The Laennec capsule is an intrinsic fibrous connective tissue covering the intrahepatic and extrahepatic parenchyma. The Chinese Chapter of the International Hepato‐Pancreato‐Biliary Association organized domestic experts in this field to formulate the Expert consensus on Laennec capsule guided hepatobiliary surgery (2026 edition). Based on evidence‐based medicine principles, the consensus systematically summarizes the anatomical definition of Laennec capsule and its applications in hepatobiliary surgery, clarifies the anatomical spaces between Laennec capsule and Glisson sheath, hepatic veins, and inferior vena cava, and proposes the Laennec capsule guided surgical approach, aiming to standardize surgical procedures,improve surgical safety and efficacy, promote the popularization and stardardization of surgical plans, outline future directions in researches.
Treatment of advanced liver cancer is still a major challenge in clinical settings because of its high heterogeneity, limited liver function reserve and narrow therapeutic window. In this article, the key challenges in the treatment of advanced liver cancer, including heavy disease burden, toxic accumulation of combined therapy and the balance dilemma between liver function protection and anti-tumor efficacy, were systematically reviewed. In this study, three optimization strategies were mainly illustrated: (1) Joint optimization of treatment modes. Synergistic sensitization mechanism and strategy of local and systemic therapy were investigated to explore the potential to enhance clinical efficacy for advanced liver cancer. (2) Functional protection of tumor treatment. Through dose optimization and course adjustment, the liver and systemic toxicities are minimized while ensuring clinical efficacy, thereby prolonging long-term survival. (3) Precise prediction of tumor treatment. Individualized therapy is achieved through biomarkers, molecular typing and artificial intelligence. The establishment of MDT under the framework of liver cancer center provides organizational guarantee for clinical translation of these strategies. In the future, it is necessary to further deepen the research of mechanism, optimize treatment strategies and spread successful experiences, eventually achieving the dual goals of prolonging survival time and improving the quality of life of patients with advanced liver cancer.
Primary liver cancer (PLC) ranks the sixth in the incidence of malignant tumors and fourth in the cancer-related mortality. Surgical resection and liver transplantation are still considered as the gold standard treatments for patients with resectable PLC. However, only 30.2% of newly-diagnosed patients have surgical indications. For patients ineligible for surgery, local treatment methods including TACE, radiofrequency ablation (RFA), external beam radiotherapy (EBRT) and Yttrium-90 microsphere brachytherapy are commonly adopted in clinical practice. Among them, radiotherapy is an important non-invasive treatment option, and its clinical application value is increasingly prominent. In recent years, revolutionary technological progress has been achieved in radiotherapy including intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), image-guided radiotherapy (IGRT) and charged particle therapy (CPT) such as protons and carbon ions. In this article, radiotherapy strategies and side effects of ablation radiotherapy for early PLC, TACE combined with EBRT, radiotherapy for PLC complicated with great vessel invasion, neoadjuvant radiotherapy and downstaging radiotherapy, and SBRT as a bridging therapy to liver transplantation were systematically illustrated. Local radiotherapy combined with immune checkpoint inhibitors has achieved favorable outcomes in advanced PLC patients. It is still urgent to explore combined regimen of radiotherapy and immunotherapy with both targeted and distant effects.
The treatment mode of hepatocellular carcinoma (HCC) is gradually evolving towards individualized sequential local combined with systemic therapy. TACE combined with microwave ablation (MWA) is an important local combined therapy for HCC, and its efficacy is affected by both tumor volume and sequential time window. In this article, clinical evidence and mechanism of TACE-MWA in different stratifications of tumor volume (≤3 cm, 3-5 cm, ≥5 cm) and different sequential time windows (synchronous/ultrashort, 1-4 weeks, long interval/sequential). TACE can reduce the ‘heat sink effect’ by reducing the blood supply of tumors, while lipiodol deposition can improve the development and thermal efficiency of MWA. Both of them can induce immunogenic cell death and activate systemic anti-tumor immunity. For medium-sized HCC (3-5 cm), MWA within 1-4 weeks after TACE can significantly improve the complete remission rate and prolong the tumor progression time. For large/huge HCC (≥5 cm), multi-modal strategy of sequential tumor reduction or combined with targeted therapy/immunotherapy. Existing evidence is still mainly based upon retrospective research, with a significant degree of heterogeneity, including differences in TACE/MWA technology, inconsistent definition of endpoint, and different baselines of patients, which limit the universality of the conclusion. Individualized sequential strategy based on tumor volume and time window possesses definite pathophysiological evidence and clinical benefit trend. However, it is necessary to comprehensively weigh between‘the optimal window of hemodynamics’and‘the safe window of liver function’. Peripheral immune markers (such as NLR and NK cell dynamics) may provide potential evidence for time window optimization, whereas the causal effects remain to be verified by prospective study. Subsequently, multi-center stratified randomized trials should be carried out, with‘time window’as the core variable, and dynamic indexes of hemodynamics, immunity and liver function should be systematically collected. In addition, it is necessary to unify technical specifications and endpoint evaluation standards, aiming to establish an individualized treatment system based on‘tumor volume-time window-hemodynamics/immune dynamics’and promote the evolution of combined therapy for HCC in the precise and evidence-based direction.
