Summary
Background
Calcineurin‐inhibitor immunosuppressants (tacrolimus and ciclosporin) have been associated with an exposure‐related increase in tumour recurrence following liver transplantation for hepatocellular carcinoma (HCC). Conversely, mechanistic target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been suggested to reduce recurrence rates and improve survival in this patient group.
Aim
To clarify the potential benefit of mTOR‐inhibitors in HCC transplant patients by comparing recurrence and survival outcomes with calcineurin‐inhibitor‐based immunosuppression.
Methods
A systematic review and meta‐analysis was performed. The inclusion criteria were observational or interventional studies reporting the effect of early‐initiated (<6 months post‐transplant) mTOR‐inhibitor‐based immunosuppression on survival or tumour recurrence in patients transplanted with HCC, compared to a control of calcineurin‐inhibitor‐based therapy.
Results
Meta‐analysis demonstrated that compared with calcineurin‐inhibitor controls, recurrence‐free‐survival was significantly increased with mTOR‐inhibitor‐based therapy at 1‐year (Risk‐Ratio (RR): 1.09, 95% CI: 1.01‐1.18) and 3‐years (RR: 1.1, 95% CI: 1.01‐1.21) post‐transplant, with a nonsignificant increase at 5‐years (RR: 1.15, 95% CI: 0.99‐1.35). Overall survival was improved at 1‐year (RR: 1.07, 95% CI: 1.02‐1.12), 3‐years (RR: 1.1, 95% CI: 1.02‐1.19), and 5‐years (RR: 1.18, 95% CI: 1.08‐1.29). Recurrence‐rate was lower in the mTOR‐inhibitor arm (RR: 0.67, 95% CI: 0.56‐0.82), with no significant increase in acute rejection (RR: 1.1, 95% CI: 0.94‐1.28).
Conclusions
mTOR‐inhibitor‐based immunosuppression may be a preferable option in patients transplanted with HCC. It improves recurrence‐free‐survival over at least three years and reduces the recurrence rate compared with standard calcineurin‐inhibitor‐based therapy, with no significant increase in the rate of acute rejection. Future research should clarify the effect in higher vs lower risk cohorts.
Background and Aim
Owing to wide‐spread use, low‐dose aspirin (LDA) produces a substantial amount of peptic ulcer disease. Current guidelines are ambivalent about the need for Helicobacter pylori eradication to protect against LDA ulcers. This study aimed to determine, through meta‐analysis, if (and by how much) infection alters the baseline risk of peptic ulcers during LDA therapy.
Methods
Literature screening was performed in MEDLINE and EMBASE from inception to May 2018. Original studies reporting prevalence or incidence of uncomplicated ulcers in LDA users were included. Ulcer endpoints needed to be specified separately, according to H. pylori infection status. Meta‐analysis was performed in MIX 2.0 Pro.
Results
Ten cross‐sectional studies and seven randomized controlled trials were included (n = 5964). The pooled odds ratios with 95% confidence intervals (CI) for the risk of LDA ulcers in H. pylori‐positive versus H. pylori‐negative individuals were 1.68 (95%CI 1.40–2.02) and 1.65 (95%CI 1.29–2.08) under fixed‐effects and random‐effects models, respectively. Heterogeneity among studies was minimal (I2 = 26.9%). After adjusting for the protective effects of antisecretory drugs, the odds ratios increased to 1.94 (95%CI 1.54–2.46).
Conclusion
This analysis suggests that H. pylori increases the risk of LDA ulcers by almost 70% in a population where some were taking proton pump inhibitors and/or other acid suppressants. Without antisecretory drugs, the risk almost doubles. Clinically, these findings may support the use of a test‐and‐treat approach to H. pylori in LDA users, particularly those already at higher risk of developing peptic ulcers.
Background: Plasmablastic lymphoma (PBL) is a rare, aggressive subtype of non-Hodgkin's lymphoma. Effective treatment options are lacking due to the rarity of the disease.Methods: We conducted a systematic review of the PubMed and our internal records to retrieve cases with PBL diagnosis with evaluable treatment outcomes. Aggressive chemotherapy was defined as more intense regimens than CHOP.
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