Malignant Liver Tumors Research Articles

Gradual expansion of the indications for minimally invasive liver resection to include highly complex procedures may improve postoperative outcomes

Aim: Liver resection is performed in patients with benign and malignant liver tumors. Advancements in surgical instruments and improved perioperative management have enabled safe laparoscopic and robotic liver resections. Herein, we aimed to evaluate the patients who underwent minimally invasive liver resection (MISLR) and compare their short-term outcomes with those of patients who underwent open liver resection (OLR), according to surgical complexity. Methods: Data of patients who underwent liver resection at our institution from January 2011 to August 2023 were obtained from a prospectively maintained database. We gradually expanded the indications for MISLR from technically less demanding procedures to intermediate- and high-complexity MISLRs. The procedures were categorized into three grades (low, intermediate, and high) according to the liver resection complexity classification. Results: Of the 1,866 patients who underwent liver resection, 953 were included in the analysis. Of the 953 patients, 781 underwent OLR and 172 underwent MISLR. The operative time and estimated blood loss increased with the increase in surgical complexity in the MISLR group, which was similar to finding in the OLR group. The complication rate also increased with the increase in surgical complexity in the OLR group (low complexity vs. high complexity, 34.8% vs. 50.1%). However, the complication rate was steadily low and approximately 10% across all complexity grades in the MISLR group. Conclusion: Careful selection and gradual expansion of the indications of MISLR may facilitate improved postoperative outcomes in patients undergoing highly complex MISLRs.

Obesity and risk for liver disease: a two-sample Mendelian randomisation study.

The associations between obesity and liver diseases are complex and diverse. To explore the causal relationships between obesity and liver diseases, we applied two-sample Mendelian randomisation (MR) and multivariable MR analysis. The data of exposures (BMI and WHRadjBMI) and outcomes (liver diseases and liver function biomarker) were obtained from the open genome-wide association study database. A two-sample MR study revealed that the genetically predicted BMI and WHRadjBMI were associated with non-alcoholic fatty liver disease, liver fibrosis and autoimmune hepatitis. Obesity was not associated with primary biliary cholangitis, liver failure, liver cell carcinoma, viral hepatitis and secondary malignant neoplasm of liver. A higher WHRadjBMI was associated with higher levels of biomarkers of lipid accumulation and metabolic disorders. These findings indicated independent causal roles of obesity in non-alcoholic fatty liver disease, liver fibrosis and impaired liver metabolic function rather than in viral or autoimmune liver disease.

Laparoscopic versus open surgery for liver resection: a multicenter cohort study

The relative risk and benefits of Laparoscopic liver resection (LLR) are still controversial. This study aimed to evaluate perioperative and survival outcomes for three primary malignant liver tumors related outcomes following LLR. Data from three Homogeneous-High-Volume-Expert-Centers were collected. Multivariable logistic regression analysis was performed for the association between LLR, and major complications defined as Clavien-Dindo Classification grade ≥ II. Multivariable Cox proportional hazards regression was used to explore the impact of LLR on primary malignant liver tumor survival. Overall, 5886 patients underwent liver resection, of which 1991 underwent LLR. After adjusting for covariables, LLR had significantly lower rate of CDC grade ≥ II (OR = 0.56, 95% CI: 0.48–0.67, P < 0.001). Interaction analysis showed that LLR had significant association with sex, drinking status, history of abdominal surgery, and platelet count (all P < 0.05). The overall survival for each primary malignant liver tumor shown potential risk but without significantly different between LLR and OLR (all P > 0.05). LLR was associated with lower rate of major complications, especially in women, non-drinkers, those without a history of abdominal surgery, and those with normal platelet. For primary malignant liver tumors, the survival outcomes did not differ significantly between LLR and OLR.

Analysis of metalothionein in patients with malignant liver tumors.

