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ObjectiveTo investigate the symptoms and symptom clusters in patients with advanced hepatocellular carcinoma (HCC) receiving molecular-targeted therapy with lenvatinib, as well as the clinical significance of the management of symptoms and symptom clusters in reducing lenvatinib-related grade 3 or above adverse events (AEs) and AEs leading to treatment termination. MethodsA total of 98 patients with advanced HCC who were treated with lenvatinib in The Fifth Medical Center of Chinese PLA General Hospital from May 2017 to December 2018 were enrolled. The AEs associated with lenvatinib were observed according to National Cancer Institute Common Toxicity Criteria, and the primary endpoint was the number of cases with a reduced dose or interruption of lenvatinib or treatment termination due to lenvatinib-related AEs after the management of symptoms or symptom clusters. ResultsAll 98 patients completed the whole procedure. As for the lenvatinib-related AEs with an incidence rate of ＞20%, hypertension had the highest incidence rate of 42.9%, followed by diarrhea (33.6%), hepatic encephalopathy (30.6%), anorexia (30.6%), proteinuria (25.5%), fatigue (25.5%), hand-foot syndrome (22.4%), hoarseness (20.4%), and weight loss (20.4%). The incidence rate of grade 3 or 4 AEs was 55.1% (54/98); the most common grade 3 AEs were hypertension (8.2%) and hepatic encephalopathy (6.1%), and grade 4 AE was observed in 1 patient (1%). The most common symptom clusters included hypertensive proteinuria (56.1%), digestive tract syndrome (50%), and pain syndrome (36.7%). Among the 98 patients, 41 (41.8%) had a reduced dose or interruption of lenvatinib due to lenvatinib-related AEs after the management of symptoms and symptom clusters and 4(4.1%) experienced treatment termination, which was lower than the percentages of 52.9% and 8.8% in the REFLECT study. ConclusionHypertension and diarrhea are common AEs associated with lenvatinib. Hypertensive proteinuria, digestive tract syndrome, and pain syndrome are the main symptom clusters. Symptom cluster management is an effective means to reduce lenvatinib-related AEs leading to treatment termination.
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BACKGROUND:Hepatocyte transplantation has attracted more and more attention as a therapeutic measure for liver failure and genetic metabolic liver diseases.OBJECTIVE:TO evaluate the efficacy and safety of human hepatocyte transplantation in treating hepatitis B related liver failure in one case by a 2-year follow-up.DESIGN:A case-report of 2-year follow-up.SETTING:No.9 Department of Infectious Diseases,Bioengineering Research Room,the 302 Hospital of Chinese PLA.PARTICI PANT:One inpatient with hepatitis B related liver failure was selected from the 302 Hospital of Chinese PLA.and she was diagnosed according the laboratory tests.The transplanted hepatocytes were originated frOm the healthy liver of a 24-year-old man,who had signed the protocol for liver donation before death.METHODS:The hepatocyte transplantation was completed in the Department of Radiology,the 302 Hospital of Chinese PLA in December 2004.Liver was isolated to obtain human primary hepatocytes, and then cryopreserved.The hepatocytes were transplanted into recipient spleen via femoral vein after resuscitation.The clinical symptoms,changes of blood biochemical indexes,and changes of spleen MRI signals were observed before and after operation.The patient was reexamined every half a year after operation, including liver function, blood coagulation function,B-mode ultrasonography,gastroscopy and MRI,and she was followed up for 2 years. MAIN OUTCOME MEASURES:Liver function,blood coagulation function, imaging indexes, immunological indexes,complication and rejection.RESULTS:①Totally(1-2)×1010 hepatocytes were harvested,and the viability of rewarmed hepatocytes was 60%,and finally 2×109 hepatocytes were transplanted.②Two months later,the clinical symptoms of the recipient were obviously ameliorated,and serum bilirubin and aspartate aminotransferase(AST)were obviously decreased,while prothrombin activity was markedly increased.20 months later,the MRI results showed that there was hepatocyte image in spleen.Two years after operation.the total bilirubin level was 20 μmol/L,direct bilirubin level was 7 μmol/L, alanine aminotransferase was 416.75 nkat/L,AST was 533.44 nkat/L,albumin was 37 g/L,prothrombin activity was 90%,which were all obviously ameliorated as compared with those before operation(474.5 μmol/L,340.3 μmol/L,400.08 nkat/L,1 200.24 nkat/L,38 g/L,25%).The patient left the hospital 2 months later and could do light-burdened job.No complications of hydroperitonia and liver function failure, etc.were observed,and no rejection occurred.Several reexaminations by B-mode ultrasonography all indicated the further aggravations of liver cirrhosis and esophageal varices.She was admitted to hospital for twice because of esophageal varices bleeding,and cured by endoscopic variceal sclerosis therapy.CONCLUSION:Hepatocyte transplantation can ameliorate liver function without rejection,but it cannot relieve portal hypertension.