Abstract:China is a high-incidence country for hepatocellular carcinoma (HCC), with consistently high rates of both morbidity and mortality. The majority of HCC patients are already in the advanced stages at the time of diagnosis, losing the opportunity for surgery. Combined targeted therapy and immunotherapy (targeted-immune combination) and targeted-immune combination local therapy have become the hot topic in the treatment of advanced-stage HCC in recent years. Combination therapy based on immune checkpoint inhibitors has significantly improved the efficacy for patients with advanced-stage HCC. However, there is a significant difference in treatment plans and experiences among different medical institutions, lacking a unified consensus and a model for comprehensive management as a reference. Recently, the Hepatic Oncology Branch and Immunology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Expert Consensus Collaborative Group on Targeted-Immune Combination Local Therapy for Advanced Hepatocellular Carcinoma took the lead in formulating and releasing the Chinese expert consensus on targeted-immune combination local therapy for advanced hepatocellular carcinoma. This consensus provides detailed explanations from various perspectives on the definition of targeted-immune combination local therapy for HCC, the eligible population and management, the selection of treatment methods, strategies for converting unresectable tumors into resectable tumors, treatment strategies for tumor progression, and the management of common adverse reactions. Here, the authors interpret the key points of this consensus and look ahead to how the consensus can adapt to the current background of research or practice.

Abstract:Background and Aims Antibody-mediated rejection (AMR) is relatively uncommon after liver transplantation, but it poses a significant risk factor for graft function loss. This study investigated the occurrence of AMR after liver transplantation, its relationship with biliary strictures, and the associated diagnostic and therapeutic strategies.Methods The clinical data from 203 patients who underwent brain death donation liver transplantation at the First People's Hospital of Kunming from January 2016 to October 2023 were retrospectively analyzed.Results Among the 203 liver transplant recipients, 20 cases developed acute rejection after transplantation, including 7 cases of AMR and 13 cases of T-cell-mediated acute rejection (TCMR). Additionally, 18 cases had biliary strictures. Among patients with acute rejection, 6 cases (30.0%) developed biliary strictures, while among those without acute rejection, 12 cases (6.6%) developed biliary strictures, indicating a significantly higher incidence in the former group (P=0.002). In the AMR group, 5 cases (71.4%) developed biliary strictures, of whom 3 cases had concomitant biliary strictures at the time of acute AMR diagnosis and were treated accordingly, while 2 cases developed biliary strictures during the one-year follow-up after AMR treatment. Only 1 TCMR patient (7.7%) developed biliary stricture 3 years after operation， the incidence of biliary strictures in AMR patients was significantly higher than in TCMR patients (P=0.007). Among the 7 AMR patients, one experienced rapid deterioration of liver function within two months after transplantation, leading to death despite steroid pulse therapy. The remaining 6 patients, after managing biliary strictures and receiving AMR-specific treatment, showed normalization of liver function.Conclusion AMR after liver transplantation increases the risk of biliary strictures. For patients with acute AMR and concurrent biliary strictures, prompt consideration of AMR diagnosis and corresponding treatment is essential, in addition to ensuring biliary drainage.