Malignant liver tumors are highly aggressive with a poor prognosis. Metalothionein (MT) is a low-molecular intracellular protein, whose primary function is to regulate the homeostasis of heavy metals in many organisms. There are only few studies focusing on the molecular mechanisms of MT expression. Recent studies show its significant relations to carcinogenesis, spontaneous mutagenesis and efficiency of antitumor medicine. In previous studies, the increase of MT levels in cancer patients was proven. The aim of this work is to study MT as well as to increase the efficiency of malignant liver tumor diagnosis. In our pilot study (2022-2023) we observed a group of 15 patients with hepatocellular carcinoma (diagnosis C220) and a group of 15 patients with hepatoblastoma (diagnosis C222). The control group included 20 healthy probands. We developed our own modified method for the analysis. Blood serum samples of the probands were denaturated (99 ˚C, 20 min). MT was determined by an electrochemical method. Obtained data were stored and processed in the laboratory information system QINSLAB. In denaturated blood serum samples, we obtained voltametric curves of MT. We determined concentrations of MT by evaluating the area under the curve (AUC). To differentiate normal and abnormal concentrations of MT, blood samples of healthy probands were used (N = 20), with the average MT levels of 2.0 ± 1.3 µg/L and median 1.9 µg/L. In patients diagnosed with HCC, the average MT levels were 9.1 ± 6.5 µg/L and median 9.0 µg/L. The receiver operating characteristic (ROC) analysis showed AUC 0.864 (95% CI 0.736-0.992), sensitivity 0.74 and specificity 0.75. In patients diagnosed with hepatoblastoma, the average MT concentrations measured were 11.5 ± 7.5 µg/L and the median was 10.9 µg/L. The ROC analysis displayed AUC 0.868 (95% CI 0.751-0.993), sensitivity 0.84 and specificity 0.86. The correlation analysis showed correlation between MT and carcinoembryonic antigen (CEA) (r = 0.99), uric acid (r = -0.86) and potassium ions (r = -0.94). In this pilot study, we observed the association of MT levels in healthy probands and malignant liver tumor patients. Many previous studies show that MT concentrations are increasing as the illness progresses. We assume that this increase is connected to the high metabolic activity of cancer cells. This study will continue with collecting a larger number of samples.

Establishing prognostic models for intrahepatic cholangiocarcinoma based on immune cells.

Intrahepatic cholangiocarcinoma (ICC) is a malignant liver tumor that is challenging to treat and manage and current prognostic models for the disease are inefficient or ineffective. Tumor-associated immune cells are critical for tumor development and progression. The main goal of this study was to establish models based on tumor-associated immune cells for predicting the overall survival of patients undergoing surgery for ICC. To establish 1-year and 3-year prognostic models for ICC after surgical resection. Immunohistochemical staining was performed for CD4, CD8, CD20, pan-cytokeratin (CK), and CD68 in tumors and paired adjacent tissues from 141 patients with ICC who underwent curative surgery. Selection of variables was based on regression diagnostic procedures and goodness-of-fit tests (PH assumption). Clinical parameters and pathological diagnoses, combined with the distribution of immune cells in tumors and paired adjacent tissues, were utilized to establish 1- and 3-year prognostic models. This is an important application of immune cells in the tumor microenvironment. CD4, CD8, CD20, and CK were included in the establishment of our prognostic model by stepwise selection, whereas CD68 was not significantly associated with the prognosis of ICC. By integrating clinical data associated with ICC, distinct prognostic models were derived for 1- and 3-year survival outcomes using variable selection. The 1-year prediction model yielded a C-index of 0.76 95% confidence interval (95%CI): 0.65-0.87 and the 3-year prediction model produced a C-index of 0.69 (95%CI: 0.65-0.73). Internal validation yielded a C-index of 0.761 (95%CI: 0.669-0.853) for the 1-year model and 0.693 (95%CI: 0.642-0.744) for the 3-year model. We developed Cox regression models for 1-year and 3-year survival predictions of patients with ICC who underwent resection, which has positive implications for establishing a more comprehensive prognostic model for ICC based on tumor immune microenvironment and immune cell changes in the future.

