Incidence, Risk Factors, and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases.

OBJECTIVE: Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma (HCC). This study aimed to examine the age-related incidence, demographics, and survival of patients with HCC and brain metastases. METHODS: Data of HCC patients from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) Registry were screened for the presence of brain metastases. They were stratified by age and ethnicity. Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival (OS) and liver cancer-specific survival (CSS), respectively. RESULTS: A total of 141 HCC patients presenting with brain metastases were identified, accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease. Among all HCC patients, the incidence rate was the highest among patients aged 30-49 years old (0.47%). Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African-American patients presented with a significantly lower disease-specific survival [median time: 1 month; interquartile range (IQR): 0-3.0 months)]. Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases [odds ratio (OR): 12.62, 95% confidence interval (CI): 8.40-18.97] but was not associated with a worse OS or CSS among those with brain metastases. CONCLUSION: This study identified the age-related incidence and risk factors of brain metastases in HCC patients. These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases, and influence the counseling of this patient population regarding their prognosis.

Serum uric acid levels and risk of cardiovascular disease in type 2 diabetes: results from a cross-sectional study and Mendelian randomization analysis.

Aims: Serum uric acid (SUA) levels have been previously linked to a higher risk of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) according to various observational studies. However, whether this association is causally linked or simply influenced by confounding factors is unclear. Therefore, this study utilized Mendelian randomization (MR) analysis to explore the causality between SUA levels and the risk of CVD in individuals with T2D. Methods: Our study cohort consisted of 5723 participants who were diagnosed with T2D in the National Health and Nutrition Examination Survey (NHANES) from 1999-2018. The study assessed the association between SUA levels and the risk of CVD using a multivariable logistic regression model. To further examine causality between SUA levels and CVD, a two-sample MR study was conducted utilizing genetic data from genome-wide association studies (GWAS) involving over 140,000 individuals. The main MR analysis employed the inverse-variance-weighted (IVW) method. Additionally, several sensitivity analyses were performed to evaluate the robustness and pleiotropy of the results. Results: In the cross-sectional study, after multivariable adjustment, participants with SUA levels >6.7 mg/dL exhibited odds ratios (ORs) of 1.51 (95% CI: 1.01-2.26, p=0.049) for heart failure, 1.02 (95% CI: 0.69-1.50, p=0.937) for coronary heart disease, 1.36 (95% CI: 0.78-2.38, p=0.285) for angina, and 1.22 (95% CI: 0.80-1.85, p=0.355) for myocardial infarction when compared to participants with SUA levels ≤ 4.6 mg/dL. However, in the IVW analysis, no causality between SUA levels and the risk of heart failure was observed (OR = 1.03, 95% CI: 0.97-1.09, p = 0.293). The secondary analysis yielded similar results (OR = 1.05, 95% CI: 0.96-1.14, p = 0.299). The sensitivity analyses further supported our primary findings. Conclusion: Based on the MR study, we did not find supporting evidence for a causal association between SUA levels and the risk of heart failure.

Factors Influencing Overall Survival for Patients with Fibrolamellar Hepatocellular Carcinoma: Analysis of the Surveillance, Epidemiology, and End Results Database.

BACKGROUND: The study aimed to develop a nomogram to predict overall survival (OS) for patients with FLC using a national database. METHODS: The Surveillance, Epidemiology, and End Results database of the National Cancer Institute was reviewed to identify FLC cases with histological confirmation between 2004 and 2014. Cox proportional hazards models were used to identify factors associated with OS. The validation of the nomogram was performed using concordance index (C-index) and calibration curves. RESULTS: Out of 170 cases with complete follow-up, 87 received surgery/ablation and 12 received transplantation with significantly higher OS than chemotherapy alone while transplantation combined with chemotherapy showed better survival than solely transplantation. The combination of surgery and chemotherapy showed worse OS than surgery alone. Survival was negatively influenced by T4 stadium (HR = 5.91), while young age and surgery were positive predictive factors. There was no influence of gender, ethnicity or nodal status on survival. The rate of AFP positivity was comparable with and without the presence of distal metastases. CONCLUSION: FLC survival is greatly dependent upon appropriate surgical management irrespective of tumor stadium.

Pulmonary metastases in newly diagnosed hepatocellular carcinoma: a population-based retrospective study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major form of primary liver cancer with steadily increasing incidence for the decades, and has propensity to have extrahepatic metastases, especially pulmonary metastases (PM). This study aimed to investigate temporal incidence trends, treatment, and survival of patients with HCCPM. METHODS: Patients with HCCPM were retrospectively reviewed from 2010 to 2016 in US National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results registry (SEER). RESULTS: 2242 patients with HCCPM were identified. Overall HCCPM incidence did not change from 2010 to 2016, with an annual percent change (APC) of 0.87% (95% CI = -2.50%-4.35%, P = 0.542). Similar incidence trends patterns were found in subgroup analyses of sex, age, and race. 1-year observed survival for HCCPM was 10.8% (95%CI = 8.9%-12.8%) and relative survival was 11.0% (95%CI = 9.1%-13.1%). Better outcomes were noted among patients who underwent liver-directed surgery, those who treated with chemotherapy, and those who received radiation. CONCLUSIONS: The incidence of HCCPM does not increase with the increasing incidence of HCC. Patients with HCCPM have a dismal prognosis with low survival rates. Liver-directed surgery, use of chemotherapy, and radiation may be associated with improved outcomes.

Incidence trends and survival prediction of hepatoblastoma in children: a population-based study.