Abstract:Background and Aims Hilar cholangiocarcinoma refer to a malignant tumor originating from the epithelial cells involving the left, right hepatic ducts, biliary confluence or the upper segment of the common hepatic duct. Due to the complex anatomy of the hilar region and its proximity to major vessels such as the portal vein and hepatic artery, this tumor is prone to vascular or neural invasion, and lymph node metastasis. Additionally, its inconspicuous location and lack of early specific symptoms often result in patients seeking medical treatment only when advanced symptoms like jaundice appear. Currently, surgical resection remains the primary effective treatment for improving prognosis. However, surgical management of hilar cholangiocarcinoma remains one of the most challenging tasks for hepatobiliary surgeons. Here, the authors report a case of hilar cholangiocarcinoma invading the stomach, duodenum, and pancreas, treated with total pancreatectomy and duodenectomy combined with total hepatectomy and orthotopic liver transplantation, aiming to provide further reference for the diagnosis and treatment of this disease.Methods The clinical data of a case of hilar cholangiocarcinoma, collaboratively treated by the PLA Rocket Force Characteristic Medical Center and Hebei Medical University Third Hospital were retrospectively analyzed. Relevant literature was reviewed and pertinent experiences and lessons learned from this case were summarized.Results The patient, a 51-year-old male with a history of hepatitis B, sought medical attention due to abdominal ascites. Abdominal exploration (revealing a tumor involving an inseparable region of the liver, pancreatic head, and hepatoduodenal ligament) and PET-CT scan (indicating a slightly low-density lesion with increased FDG metabolism in the right lobe of the liver, possibly involving the main portal vein and right branch, with no apparent distant metastasis) suggested a malignant tumor, but preoperative biopsy failed to provide a definitive diagnosis. After discussion, the patient underwent total pancreatectomy and duodenectomy combined with total hepatectomy and orthotopic liver transplantation (anastomosing the superior mesenteric vein with the donor portal vein and anastomosing the inverted splenic artery with the proper hepatic artery of the donor, due to preoperative CT indicating occlusion or tumor invasion of the portal vein and hepatic artery). The postoperative recovery was uneventful, and the pathology revealed moderately to well-differentiated cholangiocarcinoma of the hepatic hilar region involving the duodenum, stomach, and pancreas, with multiple neural invasions, no clear vascular tumor thrombus, and margins free of cancer. The patient died of gastrointestinal bleeding and infection 8 months after surgery.Conclusion Surgical resection remains the primary treatment for hilar cholangiocarcinoma. For patients ineligible for radical resection, liver transplantation is an option that can achieve R₀ resection, providing a potential opportunity for cure. However, there are currently still relatively few reported cases of combined total pancreaticoduodenectomy. The analysis and summary of this case will contribute to further exploration and practice in the future.

Abstract:Background and Aims Currently, there are multiple assessment systems available for evaluating prognosis indicators in liver cancer, each with its own strengths and limitations. Joint assessment may enhance predictive efficiency. Therefore, this study was conducted to investigate the predictive value of the combination of age-adjusted Charlson complication index (aCCI), tumor burden score (TBS), and albumin-bilirubin (ALBI) score (aCTA score), integrating complications, morphological features, and liver function, in predicting post-hepatectomy liver failure (PHLF). Methods The clinical data of 236 patients with primary liver cancer undergoing hepatectomy in Renmin Hospital of Wuhan University from January 2020 to February 2023 were retrospectively collected. Patients were divided into the PHLF group (19 cases) and non-PHLF group (217 cases) based on the occurrence of liver failure within 1 week after surgery. Univariate and multivariate Logistic regression analyses were conducted to identify the independent risk factors for PHLF. Receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of the combined indicators. A weighted risk score for PHLF was constructed using the Framingham Research Center Logistic model. Internal validation was performed using the concordance index (C-index), ROC curves, and calibration curve. The clinical utility of the score was assessed using decision curve analysis (DCA). Results Among the 236 patients undergoing liver resection for liver cancer, 19 cases (8.1%) developed PHLF. Multivariate Logistic regression analysis revealed that aCCI ( OR=1.557, 95% CI=1.014-2.391, P=0.043), TBS ( OR=1.214, 95% CI=1.022-1.442, P=0.027), and ALBI ( OR=5.387, 95% CI=1.844-15.733, P=0.002) were independent risk factors for PHLF in liver cancer patients (all P<0.05). The area under ROC (AUC) for aCCI, TBS, ALBI, and the combination of the three scoring systens were 0.662, 0.733, 0.768, and 0.822, respectively. Based on aCCI, TBS, and ALBI, the jointly constructed aCTA scoring system (with a maximum score of 10) had a C-index of 0.828 (95% CI=0.732-0.925). and the AUC was 0.809 ( P<0.05), indicating good discriminative ability. The calibration curve showed close agreement between predicted and observed values, suggesting good accuracy of the score. DCA demonstrated a net benefit for patients from the aCTA score model, indicating its good clinical applicability. Conclusion aCCI, TBS, and ALBI are independent risk factors for PHLF in liver cancer patients. The aCTA score, constructed based on them, has good predictive value and clinical guidance for high-risk patients.

