To compare the prognostic power of commonly used staging systems of hepatocellular carcinoma (HCC) for predicting overall survival after transarterial chemoembolization (TACE).

This retrospective single center study included patients with HCC who underwent TACE between 2008 and 2019 in a single tertiary care center. After initial screening of 408 consecutive patients, 317 patients with HCC treated with conventional or drug-eluting beads-TACE were included. Five HCC staging systems (Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, Japan Integrated Staging, Cancer of the Liver Italian Program and Okuda) were compared using Kaplan Meier survival analysis and a log-rank test with overall survival (OS) as the study endpoint. Uni- and multivariate analyses of system-specific variables were applied to stratify outcomes and compare the ability to predict OS of patients after TACE. Four different measures were used to assess the homogeneity (Likelihood ratio:LR), discriminatory ability (linear trend:LT and C-index) and explanatory ability (Akaike Information Criterion:AIC).

The OS of the total cohort was 29.8 months. In terms of prognostic stratification, the BCLC staging system had the best performance (LT: 8.209, LR: 26.639, AIC: 317, c-index: 0.818) compared to HKLC (LT: 10.919, LR: 25.802, AIC: 443, c-index: 0.835), JIS (LT: 4.611, LR: 16.880, AIC: 449, c-index: 0.548), CLIP (LT: 6.738, LR: 13.109, AIC: 501, c-index: 0.782), and Okuda (LT: 7.185, LR: 0.760. LR: 16.356, AIC: 487, c-index: 0.760).

Across five commonly utilized international staging systems, the BCLC staging system demonstrated the greatest prognostic accuracy with respect to predicting OS of patients undergoing TACE.

HCC is the fourth leading cause of cancer-related mortality with increasing incidence worldwide. Historically, treatment for early disease includes liver transplantation, surgical resection, and/or other local therapies, such as thermal ablation. As a result of technical advances and high-quality prospective data, the use of definitive external beam radiotherapy with ablative doses has emerged. Intermediate-stage disease has been generally addressed with arterially directed therapies (eg, chemoembolization or radioembolization) and external beam radiotherapy, while advanced stages have been addressed by systemic therapy or best supportive care. The role of each local/locoregional therapy has rapidly evolved in the context of novel pharmacotherapies, including immunotherapies and antiangiogenic agents. The combinations, indications, and timing of treatments vary widely among specialties and geographies. Here, we aim to synthesize the best quality evidence available regarding the efficacy and safety of different liver-directed modalities, with a focus on recent prospective clinical data of external beam radiotherapy within the context of other available liver-directed therapies across Barcelona Liver Classification (BCLC) stages.

Changes in liver function in patients with unresectable hepatocellular carcinoma (u-HCC), following extended periods from the initiation of atezolizumab plus bevacizumab (Atez/Bev), have not been fully investigated.

Of 148 u-HCC patients treated with first-line Atez/Bev, the study enrolled 38 u-HCC patients treated with first-line Atez/Bev, whose treatment response was initially evaluated as non-progressive disease (non-PD) and later as PD on imaging, and who then received second-line systemic chemotherapy. We evaluated the relationship between the period from the initiation of first-line Atez/Bev to that of second-line systemic chemotherapy with liver function and prognosis.

According to the periods from the initiation of Atez/Bev to that of the second-line therapy, patients were classified into a long continuation group (Group-L, n = 19), ≥11 months; or a short continuation group (Group-S, n = 19), <11 months. The albumin-bilirubin (ALBI) score at the initiation of the second-line therapy did not differ significantly between the groups (median: -2.38 vs. -2.02, p = 0.559), and the change in ALBI score also did not differ significantly between the groups (median: 0.42 vs. 0.51, p = 0.770). Group-L had significantly better overall survival (OS) than Group-S (not reached vs. 18 months, p = 0.008).

Liver function did not decrease even after long-term treatment with first-line Atez/Bev in patients who were able to progress to second-line therapy, indicating that long continuation of first-line Atez/Bev may be valuable for improving OS.

Identifying alpha-fetal protein (AFP)-negative focal hepatic lesions presents a significant challenge, particularly in China. We sought to develop an economically portable tool for the diagnosis of benign and malignant liver lesions with AFP-negative status, and explore its clinical diagnostic efficiency.

A retrospective study was conducted at Peking University Shenzhen Hospital from January 2017 to February 2023, including a total of 348 inpatients with AFP-negative liver space-occupying lesions. The study used a training set of 252 inpatients from January 2017 to September 2021 to establish a diagnostic model for differentiating benign and malignant AFP-negative liver space-occupying lesions. Additionally, a validation cohort of 96 inpatients from October 2021 to February 2023 was used to confirm the diagnostic performance of the model. From January 2017 to February 2023, patients at JingNing People's Hospital, Gansu Province were assigned to the external cohort (n = 78).

