Inequitable access to nonpharmacologic pain treatment providers among cancer-free U.S. adults.

OBJECTIVE: Using evidence-based nonpharmacologic pain treatments may prevent opioid overuse and associated adverse outcomes. There is limited data on the impact of access-promoting social determinants of health (SDoH: education, income, transportation) on use of nonpharmacologic pain treatments. Our objective was to examine the relationship between SDoH and use of nonpharmacologic pain treatment providers. Our goal was to understand policy-actionable factors contributing to inequity in pain treatment. METHODS: Based on Andersen's Health Utilization Model, this cross-sectional analysis of 2016-2019 Medical Expenditure Panel Survey data evaluated whether use of outpatient nonpharmacologic pain treatment providers is driven by enabling (i.e., advantageous socioeconomic resources) or need (i.e., perceived disability and diagnosed disease) factors. The study sample (unweighted n = 28,188) represented a weighted N = 81,912,730 noninstitutionalized, cancer-free, U.S. adults with pain interference. The primary outcome measured use of nonpharmacologic providers relative to exclusive prescription opioid use or no treatment (i.e., neither opioids nor nonpharmacologic). To quantify equitable access, we compared the variance-between access-promoting enabling factors versus medical need factors-that explained utilization. RESULTS: Compared to enabling factors, need factors explained twice the variance predicting pain treatment utilization. Still, the adjusted odds of using nonpharmacologic providers instead of opioids alone were 39% lower among respondents identifying as Black (95% Confidence Interval [CI], 0.49-0.76) and respondents residing in the U.S. South (95% CI, 0.51-0.74). Higher education (95% CI, 1.72-2.79) and income (95% CI, 1.68-2.42) both facilitated using nonpharmacologic providers instead of opioids. CONCLUSIONS: These findings highlight the substantial influence access-promoting SDoH have on pain treatment utilization.

Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy.

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume.

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

Cross-sectional study of food insecurity and medical expenditures by race and ethnicity.

OBJECTIVE: Food insecurity is a risk factor for morbidity and mortality leading to high medical expenditures, but race/ethnicity was used as adjustments in the literature. The study sought to use race/ethnicity as a key predictor to compare racial differences in associations between food insecurity and expenditures of seven health services among non-institutionalized adults. DESIGN: This cross-sectional study used Medical Expenditure Panel Survey that collects information on food insecurity in 2016 (n=24,179) and 2017 (n=22,539). We examined the association between race/ethnicity and food insecurity status and documented the extent to which impacts of food insecurity on medical expenditures varied by race/ethnicity. We fit multivariable models for each racial group, adjusting for states, age, gender, insurance, and education. Adults older than 18 years were included. RESULTS: The results show that blacks experienced an inter-racial disparity in food insecurity whereas Hispanics experienced intra-racial disparity. A higher percentage of blacks (28.7%) reported at least one type of food insecurity (11.2% of whites). Around 20% of blacks reported being worried about running out of food and the corresponding number is 8.4% among whites. Hispanics reported more food insecurity issues than whites. Moreover, food insecurity is positively associated with expenditures on emergency room utilization (99% increase for other races vs. 51% increase for whites) but is negatively associated with dental care utilization (43% decrease for blacks and 44% for whites). Except for Hispanics, prescription expenditure has the most positive association with food insecurity, and food insecure blacks are the only group that did not significantly use home health. CONCLUSION: The study expanded our understanding of food insecurity by investigating how it affected seven types of medical expenditures for each of four racial populations. An interdisciplinary effort is needed to enhance the food supply for minorities. Policy interventions to address intra-racial disparities among Hispanics and inter-racial disparities among African Americans are imperative to close the gap.

Anxiety, pain intensity, and decision regret of living liver donors during postoperative period.

