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Surgery Sep 2022Ex situ liver resection and autotransplantation, a surgical technique introduced for managing advanced and unresectable malignant tumors, never became a popular surgical... (Review)
Review
BACKGROUND
Ex situ liver resection and autotransplantation, a surgical technique introduced for managing advanced and unresectable malignant tumors, never became a popular surgical procedure, due mainly to the high incidence of adverse events and postoperative recurrences. This study aims to assess the clinical outcomes of ex situ liver resection and autotransplantation in the currently available literature.
METHODS
The PubMed electronic database was used to retrieve studies that meet the inclusion criteria for the topic.
RESULTS
Twenty-nine studies were included. The mean (range) 90-day mortality rate was 11.6% (0%-50%) and the mean overall survival was 55.8% (12.5%-100.0%). R0 resection was achieved in 100% of cases. In the overall study sample, the maximum tumor size was found to be positively correlated with the 90-day mortality rate (P = .047) and negatively correlated with the overall survival (P = .048). The mean number of total resected segments appeared to be positively correlated with the length of hospital stay (P = .039). In the malignant tumor sample, there was a significant relationship between the maximum tumor size and postoperative liver failure, 90-day mortality rate (P = .027 and P = .034, respectively), and between the mean length of anhepatic phase and mean length of hospital stay (P = .0092).
CONCLUSION
The ex situ liver resection and autotransplantation appears to be a valuable option in selected patients with conventionally unresectable hepatic tumors and normal liver function. However, it was not possible to provide clear and unequivocal recommendations about this procedure. To rectify this, an international database to help surgeons in their decision-making process ought to be established.
Topics: Hepatectomy; Humans; Liver Failure; Liver Neoplasms; Liver Transplantation; Transplantation, Autologous
PubMed: 35791978
DOI: 10.1016/j.surg.2022.04.002 -
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 -
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 -
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 -
Nutrition and Cancer 2021The relationship of dairy consumption and liver cancer risk is still controversial. We conducted a meta-analysis of published cohort and case-control studies to... (Meta-Analysis)
Meta-Analysis
The relationship of dairy consumption and liver cancer risk is still controversial. We conducted a meta-analysis of published cohort and case-control studies to summarize the epidemiologic evidence on the relationship between dairy products consumption and the risk of liver cancer. The literatures were screened from PubMed, EMBASE, and Cochrane Library before May 2020. A total of seven cohort studies and eight case-control studies (5,121 cases) were included. The summary relative risks (RRs) were 1.17 (95% CI: 0.87‒1.57) and 1.08 (95% CI: 0.78‒1.51) for milk and total dairy, respectively. 0.50 (95% CI: 0.27-0.91) and 1.16 (95% CI: 0.83-1.52) were yogurt, cheese, and curd. Subgroup analysis revealed that study duration, alcohol, and design were associated the RRs. Dose-response analysis showed that the liver cancer risk was decreased by 5.4% ( for linear trend = 0.002) with a 40 g/day increment of yogurt intake. These results suggested that total dairy, milk, cheese, and curd were positive associations with the liver cancer risk although they were not statistically significant, however higher yogurt intake would reduce the risk. Further studies are necessary to verify the relationship of dairy foods with cancer.
Topics: Animals; Dairy Products; Diet; Humans; Liver Neoplasms; Milk; Risk Factors; Yogurt
PubMed: 33349059
DOI: 10.1080/01635581.2020.1862255 -
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 -
Acta Obstetricia Et Gynecologica... Apr 2024Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis... (Review)
Review
INTRODUCTION
Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis or chronic hepatitis B virus infection. Ultrasound evaluation, CT scan, and MRI are used to detect HCC. α-fetoprotein (AFP) is a common marker used to detect HCC in the non-pregnant population, which notoriously increases in pregnant women in relation to gestational age. Treatment is driven by the extent of the disease and the severity of underlying liver disease. Pregnancy may represent an obstacle to diagnosis and appropriate treatment of HCC. The aim of this descriptive systematic review was to describe the clinical features and maternal and neonatal outcomes of HCC in pregnancy.
MATERIAL AND METHODS
We performed a systematic review of the literature about HCC diagnosed in pregnancy and the postpartum period, with signs or symptoms arising in pregnancy. We included case reports and case series describing the clinical features of women diagnosed with HCC, fibrolamellar variant of HCC, and mixed HCC and cholangiocarcinoma during pregnancy or the postpartum period (with onset of symptoms during pregnancy), from inception to March 2023. The study protocol was registered with the PROSPERO database (Registration number: ID CRD42021275584).
RESULTS
We identified 180 records. The articles included in this systematic review were 47 case reports and 5 case series, for a total of 63 pregnancies. The two most frequent predisposing conditions were hepatitis B virus infection (30/63; 47%) and liver cirrhosis (14/63; 22%). Ultrasound evaluation was the most used technique to detect HCC. AFP was higher than normal in 28/46 patients tested (61%). Surgical treatment was the most used therapy, both during pregnancy and after delivery. Twenty-six patients (26/63; 42%) died within 6 months of diagnosis. Survival >24 months was 9% (4/46) in symptomatic and 29% (5/17) in asymptomatic women. No patient with cirrhotic liver survived more than 12 months. Thirty-eight newborns were alive at 28 days of age (38/63; 61%).
CONCLUSIONS
Hepatocellular carcinoma in pregnancy is associated with a high risk of maternal and neonatal mortality. Diagnosis in asymptomatic high-risk women or following abnormal maternal serum AFP screening is associated with better maternal outcomes.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Hepatitis B, Chronic; Liver Cirrhosis
PubMed: 37533304
DOI: 10.1111/aogs.14640 -
Cancer Jun 2022The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver... (Review)
Review
The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver transplantation (LT) in those with colorectal liver metastases (CRLM) showed poor outcomes, with 5-year survival rates between 12% and 21%. More recently, limited data have shown improved outcomes in select patients with 5-year overall survival rates of approximately 60%. Despite these reported survival improvements, there is no significant improvement in disease-free survival. Given the uncertain benefit with this therapeutic approach and a renewed investigational interest, we aimed to conduct a contemporary systematic review on LT for CRLM. A systematic review of the literature was performed according to the preferred reporting items for systematic reviews and meta-analysis statement. English articles reporting on data regarding LT for CRLM were identified through the MEDLINE (via PubMed), Cochrane Library, and ClinicalTrials.gov databases (last search date: December 16th, 2021) by 2 researchers independently. A total of 58 studies (45 published and 13 ongoing) were included. Although early retrospective studies suggest the possibility that some carefully selected patients may benefit from LT, there is minimal prospective data on the topic and LT remains exploratory in the setting of CRLM. Additionally, several other challenges, such as the limited availability of deceased donor organs and defining appropriate selection criteria, remain when considering the implementation of LT for these patients. Further evidence from ongoing prospective trials is needed to determine if and to what extent there is a role for LT in patients with surgically unresectable CRLM.
Topics: Colorectal Neoplasms; Hepatectomy; Humans; Liver Neoplasms; Liver Transplantation; Prospective Studies; Retrospective Studies
PubMed: 35285949
DOI: 10.1002/cncr.34170 -
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