Abstract:Background and Aims For borderline resectable primary liver cancer, the recommended treatment options currently in China according to the Diagnosis and Treatment Guidelines for Primary Liver Cancer (2022 edition) are still transcatheter arterial chemoembolization (TACE), surgical resection, or systemic anti-tumor therapy. Preoperative conversion therapy for primary liver cancer has made significant progress, but specific conversion therapy strategies are still under exploration. This study was performed to explore the real-world efficacy of local conversion therapy using FOLFOX regimen-based hepatic arterial infusion chemotherapy (HAIC) plus transarterial embolization (TAE) in the treatment of borderline resectable liver cancer.Methods The clinical data of 22 patients with borderline resectable (CNLC stage IIb) primary liver cancer who underwent conversion therapy using FOLFOX regimen-based HAIC combined with TAE from April 2019 to February 2022 were collected. Tumor objective response rate (ORR) and disease control rate (DCR) were assessed based on the modified response evaluation criteria in solid tumors (mRECIST). The conversion surgery rate, pathological response rate in postoperative specimens, and the prognosis of patients undergoing or not undergoing surgery after conversion therapy were analyzed.Results All 22 patients completed HAIC combined with TAE treatment. Main adverse reactions included upper abdominal pain, low-grade fever, and short-term liver dysfunction, but no irreversible severe complications occurred. After conversion therapy, the tumor ORR and DCR were 63.6% and 86.3%, respectively, and 3 patients (13.6%) experienced tumor progression. Following the completion of conversion therapy, 14 patients underwent liver cancer resection, and the conversion surgery rate was 63.6%. All surgeries were successfully performed and all achieved R₀ resection. There were no postoperative deaths. Postoperative pathology showed major pathological response (MPR) in 10 cases (71.4%), but none achieved complete pathological response (CPR). The average disease-free survival for surgical patients was 14.7 months, and their overall survival was significantly better than non-surgical patients (22.7 months vs. 13.2 months, P=0.018).Conclusion HAIC plus TAE conversion therapy for borderline resectable liver cancer demonstrates excellent tolerability, proving to be a safe and feasible approach that achieves higher ORR, DCR, and conversion surgery rate. Although most patients achieve MPR after preoperative conversion therapy, CPR remains low. So, surgical resection still the key approach for patients to attain long-term survival after liver cancer conversion therapy.

Abstract:Background and Aims Adult immune thrombocytopenia (ITP) combined with hepatic hemangioma is clinically rare and prone to misdiagnosis and mistreatment. Here, the authors report the diagnosis and treatment process of a case of adult ITP combined with hepatic hemangioma, aiming to provide reference and insights for clinical practice.Methods A retrospective analysis of the clinical data of an adult patient with ITP and concomitant hepatic hemangioma admitted to the Second Affiliated Hospital of Guilin Medical College was conducted. The clinical features and treatment characteristics of the disease were summarized in conjunction with relevant literature.Results The patient, a 46-year-old female, was admitted to the Department of Hematology due to generalized skin and mucosal bleeding for over a month, and thrombocytopenia for 1 d. Blood cell analysis revealed a platelet count of 4.0×10⁹/L, normal coagulation function, and bone marrow aspiration biopsy suggested a relative increase in megakaryocytes with rare platelets. The diagnosis was highly suspicious of ITP. After treatment with steroids and other measures, the skin and mucosal bleeding improved, and the platelet count increased to 59×10⁹/L. Abdominal enhanced CT indicated a massive hemangioma on the right liver, and then, the patient was transferred to the Department of Hepatobiliary and Pancreatic Surgery for resection of the liver hemangioma. After operation, there was significant bleeding in the surgical area, vaginal bleeding, and a gradual decrease in platelets to 3.0×10⁹/L. The right pleural cavity accumulated a large amount of fluid, but coagulation function remained normal. After interventions including hemostasis, transfusion, immune modulation, anti-infection measures, and thoracic puncture drainage, the patient gradually recovered. On the 13th d after operation, the platelet count increased to 220×10⁹/L. Follow-up for 32 months revealed no recurrence of skin and mucosal bleeding, with the platelet count maintained within the normal range.Conclusion In adult ITP, vigilance is necessary for the presence of concomitant hepatic hemangioma. Treatment of the hemangioma can achieve favorable long-term outcomes, but meticulous perioperative management is essential for the uneventful recovery of patients.

Abstract:Background and Aims The liquefaction degree of abscesses is a crucial factor affecting the early treatment, invasive drainage, and prognosis of patients with pyogenic liver abscesses (PLA). Effectively diagnosing PLA early and providing timely assessment and treatment are focal challenges in clinical practice. Currently, the diagnostic and treatment strategies both at home and abroad rely on enhanced CT scans, MRI examinations, and surgical conditions to determine the nature of abscesses, and there is a lack of rapid means to determine abscess characteristics. This study was conducted to construct a predictive model for the liquefaction maturity of PLA using routine admission examination indexes and the Bayesian statistical method to provide a scientific basis for the early diagnosis and treatment of PLA.Methods Data of 116 PLA patients admitted to the Fifth Affiliated Hospital of Xinjiang Medical University between January 2018 and December 2022 were collected. Patients were classified into a complete liquefied group (59 cases) and an incomplete liquefied group (57 cases) based on the abscess maturity confirmed by enhanced CT and surgical conditions. Comparison was made between the two groups regarding routine admission examination indexes and clinical characteristics. The original data was subjected to binary classification, and after screening, variables with significant diagnostic values were identified. The Bayesian statistical method was employed to establish a predictive model for the liquefaction degree of PLA. The model was validated using 23 PLA patients admitted to the Fifth Affiliated Hospital of Xinjiang Medical University from January 2023 to November 2023, and the ROC curve was generated to evaluate the model's predictive performance.Results Screening results revealed that factors such as onset time, white blood cell count, neutrophil count, neutrophil percentage, neutrophil-to-lymphocyte ratio, platelet count, procalcitonin, alanine aminotransferase, and plain CT values were significantly associated with the liquefaction degree of PLA (all P<0.05). ROC curve validation demonstrated that the Bayesian statistical predictive model based on these variables had a sensitivity of 90.0%, specificity of 84.6%, and accuracy of 87.3%.Conclusion The constructed Bayesian statistical predictive model for the liquefaction degree of PLA can effectively and rapidly determine the nature of abscesses. It can be used in the early stages of the disease when PLA is not excluded based on routine examination indicators at admission and clinical features with good sensitivity and specificity.

Abstract:Background and Aims Research has found a close relationship between transmembrane protein (TMEM) family genes and tumors. TMEM201 is a member of the TMEM family, and its expression and role in hepatocellular carcinoma (HCC) are currently unclear. Therefore, this study was conducted, uses bioinformatics methods, to analyze the expression and function of TMEM201 in HCC and predict the pathways it may be involved in, exploring the underlying mechanisms.Methods TMEM201 expression in pan-cancer is analyzed using TIMER. Data of HCC patients from TCGA and GEO databases are downloaded, and the specimens and clinical information of 106 HCC patients were collected. The expressions of TMEM201 in liver cancer tissue and adjacent tissue were analyzed, the survival curves were plotted to analyze the relationship between TMEM201 expression and the prognosis of HCC patients. Univariate and multivariate Cox analyses are employed to identify HCC-related risk factors. The relationship between TMEM201 expression and clinicopathologic characteristics of HCC patients was analyzed based on TCGA and clinical data. String and GeneMANIA databases were used to construct a network diagram of TMEM201 and its related genes. TCGA database was used to analyze the relationship between TMEM201 and immune cells. LinkedOmics database was employed to analyze co-expressed genes related to TMEM201, followed by GO functional analysis and KEGG pathway prediction of these co-expressed genes.Results Pan-cancer analysis showed that TMEM201 was highly expressed in the majority of tumors. Multiple databases analysis and immunohistochemical results of clinical HCC specimens revealed that TMEM201 expression in HCC tissue was significantly higher than that in adjacent tissue (all P<0.05). Additionally, patients with high TMEM201 expression had a significantly shorter survival time than those with its low expression. Univariate and multivariate Cox regression suggested that TMEM201 expression was an independent risk factor for overall survival in HCC patients. Protein interaction networks and GeneMANIA database analysis showed significant interactions between TMEM201 and genes such as SUN1, SUN2, LMNB1, and EMD. Immune infiltration analysis indicated a significant association between TMEM201 expression and dendritic cells, cytotoxic cells, Th2 cells, etc. Furthermore, functional enrichment analysis demonstrated that TMEM201 and its co-expressed genes were involved in various biological processes, cellular components, molecular functions, and signaling pathways related to HCC. Pathway results and correlation heatmaps suggested a strong correlation between TMEM201 and the cell cycle.Conclusion TMEM201 is highly expressed in HCC tissue and is an independent risk factor influencing the prognosis of HCC patients. The mechanism of action of TMEM201 in HCC may be related to the regulation of immune infiltration and the control of the cell cycle.

