ObjectiveTo investigate the effects of pipecolic acid oxidase (PIPOX) on the proliferation, apoptosis, migration and invasion of primary liver cancer cells. MethodsImmunohistochemical staining and analysis of The Cancer Genome Atlas (TCGA) database were used to examine the PIPOX expression levels in liver cancer tissues and paired adjacent normal tissues, and studied their relationship with patient prognosis. Liver cancer cell lines stably overexpressing or knocking out PIPOX were constructed to explore PIPOX’s impact on liver cancer cell proliferation, apoptosis, migration and invasion by conducting in vitro functional experiments such as CCK-8, EdU, apoptosis detection, and Transwell assays. In vivo, nude mice subcutaneous tumor models and lung metastasis models were used to verify PIPOX’s effect on liver cancer growth and metastasis. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were both employed to detect the expression of epithelial-mesenchymal transition (EMT) markers in liver cancer cells. ResultsImmunohistochemical staining and TCGA database analysis revealed that PIPOX expression was significantly lower in liver cancer tissues compared to paired adjacent normal tissues (P<0.05). Prognostic analysis indicated shorter overall survival and disease-free survival in PIPOX low expression group (P<0.05). In vitro gain- and loss-of-function experiments showed that PIPOX significantly inhibited liver cancer cell migration and invasion (P<0.05), while having no significant effects on their proliferation and apoptosis (P>0.05). Animal experiments also confirmed that PIPOX significantly inhibited liver cancer lung metastasis (P<0.05), but had no significant effects on tumor growth (P>0.05). Finally, RT-qPCR and western blot results revealed that PIPOX promoted the expression of the epithelial marker E-cadherin (P<0.05) and inhibited the expression of mesenchymal markers (N-cadherin, vimentin, Snail) (P<0.05). ConclusionsPIPOX significantly inhibits liver cancer cell migration and invasion, potentially via suppressing the EMT process. However, PIPOX does not significantly affect liver cancer cell proliferation and apoptosis.
Objective To investigate the value of contrast-enhanced ultrasonography in detection and diagnosis of small primary liver cancer. Methods SonoVue-enhanced ultrasonography were performed on 353 patients with 378 primary liver cancer, less than 3 cm in diameter. Enhancement patterns and enhancement phases of hepatic lesions on contrast-enhanced ultrasonography were analyzed and compared with the results of histopathology. Results In all hepatic tumors, 96.6% （365/378） lesions enhanced in the arterial phase. Among them, 317 (83.9%) tumors enhanced earlier than liver parenchyma and 48 (12.7%) tumors enhanced synchronously with liver parenchyma, and 342 (90.5%) tumors showed early wash-out in the portal and late phases. With regard to the enhancement pattern, 329 (87.0%) tumors presented whole-lesion enhancement, 35 (9.3%) to be mosaic enhancement and 14 (3.7%) to be rim-like enhancement. If taking the whole-lesion enhancement and mosaic enhancement in arterial phase as diagnotic standard for primary liver cancer on contrast-enhanced ultrasonography, the sensitivity was 92.9%(351/378), and if the earlier or synchronous enhancement of the tumor compared with liver parenchyma in arterial phase and the wash-out in portal phase were regarded as the stardand, the sensitivity was 87.3%(330/378). Conclusion Contrast-enhanced ultrasonography could display real-time enhancement patterns as well as the wash-out processes both in hepatic tumors and the liver parenchyma. It might be of clinical value in diagnosis of primary liver cancer based on the hemodynamics of hepatic tumors on contrast-enhanced ultrasonography.
ObjectiveTo investigate the effect and prognosis of emergency hepatectomy and second stage hepatectomy after transcatheter arterial chemoembolization (TACE) in spontaneous rupture and bleeding of resectable primary liver cancer.MethodsA total of 42 patients with spontaneous rupture and bleeding of resectable primary liver cancer in this hospital from January 2010 to January 2016 were retrospectively reviewed. Among them 24 cases had accepted the emergency hepatectomy in 24 h–48 h after admission (emergency hepatectomy group, n=24), 18 cases had accepted the second stage hepatectomy in 1 week–2 weeks after the TACE (second stage hepatectomy group, n=18), the intraoperative blood loss and intraoperative blood transfusion volume, perioperative mortality, postoperative incidence of hepatic insufficiency, recurrence rate and abdominal metastasis rate within 1 year after the operation, 1- and 3-year survival rates were compared between the emergency hepatectomy group and the second stage hepatectomy group.ResultsThere was no significant difference in the preoperative general data between these two groups (P>0.050). The intraoperative blood loss and transfusion volume of the emergency hepatectomy group were significantly more than those of the second stage hepatectomy group (P=0.028, P=0.017). There were no significant differences in the perioperative mortality (P=0.489), incidence of hepatic insufficiency (P=1.000), 1- and 3-year survival rates (P=0.650, P=0.463) and 1-year recurrence rate (P=0.601) between these two groups. No intraperitoneal implantation metastasis was found in these two groups.ConclusionBoth emergency hepatectomy and second stage hepatectomy after TACE are safe and effective in treatment of spontaneous rupture and bleeding of resectable primary liver cancer, appropriate treatment should be selected according to the specific conditions of patients.