AIM: The aim of this study was to explore and examine the relationship between anxiety, acute pain intensity, and decision regret of living liver donors in the postoperative stage. METHODS: This is a prospective correlational study. Data were collected consecutively for one year (from September 2017 to September 2018) at a medical center in northern Taiwan. Information about anxiety and acute pain intensity was collected preoperatively and on postoperative day (POD) 3 and POD 7. Satisfaction with pain management and decision regret was inquired about on POD 7. RESULTS: Data of 57 consecutive living liver donors (56.1 % male, mean age 34.12 ± 9.92 years) were analyzed. Living liver donors experienced moderate anxiety and acute pain levels in the postoperative period. The mean score of decision regret was 12.63 (range 0-60), indicating a low level of regret. The acute pain intensity decreased significantly between POD 3 and POD 7 (p < .001); however, the anxiety level slightly increased (p = .031). Older and married living liver donors had higher anxiety levels. The satisfaction level of pain management was negatively correlated with the POD 7 acute pain intensity (r = -0.26, p = .049) and decision regret (r = -0.37, p = .005), but it was positively correlated with POD 7 anxiety (r = 0.38, p = .004). CONCLUSIONS: The postoperative period was hard for living liver donors as they would experience moderate acute pain and anxiety. Although the decision regret was low, the satisfaction level of pain management would negatively affect it. Therefore, the effectiveness of pain management and anxiety management should be continually ensured in the postoperative period.

The American Public Health Association Endorses Single-Payer Health System Reform.

Health care is a human right. Achieving universal health insurance coverage for all US residents requires significant system-wide reform. The most equitable and cost-effective health care system is a public, single-payer (SP) system. The rapid growth in national health expenditures can be addressed through a system that yields net savings over projected trends by eliminating profit and waste. With universal health insurance coverage through SP financing, providers can focus on optimizing delivery of services, rather than working within a system covered by payers who have incentives to limit costs regardless of benefit. Rather, with a SP, the people act as their own insurer through a partnership with provider organizations where tax dollars work for everyone. Consumer choice is then based on the best care to meet need with no out-of-pocket payments. SP financing is the best option to ensure equity, fairness, and public health priorities align with medical needs, providing incentives for wellness. Consumer choice will drive market forces, not provider network profits or insurer restrictions. This approach benefits public health, as everyone will have universal access to needed care, with treatment plans developed by providers based on what works best for the patient. In 2021, the American Public Health Association adopted a policy statement calling for comprehensive reforms to implement a SP system. The proposed action steps in this policy will help build a healthier nation, saving lives and reducing wasted health care expenditures while addressing inequities rooted in social, demographic, mental health, economic, and political determinants.

Quick preparation of ABO-incompatible living donor liver transplantation for acute liver failure.

Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5 mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375 mg/m2 ) on post-operative day 1 to deplete B-cells. Eight patients received this quick preparation regimen to undergo ABO-I LDLT for acute liver failure from 2012 to 2019. They aged between 50 and 60 years. The median MELD score was 39 with a range from 35 to 48. It took 4.75 ± 1.58 days to prepare such an urgent ABO-I LDLT. All the patients had successful liver transplantations, but one patient died of antibody-mediated rejection at post-operative month 6. The 3-month, 6-month, and 1-year graft/patient survival were 100%, 87.5%, and 75%, respectively. In conclusion, this quick preparation regimen can reduce isoagglutinin titers quickly and make timely ABO-I LDLT feasible for acute liver failure.

The impact of symptom distress on health-related quality of life in liver cancer patients receiving arterial chemoembolization: the mediating role of hope.