Hepatocellular carcinoma (HCC) is one of the malignant tumors with high mortality worldwide, especially in China. Although radical resection can be achieved in the early stage, postoperative recurrence seriously limits the long-term survival of HCC patients. In recent years, perioperative comprehensive treatment strategy has become a research hotspot, the core of which is to reduce the risk of postoperative recurrence and improve clinical prognosis through multidisciplinary team (MDT) cooperation by using preoperative neoadjuvant therapy and postoperative adjuvant therapy. Preoperative neoadjuvant therapy can shrink the tumor volume through the synergistic effect of local and systemic therapy, creating favorable conditions for surgery. Traditional interventional methods, such as TACE, can achieve local control by blocking tumor blood supply, while hepatic arterial infusion chemotherapy exhibits higher efficacy due to the optimal distribution of drug concentration. Postoperative adjuvant therapy mainly targets patients with high-risk factors for recurrence (such as microvascular invasion). Some studies have shown that the combination of targeted and immune therapy shows the potential to prolong the cycle of disease control and activate the immune response, whereas special attention should be paid to the risk of tumor progression during the treatment and the influence of adverse drug reactions on surgical resection. Targeted immunotherapy has gradually become the mainstream option. Clinical evidence shows that it may delay the recurrence time, but the long-term impact on recurrence rate remains to be investigated. Subsequently, it is necessary to combine with molecular markers (such as circulating tumor characteristics or immune microenvironment indexes) to achieve precise patient stratification, optimize the treatment cycle to balance efficacy and safety, and promote the establishment of a 'local-systemic-immune' full-cycle management mode.
Liver cancer is one of the main malignant tumors worldwide. Early diagnosis and treatment are of significance for improving the survival rate of patients. In recent years, medical imaging, tumor markers and artificial intelligence (AI) technologies have played a critical role in the diagnosis and management of liver cancer. Imaging technologies, such as ultrasound, CT, MRI and radionuclide imaging, have been widely applied in the screening, diagnosis, grading and treatment evaluation of liver cancer. Tumor markers, such as AFP, AFP-L3 and PIVKA-Ⅱ, are important tools in the diagnosis of liver cancer, which are known as "triple detections of liver cancer". AI technologies, especially deep learning and neural network model, can effectively analyze medical imaging data and assist physicians to make more accurate diagnosis. Integrated application of these technologies is expected to further enhance early diagnosis rate and the overall survival of liver cancer patients.
As the core factor of tumor immune escape, CD47 sends a ‘don't eat me’ signal to macrophages by binding with receptor signal regulatory protein (SIRP)α, enabling tumor cells to evade immune clearance and promoting the progression of tumors. CD47-SIRPα axis not only regulates the homeostasis of red blood cells, Plt, hematopoietic stem cells and neurons, but also plays an adaptive immunomodulatory role resembling PD-1/PD-L1 in tumors. Multiple regulatory factors, including cytokines, oncogenes, microRNA(miR) and enzymes, are involved in the regulation of CD47 expression in tumor cells, among which IL-1, miR-340 and miR-128 have been confirmed to specifically regulate the expression level of CD47 in pancreatic cancer. Recent clinical trials show that anti-CD47 antibody has significant therapeutic potential for pancreatic cancer with low response rate to PD-1, and the adverse reactions are mainly grade 1-2 hematotoxicity, which is well controllable. Existing strategies adopted to control toxicities include dose adjustment, construction of bispecific antibodies that reduce the binding capacity of red blood cells, blocking other sites of CD47-SIRPα axis and developing novel targeted delivery systems. Anti-CD47 therapy combined with other immunotherapies shows its therapeutic potential in HER2-positive gastric cancer, which provides a new perspective for neoadjuvant therapy and comprehensive therapy for pancreatic cancer and is expected to significantly improve clinical prognosis of patients.