BACKGROUND: Hepatoblastoma is a rare disease that nevertheless accounts for the majority of liver malignancies in children. Due to limited epidemiological data, therapy for hepatoblastoma tends to be individualized. This study aimed to evaluate incidence trends of hepatoblastoma and to develop a nomogram to predict the survival of children with newly diagnosed hepatoblastoma on a population-based level. METHODS: Individuals up to 18 years of age with hepatoblastoma recorded in 18 registries of the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were examined. Joinpoint regression analyses were applied to assess incidence trends in annual percentage change (APC). Multivariable Cox regression was used to identify factors associated with overall survival (OS). A nomogram was constructed to predict OS in individual cases based on independent predictors. Concordance index (C-index) and calibration curves were used to evaluate predictive performance. RESULTS: Between 2004 and 2015, hepatoblastoma incidence increased significantly (APC, 2.2%; 95% confidence interval [CI] 0.5% to 3.8%, P < 0.05). In particular, this increase was observed among 2- to 4-year-old patients, males, and African-Americans. The 5- and 10-year OS rates were 81.5% and 81.0%, respectively. Age of 2 to 4 years, African-American ethnicity, and no surgery were independent predictors for short OS. Distant disease at presentation was found not to be an independent factor of survival. The nomogram had a C-index of 0.79 (95% CI 0.74-0.84) with appropriate calibration curve fitting. CONCLUSIONS: We constructed a nomogram that integrates common factors associated with survival for hepatoblastoma patients. It provides accurate prognostic prediction for children with hepatoblastoma.

Assessment of Survival of Pediatric Patients With Hepatoblastoma Who Received Chemotherapy Following Liver Transplant or Liver Resection.

Importance: The incidence of hepatoblastoma is increasing, and liver transplant (LT) provides a potential cure for pediatric patients with unresectable hepatoblastoma; however, the use of LT for hepatoblastoma has not been examined in a modern cohort. Moreover, data are lacking on the association between the type of surgical management received and overall risk of death among pediatric patients with hepatoblastoma. Objectives: To examine the receipt of LT among pediatric patients with hepatoblastoma and to assess overall survival of pediatric patients with hepatoblastoma who were treated with chemotherapy after LT or liver resection (LR) using data from a national cancer registry. Design, Setting, and Participants: This cohort study used data for 443 pediatric patients with histologically confirmed hepatoblastoma who received chemotherapy and surgical therapies, as documented in the Surveillance, Epidemiology, and End Results database of the National Cancer Institute, from 2004 to 2016, with follow-up through December 31, 2018. Multivariable logistic regression was used to determine factors associated with the use of LT. Cox proportional hazards models were used to assess factors associated with overall survival. Data analysis was performed from April 18, 2019, to July 25, 2019. Main Outcomes and Measures: Overall survival. Results: Among 443 patients receiving chemotherapy (mean [SD] age, 1.8 [2.6] years; 167 [37.7%] female), 350 (79%) underwent LR and 93 (21%) underwent LT. Multivariable analysis showed that patients with multiple lesions were more likely to undergo LT than LR (31% vs 13%; P < .001) and that patients with higher stage tumors were more likely to undergo LT than LR (local disease, 20% vs 58%; regional disease, 58% vs 24%; distant disease, 22% vs 18%; P < .001). There was a statistically significant 19% increase in the receipt of LT from 8% in 1998 to 27% 2016 (trend test, P = .02). Overall survival at 10 years was not significantly different for the 2 surgical management strategies (87.2% [95% CI, 78.3%-97.1%] for patients undergoing LT vs 87.8% [95% CI, 83.5%-92.4%] for those undergoing LR; P = .92). The overall risk of death was not significantly different for LT compared with LR (hazard ratio, 0.716; 95% CI, 0.309-1.657; P = .44). Conclusions and Relevance: The use of LT for the management of hepatoblastoma has increased significantly over time. Among pediatric patients with hepatoblastoma receiving chemotherapy, LT was not associated with improved overall survival compared with LR. There was no significant different between treatments with regard to the outcome variable, but this finding cannot be interpreted as indicating equivalence or lack of superiority.

Prewire channel stent: a novel stent for bifurcation lesions in a pig model.

AIMS: Avoiding side branch occlusion is challenging when treating bifurcation lesions. A newly designed stent system called the prewire channel stent (PWCS) with a side channel positioned between the metallic mesh material and the balloon is introduced. We aimed to compare the time taken to position the PWCS against that for a conventional stent. METHODS AND RESULTS: The PWCS and a conventional stent were used in a pig model. The time taken from the starting point with the stent outside the body to reaching the bifurcation of the vessel ready for further procedures such as balloon dilatation through the stent mesh opening and double kissing balloon technique, etc., was compared in the conventional stent and PWCS groups. The time taken in the PWCS stent group included the time from sending the stent from outside the body to the desired position of the bifurcation of the vessels of the heart, releasing the stent and pulling back the balloon (SB time). The time taken in the conventional stent included the time from sending the stent from outside the body to the desired position of the bifurcation of the vessels of the heart, releasing the stent, pulling back the balloon (SB time), and wire exchange (WE time). The SB times for the PWCS and the conventional stent groups were not different (28.5±3.8 vs. 25.25±0.75 seconds, n=4). The PWCS group did not have "wire exchange," and had no WE time, which was 28.5±5.7 seconds in the conventional stent group. The total time spent in the PWCS group was 28.5±3.8 seconds, which was shorter than the 53.75±6.2 seconds (n=4, p<0.05) in the conventional stent group. CONCLUSIONS: The PWCS makes "wire exchange" in the side branch (SB) unnecessary and it can be as easily manipulated as a conventional stent.

BATF inhibition prevent acute allograft rejection after cardiac transplantation.

Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection.