ABSTRACT
BACKGROUND AND AIM: The association between gallstones/cholecystectomy and cancer remains inconclusive in the current literature. This study aimed to explore the causal connections between gallstones/cholecystectomy and cancer risk by utilizing a bidirectional two-sample multivariable Mendelian randomization approach with Genome-Wide Association Studies data. METHODS: Utilizing Genome-Wide Association Studies data from the UK Biobank and FinnGen, this research employed multivariable Mendelian randomization analyses to explore the impact of gallstones and cholecystectomy on the risk of 33 distinct cancer types. Instrumental variables for gallstones and cholecystectomy were carefully selected to ensure robust analyses, and sensitivity and heterogeneity tests were conducted to verify the findings' validity. RESULTS: Multivariable Mendelian randomization analysis, incorporating data from more than 450,000 individuals for gallstones and cholecystectomy, revealed nuanced associations with cancer risk. Cholecystectomy was associated with a significantly increased risk of nonmelanoma skin cancer (OR = 1.59, 95% CI: 1.21 to 2.10, P = 0.001), while gallstones were linked to a decreased risk of the same cancer type (OR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002). Interestingly, the analysis also suggested that cholecystectomy may lower the risk of small intestine tumors (OR = 0.18, 95% CI: 0.043 to 0.71, P = 0.015), with gallstones showing an inverse relationship, indicating an increased risk (OR = 6.41, 95% CI: 1.48 to 27.80, P = 0.013). CONCLUSIONS: The multivariable Mendelian randomization analysis highlights the differential impact of gallstones and cholecystectomy on cancer risk, specifically for nonmelanoma skin cancer and small intestine tumors. These results underscore the importance of nuanced clinical management strategies and further research to understand the underlying mechanisms and potential clinical implications of gallstone disease and cholecystectomy on cancer risk.
Subject(s)
Cholecystectomy , Gallstones , Genome-Wide Association Study , Mendelian Randomization Analysis , Female , Humans , Cholecystectomy/adverse effects , Gallstones/complications , Gallstones/epidemiology , Gallstones/genetics , Gallstones/surgery , Genetic Predisposition to Disease , Neoplasms/epidemiology , Neoplasms/etiology , Risk FactorsABSTRACT
BACKGROUND: Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear. METHODS: A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35-0.60) and PFS (0.49, 95% CI, 0.35-0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%). CONCLUSIONS: The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone. TRIAL REGISTRATION: International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).
Subject(s)
Carcinoma, Hepatocellular , Immune Checkpoint Inhibitors , Liver Neoplasms , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/therapy , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Progression-Free SurvivalABSTRACT
BACKGROUND: Laparoscopic treatment has been increasingly adopted for giant hepatic hemangioma (HH), but the role of liver resection or enucleation remains uncertain. The aim of this study is to compare the laparoscopic resection (LR) with laparoscopic enucleation (LE) for HH, and to provide evidence on how to choose the most suitable approach for HH. METHODS: A retrospective analysis of HH patients underwent laparoscopic treatment between March 2015 and August 2022 was performed. Perioperative outcomes were compared based on the surgical approaches, and risk factors for increased blood loss was calculated by logistic regression analysis. RESULTS: A total of 127 patients in LR group and 287 patients in LE group were enrolled in this study. The median blood loss (300 vs. 200 mL, P < 0.001) was higher in LE group than that in LR group. Independent risk factors for blood loss higher than 400 mL were tumor size ≥ 10 cm, tumor adjacent to major vessels, tumor occupying right liver or caudate lobe, and the portal phase enhancement ratio (PER) ≥ 38.9%, respectively. Subgroup analysis showed that LR was associated with less blood loss (155 vs. 400 mL, P < 0.001) than LE procedure in patients with high PER value. Both LR and LE approaches exhibited similar perioperative outcomes in patients with low PER value. CONCLUSIONS: Laparoscopic treatment for HH could be feasibly and safely performed by both LE and LR. For patients with PER higher than 38.9%, the LR approach is recommended.
