Using extracorporeal membrane oxygenation in donations after cardiac death or brain death: A single-center experience and long-term outcome.

Aims: The use of extended criteria donors is a routine practice that sometimes involves extracorporeal membrane oxygenation (ECMO) in donations after cardiac death or brain death. Methods: We performed a retrospective study in a single center from January 2006 to December 2019. The study included 90 deceased donor liver transplants. The patients were divided into three groups: the donation after brain death (DBD) group (n = 58, 64.4%), the DBD with ECMO group (n = 11, 12.2%) and the donation after cardiac death (DCD) with ECMO group (n = 21, 23.3%). Results: There were no significant differences between the DBD with ECMO group and the DBD group. When comparing the DCD with ECMO group and the DBD group, there were statistically significant differences for total warm ischemia time (p < 0.001), total cold ischemia time (p = 0.023), and split liver transplantation (p < 0.001), and there was significantly poor recovery in regard to total bilirubin level (p = 0.027) for the DCD with ECMO group by repeated measures ANOVA. The 5-year survival rates of the DBD, DBD with ECMO, and DCD with ECMO groups were 78.1%, 90.9%, and 75.6%, respectively. The survival rate was not significantly different when comparing the DBD group to either the DBD with ECMO group (p = 0.435) or the DCD with ECMO group (p = 0.310). Conclusions: Using ECMO in donations after cardiac death or brain death is a good technology, and it contributed to 35.6% of the liver graft pool.

Racial and ethnic disparities in untreated patients with hepatitis C virus-related hepatocellular carcinoma but not in those with sustained virologic response.

BACKGROUND: Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival. AIM: To evaluate the impact of HCV treatment on such disparities. METHODS: In a retrospective cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia. RESULTS: The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001). CONCLUSION: DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.

The role of Roux-en-Y hepaticojejunostomy for the management of biliary complications after living donor liver transplantation.

INTRODUCTION: Post living donor liver transplantation (LDLT) biliary complications can be troublesome over the post-operative course of patients, especially those with recurrent cholangitis or choledocholithiasis. Thus, in this study, we aimed to evaluate the risks and benefits of Roux-en-Y hepaticojejunostomy (RYHJ) performed after LDLT as a last option to deal with post-LDLT biliary complications. METHODS: Retrospectively, of the 594 adult LDLTs performed in a single medical center in Changhua, Taiwan from July 2005 to September 2021, 22 patients underwent post-LDLT RYHJ. Indications for RYHJ included choledocholithiasis formation with bile duct stricture, previous intervention failure, and other factors. Restenosis was defined if further intervention was needed to treat biliary complications after RYHJ was performed. Thereafter, patients were categorized into success group (n = 15) and restenosis group (n = 4). RESULTS: The overall success rate of RYHJ in the management of post-LDLT biliary complications was 78.9% (15/19). Mean follow-up time was 33.4 months. As per our findings, four patients experienced recurrence after RYHJ (21.2%), and mean recurrence time was 12.5 months. Three cases were recorded as hospital mortality (13.6%). Outcome and risk analysis presented no significant differences between the two groups. A higher risk of recurrence tended to be related to patients with ABO incompatible (ABOi). CONCLUSION: RYHJ served well as either a rescue but definite procedure for recurrent biliary complications or a safe and effective solution to biliary complications after LDLT. A higher risk of recurrence tended to be related to patients with ABOi; however, further research would be needed.

Deep vein thrombosis after open hepatectomy or other major upper abdominal surgery in Taiwan: A prospective and cross-sectional study relevant to the issue of pharmacological thromboprophylaxis.

BACKGROUD/PURPOSE: Venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important complication in patients who underwent open hepatic surgery as well as other major upper abdominal surgery. This study aims to investigate the occurrence of postoperative DVT without pharmacological thromboprophylaxis in such cohorts in Taiwan. METHODS: This is a prospective, cross-sectional cohort study conducted from March 2010 to December 2011. Patients who underwent major upper abdominal surgery, including open hepatectomy, were enrolled. Color duplex compression ultrasonography (CUS) was used to detect DVT. Symptomatic PE was excluded if there were no suggestive respiratory symptoms or sudden death. Relevant clinicopathological and surgical information of each patient was collected and analyzed. RESULTS: 195 patients (118 male and 77 female) were enrolled, with a median age of 63.6 years. The majority (169/195, 88.7%) were treated for active malignancy. Totally 147 patients received open hepatectomy. Only one asymptomatic and distal postoperative DVT event was identified by CUS, which occurred on a 73-year-old female patient who received a left lateral segmental hepatectomy for removing the advanced hepatocellular carcinoma (pathologic stage, T3aN0M0). No cases of symptomatic PE or sudden death were observed. No correlation between DVT and precipitating factor was demonstrated in our cohort. CONCLUSION: Without pharmacological thromboprophylaxis, a low rate of postoperative DVT among patients undergoing open hepatectomy (0.7%, 1/147) or major upper abdominal surgery (0.5%, 1/195) in Taiwan was reported. A distinctively regional role of pharmacological thromboprophylaxis for hepatic surgery was also suggested by our data.

Using 3D Microscope for Hepatic Artery Reconstruction in Living Donor Liver Transplant.

INTRODUCTION: This study compares the intraoperative process of hepatic artery anastomosis using conventional microscope and novel 3D digital microscope and discusses our technique and operative set-up. METHOD: A retrospective comparative cohort study with 46 hepatic artery reconstructions in living donor liver transplant patients. Either an operational microscope (control group) or a 3D digital microscope Mitaka Kestrel View II (study group) was used for hepatic artery anastomosis. We then discuss and share our institution's experience of improving surgical training. RESULTS: Both operation instruments provide effective and comparable results. There was no statistical difference regarding operational objective results between conventional microscope and exoscope. Both instruments have no hepatic artery size limit, and both resulted in complete vessel patency rate. CONCLUSIONS: There was no statistical differences regarding hepatic artery anastomosis between microscope and exoscope cohorts. Microsurgeons should perform hepatic artery anastomosis efficiently with the instruments they are most proficient with. Yet, exoscope provided better ergonomics in the operation room and lessened musculoskeletal strain, allowing surgeons to work in a more neutral and comfortable posture while allowing the first assistant to learn and assist more effectively. Using exoscope with micro-forceps and modified tie technique make artery reconstruction easier.

Length of Alcohol Abstinence Predicts Posttransplant Delirium in Living Donor Liver Transplant Recipients with Alcoholic Cirrhosis.

OBJECTIVES: History of alcohol abuse is a predictive factor for posttransplant delirium. We aimed to investigate whether preoperative abstinence was associated with posttransplant delirium in liver transplant recipients with alcohol-related cirrhosis. MATERIALS AND METHODS: From January 2014 to December 2019, 84 patients with alcohol-related cirrhosis who received living donor liver transplant were retrospectively reviewed and divided into a delirium group (n = 46, 54.8%) and a nondelirium group (n = 38, 45.2%) using the Richmond Agitation- Sedation Scale and the Confusion Assessment Method for the Intensive Care Unit. RESULTS: In the delirium group versus the nondelirium group, patients were more likely to have preoperative hepatic encephalopathy (58.7% vs 31.6%; P = .013), more likely to have higher Model for End-Stage Liver Disease scores (27.05 ± 10.56 vs 18.85 ± 7.96; P < .001), less likely to have preoperative alcohol abstinence (43.5% vs 68.4%%; P = .022), had longer duration of mechanical ventilation (7.57 ± 7.82 vs 2.50 ± 5.96 days; P = .001), and had longer stays in the intensive care unit (14.85 ± 15.01 vs 8.84 ± 7.84 days; P = .021) and in the hospital (37.89 ± 18.85 vs 27.15 ± 10.43 days; P = .002). Multivariate analysis revealed that preoperative alcohol abstinence (odds ratio 4.953; 95% CI, 1.519-16.152; P = .008) was a significant predictor and that more patients had abstinence durations <3 months (60.9% vs 34.2%; P = .048) in the delirium group. CONCLUSIONS: A high incidence of posttransplant delirium in liver transplant recipients with alcohol- related cirrhosis was associated with preoperative abstinence. Abstinence >6 months before living donor liver transplant is suggested to reduce the risk of posttransplant delirium.