A predictive tool was established by screening age, gender, hepatitis B virus (HBV)/hepatitis C virus (HCV) infected, single lesion, alanine amino transferase (ALT), and lymphocyte-to-monocyte ratio (LMR) using multivariate logistic regression analysis and clinical practice. The area under the curve (AUC) of the model was 0.911 (95% CI [0.873-0.949]) in the training set and 0.882 (95% CI [0.815-0.949]) in the validation cohort. In addition, the model achieved an area under the curve of 0.811 (95% CI [0.687-0.935]) in the external validation cohort.

Our results demonstrated that the predictive tool has the characteristics of good diagnostic efficiency, economy and convenience, which is helpful for the clinical triage and decision-making of AFP-negative liver space-occupying lesions.

Spontaneous rupture is a fatal complication of advanced hepatocellular carcinoma (HCC) with an extremely poor prognosis. Although immune checkpoint inhibitors, targeted therapies, and nutritional therapy have shown potential in the treatment of advanced HCC, their combined efficacy in complex cases with high tumor burden complicated by rupture and bleeding remains unclear.

A 54-year-old male patient was diagnosed with Barcelona Clinic Liver Cancer (BCLC) stage C HCC with high tumor burden, accompanied by a history of chronic hepatitis B and moderate malnutrition. After initial treatment with apatinib (500 mg/day) and nutritional therapy, the patient experienced HCC rupture. Following emergency transarterial embolization for hemostasis, the treatment regimen was adjusted to camrelizumab (200 mg/2 weeks) combined with reduced-dose apatinib (250 mg/day), along with continued nutritional support. After 17 months of treatment, the patient underwent hepatectomy, with pathological examination showing complete remission in the left liver. Postoperative adjuvant therapy included transarterial chemoembolization, nutritional therapy, targeted therapy, and individualized immunotherapy. As of the 4-year follow-up, the patients has good quality of life and has not experienced recurrence.

This case showcases a multimodal treatment strategy for patients with advanced HCC with high tumor burden and rupture complications, integrating individualized immuno-targeted therapy, interventional treatment, and nutritional management and providing a possible approach for achieving a long-term survival. This comprehensive treatment method may offer new insights into improving the prognosis of patients with advanced HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide and a major cause of death in cirrhosis. The prognosis of HCC is poor, with a mortality rate close to the morbidity rate. Once HCC develops distant metastasis, the area affected by the cancer cells is significantly enlarged, and there is still no effective treatment for HCC. Therefore, the development of effective drugs is essential to improve the survival rate of HCC patients. We designed and optimised a delivery system for compound 1, derived from camptothecin extract, by developing a multifunctional fluorescent drug delivery platform composed of polylactic acid (PLA), chitosan (CS), and fluorescein isothiocyanate (FITC) (PLA-CS-FITC). This system successfully encapsulated CP1 and compound 1, forming a PLA-CS-FITC@CP1@1 composite nanocarrier with dual functions for drug delivery and real-time fluorescence monitoring. The effects of the system on HCC proliferation and its regulation were evaluated by treating HCC cells in vitro, which provided an experimental basis for the development of drugs for HCC.

In chronic hepatitis C (CHC), the virus may induce autoimmune responses via autoantibodies production, including antinuclear antibodies (ANA). Former studies reported great ANA predisposition in CHC and these ANAs may be related to worse prognosis including hepatocellular carcinoma (HCC). We aimed to evaluate the association between ANA incidence and CHC-related HCC development and to evaluate these molecules effect on HCC severity including tumor size and advanced stages. Results revealed that ANA seropositivity was associated with disease severity. HCC patients (54%, OR = 9.7) were associated with ANA positivity more than liver cirrhosis (24.5%) and fibrosis (10.8%). ANA positivity was significantly high in patients with severe tumor features including macrovascular invasion (61.9%; OR = 8.1), large size (68.2%; OR = 2.4), Child C (83.3%; OR = 8.1), BCLC end stage (83.3%; OR = 8.6) and advanced CLIP stage (80.9%; OR = 7.9). ANA positivity were significantly (p < 0.05) correlated with some estimated liver fibrosis related biomarkers including EMA (r = 0.206), fibronectin (r = 0.273), cytokeratin-1 (r = 0.365) and collagen III (r = 0.324). In conclusion, our observation of increased ANA+ serum samples among CHC-related HCC might suggest the oncogenic role of ANA in such patients. Also, clinicians need to appreciate value of ANA testing among HCC patients as these molecules were associated with tumor severity and worse outcomes.

Few studies have compared survival outcomes between liver resection (LR) and percutaneous radiofrequency ablation (RFA) for treating solitary 3-5 cm hepatocellular carcinoma (HCC). We aimed to clarify this issue.

