Metodologías de Medición de Volumetría Hepática / Methodologies For Measuring Hepatic Volumetry

Lograr determinar el volumen total de un hígado (VHT), o volumetría hepática, pasa a ser de relevancia en diversas situaciones, tales como, vigilancia del progreso de una enfermedad de carácter crónico, planificación de resecciones y trasplantes hepáticos; y observación del clearance hepático de algunos fármacos hepatotropos. La VHT se puede realizar utilizando métodos de segmentación en el curso de una tomografía computarizada (TC), ya sean estos manual, automáticos, y semiautomáticos; mediante resonancia nuclear (RN), utilizando softwares de distintas generaciones (1ª a 4ª). La medición de VHT está indicada en pacientes sometidos a resecciones hepáticas mayores, en el contexto del tratamiento de neoplasias (carcinoma hepatocelular, colangiocarcinoma, metástasis hepáticas o tumores benignos de gran tamaño), abscesos (piogénicos, amebianos), y después de un traumatismo hepático complejo; así como también en la etapa preoperatoria de un trasplante hepático. El objetivo de este manuscrito fue generar un documento de estudio sobre métodos para determinar volumetría hepática.

SUMMARY: Being able to determine the total hepatic volume (THV), or THV, becomes relevant in various situations, such as monitoring the progress of a chronic disease, planning resections and liver transplants; and observation of the hepatic clearance of some hepatotropic drugs. THV can be performed using segmentation methods in the course of a computed tomography (CT), whether manual, automatic, or semi-automated; by nuclear resonance (NR), using software from different generations (1st to 4st). THV measurement is indicated in patients undergoing major liver resections, in the context of treatment of neoplasms (hepatocellular carcinoma, cholangiocarcinoma, liver metastases or large benign tumors), abscesses (pyogenic, amoebic), and after liver trauma complex, as well as in the preoperative stage of a liver transplant. The aim of this manuscript was to generate a study document regarding methods for determine hepatic volumetry.

Economic burden of liver disease in Colombia

Introduction: Liver diseases have a significant impact on global morbidity and mortality rates, primarily attributed to cirrhosis and hepatocellular carcinoma. However, the true extent of their impact on patients, healthcare systems, and countries is often underestimated. Materials and methods: This descriptive, cross-sectional study aimed to determine the economic burden associated with premature deaths caused by cirrhosis and primary liver cancer. The economic assessment was conducted by analyzing potentially productive years of life lost (PPYLL) due to liver diseases in Colombia between 2009 and 2016. Results and conclusions: The total burden of liver disease accounted for 687,861 disability-adjusted life years (DALYs). Men experienced a higher number of years of life lost from mortality (YLL), while women had a greater number of years lived with a disability (YLD). The economic burden of deaths caused by cirrhosis and primary liver cancer exceeded USD 8.6 million, highlighting the urgency to enhance intervention strategies ranging from promotion and prevention to timely diagnosis and treatment.

Introducción: la enfermedad hepática representa una de las principales causas de morbimortalidad a nivel mundial, principalmente por cirrosis y hepatocarcinoma; sin embargo, se subestima su impacto para el paciente, sistema de salud y el país. Materiales y métodos: estudio descriptivo de corte transversal que determinó la carga económica asociada a las muertes prematuras por cirrosis y tumores primarios del hígado, mediante la valoración económica de los años productivos de vida potencialmente perdidos (APVPP) en Colombia y de enfermedad hepática en Colombia entre 2009 y 2016. Resultados y conclusiones: la carga total de enfermedad hepática representó 687,861 años de vida saludable perdidos ajustados por discapacidad (AVAD), los hombres con mayores años de vida perdidos por muerte prematura (APMP) y las mujeres con mayores años vividos con discapacidad (AVD). Las muertes por cirrosis y tumores primarios del hígado representan una carga económica que supera los 8,6 millones de dólares, lo cual refleja la necesidad de fortalecer las estrategias de intervención desde la promoción y prevención hasta el diagnóstico y tratamiento oportuno.

Radiological characteristics of hepatocellular carcinoma that achieved complete response after chemoembolization with drug-eluting beads for liver transplantation planning

ABSTRACT Objective To describe the radiological characteristics of hepatocellular carcinoma (HCC) lesions that achieved a complete response following drug-eluting bead transarterial chemoembolization (DEB-TACE) preceding liver transplantation. Methods This single-center case-control study enrolled patients with hepatocellular carcinoma who underwent neoadjuvant DEB-TACE therapy, were followed up with contrast-enhanced magnetic resonance imaging or computed tomography, and were successively evaluated according to the modified Response Evaluation Criteria in Solid Tumors. The HCCs were divided into two groups based on their diameter (Group A: ≤3cm; Group B: 3cm). Viability was assessed using the Kaplan-Meier method according to tumor size categories. The relationship between tumor variables was analyzed using bivariate Cox regression. Results Three-hundred and twenty-eight patients with 667 hepatocellular carcinomas who underwent their first DEB-TACE session were enrolled. A total of 105 hepatocellular carcinomas in 59 patients exhibited complete response after the initial DEB-TACE session and were divided into Group A (92 HCCs) and Group B (13 HCCs). The diameter in Group A decreased significantly compared to the pre-procedure size until the second assessment (p<0.001), with no subsequent reduction in diameter, despite maintaining a complete response. In Group B, the reduction in diameter remained significant compared with the initial value until the sixth imaging evaluation (p=0.014). The average reduction was 45.1% for Group B and a maximum of 14.9% in Group A. Conclusion HCCs >3cm exhibited a greater reduction in size and a longer time to recurrence. HCCs ≤3cm had a shorter relapse time. The recurrence rates were similar. These findings may aid in planning for liver transplantation.