The spectrum of pathogens and their resistance in patients with malignant liver and biliary tract tumors with biliary obstruction after extensive liver resections

The spectrum of pathogens and their resistance in patients with malignant liver and biliary tract tumors with biliary obstruction after extensive liver resections

ASSESSMENT OF INFLAMMATORY RESPONSE AFTER ADMINISTRATION OF ASCORBIC ACID IN A RADIATION HEPATITIS MODEL

Exposure to ionizing radiation while treating malignant liver tumors causes radiation-induced hepatitis. Under electron irradiation, ascorbic acid may be a potential liver radioprotector. Objective. The aim of the study is to conduct immunohistochemical assessment of IL-1β, IL-6, IL-10 expression levels after administration of ascorbic acid in a radiation-induced hepatitis model. Materials and Methods. Wistar rats (n=40) were divided into four groups: Group 1 (n=10) – control; Group 2 (n=10) – electron irradiation, 30 Gy; Group 3 (n=10) – administration of ascorbic acid before electron irradiation; Group 4 (n=10) – administration of ascorbic acid. One week after the last fraction, the animals were withdrawn from the experiment. Liver fragments were examined morphologically, immunohistochemically and using ELISA method (IL-1β, IL-6, IL-10). Statistical analysis of the obtained data was performed using the a Post-hoc test for Kruskal-Wallis: The Dunn's Test. Multiple comparisons were performed using the Mann-Whitney U test. Results. Electron irradiation resulted in a sharp increase in the expression of inflammatory factors and cytokine imbalance with a predominance of proinflammatory markers (IL-1β, IL-6) over anti-inflammatory ones (IL-10). In the group with pre-radiation administration of ascorbic acid, the levels of interleukins also exceeded the control values. However, the balance of pro- and anti-inflammatory factors was partially preserved. Conclusion. A week after exposure to local electron irradiation (total radiation dose – 30 Gy), signs of radiation-induced hepatitis was observed. A statistically significant increase in the expression of proinflammatory cytokines was detected in the liver. At the same time, pre-radiation administration of ascorbic acid provides partial radioprotection of healthy hepatocytes, as well as restoration of the cytokine balance and a decrease in cellular inflammatory infiltration.

Identification of hepatic metastasis from an unrevealed adenoid cystic carcinoma by PET/CT: A case report.

Adenoid cystic carcinoma is a rare malignant tumor of the salivary glands, with few reports of metastasis to the liver in the literature. We present a case where an isolated hepatic lesion of adenoid cystic carcinoma was identified using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). A 76-year-old male experienced abdominal pain and underwent an enhanced CT scan and magnetic resonance imaging, which revealed a liver mass. Subsequent 18F-FDG PET/CT identified hypermetabolic lesions in both the left and right lobes of the liver, suggesting malignancy, with no other abnormalities detected. A liver biopsy confirmed the diagnosis of adenoid cystic carcinoma. No intervention. Following confirmation of the diagnosis, the patient chose to discontinue treatment and was discharged. Hepatic metastasis from adenoid cystic carcinoma may be detected before the identification of the primary lesion. 18F-FDG PET/CT plays a critical role in differentiating benign from malignant liver tumors, selecting potential biopsy sites, and assessing the extent of metastatic disease.

The clinical significance of pyogenic liver abscess after transarterial chemoembolization or microwave ablation on malignant liver tumors: A retrospective study.