Abstract:Background and Aims Liver cancer is one of the malignant tumors of the digestive system, characterized by high incidence and mortality rates. Cuproptosis, a novel copper-dependent form of cell death, occurs as a result of mitochondrial dysfunction induced by copper overload. Cuproptosis plays a significant role in various tumors, but its relationship with liver cancer remains unclear. Therefore, this study was conducted to investigate the expression characteristics of cuproptosis-related genes in liver cancer and their association with prognosis and immune infiltration.Methods Transcriptome data of liver cancer and normal liver tissues were downloaded from TCGA and GTEx databases for differential expression and mutation analysis. The R language "clusterProfiler" package was used for GO and KEGG enrichment analysis. LASSO, univariate, and multivariate regression analyses were employed to screen genes affecting the prognosis of liver cancer patients and a risk factor graph was constructed. A nomogram was constructed using the "rms" package in R. The UALCAN database was used to analyze the relationship between cuproptosis-related genes and clinicopathologic features of liver cancer and then the findings were validated. Spearman correlation analysis was used to examine the correlation between cuproptosis-related genes and immune cell infiltration and immune checkpoint expressions. TIMER2.0 database was used to analyze the correlation between the expressions of copper cuproptosis-related genes and cancer-associated fibroblast (CAF) infiltration, while TISDB database was utilized to analyze the correlation between CDKN2A and DLAT expression and myeloid-derived suppressor cell (MDSC) infiltration abundance.Results Compared to normal liver tissue, nine cuproptosis-related genes showed significantly increased expression in liver cancer, with CDKN2A having the highest mutation frequency. These genes were mainly involved in processes such as protein lipidation, tricarboxylic acid cycle, and citric acid cycle. Based on LASSO, univariate, and multivariate regression analysis, CDKN2A and DLAT were identified as genes influencing the overall survival (OS) of liver cancer patients, and a risk factor graph was constructed. Time-dependent ROC curves indicated their good predictive ability. Univariate and multivariate regression analysis revealed that CDKN2A, DLAT, T stage, and tumor status were independent prognostic factors for OS in liver cancer patients. A nomogram was constructed based on these factors, and calibration curves demonstrated good consistency between the predicted and observed values. UALCAN database analysis found associations of CDKN2A and DLAT with clinical stage and tumor grade in liver cancer, with validation results from GEO and HPA database as well as liver cancer cells aligning with these findings. Correlation analysis indicated that the expressions of CDKN2A and DLAT were correlated with immune cell infiltration and immune checkpoint expressions. TIMER2.0 database analysis revealed a significant positive correlation between DLAT expression and CAF infiltration, while TISDB database analysis showed no correlation of CDKN2A and DLAT expression with MDSC infiltration abundance.Conclusion Cuproptosis-related genes CDKN2A and DLAT may serve as novel prognostic biomarkers and potential targets for immunotherapy in liver cancer.

Abstract:Liver cancer is the sixth most prevalent malignant tumor and the third leading cause of cancer-related deaths worldwide. Although liver resection surgery remains the primary radical treatment for liver cancer, with high efficacy, the prognosis for some patients is not ideal. Post-hepatectomy liver failure (PHLF) is one of the major causes of death during the perioperative period. The occurrence of PHLF is closely related to insufficient volume and function of the remnant liver after hepatectomy. Therefore, accurate assessment of preoperative liver reserve function is crucial. However, the progression of chronic liver disease can cause changes in hepatic functional reserve, and there are differences in function in different regions of the liver, posing significant challenges to accurate preoperative assessment. Currently, common methods for assessing liver reserve function include comprehensive scoring systems, laboratory serological tests, indocyanine green (ICG) clearance test, imaging, and nuclear medicine hepatobiliary scintigraphy. Serological tests and clinical scoring systems are commonly used tools for screening hepatic insufficiency, with low cost and easy accessibility, and are widely used in clinical practice. Currently, the ICG clearance test has been included in guidelines and expert consensus in China, but its evaluation is still for overall liver function. Gd-EOB-DTPA is a hepatobiliary-specific MRI contrast agent that not only provides anatomical information but also allows quantitative assessment of local liver function. Compared to the ICG clearance test, Gd-EOB-DTPA-enhanced MRI has higher predictive value for PHLF. However, factors such as high cost, lengthy examination processes, and complex scanning sequence parameter adjustment limit the widespread application of this technology. With the continued advancement of the concept of precision medicine, the widespread use of three-dimensional imaging technology has important clinical value in guiding precise surgical operations, improving surgical accuracy, and safety. In recent years, with the rapid development of artificial intelligence (AI) in the medical field, AI-assisted three-dimensional reconstruction can significantly shorten processing time and improve measurement accuracy. It is worth noting that three-dimensional imaging technology is based on the overall assessment of liver volume, and the remnant liver volume and function do not exactly correspond with each other. CT perfusion imaging, with its wide scanning range, high spatial resolution, and accurate blood flow measurement capabilities, is an ideal tool for liver function assessment. However, the limitations such as CT radiation exposure and poor reproducibility prevent the routine application of this technique. Elastography, as a non-invasive method, assesses the degree of liver fibrosis in patients with chronic liver disease by measuring liver stiffness, indirectly achieving the assessment of liver reserve function. The advantage of hepatobiliary scintigraphy lies in its abilities to assess both overall and regional liver function, combine with SPECT/CT for volume assessment, and consider intersegmental functional variability and potential pathological conditions. However, its current application in China is still limited, requiring further exploration of its clinical value. Currently, commonly used assessment methods still cannot comprehensively and accurately reflect liver reserve function, and all have their limitations. This article reviews the latest research progress on preoperative liver reserve function assessment methods in liver cancer, aiming to provide a scientific basis and guidance for clinical practice.

Abstract:Hepatocellular carcinoma (HCC) is the most common primary liver cancer and ranks among the most prevalent and highly lethal cancers worldwide. Radical hepatectomy remains one of the most effective treatment methods for early and some intermediate to advanced stages of HCC. Complications during the perioperative period of liver resection are critical factors affecting the long-term and short-term prognosis of HCC patients, with post-hepatectomy liver failure (PHLF) being a common complication after liver resection. PHLF is a major cause of perioperative death in liver resection patients, and the timely identification of patients with high-risk PHLF before surgery is a pressing clinical issue and research focus. Traditional methods of liver function assessment are widely used and can distinguish high-risk PHLF patients, but their predictive accuracy is relatively low. In recent years, with the development of artificial intelligence technology, an increasing number of advanced algorithms and models incorporating more comprehensive risk factors have been applied in the field of PHLF prediction. Scholars both in China and abroad have constructed new PHLF-related prediction models through various statistical methods, confirming a significant improvement in the accuracy of these models. After an extensive literature review, the authors summarize the relevant literature on PHLF risk prediction models, providing a comprehensive overview of the research progress, so as to facilitate clinicians and researchers in gaining a more comprehensive understanding of various types of PHLF prediction models.

Abstract:The liver is the site where thyroxine is converted into triiodothyronine. Liver transplantation (LT) is inevitably associated with changes in thyroid hormones (TH) during the perioperative period, and TH plays a crucial role in regulating the normal metabolic rate of all cells, including liver cells. Therefore, alterations in thyroid function are closely related to the prognosis of LT patients. In this regard, the authors provide a review of research related to thyroid function during the perioperative period of LT, with the aim of providing references for both clinical and research purposes.

Abstract:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease predominantly synthesized by the liver, with expression also found in the gastrointestinal tract, pancreas, kidneys, and central nervous system. PCSK9 is involved in regulating lipid metabolism with numerous molecular targets both inside and outside hepatocytes. In the liver, it mainly targets lysosomal degradation through binding to low-density lipoprotein receptor (LDLR) on the cell membrane surface, thereby increasing plasma levels of low-density lipoprotein cholesterol. PCSK9 has garnered widespread attention in familial hypercholesterolemia, atherosclerosis, myocardial infarction, cancer, and other diseases, which has accelerated the rapid development of PCSK9 inhibitors, and played a significant role in the treatment of hypercholesterolemia and reducing the risk of cardiovascular diseases. As research on PCSK9 deepens and the prevalence of chronic liver diseases increases, the relationship between PCSK9 and the development of chronic liver diseases is gradually being revealed. Given the aforementioned background, this article elaborates on the role of PCSK9 in various common chronic liver diseases in clinical practice, including alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, viral hepatitis, and liver cancer, aiming to offer new perspectives for the clinical diagnosis and treatment of chronic liver diseases.

Abstract:Colorectal cancer is a common malignant tumor worldwide and a significant cause of cancer-related deaths. The liver is the most frequent site of metastasis for colorectal cancer, about 20% of patients have simultaneous liver metastasis, and an additional 20% develop liver metastasis during the progression of the disease. Colorectal cancer liver metastasis (CRLM) is currently a focal and challenging aspect of colorectal cancer treatment, and also an essential factor affecting the prognosis of patients. Surgical resection remains the optimal treatment choice for long-term survival and even cure. Minimally invasive resection, in particular, combines the advantages of minimally invasive procedures with curative effects, showing equivalent long-term oncological efficacy to open surgery. However, limited by tumor size, location distribution and other anatomical factors, liver function, and general status of patients, only a few patients are suitable for surgical resection at the time of initial diagnosis. Other minimally invasive treatment strategies include ablation therapy, stereotactic body radiation therapy, interventional therapy, etc. The development of these technologies provides new therapeutic opportunities for unresectable patients and also improves the survival rates of systemic treatment alone. Ablation therapy, for selected patients, combines the minimally invasive nature with radical effect similar to surgery, and is also more advantageous for deep-seated tumors. Stereotactic body radiation therapy is an important alternative for difficult or recurrent lesions that are unsuitable for surgical resection or ablation. Furthermore, Y⁹⁰ selective internal radiation therapy has a dual effect of tumor control and enlarging the remnant liver. Its significance is continuously growing in the era of transformative treatment. With the deepening of minimally invasive concepts and technological advancements, there has been some progress in the minimally invasive treatment of CRLM. However, it still faces numerous challenges, such as how to rationally combine or sequentially use minimally invasive treatment strategies in the era of precision, personalized, and transformative therapy. When selecting minimally invasive treatment strategies, individualized evaluation and comprehensive treatment should be carried out according to the guidance of the multidisciplinary team, with the goal to achieve R₀ resection or no-evidence-of-disease status as much as possible, thereby maximizing the long-term survival rates for patients. This article provides a review of recent advances in minimally invasive treatment strategies for CRLM, so as to serve as a reference for clinical practice.

Abstract:Lipid metabolism-mediated ferroptosis plays a crucial role in the initiation and progression of tumors, making it a focal point and challenge in current cancer research. The key regulatory molecules involved in controlling lipid metabolism and ferroptosis in tumors remain not fully understood. Studies have indicated that phosphatidylinositol transfer protein cytoplasmic 1 (PITPNC1), a member of the phosphatidylinositol transfer protein family, specifically binds and transfers phosphatidylinositol and phosphatidic acid, facilitating the transfer of lipids across cell membranes and mediating lipid metabolism. Recently, it has been found that PITPNC1 is a lipid metabolism-related oncogene, highly expressed in various cancers such as breast, liver, gastric, colorectal, lung, and pancreatic cancers, and participates in regulating the growth, migration, and invasion processes of tumor cells. Here, the authors provide a review of the potential regulatory mechanisms of PITPNC1-mediated lipid metabolism-related signaling pathways on ferroptosis in tumor cells, so as to deepen our understanding of tumor cell ferroptosis and lipid metabolism, offers new perspectives for the development of targeted therapies in cancer treatment.