To evaluate the predictive value of vessels encapsulating tumor clusters (VETC) in the survival and prognosis of hepatocellular carcinoma (HCC) patients treated with lenvatinib.
Methods
Clinicopathological data of 101 patients with HCC treated with lenvatinib alone in Sun Yat-sen University Cancer Center from July 2018 to January 2020 were retrospectively analyzed. Among them, 88 patients were male and 13 female, aged from 19 to 78 years, with a median age of 51 years. Exemption from the informed consents of all patients was obtained and the local ethical committee approval was received. The status of VETC was evaluated by CD34 immunohistochemical staining. All patients were divided into the VETC positive and negative groups. Baseline characteristics between two groups were balanced by 1:2 propensity score matching (PSM). The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), extrahepatic and intrahepatic PFS. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The influencing factors of survival and prognosis were identified by Cox proportional hazards regression model.
Results
Before PSM, there were 33 patients in the VETC positive group and 68 in the VETC negative group. The incidence of portal vein tumor thrombus in the VETC positive group was 21%(7/33), significantly lower than 50%(34/68) in the VETC negative group (χ2=7.635, P=0.006). After PSM, there were 33 patients in the VETC positive group and 48 in the VETC negative group. The median PFS in the VETC positive and negative groups was 5.0 and 7.6 months, and the difference was statistically significant (HR=0.60, P=0.037). However, no statistical difference was observed in OS between two groups (HR=1.00, P=0.990). The extrahepatic PFS in the VETC positive group was significantly shorter than that in the VETC negative group (HR=0.46, P=0.004), but no significant difference was found in intrahepatic PFS between two groups (HR=0.81, P=0.475). Multivariate Cox regression analysis showed that receiving systematic therapy after the progression post-lenvatinib treatment alone was the independent protective factor of OS (HR=0.50, 95%CI: 0.30-0.84; P=0.009). However, VETC positivity (HR=1.74, 95%CI: 1.09-2.80), distant metastasis (HR=1.83, 95%CI: 1.09-3.09) and AFP≥400 μg/L (HR=2.07, 95%CI: 1.30-3.31) were the independent protective factors of PFS (all P<0.05). VETC positivity (HR=2.47, 95%CI: 1.40-4.35), distant metastasis (HR=2.03, 95%CI: 1.09-3.81) and AFP≥400 μg/L (HR=2.10, 95%CI: 1.21-3.64) were the independent risk factors of extrahepatic PFS (all P<0.05).
Conclusions
VETC positivity is the independent risk factor of PFS and extrahepatic PFS in HCC patients treated with lenvatinib. VETC positivity indicates a higher risk of extrahepatic progression and shorter PFS.
To explore the prognostic value of systemic inflammatory response index (SIRI) in patients with advanced liver cancer after TACE combined with targeted immunotherapy.
Methods
Clinical data of 128 patients with advanced liver cancer admitted to Southeast Hospital affiliated to Xiamen University from January 2020 to December 2023 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 73 patients were male and 55 female, aged from 47 to 69 years, with a median age of 58 years. All patients received TACE combined with targeted immunotherapy. According to the therapeutic effect, the receiver operating characteristic (ROC) curve was drawn to determine the optimal threshold value of SIRI. 128 patients were divided into the high SIRI (n=44) and low SIRI groups (n=84) according to the optimal threshold value of SIRI. Clinical characteristics of all patients in two groups were analyzed by Chi-square test or Fisher's exact probability test, and the overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method. The influencing factors of patients with advanced liver cancer were identified by Cox proportional hazards model.