ObjectiveTo systematically evaluate efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with Huaier granules in treatment of primary liver cancer (PLC).MethodsThe databases including the PubMed, Embase, Cochrane Library, Wanfang Data, CNKI, VIP were searched to obtain the relevant literatures of Huaier granule combined with TACE therapy (Huaier+TACE group) and alone TACE therapy (TACE group) in the treatment of PLC. The short-term curative effects (objective response rate and disease control rate), 6 and 12-month survival rates, immune function change, and adverse reactions were extracted. The RevMan 5.3 software was applied to carry out the meta analysis.ResultsFifteen studies involving 1 781 cases were enrolled in this study, of which 876 cases underwent the Huaier+TACE, 905 underwent the TACE. The meta analysis results showed that the objective response rate and disease control rate, 6 and 12-month survival rates of the Huaier+TACE group were significantly more superior as compared with of the TACE group (P<0.05), the adverse reaction incidence had no significant difference (P>0.05). Compared with the TACE group, the CD4 +/CD8 + of the Huaier+TACE group was significantly improved (P<0.05).ConclusionFrom results of meta analysis, Huaier granule combined with TACE could improve therapeutic effect, increase survival rate, and improve life quality of PLC.
“Chinese Guideline for Diagnosis and Treatment of Primary Liver Cancer （version-2022）” （China Liver Cancer Staging, Abbreviation “CNLC 2022”） was updated recently and the “Barcelona Clinical Liver Cancer Strategy for Prognosis Prediction and Treatment Recommendation: The 2022 update” （Abbreviation “BCLC 2022”） was also updated in December 2021. The similarities and differences of the two guidelines were interpreted. For the BCLC stage B and C, which are equivalent to CNLC stage Ⅱa and Ⅱb and CNLC stage Ⅲa, respectively, the recommendation of surgical treatment and radiation therapy are disparate in the CNLC 2022 and BCLC 2022. For the systematic treatment of advanced liver cancer, Atezolizumab-Bevacizumab, Renvatinib and Sorafenib were both recommended as the first-line medication in the two guidelines. However, the CNLC 2022 is more flexible than BCLC 2022, which provides more treatment options for Chinese liver cancer patients. It is worth paying attention to two important new concepts proposed in the BCLC 2022: stage migration during treatment and untreatable progression. The BCLC stage B was divided into three subgroups according to tumor burden and liver function and different clinical pathways were recommended in the BCLC 2022.
ObjectiveTo explore the clinical value and experience of enhanced recovery after surgery (ERAS) of “LEER” model with “less pain” “early move” “early eat” and “reassuring” as its ultimate goal in perioperative period of laparoscopic anatomical hepatectomy of patients with primary liver cancer.MethodsThe basic clinical data of 98 patients treated in our department from May 2017 to March 2020 who were diagnosed as primary liver cancer and underwent laparoscopic anatomical hepatectomy were retrospectively analyzed. The incidence of postoperative complications, postoperative recovery and patients’ satisfaction were compared between 40 patients managed with traditional model (traditional group) and 58 patients managed with measures of ERAS of “LEER” model (“LEER”-ERAS group).ResultsCompared with the traditional group, the “LEER”-ERAS group had lower postoperative pain scores (t=2.925, P=0.004), earlier postoperative anal exhaustion, bowel movement and normal diet (t=3.071, t=3.770, t=3.232, all P<0.005) , shorter time to postoperative off-bed activity (t=5.025, P<0.001) and earlier postoperative removal time of drainage tube (t=3.232, P=0.001). Postoperative hospital stay was shorter (t=4.831, P<0.001), the cost of hospitalization was lower (t=3.062, P=0.003), and the patient’s satisfaction with medical treatment was higher (χ2=9.267, P=0.002). There were no statistical difference in the operative time, intraoperative blood loss, rate of conversion to laparotomy, blocking time of porta hepatis, postoperative complications and postoperative adverse events between the two groups (P>0.05).ConclusionsCompared with the traditional model, the measures of ERAS of “LEER” model that applied to laparoscopic anatomical hepatectomy of patients with primary liver cancer, is safe and effective, and can relieve postoperative pain, accelerate postoperative rehabilitation, improve satisfaction of patients, shorten hospital stay, and reduce medical costs. It has further promotion and research value.
ObjectiveTo understand the latest progress of enrichment technology of circulating tumor cells (CTCs), and summarize the principle, advantages and disadvantages of various enrichment technologies and their applications in primary liver cancer (PLC). MethodThe literature relevant to the enrichment methods of CTCs in the PLC was reviewed and summarized. ResultsThe clinical significances of CTCs in the early diagnosis and staging, hierarchical diagnosis and treatment, and efficacy monitoring of patients with PLC had been recognized. There were many separation and enrichment technologies for CTC, which were mainly based on the differences of physical and biochemical characteristics, as well as the combination of enrichment methods with various principles. Each enrichment method had corresponding advantages and disadvantages, and few enrichment methods for CTC was applied to PLC. ConclusionsAlthough many problems need to be solved in enrichment method of CTCs at present, it is believed that the existing problems will be solved one by one with continuous improvement of technology. And CTC detection is expected to apply in clinical, so as to provide more efficient diagnosis and treatment methods for patients with PLC.
In 2022, there were 367.7 thousands new cases and 316.5 thousands deaths of primary liver cancer in China. Radiofrequency ablation (RFA) is one of the radical treatments for liver cancer. It has the characteristics of definite curative effect, minimal invasion and low cost. In patients with early liver cancer, the curative effect is similar to surgical resection. The concept and practice of precision surgery provide new ideas for improving the efficacy of RFA. Based on the RFA treatment experience of more than ten thousand cases, the author’s team has carried out research on the precise ablation treatment of primary liver cancer. Now, the author will combine the existing literature and our team’s experience to discuss the application and prospect of the precise surgery concept in RFA treatment.
Objective To explore therapeutic effect of radiofrequency ablation (RFA) guided by contrast-enhanced ultrasound in patient with advanced primary liver cancer following transcatheter arterial chemoembolization (TACE). Methods The patients with advanced primary liver cancer treated with the TACE firstly from January to December 2014 in this hospital were prospectively collected, then were randomly divided into a conventional ultrasound guided RFA group (control group) and contrast-enhanced ultrasound guided RFA group (study group). The complete ablation rate, liver function, serum alpha-fetoprotein (AFP) level, and 1-, 2-, and 3-year survival rates were observed in the two groups. Results A total of 42 patients with advanced primary liver cancer treated with the TACE were enrolled in this study, there were 21 patients in each group. ① There were no significant differences in the baseline data such as the gender, age, BCLC stage, AFP level, and Child grade of liver function between the two groups (P>0.05). ② All the treatments were completed according to the plan, no serious complications or treatment-related death happened. The complete ablation rate of the study group was significantly higher than that of the control group (χ2=5.717, P=0.017), and the AFP level was significantly lower than that of the control group (t=2.618, P=0.012). There was no significant difference in the Child grade of liver function between the 2 groups (P>0.05). ③ The rate of repeat RFA in the study group was significantly lower than that in the control group (χ2=4.434, P=0.035), and there was no significant difference in the TACE treatment rate between the two groups (χ2=1.659, P=0.197). ④ The survival rate of the study group was significantly better than that of the control group by comparing the survival curves (χ2=3.999, P=0.046). Conclusion Contrast-enhanced ultrasound guided RFA is superior to conventional ultrasound guided RFA in treatment of advanced primary liver cancer following TACE.
ObjectiveTo explore the relation between preoperative serum gamma-glutamyl transpeptidase to platelet ratio (GPR) and overall survival (OS) of patients with hepatitis B virus-associated hepatocellular carcinoma (Abbreviated as “patients with HCC”), and to establish a nomogram for predicting OS. MethodsAccording to the inclusion and exclusion criteria, the clinicopathologic data of patients with HCC who underwent radical resection in the Department of Hepatobiliary Surgery of Xianyang Central Hospital, from January 15, 2012 to December 15, 2018, were retrospectively analyzed. The optimal critical value of GPR was determined by receiver operating characteristic curve, then the patients were divided into a low GPR group (GPR was optimal critical value or less ) and high GPR group (GPR was more optimal critical value). The Kaplan-Meier method was used to draw the survival curve and analyze the OS of patients. The univariate and multivariate Cox proportional hazards regression model were used to analyze the factors influencing prognosis in the patients with HCC. According to the risk factors of OS for patients with HCC, a nomogram was established. The consistency index and calibration curve in predicting the 3-year and 5-year accumulative OS rates of patients with HCC were evaluated. ResultsA total of 213 patients were gathered. The optimal critical value of GPR was 0.906. There were 114 patients in the low GPR group and 99 patients in the high GPR group. The Kaplan-Meier survival curve analysis showed that the 1-, 3- and 5-year accumulative OS rates were 99.1%, 81.8%, 60.6% in the low GPR group, respectively, which were 74.2%, 49.1%, 35.7% in the low GPR group, respectively. The OS curve of the low GPR group was better than that of the high GPR group (χ2=25.893, P<0.001). The multivariate analysis results showed that the microvascular invasion, incomplete capsule, intraoperative bleeding ＞1 000 mL, postoperative complications, GPR >0.906, low tumor differentiation, and late TNM stage did not contribute to accumulative OS in the patients with HCC (P<0.05). The consistency index (95%CI) of the nomogram in predicting accumulative OS rates at 3- and 5-year for patients with HCC were 0.761 (0.739, 0.783) and 0.735 (0.702, 0.838), respectively. The calibration curves of 3- and 5-year accumulative OS rates of the nomogram were in good agreement with the actual results. ConclusionsPreoperative GPR is associated with OS, and patients with higher GPR have worse prognosis. The nomogram based on GPR has a good accuracy and differentiation.