BACKGROUND: Trans-hepatic arterial chemoembolization (TACE) is a treatment option for liver cancer patients. It can prolong patients' survival but can also cause symptom distress. Symptom distress (SDs) can directly impact quality of life (QOL) and may indirectly influence QOL by lessening hope. In this study, we wanted to explore the mediating effect of hope on the relationship between SDs and QOL among patients with liver cancer receiving TACE. METHODS: A cross-sectional study was conducted from December 20, 2017, to August 6, 2018, at a gastroenterology ward of a medical center. The participants were 92 liver cancer patients (69.6% male, mean age 67.8) who were admitted for TACE treatment. Information on SDs, hope, and QOL was collected by questionnaire on discharge day. Hayes' PROCESS model was used to test the mediating effect of hope on the relationship between SDs and QOL. RESULTS: The mean score and standard deviation (SD) of SDs, hope, and QOL were 32.08 (SD = 6.22), 27.09 (SD = 3.51), and 55.16 (SD = 17.33), respectively. SDs negatively impacts quality of life. The total effect of SDs on QOL was - 1.41 (95% confidence interval [CI]: - 1.96, - 0.86). The indirect effect via the mediation of hope was - 0.95 (95% CI: - 1.7, - 0.45). Hope partially mediated the effect of SDs on QOL. CONCLUSION: SDs after TACE is vital; it directly reduces a patient's overall QOL and can indirectly hinder it by reducing the patient's hope. In addition to symptom management, interventions that help patients maintain their hope are key to improving QOL among patients receiving TACE.

Laparoscopic liver resection is associated with less significant muscle loss than the conventional open approach.

BACKGROUND: Laparoscopic liver resections (LLR) have been shown a treatment approach comparable to open liver resections (OLR) in hepatocellular carcinoma (HCC). However, the influence of procedural type on body composition has not been investigated. The aim of the current study was to compare the degree of skeletal muscle loss between LLR and OLR for HCC. METHODS: By using propensity score matching (PSM) analysis, 64 pairs of patients were enrolled. The change of psoas muscle index (PMI) after the operation was compared between the matched patients in the LLR and OLR. Risk factors for significant muscle loss (defined as change in PMI > mean change minus one standard deviation) were further investigated by multivariate analysis. RESULTS: Among patients enrolled, there was no significant difference in baseline characteristics between the two groups. The PMI was significantly decreased in the OLR group (P = 0.003). There were also more patients in the OLR group who developed significant muscle loss after the operations (P = 0.008). Multivariate analysis revealed OLR (P = 0.023), type 2 diabetes mellitus, indocyanine green retention rate at 15 min (ICG-15) > 10%, and cancer stage ≧ 3 were independent risk factors for significant muscle loss. In addition, significant muscle loss was associated with early HCC recurrence (P = 0.006). Metabolomic analysis demonstrated that the urea cycle may be decreased in patients with significant muscle loss. CONCLUSION: LLR for HCC was associated with less significant muscle loss than OLR. Since significant muscle loss was a predictive factor for early tumor recurrence and associated with impaired liver metabolism, LLR may subsequently result in a more favorable outcome.

A comprehensive investigation of nutritional status and psoas muscle mass in predicting five-year survival in patients with liver transplant.

BACKGROUND/PURPOSE: Although nutrition and sarcopenia have impacts on the surgery outcome of patients who have received living donor liver transplant (LDLT), the use of the prognostic nutritional index (PNI) or psoas muscle mass index (PMI) as an indicator for five-year survival in those patients is still unclear. METHODS: A total of 138 patients receiving LDLT were followed at a medical center in Taiwan. As well as analysis of clinical factors using Cox regression, time-varying PNI and PMI values as before surgery (0) and at 3-, 6-, and 12- months after LDLT were analyzed by time-dependent Cox analysis. For those 124 patients who survived after 3 months of LDLT, the values of PNI-3m, PMI-3m and their combination were further analyzed. RESULTS: PNI and PMI were noted to be highly associated with mortality at three months post-LDLT (PNI-3m hazard ratio [HR] = 0.89, 95% confidence interval [CI]: 0.85-0.94, p < 0.001; PMI-3m HR = 0.58, 95% CI: 0.41-0.82, p = 0.002). Per the Youden index, the cut-off point of PNI-3m was 42.35, and that of PMI-3m was 1.94. Compared to the subjects with higher levels of PNI-3m and PMI-3m (N-high/M-high), the HRs for subjects with N-high/M-low, N-low/M-high, and N-low/M-low were 5.27 (p = 0.004), 4.46 (p = 0.010) and 12.97 (p < 0.001) respectively. CONCLUSION: PNI and PMI at the third month post-LDLT serve as excellent predictors for 5-year survival. For patients with lower levels of PNI-3m or PMI-3m, combination use of these indexes is suggested to provide better prognostic information.