Patients with Child-Pugh class A liver disease and a solitary HCC of 3-5 cm without macrovascular invasion or extrahepatic metastasis who underwent LR or percutaneous RFA between 2011 and 2021 were enrolled in this retrospective study; 310 patients underwent LR and 114 patients underwent percutaneous RFA. Propensity score matching (PSM) was used to balance baseline variables, including age, sex, alpha-fetoprotein level, and Model for End-Stage Liver Disease score, between the two groups.

Before PSM, 5-year overall survival (OS) and recurrence-free survival (RFS) were significantly lower in the percutaneous RFA group than in the LR group (both p < 0.001). After PSM, 5-year OS was comparable between the two modalities (p = 0.367); however, 5-year RFS was significantly lower in the RFA group than in the LR group (p = 0.001). The two modalities did not differ in severe post-treatment complications (p = 1.000).

Five-year OS did not differ between treatment modalities for patients with a solitary HCC of 3-5 cm; however, the LR group's 5-year RFS was superior. LR should be recommended as the first-line treatment for these patients.

This retrospective study aimed to confirm the safety and long-term efficacy of a single-session combined treatment approach with transcatheter arterial embolization (TAE) and microwave ablation (MWA) for inoperable small-to intermediate-sized hepatocellular carcinomas (HCC), focusing on their combined benefits for improving local control.

All consecutive patients with up to 2 small-to-intermediate HCC lesions (≤ 5 cm) treated with a combined single-session MWA-TAE approach were enrolled between April 2020 and October 2023. All procedures were performed in two stages: TAE and MWA. Clinical and radiological follow-up was performed 3, 6, and 12 months after treatment.

In the 21 enrolled patients (15 males, mean age 75.9 years), post-procedural contrast-enhanced CT scans confirmed a satisfactory ablation zone in all patients (100%), with minor peri-procedural complications reported in three patients (14%). At the last 12-month follow-up, one patient (8%) displayed local tumor progression, previously classified as LR-TR equivocal at the 6-month follow-up, and half of the patients (6 patients, 50%) exhibited distant tumor progression, predominantly in the form of intra-hepatic recurrence.

The combined approach of TAE and MWA is a promising method to enhance the percutaneous treatment of small to intermediate-sized HCCs with a resulting anatomic ablation area resembling a surgical sub-segmentectomy. This technique can potentially reduce the gap between percutaneous treatment and liver resection outcomes, allowing for a safe and effective option for oncological control in patients with > 3 cm lesions.

While liver resection remains the best curative option for hepatocellular carcinoma (HCC), it is unclear whether the consistent progress of multidisciplinary approaches in managing HCC over several decades has influenced the outcomes of liver resection.

Patients undergoing liver resection for HCC from 1993 to 2022 in our institution were retrospectively assessed and stratified into three periods according to the year of liver resection, P1 (1993-2000), P2 (2001-2009), and P3 (2010-2022), and tumor status using the Barcelona Clinic Liver Cancer (BCLC) staging system.

A total of 1257 patients were included (P1:P2:P3 = 385:490:382, BCLC stage 0/A:B:C = 908:214:135). In the entire cohort, long-term surgical outcomes significantly improved across the three periods. In BCLC stage 0/A HCC, the 5-year overall survival (OS) rate improved from P1 to P3 (P1: 65.5 %, P2: 71.3 %, P3: 80.4 %), with HRs of 0.655 (95 % CI: 0.536 to 0.800) and 0.595 (95 % CI: 0.455 to 0.778) for P2 vs. P1 and P3 vs. P1, respectively. Conversely, limited advancements were observed in patients with BCLC stage B or C HCC. Multivariate analysis in BCLC stage 0/A patients demonstrated that ICGR15 > 15 %, ALBI grade 2 or 3 (vs. 1), multiple tumors, microvascular invasion, and surgical period (P2 vs.P1) remained independent poor prognostic factors for OS.

Substantial advancements in the long-term outcomes for HCC patients undergoing liver resection, particularly in BCLC stage 0/A, were observed, while minimal improvement was noted for BCLC stage B and C.

Solid tumours are intricate and highly heterogeneous ecosystems, which grow in and invade normal organs. Their progression is mediated by cancer cells' interaction with different cell types, such as immune cells, stromal cells and endothelial cells, and with the extracellular matrix. Owing to its high incidence, aggressive growth and resistance to local and systemic treatments, liver cancer has particularly high mortality rates worldwide. In recent decades, spatial heterogeneity has garnered significant attention as an unfavourable biological characteristic of the tumour microenvironment, prompting extensive research into its role in liver tumour development. Advances in spatial omics have facilitated the detailed spatial analysis of cell types, states and cell‒cell interactions, allowing a thorough understanding of the spatial and temporal heterogeneities of tumour microenvironment and informing the development of novel therapeutic approaches. This review illustrates the latest discovery of the invasive zone, and systematically introduced specific macroscopic spatial heterogeneities, pathological spatial heterogeneities and tumour microenvironment heterogeneities of liver cancer.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.