Results
Among 128 patients with advanced liver cancer, the median OS was 17.5 months and the median PFS was 8.5 months. According to the Response Evaluation Criteria in Solid Tumors (RECIST), the objective response rate (ORR) was 28.1%(36/128), 7.8%(10/128) for complete response (CR) and 20.3%(26/128) for partial response (PR). SIRI had predictive value for clinical efficacy. The area under the ROC curve (AUC) was 0.891 (95%CI: 0.828-0.953), the sensitivity was 0.806, the specificity was 0.837, and the optimal threshold value of SIRI was 1.10, respectively. The incidence rates of tumor diameter≥10 cm, the number of tumor≥3, vascular invasion, BCLC stage C and no remission post-treatment in patients with high SIRI were significantly higher than those in patients with low SIRI (χ2=7.397, 4.127, 5.570, 4.987, 9.318; all P<0.05). Multivariate Cox analysis showed that vascular invasion (HR=0.681, 95%CI: 0.467-0.994), drug withdrawal due to adverse drug reactions (HR=0.349, 95%CI: 0.135-0.902), SIRI(HR=0.422, 95%CI: 0.285-0.625) were the independent influencing factors of PFS in patients with advanced liver cancer. AFP(HR=1.492, 95%CI: 1.097-2.454) and SIRI (HR=0.344, 95%CI: 0.224-0.530) were the independent influencing factors of OS in patients with advanced liver cancer. The follow-up time was 5-26 months, and the median follow-up time was 17.5 months. The median OS in the high and low SIRI groups was 14.5 and 18.5 months, and the difference was statistically significant (χ2=24.091, P<0.001). The median PFS between two groups was 4.5 and 9.5 months, and the difference was also statistically significant (χ2=30.577, P<0.001).
Conclusions
SIRI possesses predictive value for clinical efficacy of TACE combined with targeted immunotherapy in patients with advanced liver cancer, and it is an independent risk factor for PFS and OS. High SIRI is associated with tumor diameter≥10 cm, number of tumor≥3, vascular invasion, BCLC stage C and no remission post-treatment.
To construct the whole-course management mode of selective internal radiotherapy using Yttrium-90 microspheres (90Y-SIRT) for malignant liver tumors.
Methods
Since the first case of 90Y-SIRT was carried out in the First Affiliated Hospital of Jinan University in October 2022, 90Y-SIRT has been performed in 300 cases. Based on clinical experience, a 90Y-SIRT treatment system with its own characteristics was formed by continuously optimizing the treatment process, strengthening multidisciplinary cooperation and improving medical quality. In addition, whole-course management mode of 90Y-SIRT for patients with malignant liver tumors was constructed. The whole-course management mode mainly covers three aspects: (1) medical guidance for 90Y-SIRT; (2) standardized treatment of 90Y-SIRT; (3) post-90Y-SIRT follow-up. This mode ensures that patients can receive standardized, comprehensive and systematic treatment through multidisciplinary cooperation, information management and personalized nursing care.
Results
A whole-course management mode of 90Y-SIRT covering medical guidance, standardized treatment and post-90Y-SIRT follow-up was successfully constructed. Subjective and objective evaluation indexes of this mode were proposed. The whole-course management mode guarantees that all aspects of patients are fully considered and managed according to scientific and standardized medical guidance, treatment process and follow-up system. Formulation and implementation of multidisciplinary cooperation and individualized treatment regimen enhanced treatment specificity and effectiveness, lowered the incidence of complications and improved the quality of life of patients.The whole-course management mode integrated multidisciplinary resources and optimized treatment process as well as the allocation of medical resources and improved the efficiency and quality of medical services. By making full use of professional knowledge and technological advantages of various disciplines, this mode provided patients with more comprehensive and personalized treatment regimens. Meantime, by optimizing treatment process and reducing unnecessary examination and treatment procedures, it lowered medical costs and enhanced the efficiency and quality of medical services. The whole-course management mode adhered to the patient-centered service concept and highlighted the communication and exchange with patients. By answering patients' questions in a timely manner and caring about their needs and willingness, this mode increased patients' compliance and the degree of satisfaction. Psychological support and counseling could help patients to alleviate anxiety, fear and negative emotions, and improve their quality of life. Besides, it delivered personalized rehabilitation guidance and suggestions to promote patients' physical rehabilitation and social function recovery.
Conclusions
In our center, a scientific management mode of 90Y-SIRT is successfully constructed, which is helpful to improve clinical efficacy, the degree of satisfaction and quality of life, and reduce adverse reactions. It also establishes the evaluation indexes of the whole-course management mode, providing evidence for comprehensively evaluating the implementation effect of the whole-course management mode.
