[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

[Research progress of radiomics with artificial intelligence in precise diagnosis and treatment of hepatocellular carcinoma].

With the advent of the era of artificial intelligence, radiomics is an emerging field in which high-throughput imaging data are extracted from different types of images to model and predict clinical prognosis in a non-invasive manner. Currently, this field is in its initial stage of development and lacks standardized assessment criteria, but still remains a promising tool for the future research direction. Radiomics analysis of hepatocellular carcinoma will aid in the early diagnosis, prognostic evaluation and treatment plan, thereby promoting the continuous improvement of clinical treatment strategies, and providing precise treatment methods to improve the survival rate and cure rate of patients. This article introduces the radiomics research process of hepatocellular carcinoma, and discusses its application progress, challenges and future development directions in the precise diagnosis and treatment of hepatocellular carcinoma.

[Efficacy of three-dimensional visualization technology in the precision diagnosis and treatment for primary liver cancer: a retrospective multicenter study of 1 665 cases in China].

Objective: To evaluate the efficacy of three-dimensional(3D) visualization technology in the precision diagnosis and treatment for primary liver cancer. Methods: A total of 1 665 patients with primary liver cancer who admitted to seven medical centers in China between January 2009 to January 2019, diagnosed and treated by 3D visualization protocol were analyzed, and their clinical data were retrospectively reviewed. There were 1 255 males(75.4%) and 410 females(24.6%), with age of (52.9±11.9) years (range: 18 to 86 years). The acquisition of high-quality CT images with submillimeter spatial resolution were conducted using a quality control system. By means of homogenization methods, 3D reconstruction and 3D visualization analysis were performed. Postoperative observation: pathology reports, microvascular invasion, perioperative complications and follow-up. SPSS 25.0 statistical software was used for statistical description and analysis of clinical data. Kaplan-Meier curve was used to calculate overall survival and disease-free survival rate. Results: (1)In the sample of 1 265 patients, 3D reconstructed models clearly displayed as follows. tumor size: ≤2 cm in 155 cases (9.31%), >2 cm to 5 cm in 551 cases (33.09%), >5 cm to 10 cm in 636 cases (38.20%), >10 cm in 323 cases (19.40%). (2) Classification of hepatic blood vessels. Hepatic artery: type Ⅰ(normal type) in 1 494 cases(89.73%),variant hepatic artery in 171 cases (10.27%), including type Ⅱ in 35 cases, type Ⅲ in 38 cases, and other types in 98 cases. Hepatic vein: type Ⅰ (normal) in 1 195 cases (71.77%),variant hepatic veins in 470 cases(28.23%), including type Ⅱ in 376 cases and type Ⅲ in 94 cases. Portal vein:normal type in 1 315 cases (78.98%), variant portal veins in 350 cases (21.02%), including type Ⅰ in 189 cases, type Ⅱin 103 cases, type Ⅲ in 50 cases, type Ⅳ in 8 cases. Hepatic artery variation coexisting with portal vein variation in 24 cases (1.44%). Hepatic vein variation coexisting with portal vein variation in 113 cases (6.79%). Three types of vascular variation in 4 cases (0.24%), including coexistence of type Ⅱ hepatic artery variation or type Ⅰ portal vein variation with type Ⅲ hepatic vein variation in 2 cases,coexistence of type Ⅲ hepatic artery variation or type Ⅲ portal vein variation with type Ⅱ hepatic vein variation in 2 cases. (3) Preoperative liver volume calculation:1 499.3 (514.4)ml (range:641.7 to 6 637.0 ml) of total liver volume, including 479.1 (460.1) ml (range:10.5 to 2 086.8 ml) for liver resection and 959.9 (460.4)ml (range:306.1 to 5 638.0 ml) for residual function. (4)Operative methods: anatomical hepatectomy in 1 458 cases (87.57%); non-anatomic hepatectomy in 207 cases (12.43%). (5)the median operation time was 285(165)minutes (range: 40 to720 minutes). (6)The median intraoperative blood loss was 200(250)ml (range:10 to 4 200 ml) and 346 cases (20.78%) had intraoperative transfusion. (7)Pathology reports: hepatocellular carcinoma in 1 371 cases (82.34%), cholangiocarcinoma in 260 cases (15.62%) and mixed hepatocellular carcinoma in 34 cases (2.04%). Microvascular invasion: M0 in 199 cases, M1 in 64 cases, and M2 in 27 cases. (8)Postoperative complications in 207 cases (12.43%), including Clavien-Dindo grade Ⅰ or Ⅱ in 57 cases, grade Ⅲ or Ⅳ in 147 cases and grade Ⅴ in 3 cases.There were 13 cases (0.78%) of liver failure and 3 cases (0.18%) of perioperative death. (9) The follow-up time was 3.0 to 96.0 months, with a median time of 21.0(17.8) years. The overall 3-year survival and disease-free survival rates were 80.0% and 56.5%, respectively. The overall 5-year survival and disease-free survival rates were 59.7% and 30.0%, respectively. Conclusion: 3D visualization technology plays an important role in realizing accurate diagnosis of anatomical location and morphology of primary liver cancer, improving the success rate of surgery and reducing the incidence of complications.

[Multidisciplinary team building in enhanced recovery after surgery].

There has been 10 years to explore the road in line with China's actual enhanced recovery after surgery(ERAS) since Academician Li Jieshou introduced the view of ERAS into China. ERAS has been widely carried out in the field of surgery, and gradually formed with Chinese characteristics of ERAS clinical pathway.The clinical implementation of ERAS relies on the effective integration of a series of perioperative methods, and any single technique or method can't completely reduce the perioperative physiological and psychological traumatic stress of the patient, so as to achieve the patient's rapid rehabilitation patient-centered multidisciplinary team(MDT)collaboration is an inevitable trend in ERAS development. On the basis of drawing lessons from foreign experience, the establishment of ERAS-MDT model in line with China's national conditions is a new subject that needs to be studied at present. The construction of ERAS-MDT might promote the development of new ERAS services, new technologies, and ultimately promote the improvement of surgical treatment, and bring the greatest clinical benefit to the society and patients.

[Influential factors for failure of enhanced recovery after surgery from hepatectomy for hepatocellular carcinoma and the establishment of risk prediction model].

Objective: To investigate the influential factors for failure of enhanced recovery after surgery(ERAS) from hepatectomy for hepatocellular carcinoma(HCC) patients and then to establish a risk prediction model. Methods: The relevant clinical data of 180 patients with HCC undergoing hepatectomy at Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University from January 2016 to June 2017 were analyzed retrospectively.There were 149 male patients and 31 female patients aging of (56.5±11.0)years(from 33 to 84 years old). The factors affecting postoperative failure of ERAS of HCC patients were identified by univariate and multivariate analyses, and then, all the obtained factors and their statistical values were used to establish the risk prediction model. Results: A total of 23 patients failed in the ERAS protocol(12.8%). The preoperative total bilirubin (TBIL), alanine aminotransferase(ALT) and amount of intraoperative bleeding were independent risk factors for failure of ERAS from hepatectomy(all P<0.05). The obtained risk prediction model was presented as follows: risk coefficient(R)=0.114×(TBIL)+ 0.082×(ALT)+ 0.008×(amount of intraoperative bleeding). At the cut of value of R=7.90, the area under the ROC curve of this model for predicting failure of ERAS was 0.866(95%CI: 0.788-0.945, P<0.01), with the sensitivity and specificity of 69.6% and 91.1%, respectively.External validation results indicated that the scoring system had good differential ability(area under the ROC curve=0.889, 95%CI: 0.811-0.967, P<0.01). Conclusions: Higher level of preoperative TBIL(>21 µmol/L) and ALT(>50 U/L) and the larger amount of intraoperative bleeding (more than 400 ml) are independent risk factors for failure of ERAS inpatients undergoing hepatectomy for HCC and the established prediction model may have certain value for risk assessment.

[Clinical values of multimodal preventive analgesia in patients with partial hepatectomy for liver cancer].

Objective: To investigate the clinical values of multimodal preventive analgesia in patients with partial hepatectomy for liver cancer. Methods: A perspective study was conducted to collect data of patients with liver cancer who underwent partial hepatectomy from March 2014 to March 2015.The 90 patients involved in the study were randomly divided into two groups as multimodal analgesia and control groups, and each group had 45 cases. In multimodal analgesia group, 40 mg parecoxib sodium was injected intravenously 30 minutes before anesthetic induction, and 0.375% ropivacaine 150 mg combined with dexamethasone 5 mg were applied to transversus abdominis plane block before closing abdomen.The patients in control group without above treatment. Patient controlled intravenous analgesia was used in all patients. Three days after surgery, 40 mg parecoxib sodium was injected intravenously, twice a day for all patients.Visual analogue scales (VAS) was used to evaluate postoperative pain, and postoperative adverse events were observed.The number of cases of postoperative ambulation (>6 h for every day), time of flatus and defecation, and duration of hospital stay were recorded in two groups.Pearson chi-square test was used to compare the rate or constituent ratio between two groups.Independent sample t test or Mann-Whitney U was used to analyzed the measurement data between two groups. Results: There were no difference between two groups in aging, gender, weight, body mass index, ASA classification, blood loss volume, time of operation(all P>0.05). The scores of VAS in multimodal analgesia group was significantly lower than that in control group(3.0±0.8 vs. 4.6±1.1, t=7.814, P<0.01 for day 1; 2.2±1.0 vs. 3.6±1.2, t=5.825, P<0.01 for day 2; 1.6±0.8 vs. 2.4±1.2, t=3.894, P<0.01 for day 3). The number of cases of postoperative ambulation(>6 h) in multimodal analgesia group was significantly more than that in control group (10 cases vs. 0 case, χ(2)=11.250, P<0.01 for day 1; 21 cases vs. 5 cases, χ(2)=13.846, P<0.01 for day 2; 28 cases vs. 17 cases, χ(2)=5.378, P =0.020 for day 3). The time of flatus and defecation, and duration of hospital stay were significantly shorter than that in control group((30.2±7.3) hours vs. (36.4±7.0)hours, t=4.115, P<0.01 for flatus; (50.9±5.2)hours vs. (60.7±7.3)hours, t=7.346, P<0.01 for defecation; (6.2±0.8)days vs. (9.6±1.1)days, t=16.615, P<0.01 for hospital stay). Conclusion: Multimodal preventive analgesia effectively alleviate the postoperative pain, benefits early ambulation, improves recovery of gastrointestinal function, and shortens duration of hospital stay in patients with partial hepatectomy for liver cancer.

Combined inhibitory effects of celecoxib and fluvastatin on the growth of human hepatocellular carcinoma xenografts in nude mice.

This study was designed to investigate the in vivo growth inhibitory effects of celecoxib, a cyclo-oxygenase-2 inhibitor, and fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the hepatocellular carcinoma (HCC) cell line, BEL-7402. Athymic nude mice implanted with BEL-7402 cells were given celecoxib and fluvastatin, either alone or in combination, and the effect of treatment on tumour growth was evaluated after 6 weeks. The combination of celecoxib and fluvastatin enhanced inhibition of tumour growth, induction of apoptosis, inhibition of tumour cell proliferation, and inhibition of tumour angiogenesis compared with either treatment alone. The combination of celecoxib and fluvastatin also increased levels of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), decreased levels of p-Akt, myeloid cell leukaemia-1 (Mcl-1) and survivin protein, but had no effect on Akt protein levels in tumours. These results suggest that celecoxib combined with fluvastatin would be more efficacious for the treatment of HCC than either treatment alone and this combination of therapy warrants further research.

Expression and correlation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in experimental rat hepatocarcinogenesis.

An experimental rat hepatocellular carcinoma (HCC) model was established using diethylnitrosamine and N-nitrosomorpholine to induce carcinogenesis in Sprague-Dawley rats. During hepatocarcinogenesis, seven rats were sacrificed at 0, 4, 8, 12 and 16 weeks and 10 rats were sacrificed at 20 weeks. The levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) protein and mRNA were examined by immunohistochemistry, Western blot and semi-quantitative reverse transcriptase-polymerase chain reaction at different stages in the rat HCC model. Twenty weeks after induction of hepatocarcinogenesis, the expression of HIF-1alpha and VEGF protein and mRNA significantly increased compared with week 0. Microvessel density (MVD) increased considerably once liver cancer developed. There was a significant positive correlation between MVD and both HIF-1alpha and VEGF, and between HIF-1alpha and VEGF levels. These results suggest that HIF-1alpha and VEGF play important roles in tumour occurrence and development during rat hepatocarcinogenesis, possibly through promoting tumour angiogenesis.

High preoparative levels of serum periostin are associated with poor prognosis in patients with hepatocellular carcinoma after hepatectomy.

AIMS: Periostin (POSTN) is implicated in cancer development and progression. The aim of this study was to evaluate the diagnostic and prognostic significance of serum POSTN in patients with hepatocellular carcinoma (HCC) receiving curative surgery. METHODS: Enzyme-linked immunosorbent assay was performed to determine serum POSTN levels in 69 healthy volunteers, 30 patients with hepatolithiasis, 27 patients with cirrhosis, and 56 HCC patients. The relationships between serum POSTN and clinicopathologic features were analyzed. Receiver operating characteristics analysis was used to calculate diagnostic accuracy of serum POSTN, serum alpha-fetoprotein (AFP), and their combination. The prognostic impact of serum POSTN on overall survival (OS) and relapse-free survival (RFS) was also investigated. RESULTS: The median serum POSTN level was significantly (P < 0.05) increased in HCC patients, compared to healthy controls, patients with hepatolithiasis, and patients with liver cirrhosis. Elevated serum POSTN was only significantly associated with Edmondson grade (P = 0.007). The combination of serum POSTN and AFP had a markedly higher area under the curve (0.805 (95% confidence interval [CI]: 0.677-0.932)) than POSTN (0.582 (95% CI: 0.427-0.736)) or AFP (0.655 (95% CI: 0.504-0.806)) alone. Kaplan-Meier analysis indicated that elevated serum POSTN was associated with OS (P = 0.031) and RFS (P = 0.027). Moreover, multivariate analysis revealed elevated serum POSTN as an independent poor prognostic marker for OS and RFS. CONCLUSIONS: Preoperative serum POSTN has limited diagnostic value in distinguishing HCC from non-malignant liver diseases, but serves as independent prognostic biomarker in HCC patients.