Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma / 中华消化外科杂志

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.

Quality evaluation of Galli Gigerii Endothelium Corneum based on HPLC fingerprints and content determination of nucleosides / 中国中药杂志

Galli Gigerii Endothelium Corneum(GGEC), the dried gizzard membrane of Gallus gallus domesticus is a Chinese medicinal material commonly used for digestion. However, due to the particularity of texture and composition, its active ingre-dients have not been clarified so far, and there is also a lack of quality evaluation indicators. In this study, UPLC-Q-TOF-MS was used to analyze the chemical components from the water extract of GGEC, and ten nucleosides were identified for the first time. HPLC fingerprints of the water extracts of GGEC were established and the content of seven nucleosides was determined. The fingerprint similarities of 40 batches of GGEC samples ranged from 0.765 to 0.959, indicating that there were great differences among the GGEC products processed with different methods. In addition, SPSS 22.0 and SIMCA 14.1 were used for hierarchical cluster analysis(HCA) and principal component analysis(PCA) on the 19 common peaks of the HPLC fingerprints of GGEC, and the 40 batches of samples were divided into three categories: raw GGEC, fried GGEC and vinegar-processed GGEC. Eight differential components in GGEC were marked by orthogonal partial least squares discrimination analysis(OPLS-DA), two of which were adenine and thymine. The results of content determination showed that the total content of the seven nucleosides in raw GGEC, fried GGEC and vinegar-processed GGEC were 182.5-416.8, 205.3-368.7, and 194.2-283.0 μg·g~(-1), respectively. There were significant differences in the content of hypoxanthine, thymine and thymidine among the GGEC products processed with different methods(P<0.05), which were graded in the order of fried GGEC>vinegar-processed GGEC>raw GGEC. This suggested that the content of hypoxanthine, thymine and thymidine tended to increase during the frying process, and the variation range might be related to the degree of heat exposure. The established methods in this study were simple and reproducible, and could be used for qualitative and quantitative analysis of GGEC and its processed pro-ducts. This study also provided reference for the establishment of quality standards of GGEC with chemical components as control index.

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Chinese perspective

Liver cancer is the fourth most prevalent and the second most lethal cancer in China. Hepatitis B virus (HBV) infection represents a major risk factor for hepatocellular carcinoma (HCC). Liver ultrasonography plus alpha-fetoprotein every 6 months continues to be the predominant surveillance modality. The age-Male-ALBI-Platelets score was recommended in the recent 2022 Chinese guidelines to predict HCC occurrence. The Chinese liver cancer (CNLC) staging system proposed in the 2017 guidelines continues to be the standard model for staging with modifications in the treatment allocations. Considering the aggressive nature of HBV-associated HCC, multimodal and high-intensity strategies like the addition of immunotherapy-based systemic treatment to local therapies, including resection, ablation, and intra-arterial therapies, have been adopted in real-life practices in China. The latest Chinese guidelines recommend atezolizumab plus bevacizumab, suntilimab plus a bevacizumab analog, lenvatinib, sorafenib, donafenib, and FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy as first-line treatment without priority. Regorafenib, apatinib, camrelizumab, and tislelizumab have been added as second-line systemic therapies for patients who progressed on sorafenib. Systemic therapies adopted in real-life practice are sophisticated with various combination modalities and different sequences.

Efficacy and safety of radiotherapy combined with targeted therapy, immunotherapy and chemotherapy for unresectable intrahepatic cholangiocarcinoma / 中华放射医学与防护杂志

Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.

A novel model in predicting very early recurrence after surgical resection of hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the risk factors of very early recurrence (VER, within 3 months) after R 0 resection of hepatocellular carcinoma (HCC), and to establish a predictive model. Methods:Of 427 HCC patients [with 368 males, 59 females, aged (52.7±12.1) years] who developed early recurrence (within 2 years) after R 0 resection from January to December 2008 at Zhongshan Hospital, Fudan University were enrolled in the test cohort. Another 590 patients [with 525 males, 65 females, aged (54.7±11.0) years] who underwent R 0 resection from January to June 2009 were enrolled in the validation cohort. Risk factors were investigated and a predictive model was established. Results:In the test cohort, 126 patients (29.5%) developed VER and their survival outcomes were extremely poor. Serum α-fetoprotein (AFP) level >827 μg/L, multiple tumors, microvascular invasion (MVI) and tumor number were independent risk factors for VER. A new predictive model (0.809·AFP+ 1.262·tumor number+ 0.983·MVI) was established by logistic regression in predicting VER after surgery. The receiver operating characteristic curve showed that the area under the curve (AUC) in predicting VER was 0.722 (95% CI: 0.669-0.774, P<0.001). In the validation cohort, the AUC of this model was 0.785 (95% CI: 0.715-0.855, P<0.001). Conclusions:A high AFP level, multiple tumors, and MVI were independent risk factors for VER of HCC after R 0 resection. The prediction model consisting of these three factors demonstrated robustness and it has the potential in clinical application.