Pyogenic liver abscess (PLA) is a rare but severe complication of interventional therapy that has been little studied. We aimed to find the risk factors for PLA after transarterial chemoembolization (TACE) or microwave ablation (MWA), further explore its clinical significance and summarize our experience with its treatment. Twenty-two patients with PLA and 118 randomly selected patients without PLA after TACE/MWA were enrolled. Logistic regression was used to analyze risk factors, a nonparametric test was used to compare recovery duration, the log-rank test was used to compare progression-free survival, and Spearman correlation coefficient was calculated between the time from fever to drainage and the total duration of fever. The disease process and treatment were summarized. Sphincter of Oddi manipulation increased the risk of PLA by 70.781-fold. The PLA group took longer to recover (36.56 ± 16.42 days) than the control group (5.54 ± 4.33 days), and had a shorter progression-free survival. Escherichia coli was the major pathogenic bacterium, and multidrug resistance was found in 8 patients with E coli or Enterococcus faecium. The time from fever to drainage was 15.89 ± 13.78 days, which was positively correlated with the total duration of fever (24.29 ± 18.24 days). Overall, 18 patients recovered, and 4 patients died of PLA, for a mortality rate of 18.18%. The fever of 10 patients (45.45%) was controlled by cefoperazone sodium and sulbactam sodium or piperacillin sodium and tazobactam sodium; the fever of 7 patients (31.81%) was controlled by imipenem and cilastatin sodium; and the fever of 3 patients (13.63%) was controlled by tigecycline. Sphincter of Oddi manipulation is a high-risk factor for PLA after TACE or MWA. PLA can accelerate cancer progression and even lead to death. E coli was the major pathogenic bacterium, and multidrug resistance was most common in E coli and E faecium. Timely drainage and appropriate antibiotics are the key primary measures for treating PLA. Cefoperazone sodium and sulbactam sodium or piperacillin sodium and tazobactam sodium is a good choice for the first treatment of PLA, especially before pathogenic bacteria are identified. With the emergence of drug resistance, imipenem and cilastatin sodium, and tigecycline can be used for posterior treatment.

Causal Effect of Immunocytes, Plasma Metabolites, and Hepatocellular Carcinoma: A Bidirectional Two-Sample Mendelian Randomization Study and Mediation Analysis in East Asian Populations.

Background: Hepatocellular carcinoma (HCC) is a primary malignant liver tumor characterized by a low survival rate and high mortality. This study aimed to investigate the causal effect of immune cell phenotypes, plasma metabolites, and HCC in East Asian populations. Methods: The summary results for 731 immunocytes, 1400 plasma metabolites, and HCCs were acquired from publicly available genome-wide association studies (GWASs). This study utilized two-sample Mendelian randomization (MR) analysis to establish causal relationships, which was achieved by employing various statistical methods including inverse variance-weighted, simple mode, MR-Egger, weighted median, and weighted mode. Multiple sensitivity analyses were conducted to confirm the reliability of the MR data. Ultimately, mediation analysis was employed to ascertain the path that leads from immunocytes to plasma metabolites. Results: Among the 20 immune cells and HCC for East Asians, causal links were found, with one showing an inverse correlation. In addition, 36 metabolites were significantly associated with HCC for East Asians. Through analysis of established causative metabolites, we identified a strong correlation between the glycerophospholipid metabolic pathway and HCC for East Asians. By employing a two-step MR analysis, we identified 11 immunocytes that are causally linked to HCC for East Asians through the mediation of 14 plasma metabolites, with Linolenate [α or γ; (18:3n3 or 6)] levels showing the highest mediation proportion (19.3%). Conclusions: Our findings affirm the causal links among immunocytes, plasma metabolites, and HCC in eastern Asia populations by calculating the percentage of the impact that is influenced by plasma metabolites. This study offers innovative perspectives on the early detection, diagnosis, and therapy of HCC.

Left Lobe Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease Patient: A Case Report

Hepatocellular Carcinoma (HCC) is the second most common cause of death from cancer worldwide, affecting more men than women with a ratio of 2:1. Approximately 70–90% of HCC patients have risk factors such as chronic liver disease and liver cirrhosis. Another significant risk factor is non-alcoholic fatty liver disease (NAFLD). We report a case of left lobe hepatocellular carcinoma in a 54-year-old woman who presented with heartburn and shortness of breath, with a history of hypertension but no alcohol consumption. Chest X-ray revealed cardiomegaly without pulmonary congestion. A whole abdominal CT scan identified a left lobe hepatic tumor measuring ± 11x12x13 cm. Pathology examination revealed an epithelial mass with infiltrative, trabecular, acinar, and solid arrays, indicative of a malignant liver tumor.

