Search

Hematopoietic cell transplantation (HCT) treats many blood conditions but remains underused due to complications such as graft‐versus‐host disease (GvHD). In GvHD, donor immune cells attack the patient, requiring powerful immunosuppressive drugs like glucocorticoids (GCs) to prevent death. In this study, we tested the hypothesis that donor cell conditioning with the glucocorticoid fluticasone propionate (FLU) prior to transplantation could increase hematopoietic stem cell (HSC) engraftment and reduce GvHD. Murine HSCs treated with FLU had increased HSC engraftment and reduced severity and incidence of GvHD after transplantation into allogeneic hosts. While most T cells died upon FLU treatment, donor T cells repopulated in the hosts and appeared less inflammatory and alloreactive. Regulatory T cells (Tregs) are immunomodulatory and survived FLU treatment, resulting in an increased ratio of Tregs to conventional T cells. Our results implicate an important role for Tregs in maintaining allogeneic tolerance in FLU‐treated grafts and suggest a therapeutic strategy of pre‐treating donor cells (and not the patients directly) with GCs to simultaneously enhance engraftment and reduce GvHD upon allogeneic HCT. Synopsis: Graft‐versus‐Host Disease (GvHD) is a life‐threatening complication of allogeneic hematopoietic cell transplantation (allo‐HCT). In this study, we examined the impact of conditioning donor grafts by pre‐treating with the glucocorticoid fluticasone propionate (FLU) prior to allo‐HCT in a mouse model of GvHD. FLU pre‐treatment increased Cxcr4 expression on mouse hematopoietic stem cells (HSCs) and led to increased transwell migration activity and HSC engraftment upon transplantation.FLU pre‐treatment reduced the incidence and severity of GvHD upon allo‐HCT in a mouse model of GvHD.FLU pre‐treatment decreased the viability, activation, and Th1 effector function of conventional T cells after allo‐HCT.FLU pre‐treatment spares regulatory T cells, leading to an overall increase in the ratio of tolerogenic Tregs versus allogeneic conventional T cells. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested a potential increase in the incidence of osteoporosis for patients receiving tenofovir disoproxil fumarate (TDF), but this issue remains controversial. Methods: The retrospective cohort study of 1224 Asian chronic hepatitis B (CHB) patients greater than 18 years without baseline osteopenia/osteoporosis seen at four US centers from 2008 to 2016. Patients were categorized into three groups—treatment‐naive patients who initiated therapy with TDF (1) or entecavir (ETV) (2), or untreated patients (3). Patients were followed until the development of osteopenia/osteoporosis or end of the study. Results: Of the 1224 study patients, 276 were treated with TDF, 335 with ETV, and 613 were untreated. The prevalence of cirrhosis was lower for untreated patients (2.6% vs 16.3% for TDF and 17.6% for ETV; P < 0.001). The 8‐year cumulative incidence rate of osteopenia/osteoporosis was 13.17% for TDF, 15.09% for ETV, and 10.17% for untreated patients, with no statistically significant difference among the three groups (P = 0.218). On multivariate Cox regression controlling for demographics, osteoporosis risk factors, albumin, and hepatitis B virus (HBV) DNA levels, neither TDF (adjusted hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.34 and 1.59) nor ETV (adjusted HR = 0.98; 95% CI: 0.51 and 1.90) were associated with increased osteopenia/osteoporosis risk compared with untreated patients. Conclusions: Our retrospective study suggests that there is no significant increase in the incidence of osteopenia/osteoporosis for patients with CHB treated with TDF or ETV during a median follow‐up of about 4 to 5 years. However, further study with longer follow‐up is needed as an anti‐HBV therapy, which is often lifelong or long‐term and the development of osteopenia/osteoporosis can be a slow process. Highlights: There is no significant increase in the incidence of osteopenia or osteoporosis for patients with chronic hepatitis B treated with tenofovir disoproxil fumarate or entecavir during a median follow‐up of about 4 to 5 years.Further study with longer follow‐up is needed as an anti‐HBV therapy, which is often lifelong or long‐term and the development of osteopenia and osteoporosis can be a slow process. [ABSTRACT FROM AUTHOR]