The use of portal vein embolization combined with lenvatinib and a PD-1 inhibitor to treat patients with initially unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the safety and treatment outcomes of portal vein embolization (PVE) combined with lenvatinib plus an anti-programmed death-1(PD-1) antibody to treat patients with initially unreasectable hepatocellular carcinoma (uHCC).Methods:This study retrospectively analyzed the data of six patients with uHCC who received first-line combined systemic therapy with lenvatinib plus an anti-PD-1 antibody, and then underwent pre-hepatectomy PVE at the Department of Liver Surgery at Zhongshan Hospital, Fudan University from May 2019 to November 2020. All enrolled patients were males, aged (54.6±6.2) (ranged 46 to 63) years. Tumor response and liver volume were evaluated by medical imagings once every 2 months (±2 weeks) and evaluated using the Response Evaluation Criteria in Solid Tumours (version 1.1). Patients were followed-up by outpatient interviews or by phone calls to record their survival and tumor outcome status.Results:Three of the six enrolled patients had Barcelona Clinic Liver Cancer stage A and three had stage B disease. One patient achieved a partial response and five patients had stable diseases. The mean ± s. d. future liver remnant (FLR) percentage was (29.0±8.9) % before PVE and the combination therapy, and was (41.3±10.8) % before the last evaluation for liver surgery ( t=10.79, P<0.001). Hepatectomy was carried out in five patients, and one patient who failed to develop significant FLR hypertrophy did not undergo hepatectomy. Grade B post-hepatectomy liver failure and major postoperative complications (i.e. pleural effusion requiring additional percutaneous drainage) occurred in one patient. After a median post-operative follow-up of 4.5 (range: 1.0-12.3) months, all five patients were alive and were tumor free. Conclusion:PVE followed by hepatectomy is feasible in a uHCC patients receiving systemic therapy with lenvatinib and an anti-PD-1 antibody.

Expert guidance on overall management of liver cancer during the COVID-19 / 中华消化外科杂志

The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.

Immunotherapy for hepacellular carcinoma: where there is hope, there is brightness / 中华消化外科杂志

China has about half of hepatocellular carcinoma (HCC) patients worldwide, and the efficay of targeted therapy and systematic chemotherapy for HCC is limited. The treatment stategies based on immune checkpoint inhibitors (ICIs) bring hope to patients. Especially, the success of ICIs plus anti-angiogenic drugs as the first-line treatment in HCC open the combinational immunotherapy model for HCC, which inludes targeted therapy, chemotherapy, radiotherapy, oncolytic virotherapy and another immunotherapy. However, most patients do not derive benefits from these agents or combinational treatments, due to innate and acquired immune resistance. The authors elaborate on hot and difficult subjects of immunotherapy for HCC, and formulate the potential striving direction. It is critical to understand the determinants driving response, resistance and adverse effects to optimize the implementation of precision immunotherapy. Overall manage-ment of HCC patients with multidesciplinary team and high integration should be strengthened. More effective immunotherapeutic strategies may be achieved though deeper understanding of the underlying immune biology, targeted drug development and new comprehensive strategies. All the above efforts are for aims and missions of"Healthy China 2030".