Subject(s)
Blood Loss, Surgical , Hemangioma , Hepatectomy , Laparoscopy , Liver Neoplasms , Humans , Laparoscopy/methods , Female , Male , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Hepatectomy/methods , Retrospective Studies , Middle Aged , Hemangioma/surgery , Hemangioma/pathology , Adult , Blood Loss, Surgical/statistics & numerical data , Treatment Outcome , Risk Factors , AgedABSTRACT
The underlying mechanisms of metastasis and recurrence of liver cancer remain largely unknown. Here, we found that Brother of the Regulator of Imprinted Sites (BORIS) variant SF2(C2/A4) was highly expressed in high metastatic potential hepatocellular carcinoma (HCC) cells and clinical tumor samples, related to the formation of satellite nodules. Its over expression promoted self-renewal, the expression of tumor stem cell markers, chemoresistance, wound healing rate, invasion and metastasis of HepG2 and Hep3B cells; reinforced epithelial-mesenchymal transition (EMT), decreased the expression of E-cadherin and increased N-cadherin and Vimentin. Subcellular localization experiment showed that BORIS SF2(C2/A4) was localized in nucleus and cytoplasm. Further double luciferase reporter gene experiment confirmed that it bound to TWIST1 gene promoter and significantly increased latter expression. BORIS SF2(C2/A4) knock down induced apoptosis of HCCLM3 and PLC/PRF/5 cells, and increased the protein content of cleaved caspase 3. Additionally, BORIS SF2(C2/A4) over expression increased the expression of fibroblast growth factor 2 (FGF2) in HepG2 and Hep3B cells. FGF2 expressed higher in HCC tumor tissues than in paired peri-tumor tissues, and its expression was positively correlated with BORIS SF2(C2/A4). Interestingly, high expression of FGF2 is also associated with the formation of satellite nodules. Moreover, using the medium from BORIS SF2(C2/A4) overexpressed cell lines to coculture hepatic stellate cell (HSCs) line LX-2, the latter could be activated and increased the expression of CD90 and PIGF, which is consistent with the effect of adding bFGF alone. These results indicate that BORIS SF2(C2/A4) plays a role in deterioration of liver cancer by regulating TWIST1 to induce EMT, and by FGF2 to activate HSCs.
Subject(s)
Carcinoma, Hepatocellular , DNA-Binding Proteins , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Fibroblast Growth Factor 2/genetics , Fibroblast Growth Factor 2/metabolism , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Liver Neoplasms/pathology , Placenta Growth Factor/metabolism , DNA-Binding Proteins/geneticsABSTRACT
The future of plant cultivar improvement lies in the evaluation of genetic resources from currently available germplasm. Today's gene pool of crop genetic diversity has been shaped during domestication and more recently by breeding. Recent efforts in plant breeding have been aimed at developing new and improved varieties from poorly adapted crops to suit local environments. However, the impact of these breeding efforts is poorly understood. Here, we assess the contributions of both historical and recent breeding efforts to local adaptation and crop improvement in a global barley panel by analysing the distribution of genetic variants with respect to geographic region or historical breeding category. By tracing the impact that breeding had on the genetic diversity of Hordeum vulgare (barley) released in Australia, where the history of barley production is relatively young, we identify 69 candidate regions within 922 genes that were under selection pressure. We also show that modern Australian barley varieties exhibit 12% higher genetic diversity than historical cultivars. Finally, field-trialling and phenotyping for agriculturally relevant traits across a diverse range of Australian environments suggests that genomic regions under strong breeding selection and their candidate genes are closely associated with key agronomic traits. In conclusion, our combined data set and germplasm collection provide a rich source of genetic diversity that can be applied to understanding and improving environmental adaptation and enhanced yields.