Currently, therapeutic combinations of immune checkpoint inhibitors (ICIs) with anti-angiogenic agents have shown promising outcomes and have the potential to establish a new standard of care. The efficacy and safety of the first-line combination of envafolimab (an ICI) and lenvatinib (an anti-tumor angiogenesis drug) for the treatment of patients with inoperable hepatocellular carcinoma (HCC) have not been demonstrated. Unresectable HCC patients with an Eastern Cooperative Oncology Group (ECOG) physical status score ≤ 1 and a Child-Pugh score ≤ 7 who had not received systemic therapy were included in this single-arm, exploratory, multicentre phase II clinical study. All patients were required to meet the criteria of being at least 18 years of age, having no history of other malignancies, and existing at least one measurable lesion. The patients were treated with envafolimab (150 mg, QW, subcutaneous) in combination with lenvatinib (12 mg for patients weighing over 60 kg, 8 mg for patients weighing under 60 kg). The co-primary endpoint of the study was overall survival (OS), while surrogate endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Between March 2022 and April 2023, 36 patients were enrolled, 30 of whom were treated with envafolimab plus lenvatinib. At data cutoff, the median follow-up duration was 20 months (95% CI 18.9-21.1). Among the 30 assessable patients (patients treated according to the trial protocol), the median overall survival (mOS) and median progression-free survival (mPFS) for the therapy comprising envafolimab alongside lenvatinib were 18.5 months (95% CI 13.2-23.8) and 9.4 months (95% CI 1.6-15.6), respectively. The ORR and the DCR (evaluated according to mRECIST criteria) reached 40% and 80%, respectively. In terms of safety, 23 patients (76.7%) experienced at least one treatment-related adverse event (TRAE), of which the most common was elevated aspartate aminotransferase (AST, 23.3%). Furthermore, grade 3 and higher TRAEs occurred in 30%. This study demonstrates that envafolimab in combination with lenvatinib exhibits favourable anti-cancer activity and a manageable safety profile for the first-line treatment of patients with unresectable HCC.

Laparoscopic microwave ablation (LMWA) has yet to gain a specific place in treatment guidelines for early hepatocellular carcinoma (HCC). This study compared the outcomes of LMWA and trans-arterial chemoembolization (TACE) for early non-resectable patients with HCC, taking percutaneous radiofrequency ablation (PRFA) as the reference treatment.

A retrospective multicenter observational study was conducted, enrolling non-transplantable, non-resectable patients who had early HCC treated with LMWA (n = 658) from Padua and Milan centers, and with PRFA (n = 844), and TACE (n = 425) from the ITA.LI.CA multicenter database. The matching-adjusted indirect comparison (MAIC) method was used to obtain weighted LMWA and TACE populations similar to the reference PRFA population.

Laparoscopic ablation showed an excellent safety profile, and MAIC-weighted early postoperative deaths were comparable among the groups. The MAIC-weighted overall survival was similar between the LMWA (1-, 3-, and 5 year survival of 91.0 %, 67.9 %, 47.0 %, respectively) and PRFA (1-, 3- and 5 year survivals of 90.0 %, 64.7 %, 46.6 %, respectively) groups (p = 0.678) and significantly better for the LMWA group than for the TACE group (1-, 3- and 5 year survivals of 84.7 %, 48.8 %, 33.6 %, respectively) (p < 0.001). Weighted multivariate overall survival analysis and competing risk/subgroup analyses confirmed the non-inferiority of LMWA to PRFA and its superiority to TACE. The LMWA- and PRFA-treated patients had a significantly lower risk of HCC-related death (p = 0.004) than the TACE-treated patients (p = 0.001). Conversely, the groups did not differ significantly in terms of non-HCC-related deaths.

The non-inferiority of LMWA to PRFA, its superiority to TACE, and its applicability to a wide range of presentations with few contraindications support its inclusion among radical therapies for treating early-HCC patients.

Spontaneous regression (SR) of malignant tumors is defined as the partial or complete reduction of a tumor without medical intervention. This unusual phenomenon has been reported in various types of malignancies. We present a rare case of a 73-year-old woman with untreated chronic hepatitis C who was diagnosed with extensively diffused hepatocellular carcinoma (HCC) accompanied by a tumor thrombus in the left branch of the portal vein. Remarkably, extensive tumor regression occurred under palliative care. This case highlights the potential mechanisms responsible for SR of HCC, including tumor hypoxia, immune activation, and systemic inflammatory responses, and emphasizes the need for further research to clarify these mechanisms.

Standard treatments provide limited benefits for patients with intermediate- or advanced-stage hepatocellular carcinoma (HCC). This retrospective observational study aimed to assess the potential improvements in outcomes associated with systemic therapies in patients receiving transarterial chemoembolization (TACE) for initially unresectable HCC.