Herbal Textual Research on Zingiberis Rhizoma Recens in Famous Classical Formulas and Its Quality Evaluation / 中国实验方剂学杂志

ObjectiveTo provide references for the selection of Zingiberis Rhizoma Recens on the research of famous classical formulas and the reasonable uses for medicines and foods through herbal textural research and quality analysis of Zingiberis Rhizoma Recens from main producing areas in China. MethodBy consulting the ancient and modern literature， the name， origin， producing areas， harvest time， processing methods of Zingiberis Rhizoma Recens were summarized. According to the 2020 edition of Chinese Pharmacopoeia， the contents of 6-gingerol， 8-gingerol， 10-gingerol， and volatile oil in Zingiberis Rhizoma Recens samples were determined. ResultHerbal textural research indicated that medicinal Zingiberis Rhizoma Recens originated from the fresh rhizome of Zingiber officinale. Before Tang dynasty， Zingiberis Rhizoma Recens produced in Sichuan was the best. In the Song dynasty， Zingiberis Rhizoma Recens produced in Sichuan， Zhejiang， and Anhui was of excellent quality. The cultivation of Zingiberis Rhizoma Recens in Shandong developed during the Ming and Qing dynasties. From ancient times to the present， the harvest period extended from the autumnal equinox to the winter solstice. Quality evaluation standards of Zingiberis Rhizoma Recens were essentially the same in ancient and present documents， as those with little gluten or gluten-free and strong pungency were preferred. After determination， the contents of 6-gingerol， 8-gingerol， and 10-gingerol in 44 samples were qualified in 27 samples， with a qualified rate of 61.4%. Among them， 17 samples were unqualified in the total contents of 8-gingerol and 10-gingerol. Among these qualified samples， the content of 6-gingerol ranged from 0.067% to 0.255%， and the total contents of 8-gingerol and 10-gingerol ranged from 0.040% to 0.131%. The content of volatile oil in 36 samples were qualified in 33 samples， with a qualified rate of 91.7%. Among the qualified samples， the content of volatile oil ranged from 0.175% to 0.410%. ConclusionZingiberis Rhizoma Recens has been used as medicines and foods since ancient times， and the genuine producing areas are consistent in ancient and present times， while the quality of the products， especially the medicinal Zingiberis Rhizoma Recens， should be monitored. Medicinal Zingiberis Rhizoma Recens planted in Leshan city of Sichuan province contains high contents of effective components， followed by Qujing and Wenshan cities of Yunnan province. Zingiberis Rhizoma Recens planted in Shandong and other places is mostly edible.

Analysis on Indications and Medication Regularities of Famous Classical Formula Wuzhuyu Tang Based on Modern Clinical Literature / 中国实验方剂学杂志

Wuzhuyu Tang （WZYT）， a classical traditional Chinese medicine （TCM） formula， was first recorded in Treatise on Cold Damage by the prestigious physician ZHANG Zhong-jing in the Eastern Han Dynasty， and included in Catalogue of Ancient Classical Formulas （First Batch）. WZYT is composed of four medcinals： Euodiae Fructus， Ginseng Radix et Rhizoma， Zingiberis Rhizoma Recens， and Jujubae Fructus， which has the effects of warming the middle and tonifying deficiency， dissipating cold and descending adverse qi. Based on data mining， this paper analyzes the modern clinical research literature on WZYT， which is expected to lay a basis for clarifying the "disease-symptom-prescription-medicinal" relationship of WZYT， as well as its modern clinical indications and clinical dosage. With the search term "Wuzhuyu Tang"， 253 complete medical records were retrieved from CNKI， VIP， and Wanfang （2000-2020）， involving 292 TCM prescriptions. Microsoft Excel 2019 was employed to establish the medical record database and the main clinical indications were statistically analyzed. Moreover， the syndromes， incidence law， and medication regularity were summed up. The result indicates WZYT has a wide range of modern clinical applications， mainly including the treatment of headache， dizziness， vomiting， diarrhea， dysmenorrhea， morning sickness， and other diseases， and the "deficiency， cold， and reversal" symptoms， mainly manifested as nausea and vomiting， headache， fatigue and lack of strength， reversal cold of hands and feet， poor appetite， gloomy complexion， dizziness， aversion to wind and cold， abdominal pain， sloppy diarrhea， abdominal distension， poor sleep， pale tongue， white coating， and deep thread wiry pulse. These diseases and symptoms mainly occur in women and middle-aged people. In most cases， medicinals are added or subtracted according to the symptoms， and the common doses of Euodiae Fructus， Zingiberis Rhizoma Recens， Codonopsis Radix or Ginseng Radix et Rhizoma， and Jujubae Fructus in the original prescription are 6-15 g， 10-15 g， 10-15 g or 9-12 g， and 4-6， respectively. The added medicinals are in the descending order of Pinelliae Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Glycyrrhize Radix et Rhizoma， and Chuanxiong Rhizoma according to the frequency.