Subject(s)
Genome, Plant/genetics , Hordeum/genetics , Plant Breeding , Australia , Crop Production , Domestication , Genes, Plant/genetics , Genetic VariationABSTRACT
BACKGROUND: Endoscopic ultrasound-guided liver biopsy (EUS-LB) is an evolving technique. In this meta-analysis, we aimed to evaluate the value of EUS-LB for parenchymal and focal liver lesions. Besides, we aimed to assess the influences of needle-related factors on the performance of EUS-LB. Additionally, we aimed to assess the influence of various criteria on specimen adequacy. METHODS: We searched the PubMed, Embase, Cochrane Library databases up to 10 October 2021. The primary outcome was diagnostic yield, specimen adequacy, qualified specimens evaluated by rapid on-site evaluation (ROSE). The secondary outcome was adverse events. Subgroup analyses were based on needle type, needle size, fine-needle biopsy (FNB) needle type. A sensitivity analysis was conducted on specimen adequacy based on two definition criteria. RESULTS: In total, 33 studies were included. Pooled rates of diagnostic yield, specimen adequacy, qualified specimen by ROSE, adverse events were 95%, 84%, 93%, 3%. Subgroup analyses showed that Acquire needles generated higher diagnostic yield than SharkCore needles (99% vs. 88%, p = .047). Additionally, FNB needles demonstrated a higher rate of adverse events than FNA needles (6% vs. 1%, p = .028). Sensitivity analysis on specimen adequacy based on various criteria demonstrated that the specimen adequacy rate defined by the AASLD criterion was lower than that of the commonly-used criterion (37% vs. 84%, p = .001). CONCLUSION: EUS-LB is effective and safe for liver biopsy. Acquire needles provide better specimens than SharkCore needles. FNB needles may increase the risk of adverse events compared with FNA needles. The AASLD criterion is harder to achieve than the commonly-used criterion.
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Liver , Endoscopic Ultrasound-Guided Fine Needle Aspiration/adverse effects , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Endosonography/methods , Humans , Liver/diagnostic imaging , Liver/pathology , UltrasonographyABSTRACT
BACKGROUND: Liver parenchymal transection is the most critical step for laparoscopic liver resection (LLR). Ultrasonic scalpel (Harmonic) is a common used energy instrument in LLR; however, it is only recommended for superficial layer transection and the Cavitron Ultrasonic Surgical Aspirator (CUSA) is recommended for deep layer dissection. We herein introduce the "Harmonic mimic CUSA" technique for LLR. METHODS: We retrospectively reviewed the medical records of the patients who underwent LLR using CUSA or the "Harmonic mimic CUSA" for parenchymal transection between July 2018 and October 2020 at West China Hospital of Sichuan University. Observation indicators included general demographic information, operative time, intraoperative blood loss, blood transfusion volume, complication rate, hospital stay, and the costs. Perioperative data was compared between the two groups by propensity score matching analysis (PSM). RESULTS: A total of 298 patients, including 192 in Harmonic group and 106 in CUSA group, were enrolled in this study. After a 1:1 PSM, 99 patients using "Harmonic mimic CUSA" were matched with 99 patients via CUSA for parenchymal transection in LLRs. The Harmonic group had significantly less intraoperative blood loss (mean, 150 ml vs. 250 ml, P < 0.001), shorter operative time (mean 170 min vs. 250 min, P < 0.001) and less costs (mean 6723$ vs. 8307$, P < 0.001). The conversion to laparotomy, length of postoperative hospital stay, complications were comparable between the two groups. There perioperative mortality was nil. CONCLUSION: The "Harmonic mimic CUSA" technique is safe, simple and feasible for LLR, which may be an alternative to CUSA for LLR.