Understanding family dynamics in adult-to-adult living donor liver transplantation decision-making in Taiwan: Motivation, communication, and ambivalence.

This study investigated how multiple family members co-construct the ethical significance of living donor liver transplantation (LDLT) and how the family structure and dynamics of donor-recipient-caregiver relationships shape the communication and decision-making process within the sociocultural context of Taiwan. We conducted in-depth interviews with 36 participants from 13 families at the Chang Gung Memorial Hospital from February to December 2019. Interviews were audio recorded, transcribed, and translated from Mandarin to English and analyzed utilizing grounded theory and thematic analysis. Our findings revealed that LDLT in Taiwan is not merely a personal choice of either donor or recipient but essentially a collaborative process of family-centered medical decision-making, intertwined with socioeconomic conditions, cultural and social norms, gender roles, and the division of labor in the household. The notion of reciprocity and indebtedness for family members is a central theme underlying the entire process of motivation, deliberation, and decision-making, thereby reinforcing the naturalness of LDLT. However, our study highlighted that donors from families with traditional gender hierarchy and power imbalance may experience psychological and social vulnerabilities. Conclusively, we suggest that healthcare professionals should be sensitive to the contextual and relational factors involved in family dynamics and provide appropriate support to the ambivalent donors.

Improving outcomes of liver resection for hepatocellular carcinoma associated with portal vein tumor thrombosis over the evolving eras of treatment.

BACKGROUND: The outcomes and management of hepatocellular carcinoma (HCC) have undergone several evolutionary changes. This study aimed to analyze the outcomes of patients who had undergone liver resection for HCC with portal vein tumor thrombosis (PVTT) in terms of the evolving era of treatment. MATERIALS AND METHODS: A retrospective analysis of 157 patients who had undergone liver resection for HCC associated with PVTT was performed. The outcomes and prognostic factors related to different eras were further examined. RESULTS: Overall, 129 (82.1%) patients encountered HCC recurrence after liver resection, and the median time of recurrence was 4.1 months. Maximum tumor size ≥ 5 cm and PVTT in the main portal trunk were identified as the major prognostic factors influencing HCC recurrence after liver resection. Although the recurrence-free survival had no statistical difference between the two eras, the overall survival of patients in the second era was significantly better than that of the patients in the first era (p = 0.004). The 1-, 2-, and 3-year overall survival rates of patients in the second era were 60.0%, 45.7%, and 35.8%, respectively, with a median survival time of 19.6 months. CONCLUSION: The outcomes of HCC associated with PVTT remain unsatisfactory because of a high incidence of tumor recurrence even after curative resection. Although the management and outcomes of patients with HCC and PVTT have greatly improved over the years, surgical resection remains an option to achieve a potential cure of HCC in well-selected patients.

Models to predict disease-free survival for hepatocellular carcinoma patients with surgical resections.

BACKGROUND AND OBJECTIVES: Precise prognostic prediction for an individual hepatocellular carcinoma (HCC) patient before and after liver resection is important. We aimed to establish simple prognostic models to predict disease-free survival (DFS) for these patients. METHODS: Six hundred and ninety-eight HCC patients with liver resections were reviewed. Preoperative (model 1) and postoperative (model 2) nomogram-based scoring systems were constructed by multivariate analyses, and DFS was estimated. RESULTS: Among 698 patients, 490 (70.2%) patients had tumor recurrence at a median follow-up of 84.4 months. Risk factors of tumor recurrence in model 1 included viral hepatitis, platelet count, albumin, indocyanine green retention rate, multiplicity of tumor, and radiologic total tumor volume (TTV). Prognostic variables identified in model 2 were viral hepatitis, platelet count, multiplicity of tumor, cirrhosis, microvascular invasion, and pathologic TTV. By nomogram in model 1, the patients were classified into three groups with 5-year DFS of 61.0%, 35.7%, and 21.1%, respectively (P < .0001). In model 2, the patients were divided into five groups with 5-year DFS of 58.0%, 43.7%, 24.0%, 15.4%, and 0.0%, respectively (P < .0001). CONCLUSION: Based on nomogram models, DFS for the patients who had liver resection for HCC can be predicted before liver resection and re-assessed after liver resection.