To investigate the correlation between Onodera's Prognostic Nutritional Index (OPNI) and clinicopathological features of hepatocellular carcinoma (HCC) and assess the effect on postoperative tumor recurrence.
Methods
Clinicopathological data of 147 patients with HCC admitted to Southeast Hospital affiliated to Xiamen University from January 2018 to December 2021 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 94 patients were male and 43 female, aged (63±7) years on average. All patients underwent radical surgical resection and were followed up for 3 years or tumor recurrence. The correlation between OPNI and clinicopathological features of HCC patients was carried out by t-test.The receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of OPNI for postoperative recurrence of HCC, and the optimal threshold value was determined. The independent risk factors for postoperative recurrence of HCC were identified by univariate and multivariate Cox analyses. The cumulative recurrence rate was analyzed by Kaplan-Meier method and Log-rank test.
Results
The OPNI of all patients was 45.3±4.0. AFP≥400 μg/L, tumor diameter≥5 cm, poorly differentiated tumor, incomplete tumor capsule, microvascular invasion (MVI), CNLC stage Ⅱ and postoperative recurrence were correlated with the decrease of OPNI (t=3.114, 2.836,-3.009, 2.116, 3.946, 3.273,-7.000. all P<0.05). ROC curve showed that OPNI had predictive value for postoperative recurrence of HCC. The optimal threshold value was 43.5.The area under the ROC curve (AUC) of OPNI was 0.785 (95%CI: 0.708-0.862), the sensitivity was 0.875 and the specificity was 0.682, respectively. Univariate Cox analysis showed that female gender, AFP≥400 μg/L, tumor diameter≥5 cm, incomplete tumor capsule, MVI, CNLC stage Ⅱ, no postoperative interventional therapy and OPNI<43.5 were correlated with high recurrence rate of HCC patients. Multivariate Cox analysis revealed that tumor diameter ≥5 cm (HR=3.464, 95%CI: 1.376-8.716), no postoperative interventional therapy (HR=7.300, 95%CI: 2.415-22.070) and OPNI<43.5 (HR=16.208, 95%CI: 5.586-47.022) were the independent risk factors for postoperative recurrence of HCC. The 3-year cumulative recurrence rate of patients with OPNI<43.5 was 81.81%, and 23.91% for those with OPNI≥43.5, and the difference was statistically significant (χ2=17.177, P<0.001).
Conclusions
Preoperative decrease of OPNI is correlated with poor clinicopathological features in HCC patients. OPNI<43.5 is an independent risk factor for postoperative recurrence of HCC.
To evaluate the predictive value of model based on preoperative imaging tumor burden score (ITBS) for microvessel invasion (MVI) of single hepatocellular carcinoma (HCC).
Methods
Clinical data of 213 patients with single HCC who underwent surgical resection in the 900th Hospital from January 2015 to December 2021 were retrospectively analyzed. Among them, 148 patients were male and 65 female, aged (53±12) years. The predictive value of ITBS for MVI was assessed by the receiver operating characteristic (ROC) curve. The threshold value of ITBS was determined. All patients were divided into the high and low ITBS groups. Univariate and multivariate Logistic regression analyses were used to analyze the correlation with MVI. Nomogram model was constructed based on Akachi Information Criterion (AIC). The consistency and predictive ability of this model were validated by the calibration curve and ROC curve. The application value of prediction model in actual clinical decision was evaluated by the decision curve analysis (DCA).
Results
The ITBS value of HCC patients was 1.28-18.03. The area under the ROC curve (AUC) of ITBS for predicting MVI in HCC patients was 0.681 (95%CI: 0.592-0.769), the sensitivity was 0.647, the specificity was 0.710, and the optimal threshold value was 5.9, respectively. According to this threshold value of ITBS, all patients were divided into the low (n=132) and high ITBS groups (n=81). Multivariate Logistic regression analysis showed that male gender, complicated with diabetes mellitus, low ALB and low Child-Pugh score were the risk factors for MVI in HCC patients (OR=2.432, 2.545, 0.919, 5.158; all P<0.05). Based on independent risk factors and ITBS, nomogram model was constructed according to AIC. ROC curve analysis showed that the AUC, sensitivity and specificity of the nomogram model were 0.767, 0.608 and 0.809, indicating high prediction efficiency. The calibration curve demonstrated that the the probability predicted by the nomogram model was consistent with the actual results. External validation also suggested the reliability of this nomogram model. DCA curve showed that the nomogram model can be utilized as a valuable prediction tool for the risk of MVI in patients with single HCC.