Establishment of a novel co-cultured liver cancer model based on tumor microenvironment / 中华肿瘤杂志

Objective: To construct a new co-cultured liver cancer research model composed of activated hepatic stellate cells (aHSC) and liver cancer cells, explore the efficacy difference between it and traditional model, so as to establish a liver cancer research model in vitro and in vivo that can reflect the real clinical efficacy. Methods: A new co-culture model of liver cancer consisting of aHSC and liver cancer cells was constructed. The differences in efficacy between the new co-culture model and the traditional single cell model were compared by cytotoxicity test, cell migration test, drug retention test and in vivo tumor inhibition test. Western blot was used to detect the drug-resistant protein P-gp and epithelial-mesenchymal transition-related proteins. Masson staining was used to observe the deposition of collagen fibers in tumor tissues of tumor-bearing mice. CD31 immunohistochemical staining was used to observe the microvessel density in tumor tissues of tumor-bearing mice. Results: The cytotoxicity of single cell model and co-culture model was dose-dependent. With the increase of curcumin (CUR) concentration, the cell viability decreased, but the cell viability of single cell model decreased faster than that of co-culture model. When the concentration of CUR was 10 μg/ml, the cell viability of the co-culture model was 62.3% and the migration rate was (28.05±3.68)%, which were higher than those of the single cell model [38.5% and (14.91±5.92)%, both P<0.05]. Western blot analysis showed that the expressions of P-gp and vimentin were up-regulated in the co-culture model, which were 1.55 and 2.04 fold changes of the single cell model, respectively. The expression of E-cadherin was down-regulated, and the expression level of E-cadherin in the single cell model was 1.17 fold changes of the co-culture model. Drug retention experiment showed that the co-culture model could promote drug efflux and reduce drug retention. In vivo tumor inhibition experiment showed that the m-HSC+ H22 co-transplantation model had faster tumor growth and larger tumor volume than those of the H22 single cell transplantation model. After CUR treatment, the tumor growths of m-HSC+ H22 co-transplantation model and H22 single cell transplantation model were inhibited. Masson staining showed that the deposition of collagen fibers in tumor tissues of m-HSC+ H22 co-transplantation model mice was more than that of H22 single cell transplantation model. CD31 immunohistochemical staining showed that the microvessel density in tumor tissue of m-HSC+ H22 co-transplantation model was higher than that of H22 single cell transplantation model. Conclusions: The aHSC+ liver cancer cell co-culture model has strong proliferation and metastasis ability and is easy to be resistant to drugs. It is a new type of liver cancer treatment research model superior to the traditional single cell model.

Research progress of liver regeneration after hepatectomy for hepatocellular carcinoma / 中华肝胆外科杂志

Liver is an organ with strong regenerative potential. After trauma, infection, surgery and so on, it will initiate a series of regulation for orderly regeneration to rapidly restore liver function and liver volume and thus maintain normal physiological function. This article summarizes the process of liver regeneration after hepatectomy, the evaluation methods for liver regeneration and the factors affecting liver regeneration, so as to provide references for clinical precision liver surgical treatment.

Integrative treatment for primary liver cancer with tumor thrombosis in hepatic vein or inferior vena cava: a review / 中华肝胆外科杂志

Primary liver cancer is a common malignant tumor. Early liver cancer is suitable for surgical resection, local ablation, liver transplantation and other radical treatment, and the prognosis is better. Patients with advanced liver cancer often have tumor thrombosis in hepatic vein and inferior vena cava. With high rates of recurrence and metastasis, the prognosis is poor. Chinese guidelines recommend multidisciplinary treatment to patients with hepatic vein thrombosis and inferior vena cava thrombosis including local treatment, systematic anti-tumor drug treatment, surgical resection and other treatment. This article reviewed the progress in diagnosis and treatment of primary liver cancer with tumor thrombosis in hepatic vein and inferior vena cava in the past decade.