Immune checkpoint inhibitors for treatment of biliary malignant tumors / 临床肝胆病杂志

Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future.

Connotation of Baimai disease and analysis of compatibility and usage of Baimai Ointment: based on Tibetan medicine theory / 中国中药杂志

Baimai is a complex of structure and function with the characteristics of wide distribution, complex structure, and multi-dimensional functions. Baimai, consisting of the channels in brain, the internal hidden channels connecting the viscera, and the external channels linking the limbs, governs the sensory, motor, and information transmission functions of human. According to Tibetan medicine, Baimai functions via "Long"(Qi) which moves in Baimai. "Long" is rough, light, cold, tiny, hard, and dynamic. The dysfunction of Baimai is manifested as numbness, swelling and pain, stiffness, atrophy, contracture, disability, hyperactivity, etc. The clinical manifestations of Baimai disease are facial paralysis, limb numbness, hemiplegia, contracture and rigidity, pain, opistho-tonos, paralysis, unconsciousness, head tremor, aphasia and tongue stiffness, and other abnormalities in facial consciousness, limb movement, and tactile sensation. Baimai Ointment for external use is used for the treatment of Baimai disease. It is mainly composed of medicinals which are spicy and bitter, warm, soft, mild, heavy, moist, and stable, and thus it is effective for the rough, light, cold, tiny, hard, and dynamic "Long" of Baimai disease. In clinical practice, it is mainly used for musculoskeletal diseases, such as osteoarthritis, scapulohumeral periarthritis, cervical spondylosis, low back pain, myofascitis, and tenosynovitis, nervous system diseases, such as paralysis and shoulder-hand syndrome, and limb stiffness caused by stroke, spastic cerebral palsy, trigeminal neuralgia, and facial neuritis, and limb motor and sensory dysfunction caused by trauma. According to the main symptoms of Baimai disease such as stiffness, rigidity, contraction, numbness, sensory disturbance and pain, clinicians should apply the Baimai Ointment via the inunction treatment of Tibetan medicine and in combination with Huo'ermai therapy and physiotherapy.

Chinese expert consensus on the management of immune-related adverse events of hepato-cellular carcinoma treated with immune checkpoint inhibitors (2021 edition) / 中华消化外科杂志

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Analysis of the risk factors influencing the prognosis of patients with recurrent hepatocellular carcinoma after liver transplantation within Fudan criteria and summary of relevant clinical experience / 中华器官移植杂志

Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.