Background: The treatment of ductal carcinoma in situ (DCIS) remains controversial and may be particularly difficult for patients with minimal disease. There is a dearth of information regarding patients who have been diagnosed with DCIS on core needle biopsy (CNB), who have no residual disease in the lumpectomy specimen. The purpose of this study was to explore the frequency of this presentation and short‐term outcomes in these patients. Methods: Our institutional Breast Cancer Database was queried for all women who were diagnosed with pure DCIS from 2010 to 2016 and treated with lumpectomy. Variables included patient and tumor characteristics, adjuvant treatment, and ipsilateral breast tumor recurrence (IBTR). Statistical analyses included Pearson's chi‐square, Fisher's exact tests, and Kaplan‐Meier analysis. Results: Of 547 patients with pure DCIS, 50 (14%) had DCIS on CNB only. Of the patients with DCIS on CNB only, 15 were treated with lumpectomy and radiation therapy (RT), while 35 underwent lumpectomy without RT. At a median follow‐up of 4 years, there were 3 (6%) IBTR all within the same quadrant as the original lumpectomy site. None of the patients who recurred received adjuvant RT or hormonal therapy. Conclusions: Despite the minimal extent of disease exhibited in these cases, 6% of patients with DCIS on CNB only had IBTR at a median follow‐up of 4 years. These data suggest that even minimal DCIS represents a significant risk of recurrence to the patient. Size and margins are not sufficient criteria to stratify risk and guide decisions for adjuvant therapies. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the few cancers whose incidence continues to increase. The goal of the current study was to investigate the presentation and survival trends of patients with HCC presenting to a university hospital between 1998 and 2015.Methods: Study data were ascertained by individual chart review with survival data also supplemented by National Death Index query up to December 31, 2015. Patients were divided into three 6-year groups by diagnosis date (1998-2003, 2004-2009, and 2010-2015).Results: A total of 2106 consecutive patients with HCC were included. The majority of patients had either hepatitis C (56.7%) or hepatitis B (22.1%), but cases of nonalcoholic steatohepatitis HCC increased by 68% over the most recent time period. Screening/surveillance identified 61% of HCC cases, but only 31% of these patients underwent curative treatment, which did not increase significantly over time. The overall median survival was 29.8 months (2.48 years) and without improvement over time. On multivariable analysis, Asian or Hispanic ethnicity, meeting Milan criteria, and receiving any of the standard HCC treatments were found to be significantly associated with improved survival, but diagnosis time period and liver disease etiology were not.Conclusions: Over the last 18 years, the percentage of cases of nonalcoholic steatohepatitis HCC has increased but not overall survival. It is interesting to note that only 31% of patients with HCC identified via screening/surveillance received any curative treatment. Further research is needed to better understand the barriers to curative care for patients with HCC and the causes of the lack of improvement in survival in the more recent patient cohort. Cancer 2018;124:2588-98. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non‐viral causes of HCC, particularly non‐alcoholic fatty liver disease (NAFLD), are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC. Methods: We conducted a retrospective cohort study involving 3878 consecutive HCC patients seen at two tertiary centres in the United States and one in Taiwan from 2004 to 2014. We compared the clinical characteristics, treatment and survival of patients by underlying aetiology: cryptogenic (n = 696), HBV (n = 1304) or HCV (n = 1878). Results: Cirrhosis was present in 66.8% of the cryptogenic HCC patients, compared with 74.7% of HBV‐related HCC (HBV‐HCC) (P = .001) and 85.9% of HCV‐HCC (P < .001). Compared to viral HCC, cryptogenic HCC patients presented with larger tumours and at later stages of