Efficacy and safety of laparoscopic surgery in treatment of recurrent hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the efficacy and safety of laparoscopic surgery in treatment of recurrent hepatocellular carcinoma.Methods:The clinical data of 58 patients with recurrent hepatocellular carcinoma who underwent surgical treatment from January 2010 to January 2018 at Hunan Provincial People’s Hospital were retrospectively analyzed. There were 50 males and 8 females, ranging in age from 28 to 78 (53.0±10.8) years old. Patients were divided into laparoscopic group ( n=27) and laparotomy group ( n=31) according to different surgical procedures. The differences in operative time, intraoperative blood loss, hospital stay, postoperative anal exhaustion time, postoperative complications and prognosis between the two groups were compared. Results:The intraoperative blood loss of laparoscopy group and laparotomy group were 100.0(50.0, 400.0) ml vs 300.0(100.0, 500.0) ml, the postoperative anal exhaustion time were (2.7±0.6) d vs (3.3±0.6) d, the hospital stay were (14.8±3.8) d vs (21.4±6.3) d, and these differences were statistically significant (all P<0.05). The operative time of the two groups were (243.4±27.2) min vs (217.5±34.7) min, with no statistical significance ( t=0.59, P=0.344). There were no significant differences between the two groups in postoperative complications (bile leakage, abdominal infection, hemorrhage, pleural effusion and hepatic encephalopathy) (all P>0.05); thetumor free survival, 1-year, and 3-year overall survival rates of the two groups were also not significantly different (both P>0.05). Conclusion:Laparoscopic surgery is safe and effective in the treatment of recurrent hepatocellular carcinoma, and its prognosis is similar to laparotomy, its complications are not significantly increased, which is worthy of promotion in clinic.

Mechanism of Bielong Ruangan decoction in treatment of liver cancer based on network pharmacology and molecular docking / 中国医师杂志

Objective:To explore the key targets and mechanism of Bielong Ruangan decoction in the treatment of liver cancer based on network pharmacology and molecular docking.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, PubChem database and PharmMapper database were used to search and screen the chemical components and related targets of Bielong Ruangan decoction and the targets of liver cancer diseases. The network diagram of " Bielong Ruangan decoction-traditional Chinese medicine-active ingredient-predicted target-disease" was constructed; Protein-protein interaction (PPI) network were analyzed through String database; gene ontology (GO) enrichment analysis was performed through WebGestalt database; Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out through KEGG Orthology Based Annotation System (KOBAS) database; Molecular docking of the active components and core target proteins of Bielong Ruangan decoction was carried out by using PyMOL, Auto DockVina and other software.Results:Bielong Ruangan decoction had 67 active components, 154 liver cancer targets and 244 pathways. According to the analysis of network pharmacology, Bielong Ruangan decoction may play an anti-cancer role through key targets such as epidermal growth factor receptor (EGFR), mitogen activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), MAPK8, serine threonine protein kinase 1 (AKT1), MAPK14, cysteine protease 3 (CASP3), cyclin-dependent kinase 2 (CDK2), bone morphogenetic protein 2 (BMP2), aldose reductase (AKR1B1) and other key targets. KEGG enrichment analysis showed that the treatment of liver cancer by Bielong Ruangan decoction involved the regulation of vascular endothelial growth factor (VEGF) signaling pathway, tumor necrosis factor (TNF) signaling pathway, thyroid hormone signaling pathway, T cell receptor signaling pathway and other pathways. The results of molecular docking showed that the binding energy of all compounds to protein was less than -5.6 kcal/mol, indicating that each compound and each protein could bind well.Conclusions:Bielong Ruangan decoction participates in the treatment of liver cancer through " multi-component, multi-target and multi-channel" ways, and plays an anti-cancer role mainly by regulating the proliferation and invasion of tumor cells and tumor inflammatory microenvironment.

Effects of primary location of colorectal cancer on surgical outcome of liver metastases / 中国基层医药

Objective:To analyze the effects of the primary location of colorectal cancer on the surgical outcome of liver metastases.Methods:A cross-sectional study was conducted on 178 patients with liver metastases from colorectal cancer admitted to Binzhou Central Hospital from January 2012 to January 2022. According to whether the patients had recurrence after surgery, they were divided into a recurrence group ( n = 88) and a control group ( n = 90). The general and clinical data were compared between the two groups. Logistic multivariate analysis of the factors with statistical significance was further performed to identify the risk factors of postoperative recurrence of liver metastases from colorectal cancer after surgery. The correlation between the primary location of colorectal cancer and each risk factor was analyzed. The recurrence of colorectal cancer was compared anong patients with different primary locations of colorectal cancer at 12 months after surgery. Results:Primary location at the right colon [55.68% (49/88), lymph node metastasis [92.05% (81/88)], D-dimer ≥ 180 μ g/L, albumin < 29 g/L, ineffective/no neoadjuvant chemotherapy [43.18% (33/38)], and high-risk clinical risk score [53.41% (47/88)] were risk factors for postoperative recurrence of liver metastases from colorectal cancer after surgery ( P = 0.024, 0.019, 0.001, 0.028, < 0.001, 0.001). The primary location of colorectal cancer was positively correlated with lymph node metastasis, D-dimer, and clinical risk score ( P = 0.043, 0.046, 0.030), and negatively correlated with albumin and the efficacy of neoadjuvant chemotherapy ( P = 0.004, 0.033). In 178 patients, the recurrence rate of liver metastases from colorectal cancer at 3 months [53.57% (15/70)], 6 months [55.17% (32/70)], and 12 months [55.68% (49/70)] was significantly higher in the right colon compared with the left colon [32.14% (9/40), 24.14% (14/40), 26.14% (23/40) and the rectum [14.29% (4/68), 20.69% (12/68), 18.18% (16/68)] ( χ2= 4.73, 7.85, 6.27, all P < 0.05). Conclusion:Right colon, lymph node metastasis, D-dimer, albumin, neoadjuvant chemotherapy efficacy, and clinical risk score are the risk factors for postoperative recurrence of liver metastases from colorectal cancer. Patients with the primary location at the right colon have a higher postoperative recurrence rate.