Conclusions
ITBS can predict the occurrence of MVI in patients with single HCC. The nomogram model based on gender, diabetes mellitus, ALB, Child-Pugh class and ITBS can reliably and intuitively predict the risk of MVI in patients with single HCC.
To investigate the relation between tumor budding in pathological specimens of patients with hepatocellular carcinoma and clinicopathological characteristics, and its impact on the recurrence after hepatectomy.
Methods
A retrospective analysis was performed on the clinicopathological data of 107 patients who underwent hepatectomy for hepatocellular carcinoma in Southe Hospital to Xiamen University from January 2020 to December 2021. There were 58 males and 49 females; the age was (60±6) years. The informed consents of all patients were obtained and the local ethical committee approval was received. Based on postoperative pathological findings, the relation between tumor budding in cancer tissue and clinicopathological characteristics was analyzed. According to whether tumor recurrence occurred, patients were divided into a recurrence group (n=39) and a non-recurrence group (n=68). The correlation between tumor budding and clinicopathological characteristics was analyzed using the χ2 test. Cox univariate and multivariate analyses were used to identify factors associated with recurrence of hepatocellular carcinoma. Recurrence-free survival was analyzed using the Kaplan-Meier method and the Log-rank test.
Results
Compared with low-grade tumor budding, patients with high-grade tumor budding had higher proportions of maximum tumor diameter ≥ 5 cm, multiple tumors, microvascular invasion (MVI), incomplete capsule, moderate-to-poor differentiation, venous invasion, and TNM stage Ⅲ-Ⅳ (χ2=7.666, 9.805, 12.022, 6.847, 4.142, 6.538, 4.503; P < 0.05). Cox univariate analysis showed that multiple tumors (HR=3.155, 95%CI: 1.074-9.267), MVI (HR=2.791, 95%CI: 1.516-5.048), incomplete capsule (HR=4.903, 95%CI: 1.266-5.984), high-grade tumor budding (HR=6.406, 95%CI: 1.349-8.071), and TNM stage Ⅲ-Ⅳ (HR=4.102, 95%CI: 1.698-5.807) were associated with postoperative recurrence (P < 0.05). Cox multivariate regression analysis indicated that multiple tumors (HR=3.342, 95%CI: 1.840-5.049), MVI (HR=5.722, 95%CI: 1.928-7.387), incomplete capsule (HR=3.693, 95%CI: 1.492-6.427), high-grade tumor budding (HR=4.556, 95%CI: 1.912-7.908), and TNM stageⅢ-Ⅳ (HR=4.470, 95%CI: 1.846-7.631) were risk factors for postoperative recurrence of hepatocellular carcinoma (P < 0.05). The follow-up duration ranged from 9 to 57 months, with a median follow-up of 39 months. Survival analysis showed that the cumulative recurrence rates at 1, 3, and 5 years after surgery were 8.53%, 78.65%, and 86.71% in the high-grade tumor budding group, and 0, 18.62%, and 31.36% in the low-grade group, with a statistically significant difference (χ2=14.039, P < 0.001).
Conclusions
In patients with hepatocellular carcinoma, high-grade tumor budding is correlated with adverse pathological features, including maximum tumor diameter ≥5 cm, multiple tumors, MVI, incomplete capsule, moderate-to-poor differentiation, venous invasion, and TNM stageⅢ-Ⅳ.High-grade tumor budding is an independent risk factor for postoperative recurrence, and patients with high-grade tumor budding have a higher postoperative recurrence rate and a poorer prognosis.
To explore the pathogenesis, clinical diagnosis and treatment characteristics of FHA through analyzing the pedigree of FHA and gene mutation of family members.
Methods
Clinical data of 1 FHA patient admitted to Sun Yat-sen University Cancer Center in March 2016 were retrospectively analyzed. In this 24-year-old female patient, gadoxetate disodium-enhanced MRI showed a space-occupying lesion in the right lobe of the liver with clear margin and uneven signal, 14.9 cm×9.9 cm×13.2 cm in size, complicated by liver cirrhosis and multiple diffuse liver cirrhosis nodules, and suspicious cancerous nodules were seen in liver segment 5/6 (S5/6). In August, 2016, abnormal elevation of prothrombin (PIVKA-Ⅱ) was detected (307 mAU/ml). Ultrasound-guided puncture biopsy confirmed necrotic and hyperplastic tissues in S8, and hepatocellular hyperplasia with atypia and fatty degeneration of partial cells in S6. Immunohistochemistry was combined to make the diagnosis of hepatocellular adenoma (HCA). No evidence of malignant tumor was found. Considering the large range and multiple lesions of HCA, and no surgical indication, intimate follow-up was recommended. In her family, multiple members were confirmed and suspected with HCA. Whole-exome sequencing was performed in the tumor tissues and blood samples from multiple family members.
Results
Five family members of three generations had a history of liver disease, and 4 of them were diagnosed with liver tumors (2 diagnosed with HCA by imaging and pathological examinations, and the other 2 patients were diagnosed with hemangioma or HCA by imaging examination). All these 4 patients diagnosed with liver tumors were female, and they had no history of hepatitis B, normal AFP level, and no history of taking contraceptives or hormones. A total of 2522 candidate mutation loci were screened by whole-exome sequencing. After eliminating 488 common mutation loci and 10 suspected false-positive loci, a series of rare mutation loci were finally obtained, mainly distributed in the exon region. However, no gene mutation related to HCA was found.
Conclusions
FHA is characterized with familial genetic susceptibility, and clinical treatment of FHA is complicated. In this study, rare mutation loci are identified, suggesting the pathogenesis of FHA may be associated with gene mutation.
To evaluate the feasibility of fast-track anesthesia with early tracheal extubation in orthotopic liver transplantation.
Methods
Clinical data of 8 patients who underwent liver transplantation in the First Affiliated Hospital of Guangzhou Medical University from January 2024 to January 2025 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 7 patients were male and 1 female, aged from 34 to 62 years, with a median age of 48 years. Intraoperative and postoperative conditions were observed. The length of ICU and postoperative hospital stay were recorded.
Results
All 8 patients successfully completed the surgery. Early tracheal extubation was performed. The operation time was 347 (255-510) min, the anhepatic phase was 50 (38-79) min, intraoperative blood loss was 400 (50-800) ml, and the time of tracheal extubation was 45 (20-70) min after surgery. No second intubation in ICU stay, postoperative pulmonary infection or perioperative death occurred. ALT and TB levels tended to decline within postoperative 1 week. Blood gas and pH were basically maintained within the normal range within postoperative 3 d. No serious acid-base balance disorder occurred. The length of ICU stay was 2 (0-5) d. The length of postoperative hospital stay was 21 (12-41) d.
Conclusions
For eligible cases, it is safe and feasible to perform early tracheal extubation after liver transplantation. Fast-track anesthesia exerts a positive effect on rehabilitation after liver transplantation.
To explore the predictive value of triglyceride glucose (TyG) index for the severity of acute pancreatitis (AP).
Methods
Original studies comparing TyG index between severe acute pancreatitis (SAP) and non-SAP patients were searched from PubMed, CNKI and other databases. Random effect model combined with standardized mean difference (SMD) was used to perform heterogeneity, subgroup, sensitivity and publication bias analyses. The quality of studies was evaluated according to Newcastle-Ottawa Scale (NOS). Publication bias was evaluated by Egger, Begg test and funnel plot.
Results
12 studies comprising 3 407 patients were included. Meta-analysis showed that the TyG index in SAP patients was significantly higher than that in non-SAP counterparts (SMD=1.09, 95%CI: 0.99-1.18, P<0.05). Heterogeneity analysis revealed that high degree of heterogeneity was observed among different studies (I2=93.4%, P<0.001). According to the research quality, the SMD of high-quality studies was 1.13 (95%CI: 1.00-1.26, I2=82.0%),1.04 for medium-quality studies (95%CI: 0.90-1.17, I2=95.8%), and no statistical difference was noted between two groups (P=0.334). According to the average age in the SAP group, the SMD for SAP patients aged<50 years was 1.41 (95%CI: 1.26-1.57, I2=96.9%), and 0.88 for those aged≥50 years (95%CI: 0.76-1.00, I2=0.0%), indicating the prediction performance of TyG index was higher in the young SAP patients (P<0.001). A single study was excluded and the effect value was repeated combined. The results showed that combined SMD caused slight changes, and statistical significance was maintained in all analyses, indicating that the results of this study were robust and not significantly affected by individual studies. The overall distribution of funnel plot was basically symmetrical, with deviations of only a few studies. Egger and Begg regression tests detected no publication bias (t=0.64, Z=0.89; both P>0.05).
