Progress and strategies of surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus / 中华消化外科杂志

The incidence of portal vein tumor thrombus (PVTT) in patients with hepato-cellular carcinoma (HCC) is high and the prognosis is poor. The treatment mode of HCC+PVTT is changing to multidisciplinary comprehensive treatment. The authors make a deep investigation on the occurrence basis, classification, surgical treatment indication, postoperative adjuvant treatment and preoperative conversion treatment plan of HCC+PVTT, in order to provide reference for the diagnosis and treatment of this disease.

Serine protease inhibitor Hespintor’s potential mechanism based on integrated transcriptomics in inhibiting the growth of transplanted hepatoma in nude mice / 西安交通大学学报(医学版)

【Objective】 To investigate the relationship between differential expressions of lncRNAs and mRNAs and Hespintor’s possible anti-tumor mechanism using transcriptome sequencing technology. 【Methods】 First， a nude mouse model of human hepatoma tumors was established. The tumor tissue mass was collected after 4 weeks of group treatment. The cDNA libraries of tumor tissues were established in the Hespintor treatment group and the solvent control group， and transcriptome sequencing was performed. Based on RNA-seq data， the differentially expressed lncRNA and mRNA genes were screened， and the functional enrichment and interaction analysis were performed. The network module division approach was utilized to identify the target genes of Hespintor and build its regulatory network. 【Results】 The Hespintor treatment group yielded a high-confidence differentially expressed gene collection of 2 003 lncRNAs （DEGs lncRNA） and 1 038 mRNAs （DEGs mRNA）. Target mRNAs regulated by DEGs lncRNA were mainly enriched in PIP3 to activate the Akt signal， p53 signal pathway， FOXO-mediated transcription， and cell cycle， among other things. DEGs mRNA were primarily enriched in chemokine signaling pathways， extracellular matrix receptor interactions， complement， and coagulation cascades. Both of them were related in three ways： cell behavior， transcriptional regulation， and cell cycle. 【Conclusion】 The PI3K/Akt signaling pathway may play a key role in the inhibitory effect of Hespintor on tumor， inducing G1/S phase cell cycle arrest and apoptosis.

Effect of ozone oil for prevention and treatment of sorafenib-induced hand-foot skin reactions: a randomized controlled trial / 南方医科大学学报

OBJECTIVE@#To compare the effects of medical ozone oil and urea ointment for prevention and treatment of hand-foot skin reaction (HFSR) caused by sorafenib in patients with hepatocellular carcinoma (HCC).@*METHODS@#A total of 99 patients diagnosed with advanced HCC according to National Comprehensive Cancer Network (NCCN) who were scheduled to receive sorafenib treatment for the first time were enrolled in this study between April, 2018 and January, 2020. The patients were randomized into medical ozone oil group (@*RESULTS@#Eight patients were excluded for poor compliance or protocol violations, leaving a total of 91 patients for analysis, including 44 in medical ozone oil group and 47 in urea ointment group. Sixteen (36.4%) of patients in ozone oil group developed HFSR, a rate significantly lower than that in urea ointment group (57.4%; @*CONCLUSIONS@#Medical ozone oil can significantly reduce the incidence and severity of HFSR to improve the quality of life of HCC patients receiving sorafenib treatment.

Efficacy and Safety of Apatinib Combined with TACE in the Treatment of Moderate and Advanced Liver Cancer ： A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate the efficacy an d s afety of apatinib combined with transcatheter arterial chemoembolization（TACE）in the treatment of moderate and advanced liver cancer ，and to provide evidence-based reference for rational drug use in the clinic. METHODS ：Retrieved from Cochrane Library ，Embase，PubMed，Web of Science ，SinoMed， CNKI，Wanfang，VIP database ，RCTs about apatinib combined with TACE （trial group ）versus TACE （control group ）in the treatment of moderate and advanced liver cancer were collected from inception to Sep. 2019. After screening the literature and extracting the data ，the quality of included literatures was evaluated by using bias risk assessment tool recommended by the Cochrane system evaluator manual 5.1.0 and the modified Jadad scale. Meta-analysis was carried out by using Stata 12.0 software. RESULTS：Totally 16 RCTs were included ，involving 1 043 patients. Results of Meta-analysis showed that objective response rate [OR ＝3.10，95％CI（2.38，4.03），P＜0.001]，disease control rate [OR ＝3.56，95％CI（2.62，4.83），P＜0.001] and survival rate [OR ＝2.40，95％ CI（1.86，3.10），P＜0.001]，the incidence of diarrhea [OR ＝2.27，95％ CI（1.21，4.24），P＝0.011]， hypertension [OR ＝6.97，95％ CI（1.21，40.15），P＝0.030]， proteinuria [OR ＝12.44，95％CI（2.51，61.71），P＝0.002] and com hand foot syndrome [OR ＝32.50，95％CI（12.03，87.77），P＝ 0.001] of trial group were significantly higher than those of control group. The serum level of VEGF [SMD ＝－ 3.64， 95％CI（－5.06，－2.22），P＜0.001]，MMP-9 [SMD＝－3.21，95％CI（－4.31，－2.10），P＜0.001]，AFP [SMD ＝－3.54， 95％CI（－7.03，－0.06），P＝0.046] after treatment ，the incidence of myelosuppression [OR ＝0.61，95％CI（0.39，0.97），P＝ 0.035]，fever [OR ＝0.63，95％CI（0.42，0.95），P＝0.027]，nausea and vomiting [OR ＝0.70，95％CI（0.51，0.97），P＝0.030] in trial group were significantly lower than those of control group. There was no statistical significance in the incidence of abdominal pain [OR ＝0.87，95％CI（0.54，1.39），P＝0.547] and skin itching [OR ＝1.63，95％CI（0.36，7.50），P＝0.530] between 2 groups. CONCLUSIONS：Apatinib combined with TACE can significantly improve clinical efficacy ，prolong survival time ，reduce tumor recurrence and metastasis. It can reduce the occurrence of related ADR as diarrhea after TACE ，but increase the occurrence of apatinib-related ADR as myelosuppression.

Sorafenib-induced Pancreatic Pseudocyst in a Patient with Advanced Hepatocellular Carcinoma: a Rare Adverse Event

A 54-year old man diagnosed with advanced hepatocellular carcinoma began treatment with sorafenib. After 3 weeks of treatment, he complained of abdominal pain and nausea. Abdominal sonography showed multiple hepatic lesions only. Serum amylase and lipase levels were 35 U/L and 191 U/L, respectively. The patient was diagnosed with sorafenib-induced acute pancreatitis. After 10 days of discontinuing sorafenib he still complained of nausea and loss of appetite. Esophagogastroduodenoscopy showed a large bulging lesion, which was suspected to cause extrinsic compression on the high body of the gastric anterior wall. Computed tomography scan revealed a cystic lesion, 8.3 cm in size, in the pancreatic tail, suggesting a pancreatic pseudocyst. After the withdrawal of sorafenib, systemic chemotherapy with Adriamycin and cisplatin was administered. Four months after the discontinuation of sorafenib, the size of the pancreatic pseudocyst decreased from 8.3 cm to 3 cm. The patient's symptoms were also relieved.

The Genomic Landscape and Its Clinical Implications in Hepatocellular Carcinoma

The pathogenesis of hepatocellular carcinoma (HCC) is a complex process. During the last decade, advances in genomic technologies enabled delineation of the genomic landscape of HCC, resulting in the identification of the common underlying molecular alterations. The tumor microenvironment, regulated by inflammatory cells, including cancer cells, stromal tissues, and the surrounding extracellular matrix, has been extensively studied using molecular data. The integration of molecular, immunological, histopathological, and clinical findings has provided clues to uncover predictive biomarkers to enhance responses to novel therapies. Herein, we provide an overview of the current HCC genomic landscape, previously identified gene signatures that are used routinely to predict prognosis, and an immune-specific class of HCC. Since biomarker-driven treatment is still an unmet need in HCC management, translation of these discoveries into clinical practice will lead to personalized therapies and improve patient care, especially in the era of targeted and immunotherapies.

The perioperative bundle of care for advanced HCC patients receiving CT-guided percutaneous minimally-invasive argon-helium knife cryoablation / 介入放射学杂志

Objective To discuss the clinical effect of perioperative bundle of care for patients with advanced hepatocellular carcinoma (HCC) who are receiving CT-guided percutaneous minimally-invasive argon-helium knife cryoablation.Methods A total of 30 HCC patients,who underwent percutaneous argonhelium knife cryoablation,were enrolled in this study.Perioperative measures based on the concept of bundle of care were implemented,which included training of nursing team members,perfect preoperative psychological nursing,dietary guidance,preoperative routine preparations,effective intraoperative guidance and close observation of the patient's condition,postoperative activity guidance,prevention and observation of complications,etc.Results All 30 advanced HCC patients could actively cooperate with physicians for the performance of percutaneous argon helium cryoablation.After the treatment,two patients developed nausea and vomiting and one patient developed chills and fever,which were improved after symptomatic treatment.All the 30 patients recovered well during the perioperative period and were discharged from hospital smoothly.Conclusion Perioperative bundle of care can help patients restore the surgical damage as soon as possible,reduce the pain and improve the quality of life.