Relationship between peripheral blood lipid level and hepatitis B-related liver cancer / 中国基层医药

Objective:To investigate the relationship between peripheral blood lipid levels and hepatitis B-related liver cancer, and to provide a theoretical basis for the early prevention and treatment of liver cancer.Methods:A total of 188 patients with hepatitis B-related liver cancer who received treatment in The First Hospital of Shanxi Medical University from June 2018 to June 2021 met the inclusion and exclusion criteria and had complete data, were included in this study. They were divided into three groups: chronic hepatitis B group ( n = 72), hepatitis B cirrhosis group ( n = 62), and hepatitis B-related liver cancer group ( n = 54) according to different stages of the disease. All patients' medical records were obtained from the medical data room. Fasting venous blood was collected in all patients on the second day after admission to detect peripheral blood lipid, liver function, and other relevant indicators. General data and biochemical indicators were collected. The Kruskal-Wallis test was performed to compare the measurement data among groups. The chi-squared test was performed to compare the count data among groups. Spearman's correlation (bivariate) was performed. Binary logistic regression was performed to analyze the influential factors of liver cancer. Results:There were significant differences in the levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) among the three groups ( F = 32.14, 27.59, 10.88, 34.09, all P < 0.05). TC and LDL-C levels in the hepatitis B-related liver cancer group were significantly higher than those in the hepatitis B cirrhosis group ( F = -32.31, -50.19, both P < 0.05). There were no significant differences in TG and HDL-C levels between hepatitis B-related liver cancer and hepatitis B cirrhosis groups ( F = -10.69, 4.46, both P > 0.05). TC, TG, HDL-C and LDL-C levels in the hepatitis B cirrhosis group were significantly lower than those in the chronic hepatitis B group ( F = 53.30, 46.98, 24.61, 48.57, all P < 0.05). LDL-C level was positively correlated with the occurrence of liver cancer ( r = 0.20, P < 0.05). HDL-C level was negatively correlated with the occurrence of liver cancer ( r = -0.15, P < 0.05). LDL-C was an independent risk factor for liver cancer ( OR = 3.35, P < 0.05), and HDL-C was a protective factor for liver cancer ( OR = 0.12, P < 0.05). Conclusion:Compared with patients with chronic hepatitis B and hepatitis B cirrhosis, patients with hepatitis B-related liver cancer had abnormal peripheral blood lipid levels, which may be related to the abnormal lipid metabolism of tumor cells. Moreover, peripheral blood lipid levels may affect the occurrence and development of tumor cells.

The clinical effect of stereotactic radiation therapy combined with sorafenib in the treatment of primary hepatic cancer / 中国医师进修杂志

Objective:To investigate the clinical effect of stereotactic radiation therapy combined with sorafenib in the treatment of primary hepatic cancer (PHC).Methods:Ninety-two PHC patients admitted to Cancer Hospital of China Medical University from January 2017 to May 2018 were selected and divided into the observation group and the control group according to the random number table method, with 46 cases in each group. The control group was treated with stereotactic radiation therapy, and the observation group was treated with sorafenib on the basis of the control group. Clinical efficacy and incidence of adverse reactions in the two groups were compared; the scores of Karnofsky performance scale (KPS) and the levels of serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hypoxia-inducing factor (HIF-1α), soluble interleukin-2 receptor (sIL-2R), transforming growth factor (TGF-β1) and alpha-fetoprotein (AFP) before and after the treatment between the two groups were compared. The overall survival (OS) of patients in both groups was recorded after 36 months of follow-up.Results:The total effective rate in the observation group was higher than that in the control group: 84.78%(39/46) vs. 65.22%(30/46), there was statistical difference ( χ2 = 4.70, P<0.05). After the treatment, the score of KPS in the observation group was higher than that in the control group: (85.06 ± 7.19) scores vs. (71.16 ± 7.08) scores; the levels of VEGF, bFGF, HIF-1α, AFP, TGF-β1, sIL-2R in the observation group were lower than those in the control group: (189.52 ± 31.47) ng/L vs. (235.81 ± 35.45) ng/L, (3.89 ± 0.97) ng/L vs. (6.74 ± 1.85) ng/L, (50.17 ± 6.09) ng/L vs. (53.07 ± 6.28) ng/L, (85.76 ± 14.09) μg/L vs. (131.51 ± 18.74) μg/L, (81.07 ± 12.96) μg/L vs. (106.58 ± 15.07) μg/L, (311.58 ± 74.81) kU/L vs. (405.97 ± 85.74) kU/L, there were statistical differences ( P<0.05). The results of 36 months follow-up showed that the 1-year and 3-year OS in the observation group were higher than those in the control group: 69.57% (32/46) vs. 58.70% (27/46), 43.47% (20/46) vs. 28.26 %(13/46), there were significant differences ( χ2 = 4.78, 3.94, P<0.05). Conclusions:Stereotactic radiation therapy combined with sorafenib can effectively improve the efficacy of PHC patients, reduce the expression of VEGF and bFGF, effectively inhibit tumor growth, but also prolong the survival time of patients, with both safety and high effectiveness, and good use value.