Conclusion
The existing evidence suggests that TyG index has certain potential value in predicting the severity of AP, especially in young patients.
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and it is also one of the leading causes of tumor-related death worldwide. Due to hidden early symptoms, most patients are diagnosed in the intermediate-advanced HCC upon admission. For them, surgical resection, local ablation and liver transplantation are potential therapeutic options, whereas most patients have lost the opportunity of surgery. Along with recent in-depth exploration of the molecular mechanism of HCC and successful development of multiple targeted drugs, systemic therapy has become increasingly prominent in the treatment of HCC. Among them, targeted therapy combined with immunotherapy showcases significant therapeutic advantages. At present, multiple regimens of targeted therapy combined with immunotherapy have completed phase Ⅲ clinical trials and verified their efficacy and safety, which have been widely applied in clinical practice. Therefore, the combination of targeted therapy and immunotherapy will applied more through the whole process of treatment for intermediate-advanced HCC, which is expected to significantly improve the survival and prognosis of patients. In this article, the latest research progress in the field of first-line treatment for intermediate-advanced HCC was reviewed, providing theoretical basis and clinical guidance for targeted therapy combined with immunotherapy for HCC.
Liver transplantation has become the most effective therapeutic option for end-stage liver disease. Graft rejection is the main obstacle to the long-term survival of organ transplantation recipients. Although widespread use of immunosuppressants can significantly improve the short-term prognosis and survival of patients, long-term use of immunosuppressants will increase the risk of adverse events, such as drug poisoning, systemic infection and tumor recurrence, and exerts limited effect on improving the overall survival rate of grafts. Therefore, how to induce the immune tolerance of liver transplantation and maintain the long-term survival of grafts without use of immunosuppressants remains an urgent scientific challenge in the field of organ transplantation. In recent years, the mechanism research and clinical trials of tolerogenic dendritic cell (tolDC) in immune tolerance after liver transplantation have achieved initial outcomes. In this article, biological characteristics, immunomodulation and application of tolDC in clinical liver transplantation were reviewed, and the application value of tolDC in inducing immune tolerance in liver transplantation was evaluated.
Echinococcosis is a zoonotic parasitic disease that is distributed widely around the world, with hidden onset and long incubation period, which seriously threatens human health. The interaction between immune escape and host immune system is complex, and especially the helper T(Th) cell subsets and their secreted cytokines play a key role in disease progression. In this article, the role of IL-23/IL-17 axis in echinococcosis was reviewed. IL-23 is secreted by activated dendritic cells and macrophages, which can promote the differentiation of Th17 cells and secrete IL-17. Studies have shown that the changes of IL-23 and IL-17 levels in cystic echinococcosis are closely associated with the infection stage and immune response, and affected by drug intervention. In alveolar echinococcosis, IL-23 and IL-17 levels are increased in the early stage of infection, and are associated with disease activity in the late stage. IL-23/IL-17 axis can regulate inflammatory response and immune cell function through the JAK/STAT signaling pathway, which plays an important role in immune regulation of echinococcosis. Further study of the mechanism underlying IL-23/IL-17 axis in echinococcosis will contribute to developing novel therapeutic targets and biomarkers, providing new ideas for early diagnosis, prognostic evaluation and immunotherapy of echinococcosis.
Pancreatic cancer is a highly-invasive malignancy, with an increasing incidence rate. Upon admission, most cases are diagnosed with advanced stage, complicated with unresectable locally advanced or metastatic diseases. Recurrence is commonly seen even in individuals undergoing radical resection. For high-risk groups, there is no widely-accepted screening method. Diagnosis, treatment evaluation and recurrence detection mainly depend on imaging examination. Effective methods are urgently required to assist diagnosis, efficacy evaluation and recurrence detection. Emerging technologies such as circulating tumor DNA (ctDNA), circulating tumor cells and exosomes have gradually matured and applied, which showcase potential advantages in the study of pancreatic cancer. In this article, research progress in the application of ctDNA in the early diagnosis of pancreatic cancer was reviewed.