disease. Five‐year overall survival was 16.3% among cryptogenic HCC patients compared with 31.9% among HBV‐HCC patients and 27.7% among HCV‐HCC patients (P < .001 for both by the log‐rank test). HCC aetiology was not an independent predictor of survival, though ethnicity, cirrhosis status, meeting Milan criteria and treatment allocation were. Conclusions: Compared with viral HCC patients, those with cryptogenic HCC had lower prevalence of cirrhosis, were diagnosed with larger tumours at more advanced stages of disease, and had poorer overall survival. Additional efforts are needed to identify patients at risk of cryptogenic HCC and to identify cryptogenic HCC at earlier stages of disease. [ABSTRACT FROM AUTHOR]

Background: Economic burden of HBV and HCV infection are trending upwards. Aims: Compare hepatitis B virus (HBV) and hepatitis C virus (HCV) related hospital admission rates, charges, mortality rates, causes of death in a US population-based study. Methods: Retrospective cohort analysis of HBV and HCV patients from the California Office of Statewide Health Planning and Development (2006–2013) database. Results: A total of 23,891 HBV and 148,229 HCV patients were identified. Across the 8-year period, the mean increase for all-cause ($1,863 vs $1,388) and liver-related hospitalization charges ($1,175 vs $675) were significantly higher for the HBV cohort compared to the HCV cohort. HBV patients had significantly higher liver-related hospital charges per person per year than HCV patients after controlling for covariates ($123,239 vs $111,837; p = 0.002). Compared to HCV patients, adjusted mortality hazard ratio was slightly lower in HBV patients (relative risk = 0.96; 95% CI 0.94–0.99). The major causes and places of death were different. The three major causes of death for HBV were: other malignant neoplasms (35%), cardiovascular disease/other circulatory disorders (17%), and liver-related disease (15%) whereas for HCV patients were: liver-related disease (22%), other malignant neoplasms (20%), and cardiovascular disease (16%). Regarding the place of death, 53% of HBV patients and 44% of HCV patients died in hospital inpatient, respectively. Conclusions: HBV patients incurred higher liver-related hospital charges and higher mean increase for all-cause and liver-related hospitalization charges over the 8-year period compared to HCV patients. HBV patients had slightly lower mortality rate and their major causes and places of death were noticeably different from HCV patients. [ABSTRACT FROM AUTHOR]

Background & aims: Treatment rates with interferon-based therapies for chronic hepatitis C have been low. Our aim was to perform a systematic review of available data to estimate the rates and barriers for antiviral therapy for chronic hepatitis C. Methods: We conducted a systematic review and meta-analysis searching MEDLINE, SCOPUS through March 2016 and abstracts from recent major liver meetings for primary literature with available hepatitis C treatment rates. Random-effects models were used to estimate effect sizes and meta-regression to test for potential sources of heterogeneity. Results: We included 39 studies with 476,443 chronic hepatitis C patients. The overall treatment rate was 25.5% (CI: 21.1–30.5%) and by region 34% for Europe, 28.3% for Asia/Pacific, and 18.7% for North America (p = 0.008). On multivariable meta-regression, practice setting (tertiary vs. population-based, p = 0.04), region (Europe vs. North America p = 0.004), and data source (clinical chart review vs. administrative database, p = 0.025) remained significant predictors of heterogeneity. The overall treatment eligibility rate was 52.5%, and 60% of these received therapy. Of the patients who refused treatment, 16.2% cited side effects, 13.8% cited cost as reasons for treatment refusal, and 30% lacked access to specialist care. Conclusions: Only one-quarter of chronic hepatitis C patients received antiviral therapy in the pre-direct acting antiviral era. Treatment rates should improve in the new interferon-free era but, cost, co-morbidities, and lack of specialist care will likely remain and need to be addressed. Linkage to care should even be of higher priority now that well-tolerated cure is available. [ABSTRACT FROM AUTHOR]