Artery Reconstruction in Right Lobe Living Donor Liver Transplantation: Donor-Recipient Vessel Ratio Is Key to Choosing Recipient Artery.

BACKGROUND: The aims of this study were to investigate if recipient artery choice in right lobe living donor liver transplant affects postoperative complications and discuss solutions accordingly. METHODS: Three hundred fourteen right lobe living donor liver transplantation patients were divided into 2 groups: 163 patients using right hepatic artery as the recipient vessel and 151 patients using left hepatic artery as the recipient vessel. Cases involving 2 recipient blood vessels or the use of other blood vessels as recipient vessels were excluded. RESULTS: Overall vascular embolism rate in both groups was 1.3%, and our complication rate was lower than those in previous studies. There was no significant difference in complication rate between the groups, but a significant difference in recipient/donor artery size ratio was noted. CONCLUSIONS: Although left hepatic artery's anatomical position makes it less affected by bile duct anastomosis and thus fewer postoperative complications, we believe that the ratio of the donor-recipient blood vessel size and the length of the anastomosis vessel stumps are the key factors that affect the outcome of the vascular anastomosis.

Using the Cystic Duct for Biliary Reconstruction in Dual-Graft Living Donor Liver Transplantation: A Case Report.

In Taiwan, living donor liver transplant (LDLT) has accounted for the majority of liver transplantation due to organ shortage. Dual-graft LDLT is a feasible way to resolve the insufficient graft size and remnant liver in donors. We presented a heavy-weight patient underwent dual-graft LDLT, and cystic duct was used to resolve the inadequate bile duct length and limited appropriate position in dual-graft LDLT. We harvested a right lobe graft (segment 5, 6, 7, and 8 without middle hepatic vein) and a left lobe graft (segment 1, 2, 3, and 4 without middle hepatic vein) stepwise, and placed the grafts orthotopically. For proper tension and length of biliary reconstruction, we anastomosed the right intrahepatic duct of the right lobe graft to cystic duct of the recipient. Before the biliary reconstruction, the metal probe was inserted in the lumen of cystic duct in recipient to ensure the patency and destroy the Heister valve of cystic duct, then the internal biliary stent (5 Fr pediatric feeding tube) was placed in the donor's right intrahepatic duct to recipient's cystic duct and common bile duct, which allows the endoscopic removal of the internal stent. The patient has survived more than 16 months with normal liver function.

Secular Trends of Clinical Characteristics and Survival of Hepatocellular Carcinoma in Taiwan from 2011 to 2019.

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Taiwan, and in the past 30-40 years, Taiwan has been committed to its prevention and treatment. We aimed to investigate the secular trends of characteristics and the survival of HCC in recent decades after making increased efforts. Between 2011 and 2019, a total of 73,817 cases were enrolled from the TCR database. The overall male-to-female ratio was 7/3. The overall, male and female mean ages increased from 63.8 to 66.1 years, 62.0 to 64.3 years and 68.3 to 70.4 years, respectively. After dividing by viral etiologies and gender, the mean age showed increasing trends in all subgroups. The proportions of HBV-HCC, HCV-HCC, HBV+HCV-HCC and Non-HBV+non-HCV-HCC were 48.3%, 25.2%, 5.3% and 21.3% in males, compared with 25.5%, 48.6%, 5.3% and 20.5% in females, respectively. The 5-year survival rates of BCLC stages 0, A, B, C and D were 70%, 58%, 34%, 11% and 4%, respectively. The proportion of BCLC stage 0 increased from 6.2% to 11.3%. Multivariate analysis showed that being female, older age, diagnostic year, BCLC stages, hospital level, body mass index, smoking, alcohol consumption, AFP, Child-Pugh classification and HBV/HCV status were independent predictors for survival. In recent decades, the overall survival of HCC in Taiwan has been improving and might be partly associated with increased BCLC 0 and Child-Pugh A patients, while with the consequent age of patients increasing over time. The proportion of viral-related HCC is decreasing, while nonviral-related HCC is increasing.