Subject(s)
Laparoscopy , Liver Neoplasms , Humans , Blood Loss, Surgical , Retrospective Studies , Ultrasonics , Hepatectomy/methods , Liver/surgery , Liver Neoplasms/surgery , Length of StayABSTRACT
BACKGROUND AND AIMS: Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic Lactobacillus rhamnosus GG (LGG) on hepatic BA synthesis, liver injury, and fibrosis in bile duct ligation (BDL) and multidrug resistance protein 2 knockout (Mdr2-/- ) mice. APPROACH AND RESULTS: Global and intestine-specific farnesoid X receptor (FXR) inhibitors were used to dissect the role of FXR. LGG treatment significantly attenuated liver inflammation, injury, and fibrosis with a significant reduction of hepatic BAs in BDL mice. Hepatic concentration of taurine-ß-muricholic acid (T-ßMCA), an FXR antagonist, was markedly increased in BDL mice and reduced in LGG-treated mice, while chenodeoxycholic acid, an FXR agonist, was decreased in BDL mice and normalized in LGG-treated mice. LGG treatment significantly increased the expression of serum and ileum fibroblast growth factor 15 (FGF-15) and subsequently reduced hepatic cholesterol 7α-hydroxylase and BA synthesis in BDL and Mdr2-/- mice. At the molecular level, these changes were reversed by global and intestine-specific FXR inhibitors in BDL mice. In addition, LGG treatment altered gut microbiota, which was associated with increased BA deconjugation and increased fecal and urine BA excretion in both BDL and Mdr2-/- mice. In vitro studies showed that LGG suppressed the inhibitory effect of T-ßMCA on FXR and FGF-19 expression in Caco-2 cells. CONCLUSION: LGG supplementation decreases hepatic BA by increasing intestinal FXR-FGF-15 signaling pathway-mediated suppression of BA de novo synthesis and enhances BA excretion, which prevents excessive BA-induced liver injury and fibrosis in mice.
Subject(s)
Bile Acids and Salts , Cholestasis , Fibroblast Growth Factors/metabolism , Lacticaseibacillus rhamnosus/metabolism , Liver Cirrhosis , Receptors, Cytoplasmic and Nuclear , ATP Binding Cassette Transporter, Subfamily B/genetics , Animals , Bile Acids and Salts/biosynthesis , Bile Acids and Salts/metabolism , Chenodeoxycholic Acid/pharmacology , Cholestasis/complications , Cholestasis/metabolism , Cholestasis/therapy , Cholic Acids/pharmacology , Gastrointestinal Microbiome/drug effects , Humans , Intestines/microbiology , Liver Cirrhosis/etiology , Liver Cirrhosis/prevention & control , Mice , Mice, Knockout , Probiotics/pharmacology , Receptors, Cytoplasmic and Nuclear/agonists , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction/drug effects , ATP-Binding Cassette Sub-Family B Member 4ABSTRACT
KEY MESSAGE: Using genomic structural equation modelling, this research demonstrates an efficient way to identify genetically correlating traits and provides an effective proxy for multi-trait selection to consider the joint genetic architecture of multiple interacting traits in crop breeding. Breeding crop cultivars with optimal value across multiple traits has been a challenge, as traits may negatively correlate due to pleiotropy or genetic linkage. For example, grain yield and grain protein content correlate negatively with each other in cereal crops. Future crop breeding needs to be based on practical yet accurate evaluation and effective selection of beneficial trait to retain genes with the best agronomic score for multiple traits. Here, we test the framework of whole-system-based approach using structural equation modelling (SEM) to investigate how one trait affects others to guide the optimal selection of a combination of agronomically important traits. Using ten traits and genome-wide SNP profiles from a worldwide barley panel and SEM analysis, we revealed a network of interacting traits, in which tiller number contributes positively to both grain yield and protein content; we further identified common genetic factors affecting multiple traits in the network of interaction. Our method demonstrates an efficient way to identify genetically correlating traits and underlying pleiotropic genetic factors and provides an effective proxy for multi-trait selection within a whole-system framework that considers the joint genetic architecture of multiple interacting traits in crop breeding. Our findings suggest the promise of a whole-system approach to overcome challenges such as the negative correlation of grain yield and protein content to facilitating quantitative and objective breeding decisions in future crop breeding.
Subject(s)
Chromosomes, Plant/genetics , Crops, Agricultural/growth & development , Crops, Agricultural/genetics , Genome, Plant , Plant Breeding/methods , Quantitative Trait Loci , Selection, Genetic , Chromosome Mapping/methods , Polymorphism, Single NucleotideABSTRACT
Sclerotinia sclerotiorum is an important fungal pathogen of chickpea (Cicer arietinum L.), and it can cause yield losses up to 100%. The wild progenitors are much more diverse than domesticated chickpea, and this study describes how this relates to S. sclerotiorum resistance. Initially, the pathogenicity of nine Australian S. sclerotiorum isolates was examined on three Cicer lines to develop a robust phenotyping assay, and significant differences in isolate aggressiveness were identified with six isolates being classed as highly aggressive and three as moderately aggressive. We identified two S. sclerotiorum isolates, CU8.20 and CU10.12, to be highly aggressive and moderately aggressive, respectively. A subsequent phenotyping assay was conducted using the two isolates to evaluate 86 wild Cicer accessions (Cicer reticulatum and Cicer echinospermum) and two C. arietinum varieties for resistance to S. sclerotiorum. A subset of 12 genotypes was further evaluated, and subsequently, two wild Cicer accessions with consistently high levels of resistance to S. sclerotiorum were examined using the initially characterized nine isolates. Wild Cicer accessions Karab_084 and Deste_063 demonstrated consistent partial resistance to S. sclerotiorum. There were significant differences in responses to S. sclerotiorum across wild Cicer collection sites. The Cermik, Karabahce, and Destek sites' responses to the aggressive isolate CU8.20 ranged from resistant to susceptible, highlighting an interaction between isolate genotype and chickpea collection site for sclerotinia stem rot resistance. This is the first evidence of partial stem resistance identified in wild Cicer germplasm, which can be adopted in chickpea breeding programs to enhance S. sclerotiorum resistance in future chickpea varieties.
Subject(s)
Ascomycota , Cicer , Ascomycota/genetics , Australia , Cicer/genetics , GenotypeABSTRACT
In the present study, four large-scale field trials using two doubled haploid wheat populations were conducted in different environments for two years. Grain protein content (GPC) and 21 other yield-related traits were investigated. A total of 227 QTL were mapped on 18 chromosomes, which formed 35 QTL clusters. The potential candidate genes underlying the QTL clusters were suggested. Furthermore, adding to the significant correlations between yield and its related traits, correlation variations were clearly shown within the QTL clusters. The QTL clusters with consistently positive correlations were suggested to be directly utilized in wheat breeding, including 1B.2, 2A.2, 2B (4.9-16.5 Mb), 2B.3, 3B (68.9-214.5 Mb), 4A.2, 4B.2, 4D, 5A.1, 5A.2, 5B.1, and 5D. The QTL clusters with negative alignments between traits may also have potential value for yield or GPC improvement in specific environments, including 1A.1, 2B.1, 1B.3, 5A.3, 5B.2 (612.1-613.6 Mb), 7A.1, 7A.2, 7B.1, and 7B.2. One GPC QTL (5B.2: 671.3-672.9 Mb) contributed by cultivar Spitfire was positively associated with nitrogen use efficiency or grain protein yield and is highly recommended for breeding use. Another GPC QTL without negatively pleiotropic effects on 2A (50.0-56.3 Mb), 2D, 4D, and 6B is suggested for quality wheat breeding.
Subject(s)
Chromosomes, Plant/genetics , Genetic Linkage , Plant Breeding , Plant Proteins/genetics , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Triticum/genetics , Chromosome Mapping , Phenotype , Triticum/classificationABSTRACT
Single-marker genome-wide association studies (GWAS) have successfully detected associations between single nucleotide polymorphisms (SNPs) and agronomic traits such as flowering time and grain yield in barley. However, the analysis of individual SNPs can only account for a small proportion of genetic variation, and can only provide limited knowledge on gene network interactions. Gene-based GWAS approaches provide enormous opportunity both to combine genetic information and to examine interactions among genetic variants. Here, we revisited a previously published phenotypic and genotypic data set of 895 barley varieties grown in two years at four different field locations in Australia. We employed statistical models to examine gene-phenotype associations, as well as two-way epistasis analyses to increase the capability to find novel genes that have significant roles in controlling flowering time in barley. Genetic associations were tested between flowering time and corresponding genotypes of 174 putative flowering time-related genes. Gene-phenotype association analysis detected 113 genes associated with flowering time in barley, demonstrating the unprecedented power of gene-based analysis. Subsequent two-way epistasis analysis revealed 19 pairs of gene×gene interactions involved in controlling flowering time. Our study demonstrates that gene-based association approaches can provide higher capacity for future crop improvement to increase crop performance and adaptation to different environments.
Subject(s)
Epistasis, Genetic/genetics , Flowers , Genome-Wide Association Study/methods , Hordeum/genetics , Chromosome Mapping , Gene Regulatory Networks/genetics , Genotype , Linkage Disequilibrium/genetics , Polymorphism, Single Nucleotide/genetics , Quantitative Trait Loci/geneticsABSTRACT
BACKGROUND: In the presence of cholecystitis or portal hypertension, hemorrhage is common during laparoscopic cholecystectomy (LC) because the vessels of Calot's triangle are fragile and tortuous. Bleeding can obstruct surgical field visibility and increase conversion rates and risk of common bile duct injury. The Pringle maneuver is a simple occlusion approach that could limit blood flow from the hepatic pedicle, thus controlling bleeding to provide a clear surgical field to reduce conversion rate. In this study, we aimed to investigate the feasibility, effectiveness and safety of hepatic pedicle occlusion with the Pringle maneuver during difficult LC. METHODS: From 2011 to 2015, LC with hepatic pedicle occlusion by the Pringle maneuver was performed in 67 patients (Pringle group). Another group of 67 cases with matched clinical parameters where LC was performed without the Pringle maneuver (non-Pringle group) was retrieved from a database to serve as the control group. RESULTS: The Pringle group had a significantly lower conversion rate (1.49% vs. 11.9%; P = 0.038), less blood loss (37.5 ± 24.1 mL vs. 94.5 ± 67.8 mL; P = 0.002), shorter postoperative hospitalization (2.5 ± 1.4 days vs. 3.5 ± 2.5 days; P = 0.005), and lower cost ($1343 ± $751 USD vs. $1674 ± $609 USD; P = 0.024) than non-Pringle group. There was one case each of bile duct injury and readmission within 30 days because of bile leakage in the non-Pringle group, but none in the Pringle group. CONCLUSIONS: Hepatic pedicle occlusion could provide a clear surgical field and enable the recognition of structures during LC. The Pringle maneuver offers a feasible and safe approach to lower conversion rates in difficult LC.
Subject(s)
Cholecystectomy, Laparoscopic , Conversion to Open Surgery/statistics & numerical data , Hemostatic Techniques , Liver/surgery , Adult , Aged , Case-Control Studies , Feasibility Studies , Female , Hemorrhage/prevention & control , Hospital Costs/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Liver/blood supply , Male , Middle Aged , Retrospective StudiesABSTRACT
AIM: We set out to acquire original pathophysiologic data of dynamic changes in portal vein pressure gradient (PVPG) following liver resection (LR) during post-operation days (POD) 1-7. METHODS: Portal vein pressure gradient was measured in 31 patients daily until POD 7 at our liver surgery center. Patients were divided into non-, mild, moderate, and severe cirrhosis groups according to histopathology and were also divided into subgroups according to the volume of hepatectomy. RESULTS: Portal vein pressure gradient reached its peak on POD 3 in mild cirrhosis (F = 7.525, P < 0.001), moderate cirrhosis (F = 11.200, P < 0.001), and severe cirrhosis groups (F = 26.634, P < 0.001). There were no significant changes in PVPG in the non-cirrhosis group (F = 1.050, P = 0.411). Moreover, PVPG on POD 3 was higher with increasing severity of cirrhosis under the same interval of LR volume (resection volume <200 cm3 : F = 13.040, P = 0.004; ≥200 cm3 but <400 cm3 : F = 13.243, P = 0.004; ≥400 cm3 : F = 43.685, P < 0.001). Finally, the LR volume had significant impact on PVPG for patients with moderate cirrhosis (F = 6.339, P = 0.033) and severe cirrhosis (t = -7.000, P = 0.020). A similar tendency was also observed when patients were divided according to the ratio of the resected liver volume to total liver volume. CONCLUSIONS: The increase in PVPG following LR was positively associated with the degree of cirrhosis, significantly peaking on POD 3. The LR volume only had a significant impact on PVPG for patients with moderate and severe cirrhosis. This represents the first time, to our knowledge, that dynamic changes of PVPG after LR were measured and compared to cirrhosis and resection volume.
ABSTRACT
BACKGROUND: Transcatheter arterial chemoembolization (TACE) and TACE in combination with sorafenib (TACE-sorafenib) have shown a significant survival benefit for the treatment of unresectable hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of TACE against TACE-sorafenib for unresectable HCC using a decision analytic model. METHODS: A Markov cohort model was developed to compare TACE and TACE-sorafenib. Transition probabilities and utilities were obtained from systematic literature reviews, and costs were obtained from West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was calculated. Sensitive analysis was performed by varying potentially modifiable parameters of the model. RESULTS: The base-case analysis showed that TACE cost $26 951 and yielded survival of 0.71 QALYs, and TACE-sorafenib cost $44 542 and yielded survival of 1.02 QALYs in the entire treatment. The ICER of TACE-sorafenib versus TACE was $56 745 per QALY gained, which was above threshold for cost-effectiveness in China. Sensitivity analysis revealed that the major driver of ICER was the cost post TACE-sorafenib therapy with stable state. CONCLUSION: TACE is a more cost-effective strategy than TACE-sorafenib for the treatment of unresectable HCC.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/economics , Liver Neoplasms/therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Carcinoma, Hepatocellular/mortality , Cost-Benefit Analysis , Humans , Liver Neoplasms/mortality , Niacinamide/therapeutic use , Quality-Adjusted Life Years , SorafenibABSTRACT
BACKGROUND: Microvascular invasion (MVI) is an important risk factor for survival of patients with hepatocellular carcinoma (HCC) after hepatectomy. However, its impact on patients with recurrent HCC who receive a second hepatectomy is unknown. METHODS: We enrolled 167 patients with HCC who underwent a second hepatectomy because of intrahepatic recurrences. We compared the patients' demographic, tumor, and pathologic characteristics with 766 cases of original hepatectomy. We analyzed the possible risk factors for survival after the first and second hepatectomies and the influence of different MVI patterns on patients' survival after the second hepatectomy. RESULTS: The median overall survival was comparable between the first and second hepatectomy groups, 34 (3-84) mo versus 27 (3-57) mo, P = 0.09. For patients who underwent a first hepatectomy, the presence of macro-VI or MVI, an early recurrence pattern, and a total tumor diameter >5 cm were independent risk factors. For survival after the second hepatectomy, MVI patterns that were positive-positive or negative-positive and a total recurrent tumor diameter >5 cm were significant risk factors for survival. CONCLUSIONS: A second hepatectomy provides satisfying survival for patients with intrahepatic recurrence of HCC after the initial operation. Different MVI patterns affect survival after the second hepatectomy. Because MVI represents the biological behavior of HCC, we place a high premium on the clinical value of MVI after each hepatectomy.
Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Microvessels/pathology , Neoplasm Recurrence, Local/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Follow-Up Studies , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Reoperation , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Hepatic artery pseudoaneurysm (HAP) and Hepatic artery dissection are rare vascular complications after living donor liver transplantation (LDLT), which may lead to graft loss and death of the recipients. Conventional gray-scale and Doppler ultrasound, as well as contrast-enhanced ultrasound (CEUS), play important roles in identifying vascular complications in the early postoperative period and during follow-up. We report a case of hepatic artery dissection secondary to HAP after LDLT, which was diagnosed and followed for one year by ultrasound. To the best of our knowledge, few studies have reported similar cases after liver transplantation in the English literature. CASE PRESENTATION: A 43-year-old man underwent right-lobe LDLT for treatment of a severe acute hepatitis B infection and was followed up with ultrasound examinations for one year. Conventional gray-scale and Doppler ultrasound combined with contrast-enhanced ultrasound (CEUS) accurately revealed the occurrence of HA dissection secondary to HAP and accompanied by thrombosis and collateral circulation, as well as secondary biliary complications, which provided a prompt diagnosis and guidance for the treatment. CONCLUSION: Our case suggests that ultrasound can help detect hepatic artery pseudoaneurysm and dissection, as well as secondary biliary lesions after LDLT in an accurate and timely manner and provide useful information for the treatment chosen. CEUS shows potential as an important complementary technique to gray-scale and Doppler ultrasound.
Subject(s)
Aneurysm, False/diagnostic imaging , Aortic Dissection/diagnostic imaging , Hepatic Artery/diagnostic imaging , Liver Transplantation , Postoperative Complications/diagnostic imaging , Thrombosis/diagnostic imaging , Adult , Aortic Dissection/therapy , Aneurysm, False/therapy , Angiography , Embolization, Therapeutic/methods , Hepatic Artery/surgery , Humans , Living Donors , Male , Postoperative Complications/therapy , Thrombosis/therapy , Ultrasonography, DopplerABSTRACT
OBJECTIVE: To explore portal vein hemodynamic changes and liver regeneration in rats after 70% partial hepatectomy (PH). METHODS: Rats were randomly subjected into sham operation group and 70% PH group. A 5-12 MHz high-frequency linear transducer was applied to measure the portal vein diameter (PVD) and the maximum portal vein velocity (PVV) before and after operation on day 1, 3, 7, 14. On the corresponding time, liver tissue morphological changes were observed, and the expression level of PCNA was measured, and the liver regeneration rate (LRR) was calculated. RESULTS: On day 1 after PH, PCNA began to increase, and hepatocyte vacuolated obviously which squeezed and narrowed the hepatic sinusoid. Meanwhile, PVD started to dilate and PVV decelerated. On day 3 after operation, PCNA peaked and active mitosis resulted in the disorders of hepatic structure. PVD peaked and PVV decelerated to the lowest. Until the 14 d after operation, the cell morphology, lobular structure and PCNA recovered gradually accompany by LRR above 90%. PVD and PVV also almost recovered to levels closed to sham group (P < 0.05). CONCLUSION: The hemodynamic parameters PVD, PVV correlated with hepatic pathology changes, mitosis status and regenerated liver volume after PH, which state the potential possibility for ultrasound image study in liver regeneration surveillance.
Subject(s)
Hemodynamics , Hepatectomy , Liver Regeneration , Portal Vein/physiology , Animals , Hepatocytes/cytology , Liver/surgery , Random Allocation , RatsABSTRACT
PURPOSE: To investigate the changes of cerebral hemodynamics pre- and post-ventricular drainage in patients with posttraumatic acute diffuse brain swelling. METHODS: Twenty-four cases of traumatic diffuse brain swelling were analyzed retrospectively. Patients in nonsurgical group were treated by medicine therapy. Patients in surgical group were treated by external ventricular drainage plus medicine therapy. The first CT perfusion scan was completed within 4-5 h after trauma and scanned again after 7 days. The changes of perfusion parameters in area-of-interest in two groups were analyzed and compared before and after treatment. RESULTS: Compared with the nonsurgical group, the value of cerebral blood volume, cerebral blood flow and mean transit time in bilateral frontal temporoparietal grey matter, basal ganglia, cerebellum, and brain stem at pre- and post-therapy were increased significantly (p < 0.05) in surgical group, and consequently the prognosis of patients undergoing surgery was also better than that of nonsurgical group. CONCLUSION: External ventricular drainage can improve cerebral perfusion and increase survival quality for the patients with posttraumatic acute diffuse brain swelling.