Acute exacerbation of hepatitis B with hepatic failure during the first trimester of pregnancy: Delivery of a healthy term baby after liver transplantation.

The severe form of acute exacerbation of hepatitis B during pregnancy is a rare but life-threatening condition for both the mother and the fetus. A 32-year-old pregnant woman at 10 weeks of gestation was diagnosed with acute decompensated liver failure due to acute exacerbation of hepatitis B. The Model for End-stage Liver Disease score was up to 37. The patient was managed carefully with antiviral treatment, fluid resuscitation, correction of coagulopathy, close monitoring of hepatic function, and regular assessment of the fetus. She was transplanted with a deceased liver at 14 weeks and 1 day of gestation. With careful post-transplant care and avoidance of medication with risk of miscarriage and teratogenicity, a healthy baby was delivered at 39 weeks and 1 day of gestation. Herein, we report this critical condition of pregnancy that was complicated with liver failure due to acute exacerbation of hepatitis B, but had favorable outcomes for both the mother and the baby after liver transplantation.

Crystal structure of the C-terminal domain of the primosomal DnaT protein: Insights into a new oligomerization mechanism.

DnaT is a replication restart primosomal protein required for re-initiating chromosomal DNA replication in bacteria. DnaT can be a monomer, dimer, trimer, tetramer, or pentamer. The oligomerization and disassembly of DnaT oligomers are critical in primosome assembly. Prior to this work, only the ssDNA-bound structure of the pentameric DnaT truncated protein (aa 84-153; DnaT84-153) was available. The mechanism by which DnaT oligomerizes as different states is unclear. In this paper, we report the crystal structure of the C-terminal domain of DnaT (aa 84-179; DnaTc) at 2.30 Šresolution (PDB entry 6AEQ). DnaTc forms a dimer both in the crystalline state and in solution. As compared with the ssDNA-bound structure of the pentameric DnaT84-153, their subunit-subunit interfaces significantly differ. The different oligomeric architecture suggests a strong conformational change possibly induced by ssDNA. Superposition analysis further indicated that the monomer of a DnaTc dimer shifted away by a distance of 7.5 Šand rotated by an angle of 170° for binding to ssDNA. Basing from these molecular evidence, we discussed and proposed a working model to explain how DnaTc oligomerizes through residue R146 mediation.

Low-dose anti-hepatitis B immunoglobulin regimen as prophylaxis for hepatitis B recurrence after liver transplantation.

BACKGROUND: Combination of anti-hepatitis B immunoglobulin (HBIg) and antiviral nucleotide/nucleoside is the most common regimen for prophylaxis against hepatitis B virus (HBV) recurrence. However, what the optimal regimen is for HBIg administration remains subject to debate. METHODS: Two hundred and thirty-two HBV patients who had liver transplantation were included in this study. According to the decline rate of HBIg, the patients were divided into quick (group Q, n = 95) and slow decline groups (group S, n = 137). Quick HBIg decline was defined as anti-HBs titer <200 IU/mL at postoperative month (POM) 1, when 24 000 IU of HBIg was given perioperatively. HBV recurrence was defined as reappearance of hepatitis B surface antigen (HBsAg). RESULTS: After a mean (range) follow-up of 42.2 (24.1-76.8) months, the HBV recurrence rate was 12.1% for all 232 patients. The median (interquartile) HBIg titer was 96.2 (41.0-158.0) IU in group Q patients, compared to 418.0 (298.8-692.8) IU in group S patients at POM 1 (P < .001). For the patients in group Q, 18 patients (18.9%) had HBV recurrence; this was higher than the 10 (7.3%) patients in group S (P = .013). Multivariate analysis showed that quick HBIg decline and hepatocellular carcinoma recurrence were the risk factors for HBV recurrence. CONCLUSION: Perioperative low-dose HBIg and antiviral nucleotide/nucleoside can effectively prevent HBV recurrence in patients with slow HBIg decline. For patients with quick HBIg decline, the idealized HBIg and antiviral agent regimen should be adjusted to establish an effective regimen as prophylaxis against HBV recurrence.