Clinical efficacy of combination therapy with lenvatinib and programmed death-1 antibodies in unresectable or advanced hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the clinical efficacy of the combination therapy of lenvatinib and programmed death-1 (PD-1) antibodies in unresectable or advanced hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 59 patients with unresectable or advanced HCC who were admitted to Zhongshan Hospital of Fudan University from September 2018 to January 2020 were collected. There were 54 males and 5 females, aged from 25 to 73 years, with a median age of 52 years. All 59 patients underwent combination therapy with lenvatinib and PD-1 antibodies including 43 cases undergoing first-line therapy and 16 cases who cannot tolerate first-line therapy or with tumor progressed after first-line therapy undergoing second-line therapy. Observation indicators: (1) clinical efficacy; (2) adverse drug reactions and treatment; (3) follow-up and survival. Follow-up was performed using outpatient examination or telephone interview to detect tumor diameter of the target lesion, overall survival and progression free survival of patients up to December 2020. Measurement data with skewed distribution were expressed as M ( P25,P75) or M (range). Count data were represented as absolute numbers and (or) percentages. The Kaplan-Meier method was used to calculate the median duration of response (DoR), median overall survival time, median progression free survival time, survival rates and draw survival curves. Results:(1) Clinical efficacy: the objective response rate (ORR), complete response rate (CR), partial response rate (PR), stable disease rate (SD), progression disease rate (PD), time to response (TTR) and median DoR of 59 HCC patients were 37.3%(22/59), 11.9%(7/59), 25.4%(15/59), 37.3%(22/59), 25.4%(15/59), 2.6 months(2.1 months, 4.0 months), 6.3 months[95% confidence interval ( CI) as 2.2 to 10.5 months], respectively. The ORR, CR, PR, SD, PD and TTR of 43 HCC patients undergoing first-line therapy were 41.9%(18/43), 16.3%(7/43), 25.6%(11/43), 37.2%(16/43),20.9%(9/43), 2.2 months(2.0 months, 3.5 months), respectively. The median DoR of 43 patients undergoing first-line therapy was not reached. The ORR, CR, PR, SD, PD, TTR and median DoR of 16 HCC patients undergoing second-line therapy were 4/16, 0, 4/16, 6/16, 6/16, 3.8 months (3.6 months, 4.1 months), 4.2 months(95% CI as 2.0 to 6.3 months), respectively. Six of 59 HCC patients underwent R 0 resection due to tumor converting to resectable HCC with the conversion and resection rate of 10.2%(6/59). Among the 6 patients, 5 cases undergoing first-line treatment had the conversion and resection rates of 11.6% (5/43) and 1 case undergoing second-line treatment had the conversion and resection rates of 1/16, respectively. (2) Adverse drug reactions and treatment: 25 of 59 HCC patients underwent 3 to 4 grade adverse drug reactions with the incidence of 42.4%(25/59). Among the 25 patients, 10 cases including 5 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of gamma glutamyltransferase >5×upper limit of normal (ULN), 9 cases including 4 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of aspartate aminotransferase >5×ULN, 5 cases including 4 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred gastrointestinal hemorrhage, 4 cases undergoing first-line therapy had the level of white blood cell count <2.0×10 9/L, 4 cases including 1 case undergoing first-line therapy and 3 cases under-going second-line therapy had the level of total bilirubin >3×ULN, 3 cases undergoing first-line therapy had the level of neutrophil count <1.0×10 9/L, 3 cases including 2 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred ascites, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy had the level of platelet count <50.0×10 9/L, 2 cases undergoing first-line therapy had the level of alanine aminotransferase >5×ULN, 2 cases undergoing first-line therapy occurred hyponatremia, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred pulmonary infection, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred type 1 diabetes, 1 case undergoing first-line therapy occurred hypokalemia, 1 case undergoing first-line therapy occurred myocarditis, 1 case undergoing first-line therapy occurred hypophysistis, 1 case undergoing first-line therapy occurred bullous dermatitis, 1 case undergoing first-line therapy occurred hypertension. Three of 59 HCC patients underwent 5 grade adverse drug reactions ,with the incidence of 5.1%(3/59), including 1 case undergoing first-line therapy with immune hepatitis, 1 case undergoing second-line therapy with immune pneumonia and 1 case undergoing second-line therapy with immune enteritis. Some of patients underwent multiple adverse drug reactions at the same time. Twenty five patients undergoing 3 to 4 grade adverse drug reactions were relieved with the treatment of drug reduction, drug withdrawal, symptomatic treatment or hormone therapy. Three patients undergoing 5 grade adverse drug reactions died after being treated with high-dose hormone shock and hepatoprotective treatment. (3) Follow-up and survival: all 59 patients were followed up for 1.5 to 25.2 months, with a median follow-up time of 13.3 months. Of them, patients undergoing first-line therapy were followed up for 1.9 to 25.2 months, with a median follow-up time of 13.5 months. During follow-up,20 cases undergoing first-line therapy died with the fatality rate of 46.5%(20/43). Patients undergoing second-line therapy were followed up for 1.5 to 24.4 months, with a median follow-up time of 10.8 months. During follow-up, 10 cases undergoing second-line therapy died with the fatality rate of 10/16. Up to the latest follow-up, the tumor diameter of the target lesion in all 59 patients, in patients undergoing first-line therapy and in patients undergoing second-line therapy was 75 mm(38 mm, 125 mm), 74 mm(36 mm, 116 mm), 84 mm(48 mm,150 mm), respectively. The ratio of tumor diameter of the target lesion at latest follow-up to tumor diameter of the target lesion at baseline were -9.05%(-27.3%, 19.7%), -16.1%(-28.8%, 13.6%), 13.2%(-24.7%, 23.5%) for all 59 patients, patients undergoing first-line therapy and patients undergoing second-line therapy, respectively. The median overall survival time and median progression free survival time of patients undergoing first-line therapy and patients undergoing second-line therapy were 17.1 months(95% CI as 11.0 to 23.2 months), 10.8 months(95% CI as 5.0 to 16.6 months) and 10.8 months(95% CI as 9.2 to 12.4 months), 3.0 months(95% CI as 1.6 to 4.4 months), respectively. Conclusion:For unresectable or advanced HCC, combination therapy with lenvatinib and PD-1 antibodies can obtain effective antitumor activity and less incidence of adverse drug reactions.

Overall management strategies for liver cancer patients during the COVID-19 outbreak / 中华消化外科杂志

The Corona Virus Disease 2019 (COVID-19) that occurred December of 2019 has a wide range of impacts, and its epidemic situation is grim. China has a large population of liver cancer, accounting for 50% of new cases of liver cancer worldwide. How to ensure the diagnosis, treatment and rehabilitation of liver cancer patients while preventing and controlling the epidemic situation is an issue that urgently need specialists pay attention to. The authors propose an overall management model for patients with liver cancer, combined with their own experience, in order to guide specialists to safely and effectively carry out clinical diagnosis and treatment of liver cancer during the prevention and control of epidemics, and to help liver cancer patients receive treatment.

Mechanisms and control measures of COVID-19 related liver injuries / 中华消化外科杂志

Although the epidemic situation of Corona Virus Disease 2019 (COVID-19) has been controlled, the epidemic situation remains grim. The COVID-19 is highly infectious, with various clinical manifestations including liver injury. The authors make a preliminary investigation on the mechanisms of liver injury related to COVID-19, and put forward correspon-ding control measures for reference.

Research advances in molecular classification for precision diagnosis and treatment of hepatocellular carcinoma / 中华消化外科杂志

Hepatocellular carcinoma (HCC),a highly prevalent malignancy and one of the leading cause of cancer death in China,remains a major public health problem in the next decades.Owing to the tremendous achievements in early diagnosis,precision liver surgery,molecular targeted therapy and immunotherapy,we have witnessed significant improvements in the long-time survival of HCC patients,if properly treated.However,HCC is a highly heterogeneous disease.Even for patients within the same clinical stage,their clinical outcome and treatment efficacy vary significantly.Great efforts to improve the molecular classification of HCC patients are needed to foster precision medicine,paving the way for novel therapeutic strategies.Advances in multi-omics,single-cell analysis,molecular imaging and artificial intelligence will lead to better understanding of the molecular classification and refine precision treatment in HCC,ultimately excluding this neoplasm from the risk list of our Healthy China.

Research advances in systemic therapy for hepatocellular carcinoma in the era of precision medicine / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice and has the features of high incidence rate, poor prognosis, and high mortality rate, and its incidence rate and mortality rate rank among the top malignant tumors in the world. High heterogeneity of HCC affects the evolution and therapeutic response of HCC. Since most HCC patients are in the advanced stage at the time of diagnosis, systemic treatment has become the main treatment option. In recent years, remarkable achievements have been made in molecular targeted therapy and immunotherapy for HCC, and the latest NCCN guidelines for the systemic treatment of HCC show that sorafenib, lenvatinib, and atezolizumab combined with bevacizumab are recommended as the first-line treatment of HCC, and regorafenib, cabozantinib, nivolumab, pembrolizumab, and ramucirumab are the second-line treatment options for HCC. In the era of precision medicine, how to select the optimal individualized systemic treatment regimen is the key problem in the systemic treatment of HCC. This article reviews the advances in the systemic treatment of HCC in the era of precision medicine and discusses the development direction of HCC treatment in the future.

Research advances in molecular classification for precision diagnosis and treatment of hepatocellular carcinoma / 中华消化外科杂志

Hepatocellular carcinoma (HCC), a highly prevalent malignancy and one of the leading cause of cancer death in China, remains a major public health problem in the next decades. Owing to the tremendous achievements in early diagnosis, precision liver surgery, molecular targeted therapy and immunotherapy, we have witnessed significant improvements in the long-time survival of HCC patients, if properly treated. However, HCC is a highly heterogeneous disease. Even for patients within the same clinical stage, their clinical outcome and treatment efficacy vary significantly. Great efforts to improve the molecular classification of HCC patients are needed to foster precision medicine, paving the way for novel therapeutic strategies. Advances in multi-omics, single-cell analysis, molecular imaging and artificial intelligence will lead to better understanding of the molecular classification and refine precision treatment in HCC, ultimately excluding this neoplasm from the risk list of our Healthy China.