Between February 2019 and March 2023, we reviewed patients diagnosed with intermediate-to-advanced HCC who were treated with either TACE or TACE combined with antiangiogenic agents and immune checkpoint inhibitors (combination therapy) as their initial treatment. To address potential confounding biases, patients were further stratified into surgical and non-surgical cohorts, and separate analyses were conducted. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety profiles also evaluated.

Among 279 patients with initially unresectable intermediate or advanced HCC, 156 successfully underwent curative-intent liver resection after preoperative treatments (TACE group, n = 69; combination group, n = 87), while 123 patients continued with non-surgical treatments (TACE group, n = 31; combination group, n = 92). After propensity score matching, 26 matched patient pairs were generated within the non-surgical cohort. The combination group exhibited significantly improved PFS in non-surgical patients compared with the TACE group (9.4 vs. 7.2 months, p = 0.043). Cox proportional hazards analysis further confirmed that combination therapy was associated with improved PFS (hazard ratio = 0.476, 95% confidence interval: 0.257-0.883, p = 0.019). For surgical patients exceeding the up-to-seven criteria, the combination group demonstrated superior median PFS (18.0 vs. 14.6 months, p = 0.03) and OS (not reached vs. 50.1 months, p = 0.049) compared with the TACE group. Adverse events were manageable, with no treatment-related fatalities reported.

Combination therapy with TACE demonstrated enhanced survival benefits for patients with intermediate to advanced HCC, particularly in surgical patients with higher tumor burdens.

To assess the relationship between survival outcomes and subtypes of radiological progressive disease (PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atezo/Bev).

A total of 462 patients with Atezo/Bev-treated HCC diagnosed with radiological PD during follow-up were enrolled. PD was classified into three categories: progression or emergence of intrahepatic lesions (PD-IH), macroscopic vascular invasion (PD-MVI), and extrahepatic spread lesions (PD-EHS). We defined PD-multiple as the presence of two or more PD categories. Subsequent analysis was categorized into the "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" groups.

The median progression-free survival (PFS) durations for patients with PD-IH, PD-MVI, PD-EHS, and PD-multiple were 5.3, 3.2, 3.9, and 3.5 months (p = 0.003). Patients with "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" had median PFS of 5.2 and 3.5 months (p < 0.001). Median overall survival (OS) for PD-IH, PD-MVI, PD-EHS, and PD-multiple was 22.3, 15.1, 19.4, and 14.2 months (p = 0.002). The OS for patients with "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" was 21.4 and 14.5 months (p < 0.001). Multivariate analysis demonstrated that ECOG-PS ≥ 1 (hazard ratio (HR), 1.508), α-fetoprotein levels ≥ 100 ng/mL (HR, 1.293), albumin-bilirubin grade ≥ 2 (HR, 1.573), liver cirrhosis (HR, 1.361), and PD subtypes PD-MVI or PD-multiple (HR, 1.735) were independently associated with OS.

Patients with HCC undergoing Atezo/Bev treatment, diagnosed with PD-multiple (not solely based on IH or EHS) or PD-MVI, experienced poor prognosis, specifically in terms of OS.

Malnutrition affects the prognosis and response to treatment in cancer patients. There is no gold standard for nutritional assessment in patients with hepatocellular carcinoma (HCC). This study aimed to compare Patient-Generated Subjective Global Assessment (PG-SGA) and Mini Nutritional Assessment (MNA) in predicting mortality in HCC patients.

We included HCC patients in the outpatient clinic at HRH Maha Chakri Sirindhorn Medical Center. The nutritional status was assessed according to PG-SGA and MNA. Patients were followed up for 1 year to verify the incidence of death and complications.

Eighty-nine HCC patients were included. The mean age was 62.2 years. Most of the patients were treated with transarterial chemoembolization. Malnutrition identified by PG-SGA and MNA was 53.9% and 51.7%, respectively. The mortality rate was 2.65 cases per 100 persons. Overall survival rate was 90% and 81.5% at 12 and 24 months, respectively. Patients with malnutrition assessed by PG-SGA and MNA had significantly higher mortality than patients without malnutrition. PG-SGA had a sensitivity of 80% for predicting mortality. PG-SGA had higher accuracy for predicting the mortality of HCC patients than MNA (AUROC PG-SGA 0.7148 and MNA 0.7098).

HCC patients with malnutrition were evaluated by PG-SGA and MNA had higher mortality than HCC patients without malnutrition. PG-SGA had higher accuracy in predicting mortality than MNA.

Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally due to HCC late diagnosis and limited treatment options. MiRNAs (miRNAs) emerged as potential biomarkers for various diseases, including HCC. However, the value of miRNA-101 as a serum biomarker for HCV-induced HCC has not been fully investigated. Our study aims to investigate the miRNA-101 differential expression in Egyptian HCV-induced HCC patients' serum versus HCV liver cirrhosis (LC) as prospective diagnostic biomarkers compared to alpha-fetoprotein (AFP). Blood samples were collected for clinical chemistry profile, liver function, and serum AFP investigations. The serum miR-101 expression levels were evaluated using real-time quantitative PCR (RT-qPCR) in 100 Egyptian subjects: 40 HCV-induced HCC, 40 HCV-induced cirrhosis, and 20 healthy controls. HCC patients showed significantly higher TB, DB, and AFP levels than those cirrhosis and control groups, whereas ALB and Total Protein exhibited significantly reduced levels. AFP sensitivity and specificity in differentiating HCC reported 60 and 67%, respectively, at the cut-off values of 7ng/dl. miR-101 shows fold change upregulation in HCC patients (P < 0.0001) compared to LC and control groups. ROC curve demonstrated miR-101 (AUC) of 0.9556, sensitivity 92.5%, and specificity 97.5%, highlighting the miR-101 diagnostic potential as a biomarker for HCC detection. Elevated miR-101 levels in HCC are significantly correlated with a higher number and larger size of focal lesions, advanced BCLC staging, and Child-Pugh score. These findings highlight the utility of miR-101 as a predictive and diagnostic non-invasive biomarker for HCV-related HCC from cirrhotic populations. More research is warranted to validate the clinical validity of miR-101 and explore underlying mechanisms in HCV-HCC progression.

Personalized precision medicine can be facilitated by clinically available preoperative microvascular invasion (MVI) prediction models that are reliable and postoperative MVI pathological grade-related recurrence prediction models that are accurate. In this study, we aimed to compare different mathematical models to derive the best preoperative prediction and postoperative recurrence prediction models for MVI.

A total of 143 patients with hepatocellular carcinoma (HCC) whose clinical, laboratory, imaging, and pathological data were available were included in the analysis. Logistic regression, Cox proportional hazards regression, LASSO regression with 10-fold cross-validation, stepwise regression, and random forest methods were used for variable screening and predictive modeling. The accuracy and validity of seven preoperative MVI prediction models and five postoperative recurrence prediction models were compared in terms of C-index, net reclassification improvement, and integrated discrimination improvement.

Multivariate logistic regression analysis revealed that a preoperative nomogram model with the variables cirrhosis diagnosis, alpha-fetoprotein > 400, and diameter, shape, and number of lesions can predict MVI in patients with HCC reliably. Postoperatively, a nomogram model with MVI grade, number of lesions, capsule involvement status, macrovascular invasion, and shape as the variables was selected after LASSO regression and 10-fold cross-validation analysis to accurately predict the prognosis for different MVI grades. The number and shape of the lesions were the most common predictors of MVI preoperatively and recurrence postoperatively.

Our study identified the best statistical approach for the prediction of preoperative MVI as well as postoperative recurrence in patients with HCC based on clinical, imaging, and laboratory tests results. This could expedite preoperative treatment decisions and facilitate postoperative management.

Several HCC risk stratification scores were developed; however, none has been prospectively validated. The primary aim is to validate the clinical utility of six HCC risk scores in large prospective study of F3-4 patients achieving SVR following DAAs according to EASL guidelines. The secondary aim is to explore whether individualized risk stratification improves detection of HCC at early stages amenable to curative treatment.

This prospective study included two cohorts: Egyptian Liver Research Institute and Hospital (ELRIAH) cohort of 463 chronic HCV patients with advanced liver disease (F3 and F4) achieved SVR with a follow-up every 6 months according to EASL guidelines using 6 simple HCC risk scores and Tanta cohort of 492 comparable patients where individualized surveillance intervals were tailored based on HCC risk assessments using GES score as follows: low-risk patients were followed yearly, intermediate-risk every 6 months and high-risk every 2-3 months.

All scores, except Watanabe post, successfully stratified patients into low-, intermediate- and high-risk groups, with log-rank p-value of 0.001 and Harrell's C ranging from 0.669 to 0.728. Clinical utility of these scores revealed that the highest percentage of patients classified as low risk was 42.5% using the GES, while the lowest was 8.9% using the aMAP. ELRIAH cohort, 25 patients developed HCC with 52% diagnosed at BCLC 0 and A. Tanta cohort, 35 patients developed HCC, with 80% diagnosed at BCLC 0 and A.

Individualized risk stratification using HCC risk scores was associated with improved early-stage detection and receipt of curative treatment.

Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, the incidence of which is rising globally. Despite recent advancements in immunotherapeutic and surgical treatment modalities, the prognosis for HCC remains poor. The surgical treatment strategy for HCC comprises a multimodal effort that ranges from ablative therapy and surgical resection to liver transplantation. Thanks to collective efforts from the surgical society, there have been rapid advances in resection strategies, such as 3D printing for surgical planning and minimally invasive techniques to minimize surgical trauma. This review examines recent advancements in surgical techniques, patient selection criteria, and perioperative management for HCC resection. The purpose of this review was to provide clinicians and researchers with an up-to-date perspective on the evolving role of surgical resection in HCC treatment, and to identify key areas for future investigation to improve patient outcomes.

Human leukocyte antigen-G (HLA-G) is a cancer-associated immune checkpoint protein implicated in tumor-driven immune escape mechanisms. This study was undertaken to determine genetic variations at the 3'-UTR of the HLA-G gene that may alter its expression, identify risk alleles and genotypes for their association with hepatocellular carcinoma (HCC), and treatment responses in the Indian population.

Case-control genetic association study of HLA-G gene UTR polymorphisms with HCC and response to locoregional therapy (LRT).

HCC cases (n = 100) and healthy controls (n = 110) were recruited for the genetic association study, of which 88 patients received LRT. Single nucleotide polymorphisms (SNPs) at the HLA-G 3'-UTR gene were genotyped by sequencing and PCR-RFLP. The genetic association of 14 SNPs with HCC and LRT responses was determined using population genetic approaches.

Three of the 14 SNPs (rs1707, rs1710, and rs1063320) were found to be genetically associated with HCC risk and treatment responses. These three UTR SNPs are important for miRNA binding. We did not observe significant association of the most studied SNP, rs371194629 (INDEL, +2960), with HCC or treatment response. Serum sHLA-G levels were found to be significantly (p = 0.027) higher in HCC patients as compared to healthy controls. Highly prevalent UTR haplotypes in Indian HCC patients were UTR-4, -1, and -7 whereas in healthy controls it was UTR-3, and 15 as determined by a linkage disequilibrium (LD) plot using 8 SNPs.

HLA-G SNPs are genetically associated with HCC and treatment response. Haplotypes associated with high levels of HLA-G expression are more prevalent in HCC than in healthy controls.

Population genetic approaches were used to study HLA-G gene polymorphisms in the Indian population for its genetic association with HCC risk, treatment response and altered gene expression. Out of the 14 SNPs studied for HLA-G UTR, three were linked to HCC and response to locoregional therapy. Linkage disequilibrium and UTR haplotyping analysis show that the UTR-4 haplotype linked to high HLA-G levels, is more common in HCC patients, while the UTR-3 haplotype, linked to low HLA-G levels, is more common in healthy controls. This study is the first to look at the UTR types based on HLA-G gene polymorphisms of Indian HCC patients and their response to therapy.

Topoisomerase is a ubiquitous enzyme in the control of DNA chain topology. There have been extensive research on topoisomerase inhibitors derived from natural sources, which act as partial inducers of tumor cell apoptosis. However, their specific efficacy in treating hepatocellular carcinoma is relatively unexplored. Hence, this comprehensive review focuses on the structural characteristics and anti-cancer properties of topoisomerase inhibitors in hepatocellular carcinoma. Furthermore, this review is also elucidating the mechanism of action, structure-activity relationships, therapeutic limitations, stage of clinical trials of described classes of natural bioactive compounds as well as their potential application in cancer chemotherapies. This broad understanding of topoisomerase medical biology will provide indispensable framework for enhancing the efficiency of rational anti-hepatocellular carcinoma drug discovery.

Hepatocellular carcinoma (HCC) is one of the most common forms of primary liver cancer worldwide. Herein, we present a review article that provides a broad overview of the current landscape of HCC, including the etiology, potential risk factors, and molecular pathways that can serve as potential therapeutic targets. The risk factors tend to vary depending on the geographic distribution; hepatitis B-induced cirrhosis and HCC occur more frequently in Asia and Sub-Saharan Africa, whereas metabolic disorders are the culprits in Western Europe and the Americas. The exact molecular alterations that drive hepatocarcinogenesis have yet to be elucidated; however, a complex interplay exists between oxidative stress and chronic inflammation. Diagnostic modalities such as tri-phasic MRI or CT also have distinct patterns for HCC, which aid significantly in diagnosis. Furthermore, the review aims to highlight treatment strategies, including transplantation, locoregional radiation therapies, and interventional radiological techniques such as chemotherapy or radioembolization. Finally, systemic therapies will be discussed, taking advantage of molecular pathways that influence cellular proliferation and survival as well as immunotherapy.

The Ohio Opportunity Index (OOI) is a multidimensional metric used to quantify neighborhood-level resources to access a wide array of factors that influence health. This study examined the relationship between neighborhood opportunity and completion of guideline-concordant hepatocellular carcinoma (HCC) screening in patients with cirrhosis.