Effect of lysophosphatidic acid on hepatoma cells and related mechanism / 临床肝胆病杂志

ObjectiveTo investigate the expression of lysophosphatidic acid （LPA） in patients with liver cancer， as well as its influence on malignant biological behavior of liver cancer and related regulatory mechanism. MethodsFrom January 2016 to December 2022， 26 patients with liver cancer， 28 patients with liver cirrhosis， and 28 individuals undergoing physical examination were enrolled. ELISIA was used to measure the content of LPA in plasma and peritoneal effusion of the patients with liver cancer or liver cirrhosis accompanied by peritoneal effusion， and the content of LPA was measured in plasma of the normal population at the same time， so as to clarify the difference in the expression of LPA in different populations， such as the patients with liver cancer and those with liver cirrhosis. MTT cell proliferation assay and cell migration assay were used to observe the influence of LPA and its inhibitor pertussis toxin （PTX） on the proliferation， migration， and invasion of SMMC7721 cells. In order to investigate the effect of LPA on the expression of RhoA and its upstream and downstream molecules FAK and P53 after binding to its receptor， qPCR and Western blot were used to observe the effect of LPA on the mRNA and protein expression levels of P53， FAK， and RhoA in SMMC7721 cells. A one-way analysis of variance was used for comparison of the means of continuous data between multiple groups， and the SNK-q test was used for comparison between two groups. ResultsCompared with the patients with liver cirrhosis， the patients with liver cancer had a significantly higher concentration of LPA in plasma （4.99±0.55 μmol/L vs 2.63±0.43 μmol/L， P<0.05） and peritoneal effusion （5.19±0.63 μmol/L vs 2.91±0.46 μmol/L， P<0.05）， and the patients with liver cancer also had a significantly higher level of plasma LPA than the normal population （4.99±0.55 μmol/L vs 1.61±0.39 μmol/L， P<0.05）. The cell proliferation assay showed that LPA significantly promoted the proliferation of SMMC7721 cells， and cell proliferation rate increased with the increase in dose and time； in particular， the middle-and high-dose groups had a significantly higher proliferation rate than the control group （P<0.05）. PTX inhibited the proliferative capacity of SMMC7721 cells in a time-dependent manner， and there was a significant difference between the groups （P<0.05）. The proliferation rate of the 72-hour high-dose LPA group was 3.6 times that of the control group， while the proliferation rate of the PTX group was 0.6 times that of the control group； the proliferation rate of the 72-hour high-dose LPA+PTX group was 1.2 times that of the control group. In addition， LPA increased the migration ability of hepatoma cells， while PTX inhibited their migration， in a time-dependent manner， and there was a significant difference between the groups （P<0.05）. The migration rate of the 72-hour high-dose LPA group was 3.09 times that of the control group， while the migration rate of the PTX group was 0.4 times that of the control group； the migration rate of the 72-hour high-dose LPA+PTX group was 0.99 times that of the control group. qPCR and Western blot showed that there were significant reductions in the mRNA and protein expression levels of P53 in SMMC7721 cells after LPA treatment， while there were significant increases in the mRNA and protein expression levels of FAK and RhoA； there was a significant difference between the LPA group and the control group （P<0.05）. ConclusionThere is an abnormal increase in the expression of LPA in patients with liver cancer， and LPA can promote the proliferation of liver cancer cells and increase their migration ability. At the same time， LPA changes the expression levels of P53， FAK， and RhoA， which may be associated with the promotion of tumor development and progression by LPA.

Research advances in the role of blood metabolic markers in the treatment response and prognosis prediction of primary liver cancer / 临床肝胆病杂志

Primary liver cancer is one of the most severe cancer burdens around the world. Metabolic reprogramming is one phenotype of cancer， and blood metabolic markers are closely associated with metabolic reprogramming and can predict the risk of recurrence and survival or assess the treatment response of liver cancer， with important significance in the stratified management of patients， the development of rational treatment strategies， and the improvement of patient prognosis. By reviewing the recent studies on blood metabolomics in assessing the treatment response or predicting the prognosis of liver cancer， this article summarizes the blood metabolites with predictive significance and their mechanism of action and analyzes the current research status， existing problems， and prospects of this field. It is believed that the metabolites， such as aromatic amino acids， lipids， and bile acids， have an important clinical value in predicting the prognosis of liver cancer， and metabolomics technology has great potential in finding useful metabolites， but there are still many issues to be solved， such as technical limitations， insufficient studies， and multiple influencing factors.

Effect of synthetic peptide cSN50.1 on the malignant behavior of hepatocellular carcinoma HepG2 cells and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the effect of cSN50.1 on the proliferation， migration， invasion， and colony formation of HepG2 cells and its mechanism. MethodsHepG2 cells were divided into cSN50.1 0 μmol/L， cSN50.1 10 μmol/L， cSN50.1 30 μmol/L， cSN50.1 50 μmol/L， cSN50.1 70 μmol/L， and cSN50.1 90 μmol/L groups， and CCK－8 assay was used to investigate the effect of different concentrations of cSN50.1 on the proliferation of HepG2 cells and calculate half－maximal inhibitory concentration （IC50）. HepG2 cells were divided into cSN50.1 0 μmol/L， cSN50.1 10 μmol/L， cSN50.1 30 μmol/L， and cSN50.1 50 μmol/L groups， and wound healing assay， Transwell assay， and colony－forming assay were used to investigate the effect of different concentrations of cSN50.1 on the migration， invasion， and colony formation of HepG2 cells. HepG2 cells were divided into Control group， SP600125 group （an inhibitor of the AP－1 signaling pathway）， and cSN50.1 group to investigate the influence of the AP－1 signaling pathway on the effect of cSN50.1 on hepatocellular carcinoma cells， and RT－PCR and Western Blot were used to measure the expression of CXCL5， TNF－α， and c－Jun protein in cytoplasm and nucleus. HepG2 cells were divided into Control group， PDTC group （an inhibitor of the NF－κB signaling pathway）， and cSN50.1 group to investigate the influence of the NF－κB signaling pathway on the effect of cSN50.1 on hepatocellular carcinoma cells， and RT－PCR and Western Blot were used to measure the expression of CXCL5， TNF－α， and NF－κB protein in cytoplasm and nucleus. A one－way analysis of variance was used for comparison between multiple groups， and the SNK－q test was used for further comparison between two groups. ResultsCompared with the 0 μmol/L group， the 10 μmol/L group had no significant changes in proliferation， migration， invasion， and colony formation abilities （P >0.05）； the 30 μmol/L group had no significant change in proliferation ability （P>0.05）， but with significant reductions in migration， invasion， and colony formation abilities （P<0.05）； the 50 μmol/L group had significant reductions in proliferation， migration， invasion， and colony formation abilities （all P<0.01）； the 70 μmol/L and 90 μmol/L groups had a significant reduction in cell proliferation ability （P<0.01）， but with a cell survival rate of below 50%. Compared with the Control group， the SP600125， PDTC， and cSN50.1 groups had significant reductions in the mRNA and protein expression levels of CXCL5 and TNF－α （all P<0.05）. Compared with the Control group， the SP600125 group， the PDTC group， and the cSN50.1 group had a significant reduction in nuclear protein of c－Jun and NF－κB expression （P<0.05）； the SP600125 group and the PDTC group had a significant reduction in cytoplasmic protein of c－Jun and NF－κB expression （P<0.05）； the cSN50.1 group had a significant increase in cytoplasmic protein of c－Jun and NF－κB expression （P<0.05）. ConclusionThis study shows that cSN50.1 can inhibit the malignant behavior of hepatocellular carcinoma cells and reduce the expression of CXCL5 and TNF－α by inhibiting the nuclear import of c－Jun and NF－κB in hepatocellular carcinoma cells.

Construction and validation of a prognostic nomogram model of programmed death receptor 1 inhibitors in treatment of hepatitis B-related hepatocellular carcinoma / 肿瘤研究与临床

