Current status of hepatocellular carcinoma detection: screening strategies and novel biomarkers

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide. Delayed diagnosis is a major factor responsible for the poor prognosis of HCC. Several advances have been made in the field of liver imaging with the use of novel imaging contrasts, improving current imaging techniques with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), introduction of new technologies such as contrast liver ultrasound, and development of novel biomarkers with the goal of early detection of HCC and improving outcomes of patients with HCC. This review focuses on current surveillance strategies and development of biomarkers with the goal of early detection of HCC

Regulatory network and interplay of hepatokines, stellakines, myokines and adipokines in nonalcoholic fatty liver diseases and nonalcoholic steatohepatitis

Fatty liver disease is a spectrum of liver pathologies ranging from simple hepatic steatosis to non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and culminating with the development of cirrhosis or hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is complex and diverse, and there is a lack of effective treatment measures. In this review, we address hepatokines identified in the pathogenesis of NAFLD and NASH, including the signaling of FXR/RXR, PPARα/RXRα, adipogenesis, hepatic stellate cell activation/liver fibrosis, AMPK/NF-κB, and type 2 diabetes. We also highlight the interaction between hepatokines, and cytokines or peptides secreted from muscle (myokines), adipose tissue (adipokines), and hepatic stellate cells (stellakines) in response to certain nutritional and physical activity. Cytokines exert autocrine, paracrine, or endocrine effects on the pathogenesis of NAFLD and NASH. Characterizing signaling pathways and crosstalk amongst muscle, adipose tissue, hepatic stellate cells and other liver cells will enhance our understanding of interorgan communication and potentially serve to accelerate the development of treatments for NAFLD and NASH

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Laparoscopic Living-Donor Nephrectomy of a Horseshoe Kidney: A Case Report and Review of the Literature

We present the case of a living-donor nephrectomy of a horseshoe kidney. The recipient was a 33-year-old male with a history of end-stage renal disease secondary to IgA nephropathy. The donor was his 33-year-old partner who on preoperative cross-sectional imaging was found to have a horseshoe kidney with a single artery, vein and ureter. The donor operation was performed using a laparoscopic hand-assisted technique with transection of the interpolar fibrotic band using a stapler device. The backtable organ preparation was performed in a standard fashion with addition of a reinforcing hemostatic suture of the stapled fibrotic band. The donated kidney was transplanted extraperitoneally in the right iliac fossa of the recipient. The patient had an unremarkable postoperative course and was discharged home on post operative day 2 with normalizing renal function. To our knowledge, this is the first living donor nephrectomy of a horseshoe kidney performed using a laparoscopic hand-assisted technique

Laparoscopic Living-Donor Nephrectomy of a Horseshoe Kidney: A Case Report and Review of the Literature

We present the case of a living-donor nephrectomy of a horseshoe kidney. The recipient was a 33-year-old male with a history of end-stage renal disease secondary to IgA nephropathy. The donor was his 33-year-old partner who on preoperative cross-sectional imaging was found to have a horseshoe kidney with a single artery, vein and ureter. The donor operation was performed using a laparoscopic hand-assisted technique with transection of the interpolar fibrotic band using a stapler device. The backtable organ preparation was performed in a standard fashion with addition of a reinforcing hemostatic suture of the stapled fibrotic band. The donated kidney was transplanted extraperitoneally in the right iliac fossa of the recipient. The patient had an unremarkable postoperative course and was discharged home on post operative day 2 with normalizing renal function. To our knowledge, this is the first living donor nephrectomy of a horseshoe kidney performed using a laparoscopic hand-assisted technique

Preserved 2-y Liver Transplant Outcomes Following Simultaneous Thoracoabdominal DCD Organ Procurement Despite Effects on Liver Utilization Rate.

BACKGROUND: Current techniques for donation after circulatory determination of death (DCD) heart procurement, through either direct procurement and machine perfusion or thoracoabdominal normothermic regional perfusion (NRP), have demonstrated excellent heart transplant outcomes. However, the impact of thoracoabdominal DCD (TA-DCD) heart procurement on liver allograft outcomes and utilization is poorly understood. METHODS: One hundred sixty simultaneous heart and liver DCD donors were identified using the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between December 2019 and July 2021. Liver outcomes from TA-DCD donors were stratified by heart procurement technique and evaluated for organ utilization, graft survival, and patient survival. Results were compared with abdominal-only DCD (A-DCD; n = 1332) and donation after brain death (DBD; n = 12 891) liver transplants during the study interval. Kaplan-Meier methods with log-rank testing were used to evaluate patient and graft survival. RESULTS: One hundred thirty-three of 160 livers procured from TA-DCD donors proceeded to transplant. TA-DCD donors were younger (mean 28.26 y; P &lt; 0.0001) with lower body mass index (mean 26.61; P &lt; 0.0001) than A-DCD and DBD donors. TA-DCD livers had equivalent patient survival ( P = 0.893) and superior graft survival (P = 0.009) compared with A-DCD. TA-DCD livers had higher rates of organ discard for long warm ischemia time (37.0%) than A-DCD (20.5%) and DBD (0.5%; P &lt; 0.0001), with direct procurement and machine perfusion procurements leading to a higher discard rate (18.5%) than NRP procurements (7.4%). CONCLUSIONS: Liver transplants after TA-DCD donation demonstrated equivalent patient outcomes and excellent graft outcomes. NRP procurements resulted in the lowest rate of organ discard after DCD donation and may represent an optimal strategy to maximize organ utilization

Higher thresholds for the utilization of steatotic allografts in liver transplantation: Analysis from a U.S. national database.

BackgroundHistorically, liver allografts with >30% macrosteatosis (MaS) on donor biopsy have been associated with early allograft dysfunction and worse graft survival; however, successful outcomes have been reported in small cohorts. This study proposes an elevated MaS threshold for organ utilization without detriment to graft survival.MethodsThe UNOS Standard Transplant Analysis and Research database was evaluated for transplants between 2006-2015. Graft survival up to 1-year was evaluated by Kaplan-Meier (KM) survival analyses, and by univariate and multivariable logistic regression analyses, including donor and recipient characteristics. Odds ratios (OR) with 95% confidence intervals (CI) for risk of graft loss are reported.ResultsThirty-day risk of graft loss was increased with MaS as low as 10-19% (OR [95% CI] 1.301 [1.055-1.605], pConclusionsIn conjunction with recipient selection, organs with MaS up to 50% may be safely used without detriment to outcomes