Living donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria: outcome of expanded criteria in tumor size.

BACKGROUND: The Milan criteria are the universal standard of liver transplantation for hepatocellular carcinoma (HCC). Numerous expanded criteria have shown outcomes as good as the Milan criteria. In Taiwan, living donor liver transplant (LDLT) accounts for the majority of transplantations due to organ shortages. METHODS: We retrospectively enrolled 155 patients who underwent LDLT for HCC from July 2005 to June 2017 and were followed up for at least 2 years. Patients beyond the Milan criteria (n = 78) were grouped as recurrent or nonrecurrent, and we established new expanded criteria based on these data. RESULTS: Patients beyond the Milan criteria with recurrence (n = 31) had a significantly larger maximal tumor diameter (4.13 ± 1.96 cm versus 6.10 ± 3.41 cm, p = 0.006) and total tumor diameter (7.19 ± 4.13 cm versus 10.21 ± 5.01 cm, p = 0.005). Therefore, we established expanded criteria involving maximal tumor diameter ≤ 6 cm and total tumor diameter < 10 cm. The 5-year survival rate of patients who met these criteria (n = 134) was 77.3%, and the 5-year recurrence rate was 20.5%; both showed no significant differences from those of the Milan criteria. Under the expanded criteria, the pool of eligible recipients was 35% larger than that of the Milan criteria. CONCLUSION: Currently, patients with HCC who undergo LDLT can achieve good outcomes even when they are beyond the Milan criteria. Under the new expanded criteria, patients can achieve outcomes as good as those with the Milan criteria and more patients can benefit.

Association of Hematuria with Renal Progression and Survival in Patients Who Underwent Living Donor Liver Transplant.

BACKGROUND: This study aimed to determine the association between episodic or persistent hematuria after liver transplantation and long-term renal outcomes. METHODS: Patients who underwent living donor liver transplantation between July 2005 and June 2019 were recruited and divided into two groups based on the finding of microscopic or gross hematuria after transplantation. All patients were followed up from the index date until the end date in May 2020. The risks of chronic kidney disease, death, and 30% and 50% declines in estimated glomerular filtration rate (eGFR) were compared between groups. RESULTS: A total of 295 patients underwent urinalysis for various reasons after undergoing transplantation. Hematuria was detected in 100 patients (group A) but was not present in 195 patients (group B). Compared with group B, group A had a higher risk of renal progression, including eGFR decline >50% [aHR = 3.447 (95%CI: 2.24~5.30), p < 0.001] and worse survival. In addition, patients who took non-steroidal anti-inflammatory drugs (NSAIDs) continuously for over seven days within six months before transplant surgery had high risks of rapid renal progression, including a >30% decline in eGFR [aHR = 1.572 (95%CI: 1.12~2.21), p = 0.009)]. CONCLUSION: Development of hematuria after surgery in patients who underwent living donor liver transplant and were exposed to NSAIDs before surgery were associated with worse long-term renal dysfunction and survival.

Evaluation of Clinical Neuropathy After Living Donor Liver Transplant.

