Treatment Of Hepatocellular Cancer Research Articles

Psychiatric disorders in patients with hepatocellular carcinoma: A large US cohort of commercially insured individuals.

Patients with hepatocellular cancer (HCC) are vulnerable to psychological distress given a new cancer diagnosis superimposed on pre-existing chronic liver disease. We aimed to characterise the psychiatric burden in HCC, risk factors for incident diagnosis and treatment patterns over time. Using IQVIA PharMetrics® Plus for Academics-a nationally representative claims database of the commercially insured US population-we identified psychiatric diagnoses and treatment among patients with newly diagnosed HCC. Multivariable logistic regression modelling identified factors associated with psychiatric diagnosis and treatment. Of 11,609 patients with HCC, 2166 (18.6%) had a psychiatric diagnosis after cancer diagnosis with depression (58.3%) and anxiety (53.0%) being most common. Women (aOR 1.33, 95% CI [1.19-1.49]), pre-existing psychiatric diagnoses (aOR 9.12 [8.08-10.3]) and HCC treatment type (transplant: aOR 2.15 [1.66-2.77]; locoregional therapies: aOR 1.74 [1.52-1.99]; hospice: aOR 2.43 [1.79-3.29]) were significantly associated with psychiatric diagnosis. Female sex, ascites, higher comorbidity and treatment type were associated with incident psychiatric diagnosis. Pharmacotherapy was used in 1392 (64.3%) patients with a psychiatric diagnosis, with antidepressants (46.2%) and anxiolytics (32.8%) being most common. Psychiatric diagnoses increased from 14.8% in 2006-2009 to 21.1% in 2018-2021 (p < 0.001). In almost 20% of patients with pre-existing psychiatric conditions, therapy was discontinued after HCC diagnosis. Nearly 2 of 10 patients with HCC were diagnosed with a psychiatric condition after cancer diagnosis with unique sociodemographic and clinical risk factors identified. This highlights a risk for increased psychological burden in need of early evaluation and treatment among patients with newly diagnosed HCC.

Examining disparities in the receipt of curative treatment for hepatocellular cancer (HCC): A multicenter retrospective study from 2016-2023.

1582 Background: Prior studies suggested disparities in hepatocellular cancer (HCC) treatment and outcomes based on region, race, and socioeconomic status. After the implementation of the Affordable Care Act, including Michigan’s Medicaid Expansion in 2014, there’s increased interest in how these changes affect HCC care. The study examines factors influencing curative treatment receipt and existing disparities, as a step toward intervention strategies. Methods: This is a retrospective study of HCC patients at 6 community-based (4 university-affiliated) hospitals, in Michigan from Jan 2016-Sep 2023. Patients without imaging or histologic confirmation were excluded. Factors associated with receiving curative treatment were determined using both univariate and multivariable logistic regressions. Analysis was done using SPSS 28, with a p-value&lt;0.05 indicating statistical significance. Results: Of 680 HCC patients screened, 347 were analyzed. The mean age was 70 years, and 71% were male. 78.3% were White and 16.9% Black. 53.9% had private insurance and 35% had government insurance. Primary HCC etiologies were alcohol and hepatitis C virus (HCV) infection; 74.4% had cirrhosis. Barcelona Clinic Liver Cancer (BCLC) stages varied: A (10.6%), B (28.2%), C (36.4%), and D (24.8%). 59.4% underwent curative treatment (4.6% resection, 30.3% liver-directed, 13.3% systemic, 10.1% combination), while 38.3% had best supportive care. Univariate analysis identified many factors associated with receipt of curative treatment, including race (White&gt;Black), insurance (private&gt;government), earlier BCLC stages, ECOG 0/1/2, Child-Pugh A, lower MELD-Na score (mean=12), &lt;400 alpha-fetoprotein levels, and better liver function (Bilirubin, INR, albumin). Tumor characteristics, such as smaller size, absence of metastasis, and absence of portal vein thrombosis, were also associated with receipt of curative treatment. Overall, the one-year survival rate was 64% for those who had curative treatment and 35% for best supportive care. All with p-value&lt;0.05. Multivariable analysis showed Black patients (OR: 0.21, CI: 0.051-0.881) with larger tumors (OR:0.89, CI: 0.783-1.00) and lower albumin levels (OR:3.81, CI: 1.649-8.805) at presentation were less likely to receive curative treatment than White. Black patients were also diagnosed at a younger age (66.7 vs. 71.0 years, p=0.01), more advanced BCLC stages C/D (74% vs. 57%, p=0.04) on presentation, and HCV coinfection (58% vs. 32%, p&lt;0.001) than White. Median survival for Black and White were 757 days and 823 days, respectively (p=0.89). Conclusions: Black patients with larger tumors and low albumin are less likely to receive curative treatment than White. HCV coinfection in the Black population suggests a focus area for early intervention. Further investigation of HCC disparities across various settings is warranted.

Sorafenib tosylate-loaded nanosuspension: preparation, optimization, and in vitro cytotoxicity study against human HepG2 carcinoma cells

This study aimed to optimize nanosuspension of sorafenib tosylate (an anticancer hydrophobic drug molecule) using a central composite design. Nanosuspension was prepared using a nanoprecipitation-ultrasonication approach. FTIR and DSC analyses demonstrated that the drug and excipients were physicochemically compatible. X-ray powder diffraction analysis confirmed amorphous form of the payload in the formulation. The optimized formulation (batch NSS6) had a zeta potential of −18.1 mV, a polydispersity of 0.302, and a particle size of 97.11 nm. SEM analysis confirmed formation of rod-shaped particles. After 24 h, about 64.45% and 86.37% of the sorafenib tosylate was released in pH 6.8 and pH 1.2, respectively. The MTT assay was performed on HepG2 cell lines. IC50 value of the optimized batch was 39.4 µg/mL. The study concluded that sorafenib tosylate nanosuspension could be a promising approach in the treatment of hepatocellular cancer.

Crosstalk between autophagy inhibitor and salidroside-induced apoptosis: A novel strategy for autophagy-based treatment of hepatocellular cancer

Autophagy regulates many cell function related to cancer, including cell proliferation, invasion and apoptosis. Therefore, we investigated the potential value of crosstalk between autophagy and apoptosis. The present study demonstrated that seven autophagy related genes were screened from the biological network of salidroside (Sal) acting on liver cancer. The GO analysis showed that these genes were mainly involved in apoptosis and autophagy. The KEGG analysis showed that these genes regulated the process of liver cancer through Th17 cell differentiation, PI3K-Akt signaling pathway and other pathways. Moreover, seven genes were positively correlated with tumor purity, number of B cells, number of CD4+ T cells, number of CD8+ T cells, number of macrophages, number of dendritic cells and number of neutrophils. The overall survival time of liver cancer patients in the high expression group of BIRC5, HSP90AB1 and MTOR was lower than that in the low expression group (P < 0.05), while the overall survival time of the liver cancer patients in the high expression group of DLC1 and FOXO1 was higher than that in the low expression group (P < 0.05). In the pan-cancer analysis, we also found that BIRC5, HSP90AB1, MTOR, and ITGA6 were highly expressed in various cancers, while DLC1, FOXO1, and FOS were low expressed in various cancers. In the molecule docking analysis, we found that FOS, HSP90AB1, and MTOR had the best binding ability. Notably, in the vitro validation experiments, Sal was confirmed to induce autophagy and apoptosis, inhibite invasion and metastasis of liver cancer cells through the PI3K/Akt/mTOR signaling pathway. Meanwhile, inhibition of autophagy by chloroquine diphosphate (CQ) promoted Sal-induced mitochondrial apoptosis via corresponding cell and animal experiments. We speculated that Sal-induced autophagy might be a protective mechanism, inhibition of autophagy could further promote the progression of liver cancer. It may provide important insight into the molecular mechanism of crosstalk between autophagy and apoptosis, and provide a new theoretical basis of Sal combined with autophagy inhibitors as a adjuvant chemotherapeutic strategy for human liver cancer.

Resection interventions in the treatment of hepatocellular cancer in a specialized surgery center

Background. The relevance of the treatment of hepatocellular cancer (HCC) is determined by a significant increase in the incidence rate and its high prevalence among primary malignant hepatic tumors.The aim of the study. To summarize the experience of providing specialized medical care to patients with hepatocellular cancer.Methods. We studied the direct results of treatment of patients with primary hepatic cancer treated at the Kuzbass Regional Hepatological Center for the period from January 2015 to August 2022. The materials for the study were medical records of patients with an established diagnosis of primary hepatic cancer, surgical records, results of pathohistologic examination. The exclusion criterion was diagnosed cholangiocellular carcinoma.Results. During the period from 2015 to 2022, 59 patients with primary hepatic cancer were treated at the Kuzbass Regional Hepatological Center. Among them, hepatocellular cancer was diagnosed in 48 cases, cholangiocellular cancer – in 11 cases; radical surgery was performed in 12 patients with hepatocellular cancer; fatal outcome was noted in 1 (2.1 %) patient, complications in the postoperative period developed in 5 (41.7 %) cases and were ranked as I-3, IIIb-1 and IVb-1 according to Clavien – Dindo classification.Conclusion. The degree of risk of severe post-resection hepatic failure should be considered one of the main criteria in choosing a strategy for radical surgical treatment. New surgical approaches (laparoscopic vascular isolation of the portal blood flow, using temporary hemostasis in laparoscopic hepatic resections and the device for its implementation) in resection surgery of primary hepatic cancer can improve the immediate results of treatment.

Anti-Glycolytic Drugs in the Treatment of Hepatocellular Carcinoma: Systemic and Locoregional Options.

Hepatocellular cancer (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death. Locoregional therapies, including transarterial embolization (TAE: bland embolization), chemoembolization (TACE), and radioembolization, have demonstrated survival benefits when treating patients with unresectable HCC. TAE and TACE occlude the tumor's arterial supply, causing hypoxia and nutritional deprivation and ultimately resulting in tumor necrosis. Embolization blocks the aerobic metabolic pathway. However, tumors, including HCC, use the "Warburg effect" and survive hypoxia from embolization. An adaptation to hypoxia through the Warburg effect, which was first described in 1956, is when the cancer cells switch to glycolysis even in the presence of oxygen. Hence, this is also known as aerobic glycolysis. In this article, the adaptation mechanisms of HCC, including glycolysis, are discussed, and anti-glycolytic treatments, including systemic and locoregional options that have been previously reported or have the potential to be utilized in the treatment of HCC, are reviewed.

Does Vascular Collapse Occur After Treatment of Hepatocellular Cancer With Stereotactic Body Radiation Therapy?

There is debate about why stereotactic body radiation therapy (SBRT) produces superior control of hepatocellular cancer (HCC) compared to fractionated treatment. Both preclinical and clinical evidence has been presented to support a "classic" biological explanation: the greater BED of SBRT produces more DNA damage and tumor cell kill. More recently, preclinical evidence has supported the concept of a "new biology", particularly radiation-induced vascular collapse, which increases hypoxia and free radical activation. This is hypothesized to cause much greater tumor cell death than was produced by the initial radiation-induced DNA damage to the tumor. We decided to investigate if vascular collapse occurs after standard SBRT for patients with HCC. Eight patients with 10 lesions underwent dynamic contrast enhanced MRI at the time of simulation and either 48 or 96 hours after the first fraction. Only three of 10 tumors showed a decrease in blood flow. These findings suggest that vascular collapse does not typically occur after SBRT for HCC.

Impact of COVID-19 on 1-Year Survival Outcomes in Hepatocellular Carcinoma: A Multicenter Cohort Study.

The COVID-19 pandemic has caused severe disruption of healthcare services worldwide and interrupted patients' access to essential services. During the first lockdown, many healthcare services were shut to all but emergencies. In this study, we aimed to determine the immediate and long-term indirect impact of COVID-19 health services utilisation on hepatocellular cancer (HCC) outcomes. A prospective cohort study was conducted from 1 March 2020 until 30 June 2020, correlating to the first wave of the COVID-19 pandemic. Patients were enrolled from tertiary hospitals in the UK and Germany with dedicated HCC management services. All patients with current or past HCC who were discussed at a multidisciplinary meeting (MDM) were identified. Any delay to treatment (DTT) and the effect on survival at one year were reported. The median time to receipt of therapy following MDM discussion was 49 days. Patients with Barcelona Clinic Liver Cancer (BCLC) stages-A/B disease were more likely to experience DTT. Significant delays across all treatments for HCC were observed, but delay was most marked for those undergoing curative therapies. Even though severe delays were observed in curative HCC treatments, this did not translate into reduced survival in patients. Interruption of routine healthcare services because of the COVID-19 pandemic caused severe delays in HCC treatment. However, DTT did not translate to reduced survival. Longer follow is important given the delay in therapy in those receiving curative therapy.

Circular RNA circBNC2 facilitates glycolysis and stemness of hepatocellular carcinoma through the miR-217/high mobility group AT-hook 2 (HMGA2) axis

Hepatocellular cancer (HCC) accounts for approximately 90% of primary liver carcinoma and is a significant health threat worldwide. Circular RNA basonuclin 2 (circBNC2) is implicated with the progression of several cancers. However, its roles in carcinogenesis and glycolysis are still unclear in HCC. In this study, the levels of circBNC2 and high mobility group AT-hook 2 (HMGA2) were highly expressed, while these of miR-217 were poorly expressed in HCC tissues and cells. Upregulation of circBNC2 was related to poor prognosis and tumor node metastasis (TNM) stage. Knockdown of circBNC2 inhibited the HCC progression. Moreover, knockdown of circBNC2 suppressed the levels of Ras, ERK1/2, PCNA, HK2, and OCT4. Notably, circBNC2 functioned as a molecular sponge of microRNA 217 (miR-217) to upregulate the HMGA2 expression. The inhibitory effects of the circBNC2 silence on the growth and stemness of HCC cells, and levels of PCNA, HK2 and OCT4 were aggravated by the miR-217 overexpression, but neutralized by the HMGA2 overexpression. Besides, silencing of circBNC2 blocked the tumor growth through upregulating the expression of miR-217 and downregulating the levels of HMGA2, PCNA2, HK2 and OCT4 in vivo. Thus, the current data confirmed that circBNC2 sponged miR-217 to upregulate the HMGA2 level, thereby contributing to the HCC glycolysis and progression. These findings might present novel insight into the pathogenesis and treatment of HCC.

Efficacy of low dose sorafenib and capecitabine in the management of hepatocellular cancer.

e16117 Background: Hepatocellular cancer (HCC) is one of the commonest cancers in Pakistan due to endemic hepatitis B and C diseases. Its incidence is continuously rising due to lack of public awareness and lack of routine screening of the affected population. Most of the patients present in advanced stage of the disease excluding option for curative surgical options. These patients are mostly not fit enough to tolerate systemic therapies in full doses. So, we have to adapt ourselves to lower dosage so that it can be tolerated without many untoward side effects. Methods: This study was aimed to assess the efficacy of low dose sorafenib (400 mg daily in two divided doses) and capecitabine (1000 mg daily in two divided doses) in advanced hepatocellular carcinoma. Patients were prescribed this treatment for six months and then response was assessed using computed tomography or ultrasound and alpha fetoprotein (AFP) levels. Progression-free survival (PFS) and overall survival (OS) were also assessed. Results: Total of one-hundred fifty-five patients were enrolled. One hundred thirteen patients completed the treatment for six months and were evaluated for response. A total of 28 (25%) of patients progressed during treatment and were shifted to other treatment options. Nine patients (8%) had complete response, thirty-four (30%) had partial response, forty-two (37%) had stable disease and twenty-eight (25%) had progressive disease. Seventy-four patients (65%) showed significant reduction in AFP levels. A total of 85/113 (75%) patients were available for assessment of PFS and OS. Two-year PFS and OS were 32% and 43% respectively. Mean and median PFS (year) were 1.82 ±0.19 (95% confidence interval 1.48 to 2.17) and 1.27±0.16 (95% confidence interval 0.94 to 1.57) respectively. Mean and median OS (year) were 2.73 ±0.24 (95% confidence interval 2.39 to 3.16) and 2.27±0.13 (confidence interval 2.02 to 2.54) respectively. Twenty-six patients had one or more episode of grade 2 diarrhea, eleven patients developed encephalopathy, thirteen patients developed hand foot syndrome and nineteen patients showed grade 2 thrombocytopenia. Conclusions: Low dose sorafenib and capecitabine is effective in the treatment of advanced HCC with excellent tolerability and minimal toxicity.

Abstract 4116: Modulating gut microbiota to improve intrahepatic immunity against hepatocellular cancer

Abstract Gut microbiota plays a pivotal role in the pathogenesis of hepatocellular cancer (HCC), significantly affecting the HCC treatment. It has been reported that the HCC patients’ response to the immunotherapy of PD-1/PD-L1 blockade was associated with their gut microbiota profiles. However, the impact of gut microbiota on anti-HCC immunity and its underlying mechanism are poorly understood. Treating HCC-bearing mice with a specific and non-hepatotoxic antibiotic cocktail caused the increased relative abundance of specific commensal bacteria such as Bacteroides, resulting in suppression of HCC growth and development which was involved in the activation of intrahepatic antitumor immune responses. Gut microbiota recolonization of Bacteroides thetaiotaomicron (B. th) in gut-sterilized HCC-bearing mice significantly improved the therapeutic efficacy of anti-PD-1 antibody (αPD-1 Ab) against HCC. Fecal microbiota transplantation (FMT) from HCC patients who received and responded to αPD-1 Ab treatment improved the efficacy of αPD-1 Ab treatment against HCC in mice model. Mechanistic studies demonstrated that the modulation of Krüppel-like factor 2 (KLF2)/Toll-like receptor 9 (TLR9) signaling and the accumulation of CpG-enriched genomic DNAs of B. th in livers/tumors activated the tumor antigen-specific CD8+ T cells through the dendritic cell in a TLR9-dependent manner. In conclusion, gut microbiota as a causative factor can be targeted to improve anti-HCC immunotherapy. Citation Format: Xiaogiang Qi, Ming Yang, Lixin Ma, Jonathan Mitchem, Jussuf Kaifi, Shiyou Chen, Aaron Ericsson, Eric Kimchi, Kevin Staveley-O’Carroll, Guangfu Li. Modulating gut microbiota to improve intrahepatic immunity against hepatocellular cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4116.

Synthesis and characterization of silica nanoparticles from rice ashes coated with chitosan/cancer cell membrane for hepatocellular cancer treatment

Dual pH-sensitive smart nanocarriers based on silica nanoparticles (SNPs) extracted from rice husk ashes (RHAs) to effectively inhibit liver cancer cell proliferation were investigated. The SNPs were coated with chitosan (CH) and loaded with doxorubicin (DOX), then functionalized with cell membrane (CM) for homologous targeting ability. The FTIR spectra showed an absorption wave number at 1083 cm−1 which confirmed the existence of the SiOSi group, ratifying that the nanocarriers belong to silica species. The Korsmeyer-Peppas kinetic model reported R2 values of 0.996 and 0.931 for pH = 5.4 and pH = 7.4, respectively, demonstrating pH-responsive behavior of the nanocarriers. The cytotoxicity test confirmed that the HepG2 cell line treated with different SNP–CH–CM concentrations had no detectable significant cell toxicity, however, SNP–CH–DOX–CM induced greater cell death. In vivo tests revealed that SNP–CH–DOX–CM suppressed liver cancer growth in nude mice, demonstrating high pharmaceutical capability. Histological examination of vital organs showed that the targeted drug delivery system (DDS) had minor in vivo toxicity. In the light of its high treatment efficacy and minimal side effects, the investigated DDS is promising for the therapy of liver cancer.

Cabozantinib in hepatocellular cancer: from preclinical experiments to observational studies

Based on the results of registration studies, the drug cabozantinib, the mechanism of action of which is determined by the inhibition of tyrosine kinases on a relatively wide range of cellular receptors, is registered in the treatment of hepatocellular cancer, kidney cancer and thyroid cancer. This literature review collects data on the mechanism of action, the results of preclinical experiments and phases I–III studies. Emphasis is placed on the tolerability and efficacy of the drug in the population of hepatocellular cancer patients.

Characteristics and treatment strategies for hepatocellular carcinoma caused by nonalcoholic fatty liver disease

In recent years, nonalcoholic fatty liver disease (NAFLD) incidence has rapidly increased, and it is gradually becoming a major contributor to liver cirrhosis and hepatocellular cancer (HCC). The degree of liver fibrosis, diabetes mellitus (DM), obesity, age, and gender are the main risk factors for nonalcoholic steatohepatitis (NASH) progression to HCC. Patients with NASH-related HCC are predominantly male, and almost all of them have at least one metabolic disorder (obesity, DM, dyslipidemia, hypertension, etc.). Most HCCs manifest as solitary tumor nodules and a significant number of NASH-related HCCs are non- cirrhotic. Case fatality rates are similar across patients with cirrhotic and noncirrhotic HCC, despite the fact that patients with noncirrhotic HCC tend to be older, have a single macronodular tumor, and have lower incidence of type 2 diabetes and liver transplantation. Controlling the risk factors for NASH might thereby minimize the likelihood of developing HCC. The BCLC staging system should be used as a guide to treat patients with NASH-related HCC. The long-term outcomes of NAFLD-related HCC treatment are similar to those for other HCCs of different etiologies. However, patients combined with metabolic syndrome are at high perioperative risk, so apporpriate preoperative preparation, especially cardiac examination, is essential to avoid this risk.

Attenuation of N-Nitrosodiethylamine -Induced Hepatocellular Carcinoma by Piceatannol and/or Cisplatin: The Interplay between Nuclear Factor (Erythroid Derived 2)-like 2 and Redox Status.

The natural compound's alternative and complementary uses have increased hopes for hepatocellular cancer treatment (HCC). The goal of this study was to see if Piceatannol (PIC) in combination with cisplatin has a synergistic effect on N, N-nitrosodiethylamine (DEN)-induced HCC in rats. Tissue antioxidant enzymes, malondialdehyde (MDA), and nuclear factor erythroid 2 related factors 2 (Nrf2) and tumor necrosis factor α (TNF-α) gene expression were all measured. Nuclear Factor Kabba B (NF-κB) was also tested, as well as hepatic caspase 3 and NAD (P) H quinone oxidoreductase 1 (NQO1). Liver specimens were subjected to histopathological analysis. When compared to the HCC group, piceatannol and/or cisplatin caused a significant improvement in liver function tests, as well as a significant modulation in Nrf2 gene expression and antioxidant enzyme activities, as well as a significant decrease in tissue MDA, TNF-α, NF-κB levels, NQO1 activity, and prompt and caspase-3 activities. When the PIC and/or cisplatin combination was compared to each of these compounds alone, the results were substantial. PIC in combination with cisplatin has been shown to have a synergistic anticancer impact through modulating Nrf2 and redox state. In addition, adding PIC to an HCC therapy plan that includes chemotherapeutic medicines may boost the efficacy of cisplatin while reducing its negative effects.

Fabrication of novel ruthenium loaded silk fibroin nanomaterials for fingolimod release improved antitumor efficacy in hepatocellular carcinoma

Cancer targeted nanomaterials-based drug delivery systems have been described as promising. In this work, we employed silk fibroin (SF), ruthenium nanomaterials (RuNMs), heptapeptide (T7), and fingolimod (FTY720) to construct a pH-responsive smart nanomaterials drug delivery system. They were spherical with a mean size of around 120 nm, which may have contributed to the improved penetration and retention of the NMs in tumour areas. T7-FTY720@SF-RuNMs had an encapsulation efficiency (EE) of 72.51 ± 4.02%. When the pH of an environment is acidic, the release of FTY720 from nanocarriers is enhanced. T7-FTY720@SF-RuNMs demonstrated increased cellular uptake selective and anticancer efficacy for hepatocellular cancer in both in vitro and in vivo experiments. Additionally, the in vivo biodistribution investigation showed that T7-FTY720@SF-RuNMs could efficiently aggregate in the tumour location, improving their in vivo potential to kill cancer cells. T7-FTY720@SF-RuNMs demonstrated little toxicity to tumour-bearing animals in investigations of histology and immunohistochemistry, showing that the fabricated NMs are biocompatible in vivo. For the treatment of hepatocellular cancer, the T7-FTY720@SF-RuNMs delivery method offers significant promise.

Effect of Comprehensive Nursing Approach in Perioperative Stage of Patients with Hepatocellular Carcinoma Interventional Therapy.

Objective To examine the efficacy of a complete nursing strategy during the perioperative phase for patients undergoing interventional treatment for hepatocellular cancer. Methods Sixty patients who were diagnosed with liver cancer and underwent interventional therapy in our hospital between February 2019 and December 2021 were recruited in this trial. All study subjects were numbered according to the time when the patients first came to our hospital, and were equally divided into a comprehensive group and a conventional group based on the odd and even number of the last number, with 30 cases in each group. Those in the conventional group received conventional nursing care, whereas patients in the comprehensive group received comprehensive nursing care. Before and after the nursing intervention, the quality of life, pain, and patient satisfaction in both groups were compared. Results The quality of survival scores, including physical, emotional, role, social, and cognitive function scores of patients in the comprehensive group, were significantly higher than those in the conventional group (P < 0.05); there was no statistically significant difference in numeric rating scales (NRS) scores between the two groups compared before treatment (P > 0.05). After treatment, the NRS scores of patients in the study group were significantly lower than those of patients in the control group (P < 0.05); before the intervention, the difference between the emotional state scores of patients in the two groups was not significant and not statistically significant (P > 0.05), while the emotional state of patients in both groups improved after the intervention, and the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) scores of patients in the comprehensive group were lower than those in the conventional group (P < 0.05); the total incidence of adverse reactions in the comprehensive group (10.00%) was significantly lower than that in the conventional group (46.67%) (P < 0.05); and the total satisfaction of patients in the comprehensive group (93.33%) was significantly higher than that of patients in the conventional group (73.33%) (P < 0.05). Conclusion The intervention of a comprehensive nursing approach in the perioperative period for patients with liver cancer is remarkable as it can relieve patients' psychological burden and pain, ensure a smooth operation, improve patients' postoperative quality of life, and also help to reduce the risk of postoperative adverse reactions, effectively enhancing patients' satisfaction, and thus deserves to be promoted in clinical practice.

P-243 Impact of relative dose intensity of bevacizumab in first-line treatment of hepatocellular cancer

Atezolizumab-Bevacizumab (AB) is the current standard of care for treatment of unresectable hepatocellular cancer (HCC), with the recommended dosage of bevacizumab at 15mg/kg. Notable adverse events with an incidence of >20% in the AB group include hypertension and proteinuria, consistent with bevacizumab’s distinctive toxicity profile. In the real-world, many physicians choose to use a lower dose of bevacizumab upfront based on patients' comorbidities, anticipated toxicities, and cost considerations. Early phase II data comparing 5mg/kg versus 10mg/kg of bevacizumab in advanced HCC suggested no difference in outcomes, though they were not powered to examine this. In other tumour types like colon cancer, the standard dose of bevacizumab is lower, though there is some data describing higher dose intensity of bevacizumab and improved survival on progression. A relative dose intensity (RDI) of ≥70% is correlated with better overall survival (OS) and radiological responses for other first-line therapies for HCC like Lenvatinib. We sought to examine the dose effect of bevacizumab in the use of AB for HCC treatment. We retrospectively analysed data on patients treated at a single-centre in Singapore who received at least one dose of AB for unresectable HCC between September 2020 and December 2021. RDI over the 1st two doses was calculated as the cumulative dose for those two cycles divided by the weight-based standard dose of bevacizumab. We evaluated the association of RDI ≥70% compared to RDI < 70%, with OS, progression free survival (PFS), and response rate (by RECIST v1.1). 57 patients were included, with a mean age of 65 years. All were ECOG 0 and majority were male (96.49%), Chinese (85.69%), had underlying viral hepatitis (56.14%) and were Child’s-Pugh A (98%) on treatment initiation. 65.91% had BCLC C disease, while the rest had BCLC B disease. Majority used AB as 1st line of systemic therapy (82.46%), and 42.11% achieved a relative dose intensity ≥70%. Patients who had RDI ≥70% were not significantly different from those with RDI < 70% in terms of baseline characteristics such as age, gender, race, cirrhosis etiology, BCLC status, or line of usage of AB (1st or later). Response rates (25.0% vs 18.2%, p = 0.742) and disease control rates (43.8% vs 54.6%, p = 0.435) did not differ between those with RDI ≥70% or < 70%. Median OS was 10.99 months (95% CI, 5.83-NR) in the RDI ≥70% group and did not differ significantly from 10.76 months (95% CI, 8.45-NR) in the RDI < 70% group (HR 0.94; 95% CI, 0.404-2.215). Median PFS was likewise similar in both groups, at 4.04 months (95% CI, 1.01-7.76) in RDI ≥70% and 3.09 months (95% CI, 1.55-NR) in RDI < 70% (HR 0.83; 95% CI, 0.45-1.70). Both OS and PFS remained not significantly different on adjustment for age, gender, BCLC status, viral/non-viral etiologies, and line of usage of AB. Frequency of common adverse events were similar between both groups. We demonstrated that a lower dose of bevacizumab at < 70% RDI achieved similar radiological and survival outcomes as ≥70% when given in combination with atezolizumab for advanced HCC. Use of reduced dose bevacizumab can be considered to reduce cost and toxicity without significantly affecting treatment outcomes. This should be explored further in a prospective setting.

Anticancer activity of hydroalcoholic extract of Enhalus acoroides

Cancer is a major public health concern in both developed and developing countries. Anticancer activity refers to the ability of natural and synthetic, biological and chemical agents to revert, stop, or halt carcinogenic progression. To treat the ailment, several synthetic pharmaceuticals are utilised, but they have negative effects, thus researchers are investigating into plant-derived chemotherapeutic treatments. Enhalus acoroides, a member of the Hydrocharitaceae family, is found along the southeast coast of India and the tropical western Pacific. Hydroalcoholic extract of Enhalus acoroides inhibits the proliferation of Liver cancer and Breast cancer. The cell viability was analysed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, which shows that Hydroalcoholic extract of Enhalus acoroides significantly reduced the growth with IC50 value for HepG2 as 112.20μg/ml and MCF-7 as 101.60μg/ml. Hence the results of current study conclude that Hydroalcoholic extract of Enhalus acoroides is a potent anticancer drug that can be utilized for the treatment of Hepatocellular cancer and Breast cancer.

Prognostic Factors for 10-Year Survival in Patients With Hepatocellular Cancer Receiving Liver Transplantation.

BackgroundLong-term survival after liver transplantation (LT) for hepatocellular cancer (HCC) continues to increase along with the modification of inclusion criteria. This study aimed at identifying risk factors for 5- and 10-year overall and HCC-specific death after LT.MethodsA total of 1,854 HCC transplant recipients from 10 European centers during the period 1987–2015 were analyzed. The population was divided in three eras, defined by landmark changes in HCC transplantability indications. Multivariable logistic regression analyses were used to evaluate the significance of independent risk factors for survival.ResultsFive- and 10-year overall survival (OS) rates were 68.1% and 54.4%, respectively. Two-hundred forty-two patients (13.1%) had HCC recurrence. Five- and 10-year recurrence rates were 16.2% and 20.3%. HCC-related deaths peaked at 2 years after LT (51.1% of all HCC-related deaths) and decreased to a high 30.8% in the interval of 6 to 10 years after LT. The risk factors for 10-year OS were macrovascular invasion (OR = 2.71; P = 0.001), poor grading (OR = 1.56; P = 0.001), HCV status (OR = 1.39; P = 0.001), diameter of the target lesion (OR = 1.09; P = 0.001), AFP slope (OR = 1.63; P = 0.006), and patient age (OR = 0.99; P = 0.01). The risk factor for 10-year HCC-related death were AFP slope (OR = 4.95; P < 0.0001), microvascular (OR = 2.13; P < 0.0001) and macrovascular invasion (OR = 2.32; P = 0.01), poor tumor grading (OR = 1.95; P = 0.001), total number of neo-adjuvant therapies (OR = 1.11; P = 0.001), diameter of the target lesion (OR = 1.11; P = 0.002), and patient age (OR = 0.97; P = 0.001). When analyzing survival rates in function of LT era, a progressive improvement of the results was observed, with patients transplanted during the period 2007–2015 showing 5- and 10-year death rates of 26.8% and 38.9% (vs. 1987–1996, P < 0.0001; vs. 1997–2006, P = 0.005).ConclusionsLT generates long-term overall and disease-free survival rates superior to all other oncologic treatments of HCC. The role of LT in the modern treatment of HCC becomes even more valued when the follow-up period reaches at least 10 years. The results of LT continue to improve even when prudently widening the inclusion criteria for transplantation. Despite the incidence of HCC recurrence is highest during the first 5 years post-transplant, one-third of them occur later, indicating the importance of a life-long follow-up of these patients.