Inflammatory Pseudotumor of the Liver or Intrahepatic Cholangiocarcinoma, That's the Question: A Review of the Literature.

An inflammatory pseudotumor of the liver is a rare tumor-like lesion composed of polymorphous inflammatory cell infiltrates and variable amounts of fibrosis that can often mimic a malignant liver neoplasm. The etiology of inflammatory pseudotumors of the liver is unknown; symptoms are faint and imaging non-specific. Thus, it is often hard to make a diagnosis preoperatively and it is not so rare to over-treat patients with this disease or vice versa. Thus, more profound knowledge is necessary to plan appropriate disease management. We reported our two cases and systematically searched the literature regarding IPTL. We selected articles published in English from four databases, PubMed, Scopus, Web of Science and Google Scholar, and we included only articles with consistent data. Twenty nine papers fulfilling criteria for the review were selected. The analysis of 69 cases published from 1953 confirmed that the risk factors are unclear, the imaging data is not specific, and biopsy is crucial but not so widely used in clinical practice due to the procedure's related risks, and relatively low effectiveness and improvement in imaging analysis. Regarding treatment, surgeons have moved towards a more conservative attitude over the years due to better imaging quality and patient surveillance. However, surgery remains the modality of choice for most cases with an indeterminate diagnosis. Even if an inflammatory pseudotumor of the liver is a benign tumor with a good prognosis, not requiring any treatment in most cases, sometimes it remains challenging to differentiate it from ICC; therefore, there is a solid recommendation to manage this condition with a multidisciplinary team.

The efficacy and safety of computed tomography-guided percutaneous cryoablation for malignant liver tumors at high-risk sites

Objective: To assess the efficacy and safety of computed tomography (CT)-guided percutaneous cryoablation in treating malignant liver tumors located explicitly at high-risk sites. Methods: Data were collected retrospectively from patients with malignant liver tumors undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. In all, 46 patients with malignant liver tumors at non-high-risk sites were matched 1∶1 according to the maximum tumor diameter. Technical success rate, complete ablation rate, and complications at 12 and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted. Univariate and multivariate logistic regression analyses were performed to identify risk factors. Results: Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. The complete ablation rate was 82.6% (38/46) and 71.7% (33/46) in the high-risk group and 84.8% (39/46) and 73.9% (34/46) in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups (P>0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤5 mm and preoperative trans-arterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. Conclusion: CT-guided percutaneous cryoablation is a safe and effective approach for patients with malignant liver tumor at high-risk sites. Our results emphasize the importance of proper preoperative planning and intraoperative manipulation.

Predicting hepatocellular carcinoma: A new non-invasive model based on shear wave elastography.

Integrating conventional ultrasound features with 2D shear wave elastography (2D-SWE) can potentially enhance preoperative hepatocellular carcinoma (HCC) predictions. To develop a 2D-SWE-based predictive model for preoperative identification of HCC. A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital. The patients were divided into the modeling group (n = 720) and the control group (n = 164). The study included conventional ultrasound, 2D-SWE, and preoperative laboratory tests. Multiple logistic regression was used to identify independent predictive factors for malignant liver lesions, which were then depicted as nomograms. In the modeling group analysis, maximal elasticity (Emax) of tumors and their peripheries, platelet count, cirrhosis, and blood flow were independent risk indicators for malignancies. These factors yielded an area under the curve of 0.77 (95% confidence interval: 0.73-0.81) with 84% sensitivity and 61% specificity. The model demonstrated good calibration in both the construction and validation cohorts, as shown by the calibration graph and Hosmer-Lemeshow test (P = 0.683 and P = 0.658, respectively). Additionally, the mean elasticity (Emean) of the tumor periphery was identified as a risk factor for microvascular invasion (MVI) in malignant liver tumors (P = 0.003). Patients receiving antiviral treatment differed significantly in platelet count (P = 0.002), Emax of tumors (P = 0.033), Emean of tumors (P = 0.042), Emax at tumor periphery (P < 0.001), and Emean at tumor periphery (P = 0.003). 2D-SWE's hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions, correlating significantly with MVI and antiviral treatment efficacy.

Surgical management of liver tumors.

Two percent of pediatric malignancies arise primarily in the liver; roughly 60% of these cancers are hepatoblastoma (HB). Despite the rarity of these cases, international collaborative efforts have led to the consistent histological classification and staging systems, which facilitate ongoing clinical trials. Other primary liver malignancies seen in children include hepatocellular carcinoma (HCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), undifferentiated embryonal sarcoma of the liver (UESL), and hepatocellular neoplasm not otherwise specified (HCN-NOS). This review describes principles of surgical management of malignant pediatric primary liver tumors, within the context of comprehensive multidisciplinary care.

NEW POSSIBILITIES OF MODERN RADIOLOGY DIAGNOSIS OF HEPATOCELLULAR CARCINOMA: A LITERATURE REVIEW

Relevance: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor (80-90%), ranks 6th among malignant neoplasms and is the 3rd leading cause of cancer mortality worldwide. Despite advances in locoregional therapy, targeted therapy, and immunotherapy, the median survival for advanced HCC does not exceed 2 years, and the 5-year survival rate is 18%. Diagnosis of the tumor at an early stage allows for resection and liver transplantation, which can increase the 5-year survival rate by 1.5-2 times. The options for biopsy are limited by sensitivity and potential complications for the patient. In most cases, HCC can be detected by non-invasive radiology. The study aimed to evaluate the effectiveness of modern methods of radiological diagnosis of HCC. Methods: This literature review included published articles and studies on the capacity of modern methods of radiological diagnosis of hepatocellular carcinoma. Data were found in PubMed, BMC Medicine, and Google Scientific using the keywords ‘hepatocellular carcinoma,’ ‘ultrasound examination,’ ‘computed tomography,’ ‘magnetic resonance imaging,’ and ‘radiomics.’ A total of 123 publications were found; 49 sources were included in this review. Results: The review article addresses current issues of HCC epidemiology, genetics, etiology, and radiology diagnosis. Updated data on the efficacy of CEUS and MFI, LDCT and DECT, and a-MRI are presented. The prospects of MRI-radiomics, which solves the problem of subjectivity in radiology and offers new possibilities in the non-invasive diagnosis of HCC, are described. The study of the possibilities of radiology methods in the diagnosis of HCC continues. Conclusion: CEUS is highly effective for imaging tumor vascularization. LDCT is superior to ultrasound in sensitivity and specificity. A shortened MRI protocol delivers better results than an ultrasound as a screening tool for high-risk groups. MRI-radiomics can determine the tumor histological classification and radiogenomics, predict recurrence after surgical resection, and evaluate measurement methodology and response to transarterial chemoembolization and systemic therapy.

Evaluation of surgical strategies and long-term outcomes in pediatric hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the second most common pediatric malignant liver tumor after hepatoblastoma, represents 1% of all pediatric tumors. A retrospective study was conducted on children with HCC treated at our center from March 2002 to October 2022, excluding those with inadequate follow-up or records. Demographic data, initial complaints, alpha-fetoprotein (AFP) values, underlying disease, size and histopathological features of the masses, chemotherapy, and long-term outcomes were analyzed. Fifteen patients (8 boys, 7 girls) with a mean age of 11.4 ± 4.1years (0.8-16.4years) were analyzed. The majority presented with abdominal pain, with a median AFP of 3.9ng/mL. Hepatitis B cirrhosis in one patient (6.6%) and metabolic disease (tyrosinemia type 1) in two patients (13.3%) were the underlying diseases. Histopathological diagnoses were fibrolamellar HCC (n:8; 53.3%), HCC (n:6; 40%). Four of the 15 patients underwent liver transplantation, and 9 underwent surgical resection. Due to late diagnosis, two patients were considered inoperable (13.3%). The survival rate for the four patients who underwent liver transplantation was found to be 75%. Surgical treatment of various variants of HCC can be safely performed in experienced centers with a multidisciplinary approach, and outcomes are better than in adults.

FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma

Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20％ of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (CHD4) have been associated with CDDP resistance in various tumors. We here analyzed the immunohistochemical expression of FOXM1 and CHD4 in HB specimens of 33 patients (mean age: 20 months) post-chemotherapy. The differentiation of specimens was assessed using the digital pathology software QuPath®, and then the relation between the FOXM1 or CHD4 expression and the differentiation and various other clinicopathological parameters was investigated. The histological type was epithelial in 19 cases (57.6%) and mixed epithelial and mesenchymal in 14 cases (42.4%). Nine cases had only a fetal component, 1 case had only an embryonal component, 22 cases had both fetal and embryonal components, and 1 case had no viable tumor. Both the FOXM1 and CHD4 immunoexpressions were found significantly more frequently in the embryonal than fetal components (p<0.0001 and p<0.0001, respectively). Regarding chemotherapy efficacy, the alpha-fetoprotein (AFP) level after chemotherapy was correlated with both the imaging shrinkage rate (R=-0.52) and histological residual rate (the percentage of the viable tumors of HB after chemotherapy)(R=0.62). High FOXM1 score was correlated with a high-postoperative AFP value (p<0.01) and a low AFP attenuation rate (p<0.05), but the FOXM1 score was not correlated with the imaging shrinkage rate (p=0.4418) or histological residual rate (p=0.4418). High CHD4 score showed a nonsignificant trend toward correlation with high postoperative AFP value (p=0.0849) and was not significantly correlated with the other parameters. Collectively, our results showed that FOXM1 expression may be useful in evaluating the response to CDDP-based chemotherapeutic regimens. Accurate measurement of FOXM1 expression by our scoring system using QuPath® is important in cases with mixed HB components of various differentiation levels.

Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms.

This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

Shedding light on the role of LAG-3 in hepatocellular carcinoma: unraveling immunomodulatory pathways

Hepatocellular carcinoma (HCC) stands as a primary malignant liver tumor characterized by chronic inflammation and complex alterations within the tumor microenvironment (TME). Lymphocyte activation gene 3 (LAG-3), also known as CD223, has gained prominence as a potential next-generation immune checkpoint, maintaining continuous expression in response to persistent antigen exposure within the TME, warranting our attention. In patients with HCC, LAG-3 expression on T cells, regulatory T cells (Tregs), and natural killer (NK) cells contributes to immune evasion, while high expression of LAG-3 leads to increased angiogenesis and poor prognosis. By interacting with major histocompatibility complex class II molecules, LAG-3 promotes T cell exhaustion and suppresses antitumor responses, often in collaboration with other immune checkpoints like programmed cell death protein 1 (PD-1), while on Tregs and NK cells, LAG-3 modulates their suppressive functions, indirectly facilitating tumor immune escape. LAG-3 expression may offer prognostic insights, correlating with disease progression and outcomes in HCC patients, while various preclinical studies highlight the potential of LAG-3-targeted therapies in reinvigorating immune responses against HCC, with a few combination approaches targeting LAG-3 alongside other checkpoints demonstrating synergistic effects in restoring T cell function. Therefore, harnessing LAG-3 as a therapeutic target holds promise for enhancing antitumor immunity and potentially improving HCC treatment outcomes. Our narrative review aims to delve into the full spectrum of LAG-3 signaling in HCC, with the goal of a better understanding of the pathophysiological and immunological basis of its use to arrest HCC growth and development.