OBJECTIVES: Neurologic complications are more common in liver transplants than in other solid-organ transplants. One such neurologic complication, peripheral neuropathy, may cause functional limitations for recipients and have a negative effect on posttransplant quality of life. We aimed to examine the risk factors associated with the occurrence of clinical neuropathy after liver transplant and to investigate the frequency of sensory deficits. MATERIALS AND METHODS: In this case-control study, we analyzed factors from medical records of 63 recipients who underwent living donor liver transplant during the period from January 2010 to December 2016. A neuropathy symptom score was assigned to identify the patients who had clinical neuropathy (case group) and the patients without clinical neuropathy (control group). Quantitative sensory testing was performed to measure the warm and cold detection thresholds, and the difference between the 2 groups was examined. RESULTS: Compared with controls, patients with clinical neuropathy were older (61.0 vs 55.4 years; P = .028), had higher rates of diabetes (46.2% vs 16.0%; P = .03), and were taking antiviral agents against hepatitis B (100% vs 62%; P = .006). Patients with neuropathic symptoms had significantly increased frequencies of impairment of warm and cold detection thresholds. In addition, the greater severity of symptoms showed higher detection thresholds of warm (control, 40.7℃; mild-to-moderate, 43.8 ℃; severe, 46.0 ℃; P = .007) and cold (control, 28.8℃ ; mild-to-moderate, 27.0 ℃; severe, 21.8 ℃ ; P = .008). CONCLUSIONS: Our findings show that older age, diabetes, and treatment with oral antiviral agents against hepatitis B virus were more likely to be associated with the occurrence of clinical neuropathy after liver transplant. Early awareness and careful monitoring are warranted.

Postoperative incision scars and cosmetic satisfaction of living liver donors.

ABSTRACT: Cosmetic appearance is a major concern for living donors. However, little is known about the impact of a surgical scar on body image changes in living liver donors. The aim of this study was to identify potential factors that cause displeasing upper midline incision scar, and to evaluate the overall satisfaction regarding body image and scarring after living donor hepatectomy.Donors who underwent right lobe hepatectomy were recruited. Exclusion criteria included reoperation, refusal to participate, and lost follow-up. All donors were invited to complete the Vancouver Scar Scale (VSS) and the body image questionnaire. According to the VSS results of upper midline incision scar, donors were divided into 2 groups: good scarring group (VSS ≤4) and bad scarring group (VSS >4). we compared the clinical outcomes, including the demographics, preoperation, intraoperation, and postoperation variables. The study also analyzed the results of the body image questionnaire.The proportion of male donors was 48.9%. The bad scarring group consisted of 63% of the donors. On multivariate analysis, being a male donor was found to be an independent predictor of a cosmetically displeasing upper midline incision scar with statistical significance. The results of body image questionnaires, there were significant differences in cosmetic score and confidence score among the 2 groups.The upper midline incision and male donors have higher rates of scarring in comparison with the transverse incision and female donors. Donors who reported having a higher satisfaction with their scar appearance usually had more self-confidence. However, the body image won't be affected. Medical staff should encourage donors to take active participation in wound care and continuously observe the impact of surgical scars on psychological changes in living liver donors.

Association between surgical volumes and hospital mortality in patients: a living donor liver transplantation single center experience.

BACKGROUND: Many factors cause hospital mortality (HM) after liver transplantation (LT). METHODS: We performed a retrospective research in a single center from October 2005 to June 2019. The study included 463 living donor LT patients. They were divided into a no-HM group (n = 433, 93.52%) and an HM group (n = 30, 6.48%). We used logistic regression analysis to determine how clinical features and surgical volume affected HM. We regrouped patients based on periods of surgical volume and analyzed the clinical features. RESULTS: Multivariate analysis revealed that donor age (OR = 1.050, 95% CI 1.011-1.091, p = 0.012), blood loss (OR = 1.000, 95% CI 1.000-1.000, p = 0.004), and annual surgical volumes being < 30 LTs (OR = 2.540, 95% CI 1.011-6.381, p = 0.047) were significant risk factors. A comparison of years based on surgical volume found that when the annual surgical volumes were at least 30 the recipient age (p = 0.023), donor age (p = 0.026), and ABO-incompatible operations (p < 0.001) were significantly higher and blood loss (p < 0.001), operative time (p < 0.001), intensive care unit days (p < 0.001), length of stay (p = 0.011), rate of re-operation (p < 0.001), and HM (p = 0.030) were significantly lower compared to when the annual surgical volumes were less than 30. CONCLUSIONS: Donor age, blood loss and an annual surgical volume < 30 LTs were significant pre- and peri-operative risk factors. Hospital mortality and annual surgical volume were associated with statistically significant differences; surgical volume may impact quality of care and transplant outcomes.

Effects of Cirrhosis and Diagnosis Scenario in Metabolic-Associated Fatty Liver Disease-Related Hepatocellular Carcinoma.

Metabolic-associated fatty liver disease (MAFLD) is a major cause of liver-related complications, including hepatocellular carcinoma (HCC). While MAFLD-related HCC is known to occur in the absence of cirrhosis, our understanding of MAFLD-related HCC in this setting is limited. Here, we characterize MAFLD-related HCC and the impact of cirrhosis and screening on survival. This was a multicenter, retrospective, cohort study of MAFLD-related HCC. MAFLD was defined based on the presence of race-adjusted overweight, diabetes, or both hypertension and dyslipidemia in the absence of excess alcohol use or other underlying cause of liver disease. The primary outcome of interest was overall survival, and the primary dependent variables were cirrhosis status and prior HCC screening. We used Kaplan-Meier methods to estimate overall survival and Cox proportional hazards models and random forest machine learning to determine factors associated with prognosis. This study included 1,382 patients from 11 centers in the United States and East/Southeast Asia. Cirrhosis was present in 62% of patients, but under half of these patients had undergone imaging within 12 months of HCC diagnosis. Patients with cirrhosis were more likely to have early stage disease but less often received curative therapy. After adjustment, cirrhosis was not associated with prognosis, but the presence of cancer-related symptoms at diagnosis was associated with poorer prognosis. Conclusion: Cirrhosis was not associated with overall survival in this cohort of MAFLD-related HCC, while diagnosis in the presence of symptoms was associated with poorer prognosis. The HCC surveillance rate in patients with MAFLD-related HCC was disappointingly low in a multicenter cohort.

Using Glissonian sheath as an alternative way to prevent biliary stricture in living-donor liver transplantation.

BACKGROUND: /Objective: The aim of this study was to report a single-institution experience involving a Glissonian sheath-to-duct method for biliary reconstruction in living donor liver transplantation, focusing on the association between surgical techniques and biliary stricture rates. METHODS: Three hundred and twenty adult right lobar living donor liver transplantation procedures were analyzed through a comparison of 200 Glissonian sheath-to-duct (GD) reconstructions and 120 duct-to-duct (DD) reconstructions in biliary anastomosis. RESULTS: At a mean follow-up period of 60.8 months, the GD group had a significantly lower biliary stricture rate (13.5%, 27/200) than the DD group (26.7%, 32/120) (p = 0.003). In biliary anastomosis with single duct anastomosis, the incidence of biliary stricture was significantly greater for the DD group (17/79, 21.5%) than for the GD group (14/141, 9.9%) (p = 0.018). CONCLUSION: This study has shown that GD anastomosis of the bile duct produced outstanding results with respect to the reduction of biliary stricture. The GD technique can therefore be suggested as an alternative method for biliary reconstruction in LDLT.

Diagnostic value of spleen stiffness by magnetic resonance elastography for prediction of esophageal varices in cirrhotic patients.