Objective:To investigate the factors influencing the prognosis of hepatitis B-related hepatocellular carcinoma treated with programmed death receptor 1 (PD-1) inhibitors, and to construct a prognostic nomogram model for these patients and evaluate its clinical significances.Methods:The clinical data of 121 patients with hepatitis B-related hepatocellular carcinoma treated with PD-1 inhibitors at the First Affiliated Hospital of Xinxiang Medical College from July 2018 to July 2021 were retrospectively analyzed. Follow-up was performed from the beginning of PD-1 inhibitor use, and the Kaplan-Meier method was used to analyze the overall survival of patients. The variables screened by the univariate Cox proportional hazards model analysis and variables clinically believed to be related to the prognosis were included in the multivariate Cox proportional hazards model for overall survival, and the stepwise regression method was used to screen the independent factors influencing overall survival. Based on the independent influencing factors of overall survival, R 3.5.1 software was used to construct a prognostic nomogram model for overall survival of hepatitis B-related hepatocellular carcinoma treated with PD-1 inhibitors. Calibration curve was used to the consistency of model prediction and practice. The Harrell consistency index and receiver operating characteristic (ROC) curve (with imaging diagnosis as the gold standard) were used to analyze the efficacy of model in predicting the 1-year and 2-year overall survival rates.Results:The median follow-up time of 121 patients was 12.40 months, and the median overall survival time was 14.30 months, with overall survival rates of 82.60% and 62.30% at 6 and 12 months. Multivariate Cox regression analysis showed that albumin (ALB) ( HR = 0.946, 95% CI 0.901-0.992), international normalized ratio (INR) ( HR = 32.034, 95% CI 5.046-203.362), aspartate aminotransferase (AST) ( HR = 1.010, 95% CI 1.007-1.012) were independent influencing factors for overall survival of patients. According to the three factors, a prognostic nomogram model for hepatitis B-related hepatocellular carcinoma treated with PD-1 inhibitors was constructed. The slope of the calibration curve of the model predicting 1-year and 2-year overall survival rates was close to 1. The Harrell consistency index of the nomogram model was 0.809 (95% CI 0.760-0.858). ROC curve analysis showed that the area under the curve (AUC) of the nomogram model predicting 1-year and 2-year overall survival rates of patients was 0.794 (95% CI 0.744-0.887, P < 0.001) and 0.791 (95% CI 0.708-0.860, P = 0.002). Conclusions:ALB, INR and AST are the influencing factors of prognosis of hepatitis B-related hepatocellular carcinoma patients treated with PD-1 inhibitors, and the nomogram model constructed based on prognostic influencing factors has a good effect on predicting the 1-year and 2-year overall survival rates of patients, which can be used to screen the population suitable for immunotherapy and is conducive to the clinical formulation of individualized and precise treatment plans.

Prenatal diagnosis and intrauterine treatment of a giant fetal hepatic hemangioma:a case report / 中华围产医学杂志

This article reported a case of fetal giant hepatic hemangioma with cardiomegaly managed with intrauterine treatment. At 23 weeks of gestation, the patient was referred to Guangdong Women and Children Hospital due to abnormal abdominal echogenicity of the fetus, which was suspected to be a hepatic hemangioma or a hepatic arteriovenous fistula. The prenatal ultrasound at 26 weeks of gestation revealed an enlarged fetal hepatic hemangioma of 45 mm×35 mm×42 mm and an enlarged heart (cardiothoracic area ratio of 0.50). So, with the patient's informed consent, the fetus was treated with intrauterine administration of propranolol and dexamethasone and closely monitored by ultrasound. The volume of the lump still increased at the beginning of the medication, but started to shrink in the 7th week. Besides, the fetal cardiac load was reduced and the condition was controlled. The patient delivered at 37 weeks of gestation. The baby received a CT examination on the fourth day after birth which revealed an abdominal mass of 40 mm×30 mm×44 mm requiring no treatment, and no abnormalities were reported during a one-year follow-up.

Clinicopathological diagnosis and treatment of undifferentiated(embryonal) sarcoma of the liver / 中华普通外科杂志

Objective:To investigate the clinicopathological features, differential diagnosis, treatment and prognosis of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Five UESL cases operated on at Hunan Provincial People's Hospital from 2014 to 2021 were retrospectively analyzed. H&E and immunohistochemical staining were done for pathological observation.Results:The 5 UESL patients(two boys,three girls) were 0.5 to 15 years old, all underwent radical surgical resection. In 3 cases tumors located in right liver, 1 in left liver, 1 in both lobes. Radiographically and visually, the tumor is a large cystic solid mass, microscopically composed of myxoid stroma and undifferentiated stromal cells, with pleomorphic tumor giant cells and characteristic eosinophilic bodies. All 5 patients are now alive after surgical resection: 1 patient achieved disease-free survival of more than 91 months after surgery alone. Two patients had recurrence after surgery and received surgical resection plus chemotherapy or chemotherapy alone. They achieved survival of more than 35 and 16 months, respectively. Two patients were treated with chemotherapy or chemotherapy plus radiotherapy after surgery and survived more than 49 and 31 months without recurrence, respectively.Conclusions:UESL is a rare and highly malignant mesenchymal tumor with characteristic pathologic morphology. Radical resection is the key to the treatment for UESL, and chemotherapy and radiotherapy should be carried out after surgery.

Effect of intraoperative cell salvage on the number and viability of cancer cells in salvaged autologous blood from patients undergoing liver cancer surgery / 中华麻醉学杂志

Objective:To evaluate the effect of intraoperative cell salvage (ICS) on the number and viability of cancer cells in salvaged autologous blood from the patients undergoing liver cancer surgery.Methods:Twenty patients undergoing open radical primary hepatocellular carcinoma were selected, and blood from the operative field was collected after exposing the liver and treated with ICS. Blood specimens 20 ml from the surgical field (S 1), blood specimens 20 ml before ICS treatment-leukocyte depletion filter (LDF) filtration (S 2) and blood specimens 20 ml after LDF filtration (S 3) were collected and enriched, of which the blood sample 10 ml was used for cancer cell identification and count by immunofluorescence staining, and the remaining blood sample 10 ml was continuously cultured for 3 weeks, and then cell viability was observed by immunofluorescence method. Results:Hepatocellular carcinoma(HCC) cells were identified in 19 S 1 specimens, 18 S 2 specimens, and 16 S 3 specimens, but there was no significant difference in the detection rate among the three specimens ( P>0.05). Compared with S 1 specimens, HCC cell count was significantly reduced in S 2 and S 3 specimens ( P<0.05). There was no significant difference in the HCC cell count between S 3 specimens and S 2 specimens ( P>0.05). After 3 weeks of culture, the results of light microscopy showed that: hepatocellular carcinoma cell clusters were found in S1 specimens, and no hepatocellular carcinoma cell cluster was found in S 2 and S 3 specimens; the results of fluorescence microscopy showed that: 400 and 14 mixed epithelial-mesenchymal HCC cells and 100 and 21 mesenchymal HCC cells were found in S 1 and S 2 specimens, respectively, while no HCC cells were identified in S 3 specimens, among which HCC cells mainly presented as clusters of hepatocellular carcinoma cells in S 1 specimen, while no clusters of hepatocellular carcinoma cells were found in S 2 and S 3 specimens. Conclusions:After treatment with ICS or ICS-LDF, the number and viability of hepatocellular carcinoma cells in salvaged autologous blood are significantly reduced, and hepatocellular carcinoma cells exist as single cells and fail to develop clusters of hepatocellular carcinoma cells; LDF can reduce the risk of hepatocellular carcinoma cell autotransfusion to a certain extent, although it can not effectively filter out hepatocellular carcinoma cells continuously.

Diagnostic and prognostic value of 68Ga-FAPI PET for malignant tumors of the liver and biliary tract / 中华核医学与分子影像杂志

Objective:To investigate the diagnostic and prognostic value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET for hepatobiliary malignancies. Methods:From July 2020 to February 2023, 33 patients (23 males, 10 females; age (55.4±13.5) years) with suspected or confirmed liver or biliary tract malignancies who underwent 68Ga-FAPI PET in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. PET images were evaluated by 3 experienced nuclear medicine physicians, and the results of biopsy or postoperative pathology, clinical and imaging follow-up were used as the gold standard. One-way analysis of variance and least significant difference t test were used to compare the differences among groups. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results:Of 33 patients, 14 performed PET for initial diagnosis and staging, and 19 for restaging. There were 14 patients with hepatocellular carcinoma (HCC), 13 patients with cholangiocarcinoma (CCA), and 6 patients with gallbladder carcinoma (GBC). The primary tumor of HCC, CCA and GBC all showed significant 68Ga-FAPI uptake, with no statistically significant difference in SUV max among groups ( F=1.58, P=0.250). The sensitivities of 68Ga-FAPI PET for initial diagnosis and restaging of hepatobiliary malignancies were 14/14 and 15/15, respectively. Compared with conventional imaging, 68Ga-FAPI PET changed the diagnosis and staging in 29.2%(7/24) patients. The treatment strategy was changed in 30.3%(10/33) patients with malignant tumors due to 68Ga-FAPI PET findings. Follow-up showed 22 cases survived and 11 cases died, with the overall survival of 355.56(80.00, 516.97) d, and 1- and 2-year survival rates were 68.2% and 57.9%, respectively. Semi-quantitative 68Ga-FAPI PET parameters such as SUV max, target-liver ratio (TLR), and target-blood ratio (TBR) had no significant prognostic value, but the prognosis of the group without distant metastases diagnosed by 68Ga-FAPI PET was significantly better than that of the group with distant metastasis ( P=0.032). Conclusion:68Ga-FAPI PET has high sensitivity for the diagnosis of hepatobiliary malignancies, which can help guide treatment decisions and prognosis evaluation.

Thought and practice of long-term management for hepatobiliary and pancreatic malignant tumors / 中华肝胆外科杂志

Radical resection is the only measurement to cure patients of hepatobiliary and pancreatic tumors. The comprehensive application of endoscopy, interventional therapy, radiotherapy and systemic therapy can not only significantly improve the early diagnosis rate of the disease, and successfully transform some borderline resectable tumors into radical resectable states, but also reduce the recurrence rate of tumors after surgery, thus prolonging the survival time of patients. In recent years, the continuous emergence of new systemic therapeutic drugs has brought new opportunities for patients with hepatobiliary and pancreatic malignancies, but the number of doctors participating in diagnosis and treatment has also increased accordingly. Therefore, the contradiction between the division system based on treatment methods and the orderly and standardized treatment is becoming more and more prominent. According to the latest progress of hepatobiliary and pancreatic cancer research at home and abroad, and combined with our clinical experience, we proposed a long-term management concept based on hepatobiliary and pancreatic comprehensive multi-technical team. Based on this concept, we have carried out new thought and practice on the diagnosis and treatment of patients with hepatobiliary and pancreatic malignant tumors.