Drug therapy for advanced hepatocellular carcinoma: approach, controversy and progress / 中华肝胆外科杂志

For unresectable advanced hepatocellular carcinoma (HCC),besides sorafenib,alternative drugs and treatment modalities are required.Clinical studies of hepatic arterial infusion chemotherapy (HAIC),transcatheter arterial chemoembolization (TACE),and system chemotherapy have shown favorable efficacy and tolerance in advanced HCC patients.In addition,the potential efficacy of sorafenib combined with focal treatment is also an interesting issue.As more therapies become available,decision-making for treating advanced HCC becomes increasingly complex.In our opinion,diverse treatment modalities should be utilized for the best interest of patients.Based on predictive biomarkers,we should develop a precise patient stratification system to select suitable candidates for each treatment modality in future studies,as is useful for improving prognosis of patients with advanced HCC.

The application of Omaha system in the clinical nursing for patients with advanced hepatocellular carcinoma treated with TACE / 介入放射学杂志

Objective To discuss the clinical application value of Omaha system-based targeting nursing care for patients with hepatocellular carcinoma (HCC) who were treated with transcatheter arterial chemoembolization (TACE).Methods A total of 60 advanced HCC patients,who were planned to receive TACE,were prospectively and randomly divided into the control group (n=30) and the observation group (n=30).Routine nursing mode was adopted for the patients in the control group,while Omaha system nursing model was employed for the patients in the observation group.The patients of the observation group were evaluated with Omaha system at the time of admission,the key common problems were screened out and targeted nursing measures were employed.Meanwhile,on the days of admission and discharge all the patients of both groups were asked to fill in the forms of Hamilton depression scale (HAMD-17),Hamilton anxiety scale (HAMA),social support rating scale (SSQ) and numerical pain rating scale (NRS);and the degrees of depression,anxiety,social support and pain were respectively assessed.Results Both nursing modes could improve the degrees of depression and anxiety as well as the social support system of HCC patients,but the curative effect of these two aspects in the observation group were obviously better than those in the control group (P＜0.05).No statistically significant difference in the improvement of pain degree existed between the two nursing models,but Omaha system-based targeting nursing mode could alleviate the patient's pain to a certain extent.Conclusion For patients with advanced HCC,Omaha system-based targeting nursing care can alleviate the patient's negative emotion and promote the patients to establish effective social support system,this nursing mode is superior to conventional nursing mode.Therefore,Omaha system-based targeting nursing has great application potential in clinical practice.

The effect of 5-FU and lobaplatin in the treatment of advanced hepatocellular carcinoma in serum AFP and TIP30 / 中国生化药物杂志

Objective To investigate the effect of 5-FU and Lobaplatin in the treatment of advanced hepatocellular carcinoma in serum AFP and TIP30.Methods 86 cases of advanced hepatocellular carcinoma in our hospital form June 2014 to June 2016 were selected and randomly divided into two groups,43 cases in the control group were treated with micro catheter perfusion 5-FU sequential therapy,43 cases in the experimental group were treated more with Lobaplatin sequential therapy.The serum levels of AFP, AFP-L3, Fer, TSGF, TIP30, clinical efficacy and adverse reactions were compared before and after treatment in the two groups.Results Compared with before treatment, levels of AFP-L3,Fer,TSGF and AFP decreased in two groups, levels of TIP30 increased (P<0.05);compared with the control group,levels of AFP-L3,Fer,TSGFand AFP in the experimental group were lower(P<0.05),and levels of TIP30 were higher(P<0.05),and the total efficiency of the experimental group was higher than the control group(P<0.05),and the incidence of adverse reactions in the experimental group was lower than the control group(P<0.05).Conclusion 5-FU and Lobaplatin in the treatment of advanced hepatocellular carcinoman can effective reduce the levels of AFP,AFP-L3,Fer,TSGF,and increased the levels of TIP30.

Nuevas terapias target y vías moleculares clínicamente relevantes en carcinoma hepatocelular avanzado / New targeted therapies and molecular routes clinically relevant in advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. Most cases occur in patients with chronic liver disease who are diagnosed at an advanced stage, and their prognosis is poor. Because HCC is resistant to conventional systemic therapies, molecular therapies have emerged and been established as the standard for advanced forms of the disease. Since the publication of phase III clinical studies on sorafenib, research has searched for new molecular targets. Thus, multiple clinical studies that inhibit relevant molecular pathways have been performed with numerous patients. Many of these trials have had unexpectedly negative results, not only due to patient complexity and the difficulty in evaluating a therapeutic response, quality of life and the survival rate but also because phase II clinical studies, without the selection of molecular targets, have continued on to poor results in phase III studies. This review article aims to evaluate different phase II and phase III clinical studies to understand the clinically relevant molecular pathways and to improve the future management of HCC patients.

El carcinoma hepatocelular (CHC) es uno de los tumores más comunes a nivel mundial. La mayoría de los casos ocurre en pacientes con enfermedad hepática crónica, quienes son diagnosticados en un estado avanzado con muy pobre pronóstico. Terapias moleculares orientadas al tratamiento del CHC han sido destacadas; estas pueden afectar la proliferación celular del tumor, diferenciación celular, angiogénesis, invasión y metástasis, entre otros procesos críticos al desarrollo del tumor. El estándar para el CHC avanzado es la terapia target usando Sorafenib, sin embargo, nuevas moléculas han sido testeadas en estudios fase III de primera línea, tales como sunitinib, brivanib, erlotinib y linifanib, sin superioridad sobre sorafenib. La investigación de nuevos tratamientos es un desafío para investigadores, hepatólogos y oncólogos. Las principales vías moleculares de CHC con relevancia en estudios clínicos fase II y III son: MAP-kinase (MAPK), PI3K/AKT/mTOR, (HGF)/c-Met, cromatina y regulación epigenética, mantenimiento de telómeros, Notch, Hedgehog, Hippo y vía señalizante Jak/STAT. Las terapias futuras en CHC pueden ser orientadas rutinariamente usando sólo objetivos adecuados para terapias moleculares y seleccionando subgrupos de pacientes sobre la base de la expresión de targets moleculares o basados en nuevas clasificaciones definidas por estudios genómicos.

Clinical Observation of TACE Combined with HIFU in the Treatment of Middle and Advanced Primary He-patocellular Carcinoma / 中国药房

OBJECTIVE To observe therapeutic efficacy and safety of transcatheter arterial chemoembolization (TACE) com-bined with high intensity focused ultrasound (HIFU) in the treatment of middle and advanced primary hepatocellular carcinoma (HCC). METHODS:76 patients with middle and advanced primary HCC were randomly divided into treatment group(36 cases) and control group(40 cases). Control group was given TACE alone,and treatment group was additionally given HIFU 2-3 weeks after TACE. Clinical efficacy,the content of alpha-fetoprotein(AFP)before and after operation,survival rate,survival period and ADR were compared between 2 groups. RESULTS:The efficiency rate and total effective rate of treatment group were 61.1% and 94.4%,which were significantly higher than those of control group(35.0%,77.5%),with statistical significance(P0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Com-pared with TACE alone,TACE combined with HIFU in the treatment of middle and advanced primary HCC can improve long-term survival rate and the short-term efficacy,with good safety.

Effect of sorafenib on serum hepatoma marker in patients with advanced hepatocellular carcinoma / 中国生化药物杂志

Objective To investigate effect of sorafenib on serum hepatoma marker in patients with advanced hepatocellular carcinoma. Methods 101 patients with advanced hepatocellular carcinoma were selected, and divided into two groups.50 cases in control group were treated with routine clinical treatment, and 51 cases in experimental group were treated with sorafenib on the basis of control group.The survival time, adverse reactions, VEGF, CTGF, HIF-1 and OPN levels were compared after the treatment.Results The survival time of experimental group was higher than control group (P<0.05).Compared with control group, the serum levels of VEGF、CTGF,HIF-1, OPN,AFP, CEA, and CA199 in experiment group were lower (P<0.05,P <0.01).There were no significant differences of total adverse reactions between experimental group and control group. Conclusion Sorafenib can effectively prolong survival time of patients with advanced hepatocellular carcinoma, reduce serum VEGF, CTGF, HIF-1 alpha and OPN levels.

Liver Transplantation for Advanced Hepatocellular Carcinoma / 대한이식학회지

Hepatocellular carcinoma (HCC) has become an important indication for liver transplantation in Korea. Even though the Milan criteria have been accepted as the gold standard in deceased donor liver transplantation, the acceptable indication for living donor liver transplantation is controversial. This review covers several key issues in liver transplantation for advanced HCC: (1) recent developments and published data on expanded criteria, (2) the role of down-staging, (3) an ethical issue in expanding the criteria in living donor liver transplantation, and (4) post-operative management, including the immunosuppressive regimen and post-transplant adjuvant chemotherapy to improve survival after transplantation for advanced HCC. Biological factors, such as AFP, PIVKA-II, and a PET scan, in addition to tumor size and number, may be helpful in selecting eligible patients for liver transplantation among patients with advanced HCC. Low-level immunosuppression with low exposure of calcineurin inhibitor may reduce HCC recurrence after transplantation.

Expanded Criteria for Living Donor Liver Transplantation in Patients with Advanced Hepatocellular Carcinoma

PURPOSE: The purpose of this study was to evaluate the possibility of expanding the indication for living donor liver transplantation (LDLT) for treatment of hepatocellular carcinoma (HCC), beyond the Milan criteria without compromising patient survival. METHODS: This was a retrospective study of 5patients (36.4%) that had undergone LDLT, beyond the Milan criteria, among 143 patients with HCC. The study was conducted in patients treated by the Department of Surgery, Catholic University of Korea from Oct 2000 to May 2008. We evaluated the survival curve, prognostic factors for survival and compared survival between our new criteria and Milan criteria. RESULTS: The 5 year patient survival and disease free survival rate in patients treated with LDLT beyond the Milan criteria were 50.2% and 61.9%, respectively. The prognostic factors affecting disease free survival and patient survival included serum AFP level, tumor size, vascular invasion, and tumor cell differentiation on univariate analysis. In multivariate analysis, AFP (200 ng/mL), tumor size (7 cm) and vascular invasion had significant influence on survival and disease free survival. According to our new criteria (size <7 cm, AFP <200 ng/ mL), 88.1% of our patients were included compare to the 63.6% that would have been if limited to the Milan criteria. With both factors met, the survival was comparable to the survival of Milan criteria (63.7% on our criteria and 78.2% on Milan criteria at 5 years) (P =0.103). CONCLUSION: A tumor size <7 cm and an AFP < 200 ng/mL appear to be useful cut-off values, beyond that criteria required by Milan. An analysis according to our criteria showed an acceptable survival outcome. Further verification of these findings by a large volume or prospective study is required for widespread adoption of our new criteria.

A Phase II Study of AP (Doxorubicin, Cisplatin) Chemotherapy in Patients with Advanced Hepatocellular Carcinoma / 대한암학회지

PURPOSE: Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma and is considered to be a highly malignant tumor with poor prognosis. We evaluated the efficacy and toxicities of AP (doxorubicin, cisplatin) comnination chemotherapy in hepatocellular carcinoma. MATERIALS AND METHODS: Between October 1989 and February 1991, 21 previously untreated patients with advanced hepatocellular carcinoma were entered and treated with AP combination chemotherapy (adriamycin 60 mg/m2, D1 and cisplatin 60 mg/m2, D1, repeated every 3 weeks). RESULTS: Among 14 evaluable patients, there was no complete response and 5 patients (36%; 95% C.I=10~62%) achieved partial response. The median survival time of all 21 patients was 17 weeks, and 63 weeks in responders (n=5) and 14 weeks in nonresponders (n=16), and the difference in two groups was statistically significant (p<0.05). The median time to progression of 14 evaluable patients was 13 weeks, and 49 weeks in the responders (n=5) and 6 weeks in the nonresponders (n=9), and the difference in two groups was statistically significant (p<0.05). Myelosuppression was minimal and non-hematologic toxicities were gererally mild and well tolerated. CONCLUSION: The results suggest that the combination chemotherpy of AP seems to be an effective regimen for hepatocellular carcinoma. Further trials are recommended for its true efficacy.

The Treatment of Moderately Advanced Carcinoma with Chemo-Immunotherapy / 中国肿瘤生物治疗杂志

A comparison of effectiveness of chemo-immunotherapy (CIT) using LAK/CD3AK 1-2 weeks after TACE in 74 patients with no surgical indication and TACE alone in 41 patients with moderately advanced HCC was carried out. The rates of remission between CIT group and TACE alone group were 72.4% and 40.4%(P