Predicting hepatocellular carcinoma recurrences: A data-driven multiclass classification method incorporating latent variables.

Hepatocellular carcinoma (HCC), a malignant form of cancer, is frequently treated with surgical resections, which have relatively high recurrence rates. Effective recurrence predictions enable physicians' timely detections and adequate therapeutic measures that can greatly improve patient care and outcomes. Toward that end, predictions of early versus late HCC recurrences should be considered separately to reflect their distinct onset time horizons, clinical causes, underlying clinical etiology, and pathogenesis. We propose a novel Bayesian network-based method to predict different HCC recurrence outcomes by considering the respective recurrence evolution paths. Typical patient information obtained in early stages is insufficiently informative to predict recurrence outcomes accurately, due to the lack of subsequent patient progression information. Our method alleviates such information deficiency constraints by incorporating an independent latent variable, dominant recurrence type, to regulate recurrence outcome predictions (early, late, or no recurrence). We use a real-world HCC data set to evaluate the proposed method, relative to three prevalent benchmark techniques. Overall, the results show that our method consistently and significantly outperforms all the benchmark techniques in terms of accuracy, precision, recall, and F-measures. For increased robustness, we use another data set to perform an out-of-sample evaluation and obtain similar results. This study thus contributes to HCC recurrence research and offers several implications for clinical practice.

Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study.

In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P < .001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P < .001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 vs. -12.1 mL/min/1.73 m2 , P = .108), and in patients continuing randomized treatment (-8.0 vs. -13.3 mL/min/1.73 m2 , P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432.

Targeting HSP60 by subcutaneous injections of jetPEI/HSP60-shRNA destabilizes cytoplasmic survivin and inhibits hepatocellular carcinoma growth.

Heat shock protein 60 (HSP60) overexpresses in various types of cancer, but its expression levels and functions in hepatocellular carcinoma (HCC) are still in dispute. We aim to clarify this issue and examine whether HSP60 could be a therapeutic target for HCC. We found drastically enhanced cell apoptosis and suppressed cell proliferation in two HCC cell lines with HSP60-silencing, and also indicated survivin was involved in this regulatory process in vitro and in vivo. However, HSP60-silencing in normal human hepatocytes only resulted in a minimal reduction of cell proliferation but without effects on cell apoptosis. We also showed HSP60 interacted with cytosolic but not mitochondrial survivin by immunoprecipitation assay. A rigorous method was used to standardize quantification from immunoblot assay to obtain more precise expression levels of HSP60 and survivin. The expression of HSP60 and survivin positively correlated in both cancerous and non-cancerous liver tissues (P < 0.001) after analyzing 145 surgically removed HCC tissues. A total of 56.6% of HCC patients overexpressed HSP60 in cancerous tissues, and 40.0% under-expressed HSP60. Higher expression of HSP60 and survivin in non-cancerous tissues both correlated with shorter overall survival (P = 0.029 and P < 0.001, respectively). Finally, we evaluated the therapeutic potential of HSP60 using extraneous delivery of jetPEI/shHSP60 complexes. The treatment results showed significant reduction of tumor weight by 44.3% (P < 0.05), accompanied by under-expression of survivin. These studies suggested that HSP60 not only served as a prognostic marker but also served as a novel therapeutic target for HCC.

Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of patients who had received curative-intent liver resection. METHODS: A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed. RESULTS: Overall, the rates of 5-years recurrence-free survival (RFS) and overall survival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients. CONCLUSION: Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients.