGROUNDS
Functional liver imaging can identify functional liver distribution heterogeneity and integrate it into radiotherapy planning. The feasibility and clinical benefit of functional liver-sparing radiotherapy planning are currently unknown.
METHODS
A comprehensive search of several primary databases was performed to identify studies that met the inclusion criteria. The primary objective of this study was to evaluate the dosimetric and clinical benefits of functional liver-sparing planning radiotherapy. Secondary objectives were to assess the ability of functional imaging to predict the risk of radiation-induced liver toxicity (RILT), and the dose-response relationship after radiotherapy.
RESULTS
A total of 20 publications were enrolled in descriptive tables and meta-analysis. The meta-analysis found that mean functional liver dose (f-MLD) was reduced by 1.0 Gy [95%CI: (-0.13, 2.13)], standard mean differences (SMD) of functional liver volume receiving ≥20 Gy (fV) decreased by 0.25 [95%CI: (-0.14, 0.65)] when planning was optimized to sparing functional liver (P >0.05). Seven clinical prospective studies reported functional liver-sparing planning-guided radiotherapy leads to a low incidence of RILD, and the single rate meta-analysis showed that the RILD (defined as CTP score increase ≥2) incidence was 0.04 [95%CI: (0.00, 0.11), P <0.05]. Four studies showed that functional liver imaging had a higher value to predict RILT than conventional anatomical CT. Four studies established dose-response relationships in functional liver imaging after radiotherapy.
CONCLUSION
Although functional imaging modalities and definitions are heterogeneous between studies, but incorporation into radiotherapy procedures for liver cancer patients may provide clinical benefits. Further validation in randomized clinical trials will be required in the future.
PubMed: 35785217
DOI: 10.3389/fonc.2022.898435 -
Health Technology Assessment... Dec 2023A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function.
OBJECTIVE
To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews.
REVIEW METHODS
Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research.
RESULTS
Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified ( ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included ( = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials.
LIMITATIONS
Many studies were small and of poor quality. No comparative studies were found for some therapies.
CONCLUSIONS
The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection.
STUDY REGISTRATION
PROSPERO CRD42020221357.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in ; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Carcinoma, Hepatocellular; Ethanol; Liver Neoplasms; Network Meta-Analysis; Prospective Studies; Randomized Controlled Trials as Topic; Ablation Techniques
PubMed: 38149643
DOI: 10.3310/GK5221 -
International Journal of Environmental... May 2021Imaging methods and the most appropriate criteria to be used for detecting and evaluating response to oncological treatments depend on the pathology and anatomical site... (Review)
Review
BACKGROUND
Imaging methods and the most appropriate criteria to be used for detecting and evaluating response to oncological treatments depend on the pathology and anatomical site to be treated and on the treatment to be performed. This document provides a general overview of the main imaging and histopathological findings of electroporation-based treatments (Electrochemotherapy-ECT and Irreversible electroporation-IRE) compared to thermal approach, such as radiofrequency ablation (RFA), in deep-seated cancers with a particular attention to pancreatic and liver cancer.
METHODS
Numerous electronic datasets were examined: PubMed, Scopus, Web of Science and Google Scholar. The research covered the years from January 1990 to April 2021. All titles and abstracts were analyzed. The inclusion criteria were the following: studies that report imaging or histopathological findings after ablative thermal and not thermal loco-regional treatments (ECT, IRE, RFA) in deep-seated cancers including pancreatic and liver cancer and articles published in the English language. Exclusion criteria were unavailability of full text and congress abstracts or posters and different topic respect to inclusion criteria.
RESULTS
558 potentially relevant references through electronic searches were identified. A total of 38 articles met the inclusion criteria: 20 studies report imaging findings after RFA or ECT or IRE in pancreatic and liver cancer; 17 studies report histopathological findings after RFA or ECT or IRE; 1 study reports both imaging and histopathological findings after RFA or ECT or IRE.
CONCLUSIONS
Imaging features are related to the type of therapy administrated, to the timing of re-assessment post therapy and to the imaging technique being used to observe the effects. Histological findings after both ECT and IRE show that the treated area becomes necrotic and encapsulated in fibrous tissue, suggesting that the size of the treated lesion cannot be measured as an endpoint to detect response. Moreover, histology frequently reported signs of apoptosis and reduced vital tissue, implying that imaging criteria, which take into account the viability and not the size of the lesion, are more appropriate to evaluate response to treatment.
Topics: Electroporation; Humans; Liver Neoplasms; Pancreas; Radiofrequency Ablation
PubMed: 34073865
DOI: 10.3390/ijerph18115592 -
Clinical and Molecular Hepatology Jul 2023Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
METHODS
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
RESULTS
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
CONCLUSION
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Liver Neoplasms; Hepatitis B virus; Antiviral Agents; Liver Cirrhosis; Fatty Liver; DNA, Viral
PubMed: 37157776
DOI: 10.3350/cmh.2023.0004 -
World Journal of Surgical Oncology Aug 2023The advantages of parenchymal-sparing resection (PSR) over anatomic resection (AR) of colorectal liver metastases (CRLM) remain controversial. Here, we aim to evaluate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The advantages of parenchymal-sparing resection (PSR) over anatomic resection (AR) of colorectal liver metastases (CRLM) remain controversial. Here, we aim to evaluate their safety and efficacy.
METHODS
A systematic review and meta-analysis of short-term perioperative outcomes and long-term oncological outcomes for PSR and AR were performed by searching Pubmed, Embase, the Cochrane Library and Web of Science databases.
RESULTS
Twenty-two studies were considered eligible (totally 7228 patients: AR, n = 3154 (43.6%) vs. PSR, n = 4074 (56.4%)). Overall survival (OS, HR = 1.08, 95% CI: 0.95-1.22, P = 0.245) and disease-free survival (DFS, HR = 1.09, 95% CI: 0.94-1.28, P = 0.259) were comparable between the two groups. There were no significant differences in 3-year OS, 5-year OS, 3-year DFS, 5-year DFS, 3-year liver recurrence-free survival (liver-RFS) and 5-year liver-RFS. In terms of perioperative outcome, patients undergoing AR surgery were associated with prolonged operation time (WMD = 51.48 min, 95% CI: 29.03-73.93, P < 0.001), higher amount of blood loss (WMD = 189.92 ml, 95% CI: 21.39-358.45, P = 0.027), increased intraoperative blood transfusion rate (RR = 2.24, 95% CI: 1.54-3.26, P < 0.001), prolonged hospital stay (WMD = 1.00 day, 95% CI: 0.34-1.67, P = 0.003), postoperative complications (RR = 2.28, 95% CI: 1.88-2.77, P < 0.001), and 90-day mortality (RR = 3.08, 95% CI: 1.88-5.03, P < 0.001). While PSR surgery was associated with positive resection margins (RR = 0.77, 95% CI: 0.61-0.97, P = 0.024), intrahepatic recurrence (RR = 0.90, 95% CI: 0.82-0.98, P = 0.021) and repeat hepatectomy (RR = 0.64, 95% CI: 0.55-0.76, P < 0.001).
CONCLUSION
Considering relatively acceptable heterogeneity, PSR had better perioperative outcomes without compromising oncological long-term outcomes. However, these findings must be carefully interpreted, requiring more supporting evidence.
TRIAL REGISTRATION
PROSPERO registration number: CRD42023445332.
Topics: Humans; Liver Neoplasms; Hepatectomy; Disease-Free Survival; Colorectal Neoplasms; Treatment Outcome
PubMed: 37553574
DOI: 10.1186/s12957-023-03127-1 -
Hepatology Communications Oct 2023Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous rare congenital cholestatic liver disease. Disease progression might necessitate liver... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous rare congenital cholestatic liver disease. Disease progression might necessitate liver transplantation (LT). The aim of this study was to describe the outcome of PFIC1-4 patients after LT.
METHODS
Electronic databases were searched to identify studies on PFIC and LT. Patients were categorized according to PFIC type, genotype, graft type, age at LT, time of follow-up, and complications and treatment during follow-up.
RESULTS
Seventy-nine studies with 507 patients met inclusion criteria; most patients were classified as PFIC1-3. The median age at LT was 50 months. The overall 5-year patient survival was 98.5%. PFIC1 patients with diarrhea after LT were at significant risk of developing graft steatosis ( p < 0.0001). Meta-analysis showed an efficacy of 100% [95% CI: 73.9%-100%] for surgical biliary diversion to ameliorate steatosis and 94.9% [95% CI: 53.7%-100%] to improve diarrhea (n = 8). PFIC2 patients with bile salt export pump (BSEP)2 or BSEP3-genotype were at significant risk of developing antibody-induced BSEP deficiency (AIBD) ( p < 0.0001), which was reported in 16.2% of patients at a median of 36.5 months after LT. Meta-analysis showed an efficacy of 81.1% [95% CI: 47.5%-100%] for rituximab-based treatment regimens to improve AIBD (n = 18). HCC was detected in 3.6% of PFIC2 and 13.8% of PFIC4 patients at LT.
CONCLUSIONS
Fifty percent of PFIC1 patients develop diarrhea and steatosis after LT. Biliary diversion can protect the graft from injury. PFIC2 patients with BSEP2 and BSEP3 genotypes are at significant risk of developing AIBD, and rituximab-based treatment regimens effectively improve AIBD. PFIC3 patients have no PFIC-specific complications following LT.
Topics: Humans; Child, Preschool; Liver Transplantation; Rituximab; Carcinoma, Hepatocellular; Liver Neoplasms; Fatty Liver; Diarrhea; Cholestasis; Cholestasis, Intrahepatic; Steroid Metabolism, Inborn Errors
PubMed: 37756114
DOI: 10.1097/HC9.0000000000000286 -
HPB : the Official Journal of the... Feb 2022Data on morbidity and mortality following liver resection after radioembolization (Y90) are limited and controversial. Therefore, the perioperative morbidity and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Data on morbidity and mortality following liver resection after radioembolization (Y90) are limited and controversial. Therefore, the perioperative morbidity and mortality of liver resections after Y90 treatment were investigated with systematic review and meta-analysis.
METHODS
A PubMed search was conducted to identify studies of liver resection after previous Y90 treatment. Systematic review and meta-analysis for perioperative morbidity and mortality were perfomed using the 2009 PRISMA guidelines and STATA 16.1 software.
RESULTS
A total of 16 studies reporting on 276 patients who underwent liver resection after Y90 met the inclusion criteria and were included in the meta-analysis. Meta-analysis of 30-day mortality rates yielded pooled mortality of 0.5% (95% CI 0.0-3.2%). Six studies (155 patients) reported a pooled 90-day mortality of 3.0% (95% CI 0.3-7.4%). The median time to resection after Y90 ranged from 2 to 12.5 months in various studies. In all studies where the median resection was undertaken eight or more months after Y90, zero 30-day mortality was reported. A meta-analysis of overall grade 3 or higher morbidity noted a rate of 26% (95% CI 16-37%).
CONCLUSIONS
Liver resection after Y90 may be safe in very well selected patients. Delaying resection after Y90 may further decrease mortality.
Topics: Carcinoma, Hepatocellular; Embolization, Therapeutic; Humans; Liver Neoplasms; Morbidity; Yttrium Radioisotopes
PubMed: 34607769
DOI: 10.1016/j.hpb.2021.08.948 -
Surgery Apr 2023Evaluation of morbidity and mortality after hepatic resection often lacks stratification by extent of resection or diagnosis. Although a liver resection for different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evaluation of morbidity and mortality after hepatic resection often lacks stratification by extent of resection or diagnosis. Although a liver resection for different indications may have technical similarities, postoperative outcomes differ. The aim of this systematic review and meta-analysis was to determine the risk of major complications and mortality after resection of intrahepatic cholangiocarcinoma.
METHODS
Meta-analysis was performed to assess postoperative mortality (in-hospital, 30-, and 90-day) and major complications (Clavien-Dindo grade ≥III).
RESULTS
A total of 32 studies that reported on 19,503 patients were included. Pooled in-hospital, 30-day, and 90-day mortality were 5.9% (95% confidence interval 4.1-8.4); 4.6% (95% confidence interval 4.0-5.2); and 6.1% (95% confidence interval 5.0-7.3), respectively. Pooled proportion of major complications was 22.2% (95% confidence interval 17.7-27.5) for all resections. The pooled 90-day mortality was 3.1% (95% confidence interval 1.8-5.2) for a minor resection, 7.4% (95% confidence interval 5.9-9.3) for all major resections, and 11.4% (95% confidence interval 6.9-18.7) for extended resections (P = .001). Major complications were 38.8% (95% confidence interval 29.5-49) after a major hepatectomy compared to 11.3% (95% confidence interval 5.0-24.0) after a minor hepatectomy (P = .001). Asian studies had a pooled 90-day mortality of 4.4% (95% confidence interval 3.3-5.9) compared to 6.8% (95% confidence interval 5.6-8.2) for Western studies (P = .02). Cohorts with patients included before 2000 had a pooled 90-day mortality of 5.9% (95% confidence interval 4.8-7.3) compared to 6.8% (95% confidence interval 5.1-9.1) after 2000 (P = .44).
CONCLUSION
When informing patients or comparing outcomes across hospitals, postoperative mortality rates after liver resection should be reported for 90-days with consideration of the diagnosis and the extent of liver resection.
Topics: Humans; Liver Neoplasms; Treatment Outcome; Postoperative Complications; Cholangiocarcinoma; Hepatectomy; Bile Duct Neoplasms; Retrospective Studies; Bile Ducts, Intrahepatic
PubMed: 36577599
DOI: 10.1016/j.surg.2022.11.027 -
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 -
European Journal of Medical Research Jul 2023Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC.
METHODS
A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions.
RESULTS
A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63-0.76, I = 84.7%, P < 0.001). Subgroup analysis showed that aspirin significantly reduced the risk of HCC by 19% in Asia (HR = 0.81, 95% CI 0.80-0.82, I = 85.2%, P < 0.001) and by 33% (HR = 0.67, 95% CI 0.61-0.73, I = 43.6%, P = 0.150) in Europe and the U.S with no significant difference. Moreover, in patients with HBV or HCV infection, aspirin reduced 19% and 24% of the risk of HCC, respectively. However, aspirin administration might increase risks of gastrointestinal bleeding in patients with chronic liver disease (HR = 1.14, 95% CI 0.99-1.31, I = 0.0%, P = 0.712). Sensitivity analysis showed no significant difference of results after excluding individual studies, suggesting that the results were robust.
CONCLUSION
Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.
Topics: Humans; Carcinoma, Hepatocellular; Aspirin; Liver Neoplasms; Prospective Studies; Retrospective Studies; Gastrointestinal Hemorrhage
PubMed: 37422691
DOI: 10.1186/s40001-023-01204-5