PURPOSE: To evaluate the diagnostic value of spleen stiffness (SS) via magnetic resonance elastography (MRE) in predicting esophageal varices. METHODS: From January 2016 to September 2018, we retrospectively reviewed 263 patients with esophagogastroduodenoscopy (EGD) records and available spleen and liver stiffness (LS) values from MRE. Clinical information including the underlying diseases, endoscopic grade of esophageal varices (EV) and laboratory data were collected from electronic medical records. RESULTS: In cirrhotic patients, MRE-SS was higher in those with EV than in those without. MRE-SS also showed significant association with EV in the multivariate analysis, whereas MRE-LS did not. The diagnostic performance of MRE-SS for EV in cirrhotic patients was demonstrated by the area under curve of 0.853 (cut-off value: 9.53 kPa, P < 0.001), 84.4% sensitivity and 73.7% specificity. CONCLUSION: For prediction of EV in cirrhotic patients, MRE-SS is a useful non-invasive tool and it demonstrates better diagnostic performance than MRE-LS does.

Exosome-derived differentiation antagonizing non-protein coding RNA with risk of hepatitis C virus-related hepatocellular carcinoma recurrence.

BACKGROUND & AIMS: Differentiation antagonizing non-protein coding RNA is associated with various types of neoplasms. Hepatitis C virus-related hepatocellular carcinoma has a high risk of recurrence. Here we determined the role of differentiation antagonizing non-protein coding RNA in hepatitis C virus-related hepatocarcinogenesis and identified potential therapeutic targets and non-invasive prognostic markers for long-term outcome of hepatitis C virus-related hepatocellular carcinoma after surgical resection. METHODS: Differentiation antagonizing non-protein coding RNAs relevant to hepatitis C virus-related hepatocellular carcinoma were identified through comparative RNA-sequencing of tumour and adjacent non-tumour (ANT) tissues in a screening set, and were validated using real-time polymerase chain reaction. Target long non-coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus-related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012. RESULTS: We confirmed that differentiation antagonizing non-protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus-related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus-related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non-protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3-11.6 and 2.7/1.5-5.1 respectively). CONCLUSIONS: Differentiation antagonizing non-protein coding RNA is highly relevant to disease progression of hepatitis C virus-related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non-protein coding RNA might serve as a non-invasive prognostic biomarker for hepatitis C virus-related hepatocellular carcinoma.

Role of doublecortin-like kinase 1 and leucine-rich repeat-containing G-protein-coupled receptor 5 in patients with stage II/III colorectal cancer: Cancer progression and prognosis.

BACKGROUND: Cancer stem cells (CSCs) are a subpopulation of cancer cells with the potential of self-renewal and differentiation. CSCs play critical roles in tumorigenesis, recurrence, metastasis, radiation tolerance and chemoresistance. AIM: To assess the expression patterns and clinical potential of doublecortin-like kinase 1 (DCLK1) and leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), as prognostic CSC markers of colorectal cancer (CRC). METHODS: The expression of DCLK1 and Lgr5 in CRC tissue sections from 92 patients was determined by immunohistochemistry. Each case was evaluated using a combined scoring method based on signal intensity staining (scored 0-3) and the proportion of positively stained cancer cells (scored 0-3). The final staining score was calculated as the intensity score multiplied by the proportion score. Low expression of DCLK1 and Lgr5 was defined as a score of 0-3; high expression of DCLK1 and Lgr5 was defined as a score of ≥ 4. Specimens were categorized as either high or low expression, and the correlation between the expression of DCLK1 or Lgr5 and clinicopathological factors was investigated. RESULTS: DCLK1 and Lgr5 expression levels were significantly positively correlated. CRC patients with high DCLK1, Lgr5 and DCLK1/Lgr5 expressions had poorer progression-free survival and overall survival. Moreover, high expression of DCLK1 was an independent prognostic factor for recurrence and overall survival in patients with CRC by multivariate analysis (P = 0.026 and P = 0.049, respectively). CONCLUSION: DCLK1 may be a potential CSC marker for the recurrence and survival of CRC patients.