PurposeTo evaluate and compare outcome of stereotactic body radiation therapy (SBRT), yttrium-90 radioembolization, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) as bridge to liver transplant (LT) in patients with hepatocellular carcinoma.Methods and materialsWe retrospectively reviewed patients treated at our institution with SBRT, TACE, RFA, or yttrium-90 as bridge to LT between 2006 and 2013. We analyzed radiologic and pathologic response and rate of failure after bridge therapy. Toxicities were reported using Common Terminology Criteria for Adverse Events, 4.0. Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival after LT.ResultsSixty patients with a median age 57.5 years (range, 44-70) met inclusion criteria. Thirty-one patients (50.7%) had hepatitis C cirrhosis, 14 (23%) alcoholic cirrhosis, and 8 (13%) nonalcoholic steatohepatitis cirrhosis. Patients received a total of 79 bridge therapies: SBRT (n = 24), TACE (n = 37), RFA (n = 9), and Y90 (n = 9). Complete response (CR) was 25% for TACE, 8.6% for SBRT, 22% for RFA, and 33% for Y90. Grade 3 or 4 acute toxicity occurred following TACE (n = 4) and RFA (n = 2). Transplant occurred at a median of 7.4 months after bridge therapy. Pathological response among 57 patients was 100% necrosis (n = 23, 40%), >50% necrosis (n = 20, 35%), <50% necrosis (n = 9, 16%), and no necrosis (n = 5, 9%). Pathologic complete response was as follows: SBRT (28.5%), TACE (41%), RFA (60%), Y90 (75%), and multiple modalities (33%). At a median follow-up of 35 months, 7 patients had recurrence after LT. DFS was 85.8% and overall survival was 79% at 5 years.ConclusionAll bridge therapies demonstrated good pathological response and DFS after LT. SBRT and Y90 demonstrated significantly less grade ≥3 acute toxicity. Choice of optimal modality depends on tumor size, pretreatment bilirubin level, Child-Pugh status, and patient preference. Such a decision is best made at a multidisciplinary tumor board as is done at our institution.
Vascular invasion provides a direct route for tumor metastasis. The degree to which microRNA (miRNA) expression plays a role in tumor vascular invasion is unclear. Here, we report that miR-494 is up-regulated in human hepatocellular carcinoma (HCC) tumors with vascular invasion and can promote HCC cell invasiveness by gene inactivation of multiple invasion-suppressor miRNAs. Our results show that ten eleven translocation (TET) methylcytosine dioxygenase, predominantly TET1 in HCC cells, is a direct target of miR-494. The reduced 5′-hydroxymethylcytosine levels observed in the proximal cytosine-phosphate-guanine (CpG) regions of multiple invasion-suppressor miRNA genes are strongly associated with their transcriptional repression upon miR-494 overexpression, whereas enforced DNA demethylation can abolish the repression. Furthermore, TET1 knockdown shows a similar effect as miR-494 overexpression. Conversely, miR-494 inhibition or enforced TET1 expression is able to restore invasion-suppressor miRNAs and inhibit miR-494-mediated HCC cell invasion. Conclusions: miR-494 can trigger gene silencing of multiple invasion-suppressor miRNAs by inhibiting genomic DNA demethylation by direct targeting of TET1, thereby leading to tumor vascular invasion. (Hepatology 2015;62:466–480
This cohort study examines overall and recurrence-free survival outcomes in adult patients with liver-confined, unresectable colorectal cancer liver metastases who underwent a living-donor liver transplant.
Background. The opioid epidemic and the deaths of otherwise healthy individuals due to drug overdose in the United States has major implications for transplantation. The current extent and safety of utilization of liver and kidney grafts from donation after circulatory death (DCD) donors who died from opioid overdose is unknown. Methods. Using national data from 2006 to 2016, we estimated the cumulative incidence of graft failure for recipients of DCD grafts, comparing the risk among recipients of organs from donors who died of anoxic drug overdose and recipients of organs from donors who died of other causes. Results. One hundred seventy-nine (6.2%) of 2908 liver graft recipients and 944 (6.1%) of 15520 kidney graft recipients received grafts from donors who died of anoxic drug overdose. Grafts from anoxic drug overdose donors were less frequently used compared with other DCD grafts (liver, 25.9% versus 29.6%; 95% confidence interval [CI] for difference, −6.7% to −0.7%; kidney, 81.0% versus 84.7%; 95% CI for difference, −7.3% to −0.1%). However, the risk of graft failure at 5 years was similar for recipients of anoxic drug overdose donor grafts and recipients of other grafts (liver risk difference, 1.8%; 95% CI, −7.8% to 11.8%; kidney risk difference, −1.5%; 95% CI, −5.4% to 3.1%). Conclusions. In the context of the current opioid epidemic, utilization of anoxic drug overdose DCD donor grafts does not increase the risk of graft failure and may help to address waitlist demands.
The field of hepatology has evolved significantly over the last two decades. Hepatology practice in Saudi Arabia (SA) was dominated by hepatitis B and C viruses but is now being overtaken by patients with non-alcoholic fatty liver disease. These patients require greater medical attention as their care is more complex compared to patients with viral hepatitis. In addition, liver transplantation (LT) has expanded significantly in SA over the last three decades. There is a necessity to increase the hepatology workforce to meet the demand in SA. The time has come to reinforce the transplant hepatology fellowship program, that was launched recently, and to develop a nurse practitioner practice model to meet these demands. In addition, SA is going through a health care reform to enhance health care delivery which may affect the financial compensation polices of various specialties including gastroenterology and hepatology. Therefore, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) established a task force to discuss the current and future demands in the hepatology workforce in SA, as well as to discuss different avenues of financial compensation for transplant hepatologists in LT centers.
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