Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy found globally. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play critical roles in HCC. However, the function of lncRNA in HCC remains poorly understood. AIM: To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms. METHODS: We measured the expression of lncRNA W42 in HCC tissues and cells (Huh7 and SMMC-7721) by quantitative reverse transcriptase polymerase chain reaction. Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression. HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42. Cell functions were detected by cell counting Kit-8 (CCK-8), colony formation, flow cytometry and Transwell assays. The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays. An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo. The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC. RESULTS: In this study, we identified a novel lncRNA (lncRNA W42), and investigated its biological functions and clinical significance in HCC. LncRNA W42 expression was upregulated in HCC tissues and cells. Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC, and inhibited cell apoptosis. LncRNA W42 directly bound to DBN1 and activated the downstream pathway. LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo. The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times. CONCLUSION: In vitro and in vivo results suggested that the novel lncRNA W42, which is upregulated in HCC, may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.

A recombinant influenza virus with a CTLA4-specific scFv inhibits tumor growth in a mouse model.

Oncolytic viruses (OV) have shown excellent safety and efficacy in preclinical and clinical studies. Influenza A virus (IAV) is considered a promising oncolytic virus. In this report, we generated a recombinant influenza virus expressing an immune checkpoint blockade agent targeting CTLA4. Using reverse genetics, a recombinant influenza virus, termed rFlu-CTLA4, encoding the heavy chain of a CTLA4 antibody on the PB1 segment and the light chain of the CTLA4 antibody on the PA segment was produced. RFlu-CTLA4 could replicate to high titers, and antibodies were produced in the allantoic fluid of infected eggs. Furthermore, the selective cytotoxicity of the virus was higher in various hepatocellular carcinoma cancer cell lines than in the normal cell line L02 in vitro, as indicated by MTS assays. More importantly, in a subcutaneous H22 mouse hepatocarcinoma model, intratumoral injections of rFlu-CTLA4 inhibited the growth of treated tumors and increased the overall survival of mice compared with injections of the PR8 virus. Taken together, these results warrant further exploration of this novel recombinant influenza virus for its potential use as a single or combination agent for cancer immunotherapy.

Long non-coding ribonucleic acid W5 inhibits progression and predicts favorable prognosis in hepatocellular carcinoma.

BACKGROUND: Accumulating evidence has revealed that several long non-coding ribonucleic acids (lncRNAs) are crucial in the progress of hepatocellular carcinoma (HCC). AIM: To classify a long non-coding RNA, i.e., lncRNA W5, and to determine the clinical significance and potential roles of lncRNA W5 in HCC. METHODS: The results showed that lncRNA W5 expression was significantly downregulated in HCC cell lines and tissues. Analysis of the association between lncRNA W5 expression levels and clinicopathological features suggested that low lncRNA W5 expression was related to large tumor size (P < 0.01), poor histological grade (P < 0.05) and serious portal vein tumor thrombosis (P < 0.05). Furthermore, Kaplan-Meier survival analysis showed that low expression of lncRNA W5 predicts poor overall survival (P = 0.016). RESULTS: Gain-of-loss function experiments, including cell counting kit8 assays, colony formation assays, and transwell assays, were performed in vitro to investigate the biological roles of lncRNA W5. In vitro experiments showed that ectopic overexpression of lncRNA W5 suppressed HCC cell proliferation, migration and invasion; conversely, silencing of lncRNA W5 promoted cell proliferation, migration and invasion. In addition, acting as a tumor suppressor gene in HCC, lncRNA W5 inhibited the growth of HCC xenograft tumors in vivo. CONCLUSION: These results showed that lncRNA W5 is down-regulated in HCC, and it may suppress HCC progression and predict poor clinical outcomes in patients with HCC. LncRNA W5 may serve as a potential HCC prognostic biomarker in addition to a therapeutic target.

Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. METHODS: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. RESULTS: The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged. CONCLUSIONS: Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.

MicroRNA-106b-5p promotes hepatocellular carcinoma development via modulating FOG2.

Background: A recent study has revealed that miR-106b-5p might promote hepatocellular carcinoma (HCC) stemness maintenance and metastasis by targeting PTEN via PI3K/Akt pathway based on HCC cell lines and animal models. Its clinical relevance remains unknown. Purpose: Herein, we aimed to evaluate associations of miR-106b-5p dysregulation with various clinicopathological features of HCC patients and investigate its functions during HCC progression. Patients and methods: At first, miR-106b-5p expression in 130 pairs of HCC and adjacent normal liver tissues was detected by quantitative PCR. Chi-square test was then performed to determine clinical significance. Further investigations on its functions were performed by miRNA target prediction and validation, as well as cellular experiments. Results: miR-106b-5p levels in HCC tissues were significantly higher than those in the adjacent normal liver tissues (P<0.001). High miR-106b-5p expression was significantly associated with advanced tumor stage (P=0.02) and high tumor grade (P=0.03). In addition, Friend of GATA 2 (FOG2) was identified as a direct target of miR-106b-5p in HCC cells. Moreover, the clinical relevance to HCC progression of the combined high miR-106b-5p and low FOG2 expression was more significant than high miR-106b-5p alone. Functionally, enforced expression of miR-106b-5p reduced FOG2 expression and promoted the proliferation and invasion of HCC cells. Furthermore, co-transfection of FOG2 restored the oncogenic roles of miR-106b-5p over-expression. Conclusion: Our data offer the convincing evidence that miR-106b-5p upregulation may promote the aggressive progression of HCC. miR-106b-5p overexpression may promote HCC cell proliferation and invasion by suppressing FOG2, implying its potentials as a promising therapeutic target for HCC patients.

International consensus statement on robotic hepatectomy surgery in 2018.

The robotic surgical system has been applied in liver surgery. However, controversies concerns exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. To promote the development of robotic hepatectomy, this study aimed to evaluate the current status of robotic hepatectomy and provide sixty experts' consensus and recommendations to promote its development. Based on the World Health Organization Handbook for Guideline Development, a Consensus Steering Group and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 22 topics were prepared analyzed and widely discussed during the 4 meetings. Based on the published articles and expert panel opinion, 7 recommendations were generated by the GRADE method using an evidence-based method, which focused on the safety, feasibility, indication, techniques and cost-effectiveness of hepatectomy. Given that the current evidences were low to very low as evaluated by the GRADE method, further randomized-controlled trials are needed in the future to validate these recommendations.

Exosomal microRNAs as potential biomarkers for cancer cell migration and prognosis in hepatocellular carcinoma patient-derived cell models.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and current treatments exhibit limited efficacy against advanced HCC. The majority of cancer-related deaths are caused by metastasis from the primary tumor, which indicates the importance of identifying clinical biomarkers for predicting metastasis and indicating prognosis. Patient-derived cells (PDCs) may be effective models for biomarker identification. In the present study, a wound healing assay was used to obtain 10 fast-migrated and 10 slow-migrated PDC cultures from 36 HCC samples. MicroRNA (miRNA) signatures in PDCs and PDC-derived exosomes were profiled by microRNA-sequencing. Differentially expressed miRNAs between the low- and fast-migrated groups were identified and further validated in 372 HCC profiles from The Cancer Genome Atlas (TCGA). Six exosomal miRNAs were identified to be differentially expressed between the two groups. In the fast-migrated group, five miRNAs (miR-140-3p, miR-30d-5p, miR-29b-3p, miR-130b-3p and miR-330-5p) were downregulated, and one miRNA (miR-296-3p) was upregulated compared with the slow-migrated group. Pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were significantly enriched in the 'focal adhesion' pathway, which is consistent with the roles of these miRNAs in tumor metastasis. Three miRNAs, miR-30d, miR-140 and miR-29b, were significantly associated with patient survival. These findings indicated that these exosomal miRNAs may be candidate biomarkers for predicting HCC cell migration and prognosis and may guide the treatment of advanced HCC.

Somatic mutation profiling of liver and biliary cancer by targeted next generation sequencing.

Liver and biliary cancers are highly lethal cancer types lacking effective treatments. The somatic mutations, particularly those with low mutant allele frequencies, in Chinese patients with liver and biliary cancer have not been profiled, and the frequency of patients benefiting from targeted therapy has not been studied. The present study evaluated the tumor tissues of 45 Chinese patients with hepatocellular carcinoma (HCC) and 12 Chinese patients with biliary tract cancer (BTC) by targeted next generation sequencing, with an average coverage of 639×, to identify alterations in 372 cancer-related genes. A total of 263 variants were identified in 139 genes, with 85.6% of these variants not previously reported in the Catalogue Of Somatic Mutations In Cancer database, and the mutation profile was different from the current datasets, including The Cancer Genome Atlas dataset and the National Cancer Center Japan (NCC_JP) dataset. Patients with hepatitis B virus (HBV) infection harbored more mutations than those without HBV infection, and the mutations in HBV carriers occurred preferentially in genes involved in vascular endothelial growth factor signaling pathways. Mutations in fibroblast growth factor and RAS signaling pathways were enriched in patients with cirrhosis, and alterations in interleukin and transforming growth factor signaling pathways were more frequently identified in individuals with abnormal bilirubin expression. Of all the patients, 7% exhibited variants in the target of sorafenib, and 42% harbored variants in the targets of drugs that have been approved to treat other types of cancer. These findings indicate diverse HCC/BTC variants patterns in different populations, and that the mutation load and patterns are correlated with clinical features. Further clinical studies are now warranted to evaluate the efficacies of other targeted drugs besides sorafenib in the treatment of patients with liver and biliary cancer.

Downregulation of BRAF-activated non-protein coding RNA in patients with hepatitis B virus-associated hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) have been investigated as a novel class of regulators of cellular processes, including cell growth, apoptosis and carcinogenesis. lncRNA BRAF-activated non-protein coding RNA (BANCR) has recently been revealed to be involved in tumorigenesis of numerous types of cancer, including papillary thyroid carcinoma, melanoma, non-small cell lung cancer and colorectal cancer. However, the expression profiles and biological relevance of lncRNA BANCR in hepatocellular carcinoma (HCC) has not yet been reported. In the present study, the expression level of BANCR in tumor tissues and para-cancerous tissues was determined by reverse transcription-quantitative polymerase chain reaction in patients with hepatitis B virus (HBV)-associated HCC, and its association with clinicopathological characteristics of patients was analyzed. The results demonstrated that the expression level of BANCR was significantly reduced in tumor tissues in comparison with in para-cancerous tissues (P<0.001). Furthermore, the present study demonstrated that BANCR expression level was closely associated with serum α-fetoprotein levels (P<0.01) and HCC tumor number (P<0.05). To the best of our knowledge, these results revealed for the first time that BANCR downregulated in patients with HBV-associated HCC and BANCR expression level may be a potential valuable diagnosis and therapeutic biomarker in HCC.

Decreased expression of long non-coding RNA LOC728290 in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. Despite progress in the diagnosis and treatment of HCC, prognosis remains unfavorable. Long non-coding RNAs (lncRNAs) are emerging as important factors in tumorigenesis and cancer progression; however, the underlying molecular mechanisms and clinical significance of lncRNAs in HCC remain largely unknown. The present study examined the expression pattern and clinical significance of a novel lncRNA, LOC728290, in HCC. Expression of LOC728290 was markedly decreased in HCC tissues compared with adjacent non-tumor liver tissues, as detected using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The area under the receiver operating characteristic curve for LOC728290 was 0.728. The expression of LOC728290 was associated with the level of α-fetoprotein and microvascular invasion. Furthermore, patients with low LOC728290 expression exhibited decreased recurrence-free survival times (P<0.05) compared with those with high LOC728290 expression. The results of the present study indicated that downregulation of LOC728290 in patients with HCC may be a powerful tumor biomarker, with potential clinical applications in prognosis as well as a therapeutic target.

Targeting the raft-associated Akt signaling in hepatocellular carcinoma.

Caveolin-1 and flotillin-1 are considered as markers of lipid rafts which can be regarded as sorting platforms for targeted transport of transmembrane proteins and are involved in fundamental cellular events such as signal transduction, cell adhesion, lipid/protein sorting, and human cancer. We addressed caveolin-1 and flotillin-1 expression in 90 human hepatocellular carcinoma (HCC) and adjacent noncancerous tissues (ANT) samples by SDS-PAGE and immunoblotting with specific antibodies. Significant caveolin-1 and flotillin-1 overexpression was found in HCC tissues compared to ANT and was confirmed by immunohistochemistry. Raft-associated Akt signaling pathway components involved in the regulation of cell survival were altered by western blotting in HCC microdomain-enriched subcellular fractions purified from paired HCC and ANT samples. Our results demonstrated that the activity of raft-associated but not total membrane Akt determines its cellular functions. Lipid rafts differ in different types of tissues, which allows for the possibility of tissue-type-specific targeting for cell survival.

The Notch1/cyclooxygenase-2/Snail/E-cadherin pathway is associated with hypoxia-induced hepatocellular carcinoma cell invasion and migration.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide; however, the prognosis of HCC patients remains poor. This poor prognosis is mainly attributed to the high rate of intrahepatic and distant metastasis. HCC often occurs in a hypoxic environment and hypoxia can activate metastatic programs, ultimately leading to tumor recurrence or metastasis. Thus, the discovery and subsequent development of novel agents to block HCC invasion and migration are the primary objectives of hepatic cancer research. The Notch1 signaling pathway might be involved in hypoxia-induced carcinoma metastasis. However, the mechanisms by which Notch1 mediates cell metastasis, particularly in hepatocellular carcinoma, are not yet entirely clear. The results of the present study show that hypoxia increases the invasion and migration capacities of different HCC cells. Activation of the Notch1 signaling pathway contributes to hypoxia-induced invasion and migration in HCC cells. The activated Notch1 signaling pathway can regulate Snail/E-cadherin through cyclooxygenase-2 (COX-2) under hypoxic conditions. The above results suggest that the Notch1/COX-2/Snail/E-cadherin pathway is possibly associated with hypoxia-induced invasion and migration in HCC cells. Thus, targeting Notch1 may be useful for devising novel preventive and therapeutic strategies for HCC.

Ex-situ liver surgery without veno-venous bypass.

AIM: To evaluate the results of hepatic resection with ex-situ hypothermic perfusion and without veno-venous bypass. METHODS: In 3 patients with liver tumor, the degree of the inferior vena cava and/or main hepatic vein involvement was verified when the liver was dissociated in the operation. It was impossible to resect the tumors by the routine hepatectomy, so the patients underwent ex-situ liver surgery, vein cava replacement and hepatic autotransplantation without veno-venous bypass. All surgical procedures were carried out or supervised by a senior surgeon. A retrospective analysis was performed for the prospectively collected data from patients with liver tumor undergoing ex-situ liver surgery, vein cava replacement and hepatic autotransplantation without veno-venous bypass. We also compared our data with the 9 cases of Pichlmayr's group. RESULTS: Three patients with liver tumor were analysed. The first case was a 60-year-old female with a huge haemangioma located in S1, S4, S5, S6, S7 and S8 of liver; the second was a 64-year-old man with cholangiocarcinoma in S1, S2, S3 and S4 and the third one was a 55-year-old man with a huge cholangiocarcinoma in S1, S5, S7 and S8. The operation time for the three patients were 6.6, 6.4 and 7.3 h, respectively. The anhepatic phases were 3.8, 2.8 and 4.0 h. The volume of blood loss during operation were 1200, 3100, 2000 mL in the three patients, respectively. The survival periods without recurrence were 22 and 17 mo in the first two cases. As for the third case complicated with postoperative hepatic vein outflow obstruction, emergency hepatic vein outflow extending operation and assistant living donor liver transplantation were performed the next day, and finally died of liver and renal failure on the third day. Operation time (6.7 ± 0.47 h vs 13.7 ± 2.6 h) and anhepatic phase (3.5 ± 0.64 h vs 5.7 ± 1.7 h) were compared between Pichlmayr's group and our series (P = 0.78). CONCLUSION: Ex-situ liver resection and liver autotransplantation has shown a potential for treatment of complicated hepatic neoplasms that are unresectable by traditional procedures.

Operative timing of liver transplantation for patients with severe hepatitis.

BACKGROUND: Fulminant hepatic failure manifests a rapid onset, serious complications, and a high mortality, but still there is a possibility of recovery. Once the patient is able to pass a crisis, the liver is able to regenerate completely and regain its normal function. Therefore it is of vital importance to determine the eligible timing for transplantation. Premature surgery might result in a loss of the chance of internal medical treatment and misuse of liver resources, whereas delayed surgery might increase the difficulty of treatment in the preoperative period and the possibility of complications and medical expense, which eventually result in decreased rate of success and survival. This problem remains worldwide how to choose the optional timing of operation. METHODS: Thirty-six patients with severe hepatitis were treated by orthotopic liver transplantation. The distribution of MELD scores in these patients was: 10-19 in 8 patients, 20-29 in 10, 30-39 in 11, and 40 in 7. They were divided into two groups: MELD score <30 and MELD score >or=30. Parameters (1-year survival rate, complications, preoperative use of artificial liver, operative time, volume of bleeding and blood transfusion, and average hospital costs) were examined as prognostic factors after liver transplantation. RESULTS: The 1-year survival rate of the MELD score <30 group was higher than that of the >or=30 group (77.8% and 33.3%, P=0.007), and the rate of complications in the <30 group was lower (P=0.012). There were no differences in the timing of artificial liver treatment, operative time, operative hemorrhage, and transfusion between the two groups (P=0.742). But the average daily hospital cost in the MELD score >or=30 group was higher (P=0.008). CONCLUSION: This study shows that when the MELD score is <30 it may be the optimal time to perform liver transplantation for patients with severe hepatitis.

[Hand-assisted laparoscopic hepatectomy for large liver cancer in 56 cases].

OBJECTIVE: To investigate the practical value of hand-assisted laparoscopic hepatectomy for large liver cancer in peripheral segments. METHODS: From March 2004 to December 2007, 56 patients with large liver cancer underwent hand-assisted laparoscopic hepatectomy including 53 cases of hepatocellular carcinoma, 2 cases of cholangiocellular carcinoma, 1 case of hepatic metastatic squamous carcinoma. RESULTS: The operation procedures were completed safely in all patients including 27 left lateral segment hepatectomy, 6 left hemi-hepatectomy and 23 atypical right hepatectomy. Thirty-one cases with hepatic hilum blocking in the procedure and the mean time was 16.7 minutes. Mean surgical time was 105.3 minutes. Mean blood loss was 97 ml. Mean gross tumor size was 8.6 cm. Mean excisional hepatic tissue volume was 10.5 cm. No serious postoperative complications occurred. Mean eating time was 2.1 days. The mean postoperative hospital stay was 7.3 days. CONCLUSION: Hand-assisted laparoscopic hepatectomy for large liver carcinoma is feasible and safe for selected patients.

Laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation.

AIM: To investigate the possibilities and advantages of laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct compaired with traditional open operation. METHODS: Laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation were performed in two groups of patients who had gallstones in the left lobe of liver and in the common bile duct. The hospitalization time, hospitalization costs, operation time, operative complications and post-operative liver functions of the two groups of patients were studied. RESULTS: The operation time and post-operative liver functions of the two groups of patients had no significant differences, while the hospitalization time, hospitalization costs and operative complications of the laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration in the common bile duct group were significantly lower than those in the traditional open operation group. CONCLUSION: For patients with gallstones in the left lobe of liver and in the common bile duct, laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct can significantly shorten the hospitalization time, reduce the hospitalization costs and the post-operative complications, without prolonging the operation time and bringing about more liver function damages compared with traditional open operation. This kind of operation has more advantages than traditional open operation.

Liver transplant for 70 patients with end-stage liver diseases.

BACKGROUND: Liver transplantation has evolved as a successful treatment for patients with end-stage liver cirrhosis and acute liver failure. Postoperative survival rates have increased to 90% in 1 year and 80% in 5 years as a result of improvements in immunosuppression, perioperative management and surgical techniques. However, a wide range of postoperative complications are of technical or medical origin. This study was undertaken to determine the relationship between the technical improvements and optimal timing of surgery and its outcome. METHODS: From April 1999 to October 2005, typical orthotopic or piggyback liver transplantation was performed in 70 patients (58 men and 12 women, aged 19-74 years). Twenty-four patients had liver carcinoma and cirrhosis, and 46 had benign liver disease. RESULTS: All patients survived the operation and 14 died in the first month after surgery because of respiratory failure (6), respiratory failure accompanied by acute renal failure (4), intra-abdominal hemorrhage and infection (2), and cerebral edema (2). A total of 76 complications occurred in the 70 patients after operation: pneumonia (34), right pleural effusion (11), bile leakage (7), postoperative intra-abdominal hemorrhage and infection (4), acute renal failure (4), acute rejection (3), wound infection (2), biliary tract stenosis (2), severe cholangitis derived from cholelith (2), morphological alteration of biliary tree (2), cerebral edema (2), empyema (1), chronic rejection (1), and wound hematoma (1). Finally, 33 patients survived more than 6 months, 16 more than 1 year, 4 more than 2 years, and 2 more than 6 years after operation. The perioperative survival rate was 80% in this series. CONCLUSIONS: Liver transplantation is an effective treatment for patients with end-stage liver disease. To obtain good results, improvements of surgical technique, optimal timing and better postoperative care are needed.

Early prevention and treatment of biliary tract complications after orthotopic liver transplantation.

OBJECTIVE: To investigate the prevention and treatment of biliary complications after orthotopic liver transplantation (OLT). METHODS: OLT was performed in 18 patients with end-stage liver disease, including 6 patients with primary liver cancer. Except 1 patient was infused only through the portal vein, others were infused through the portal vein and hepatic artery of the donor. The biliary tract was reconstructed using choledochocholedostomic anastomosis in 17 patients, and using Roux-en-Y choledochojejunostomic anastomosis in 1 patient. RESULTS: Four patients with biliary complication were found. In one patient, biliary leakage was found around the T-tube on day 14 postoperatively, and disappeared after re-opening of the tube. In one patient undergoing Roux-en-Y choledochojejunostomic anastomosis, biliary leakage was found on day 12 postoperatively and reoperation was performed. The T-tube was removed from the anastomosis after reoperation, and abdominal infection was controlled, but high fever recurred on day 49 postoperatively. The patient died on day 52 postoperatively. Autopsy revealed biliary leakage and biliary tract necrosis. In another patient, biliary leakage was found on day 3 after operation, and was treated by adequate drainage. Four months after operation, biliary sludge in the common tract was found and treated successfully with oral chemolysis. But biliary sludge or stone recur on one and half year after OLT. Spincterotomy and basket extraction were performed via endoscopic retrograde cholangiopancreatography, and the biliary sludge or stone was cleared out. In case 4, biliary drainage tube cholangiogram showed anastomotic stenosis one month after operation. Three months later, biliary sludge or stone was found beyond anastomotic stenosis. After oral chemolysis (ursodeoxycholic acid) and irrigation with heparinized saline solution via the biliary drainage tube, the biliary sludge disappeared. CONCLUSIONS: To reduce the incidence of biliary complications, adequate infusion of the hepatic artery, complete slushing of the biliary tract, and reduction of injury to the blood supply of the donor biliary tract are essential. Most biliary complications can be treated successfully by non-operative treatment or minimally invasive operation.

Apoptosis in acute rejection of hamster-to-rat liver transplantation.

OBJECTIVE: To investigate whether apoptotic cell death is involved in liver xenograft rejection and the molecular mechanism of apoptosis. METHODS: After hamster-to-rat orthotopic liver transplantation, apoptosis in the xenograft was observed histologically and by in situ end-labelling of fragmented DNA. CD8 antigen, perforin, Fas-L and TGF-beta1 were observed immunohistochemically in the graft. RESULTS: In xenogenic rejection, OX8 (CD8) positive T lymphocyte was observed on day 2 post-transplantation, evidently on day 5. The expression of perforin and Fas-L in grafts occurred on day 4 post-transplantation, and it was more evident in the rejection. In control group,the lymphocyte was rarely seen, and the expression of Fas-L and perforin was not found. Both xenogeneic and syngeneic grafts showed the expression of TGF-beta1 on the first day after transplantation. The expression of TGF-beta1, however, increased subsequently in the xenogeneic graft in contrast to its normalization in the syngeneic graft. In the xenogeneic graft, apoptosis occurred on day 1 after transplantation, decreased on day 2, increased on day 3, and peaked on day 5. Apoptosis was similar in the syngeneic and xenogeneic grafts on day 1 after transplantation, but decreased to normal one day later. The more severe apoptosis, the more severe acute rejection, and the more evident expression of perforin, Fas-L and TGF-beta1. CONCLUSION: Apoptosis as a mechanism of cell death exists in the acute rejection of liver xenograft, and it is related closely to the expression of perforin, TGF-beta1 and Fas-L.