This retrospective study included patients with cirrhosis and HCC who received care at The Ohio State University Wexner Medical Center between 1/1/2015 and 12/31/2021. High opportunity was defined as a score greater than the third quartile of the study cohort. Modified Poisson regression models with robust variance examined the association, on the prevalence ratio (aPR) scale, between guideline-concordant HCC screening and high neighborhood opportunity status.

This study included 157 cirrhosis patients newly diagnosed with HCC. Only 25.5 % of the patients completed HCC surveillance within 6 months prior to diagnosis. The OOI was a significant predictor of adherence in all models. For every ten-percentile increase in OOI score, there was a consistent increase in the prevalence ratio (PR) of pre-diagnosis HCC surveillance (PR=1.37, 95 % CI 1.10-1.71). This effect remained significant after controlling for sociodemographic, clinical, and cirrhosis-related variables (adjusted PR=1.38, 95 % CI 1.02-1.85. Compared to those with high OOI (i.e.,≥Q3), patients in the lowest opportunity quartile had a 64 % lower prevalence of HCC screening (PR=0.36, 95 % CI 0.26-0.50).

Neighborhood opportunity status has a dose-dependent effect on HCC surveillance adherence in patients with cirrhosis. Future studies should identify neighborhood-level interventions to reduce socioeconomic disparities in HCC diagnosis and outcomes.

Durvalumab plus tremelimumab (Durva/Treme) has recently been approved as a first-line or later-line treatment for patients with unresectable hepatocellular carcinoma (u-HCC) in Japan. We assessed the real-world outcomes of Durva/Treme for u-HCC, with a focus on treatment efficacy and safety.

We retrospectively evaluated 22 patients with u-HCC treated with Durva/Treme at Iwate Medical University during the period from 2023 to 2024, with a comparison of the clinical outcomes between patients who received Durva/Treme as first-line and later-line treatments. We further evaluated changes in the modified albumin-bilirubin (mALBI) grade during treatment.

There were 10 patients in the first-line group and 12 patients in the later-line treatment group. During the follow-up with a median duration of 7.6 months, the median progression-free survival (first-line versus later-line: 4.7 months versus 2.9 months, p = 0.85), the objective response rate (0.0% versus 16.7%, p = 0.48), the disease control rate (60.0% versus 58.4%, p = 1.00), and the incidence of any adverse event (50.0% versus 75.0%, p = 0.38) were not statistically different between the two groups. The changes in the mALBI scores were not statistically significant (p = 0.75).

Durva/Treme may be effective and safe for patients with u-HCC, even in patients who receive Durva/Treme as a later-line treatment.

Switching to systemic therapy after transarterial chemoembolization (TACE) refractoriness is more inclined to preserve liver function and decrease disease progression. Hence, we conducted a comparison between the advantages of sorafenib therapy and the continuation of TACE in patients with intermediate-stage hepatocellular carcinoma (HCC) who developed TACE refractoriness.

This retrospective cohort work involved 1,200 patients with HCC who received TACE therapy at our institution between January 2018 and December 2022. Out of these, a total of 436 participants were determined to be resistant to TACE treatment throughout their clinical progression. Out of them, 271 were finally included and categorized into two groups: (1) patients who shifted from TACE to sorafenib, and (2) patients who maintained TACE treatment. The study assessed the overall survival (OS) and time to disease progression (TTDP) of patients who were resistant to TACE, comparing both groups based on when they achieved Child-Pugh C or acquired advanced-stage HCC.

Following confirmation of refractoriness to TACE therapy, 163 opted to continue with TACE (TACE group), whereas 108 shifted to sorafenib treatment (sorafenib group). The median TTDP was 23.36 months, while the median OS was 25.3 months, in the sorafenib group, and 11.6 and 14.2 months, correspondingly, in the TACE group (p = 0.0001).

Switching to sorafenib treatment significantly improved OS and TTDP in patients with intermediate-stage HCC who were refractory to TACE. These finding highlights sorafenib's potential as an effective alternative for managing disease progression in patients unresponsive to TACE, offering a valuable treatment option in this challenging clinical scenario.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the third leading cause of cancer-related deaths. Imaging plays a crucial role in the screening, diagnosis, and monitoring of HCC; however, the potential mechanism regarding phenotypes or molecular subtyping remains underexplored. Radiomics significantly expands the selection of features available by extracting quantitative features from imaging data. Radiogenomics bridges the gap between imaging and genetic/transcriptomic information by associating imaging features with critical genes and pathways, thereby providing biological annotations to these features. Despite challenges in interpreting these connections, assessing their universality, and considering the diversity in HCC etiology and genetic information across different populations, radiomics and radiogenomics offer new perspectives for precision treatment in HCC. This article provides an up-to-date summary of the advancements in radiomics and radiogenomics throughout the HCC care continuum, focusing on the clinical applications, advantages, and limitations of current techniques and offering prospects. Future research should aim to overcome these challenges to improve the prognosis of HCC patients and leverage imaging information for patient benefit.