Metastasectomy and/or local ablative therapy in metastatic colorectal cancer (mCRC) patients often provide long-term survival. Health-related quality of life (HRQoL) data in curatively treated mCRC are limited. In the RAXO-study that evaluated repeated resectability, a multi-cross-sectional HRQoL substudy with 15D, EQ-5D-3L, QLQ-C30, and QLQ-CR29 questionnaires was conducted. Mean values of patients in different treatment groups were compared with age- and gender-standardized general Finnish populations. The questionnaire completion rate was 444/477 patients (93%, 1751 questionnaires). Mean HRQoL was 0.89−0.91 with the 15D, 0.85−0.87 with the EQ-5D, 68−80 with the EQ-5D-VAS, and 68−79 for global health status during curative treatment phases, with improvements in the remission phase (disease-free >18 months). In the remission phase, mean EQ-5D and 15D scores were similar to the general population. HRQoL remained stable during first- to later-line treatments, when the aim was no longer cure, and declined notably when tumour-controlling therapy was no longer meaningful. The symptom burden affecting mCRC survivors’ well-being included insomnia, impotence, urinary frequency, and fatigue. Symptom burden was lower after treatment and slightly higher, though stable, through all phases of systemic therapy. HRQoL was high in curative treatment phases, further emphasizing the strategy of metastasectomy in mCRC when clinically meaningful.
Thresholds for when a patient should be considered too healthy or too sick to undergo liver transplantation (LT) have been pursued, but have undergone little external validation and may differ between centers and countries.We investigated the ability of the Model for End-stage Liver Disease (MELD), D-MELD, Donor Risk Index (DRI) and Balance of Risk (BAR) scores to predict 1-year graft survival, and determined the 1-year survival-benefit of LT, compared with conservative management, according to MELD score and graft quality among 538 adult LT recipients with underlying chronic non-malignant liver disease.One-year graft survival rates showed small, but statistically significant variation according to MELD (p = 0.002) and D-MELD score (p = 0.04), and among LTs after year 2000 also according to BAR score (p = 0.01), but not according to DRI. Diagnostic accuracy of these scores was poor; area under the curve was 0.50-0.65 depending on the score. A 1-year survival-benefit of LT emerged at MELD scores ≥15, but also at lower MELD scores when using high-quality grafts (DRI <1.075).The performance of various prognostic scores in the Finnish setting was poor. Careful clinical evaluation is imperative when deciding on the timing of LT in the course of chronic liver disease.
Summary Background The importance of primary biliary cholangitis as an indication for liver transplantation has probably been influenced by the introduction of therapies, and changes in selection criteria and disease epidemiology. Aims To assess the time trends in liver transplantation for primary biliary cholangitis and to evaluate the characteristics of the patient population during the past three decades. Methods Patients undergoing liver transplantation from 1986 to 2015 in centres reporting to the European Liver Transplantation Registry were included. We excluded combined organ transplantations and patients <18 years. Trends were assessed using linear regression models. Results We included 112 874 patients, of whom 6029 (5.3%) had primary biliary cholangitis. After an initial increase in the first decade, the annual number of liver transplantation for primary biliary cholangitis remained stable at around 200. The proportion of liver transplantations for primary biliary cholangitis decreased from 20% in 1986 to 4% in 2015 ( P < 0.001). Primary biliary cholangitis was the only indication showing a consistent proportional decrease throughout all decades. From the first to the third decade, the age at liver transplantation increased from 54 (IQR 47‐59) to 56 years (IQR 48‐62) and the proportion of males increased from 11% to 15% (both P < 0.001). Conclusions We have found a proportional decrease in primary biliary cholangitis as indication for liver transplantation. However, despite treatment with ursodeoxycholic acid and improved disease awareness, the absolute annual number of liver transplantations has stabilised.
Long-term steroid administration may predispose liver transplant recipients to infectious and metabolic complications. Maintaining effective immunoprophylaxis while minimizing the negative consequences of steroid therapy could be a key factor in improving clinical outcomes.Six hundred two patients were randomized to receive tacrolimus (TAC) immunosuppression with a single-steroid bolus and two doses of daclizumab (DAC) or mycophenolate mofetil (MMF).The incidence of biopsy-proven acute rejection was 19.7% in the TAC/DAC group and 16.2% in the TAC/MMF group (ns). Three-month patient and graft survival were similar. Steroid use at month-3 was low at 5.5% in the TAC/DAC group and 3.9% in the TAC/MMF group. Significantly higher incidences of causally related adverse events (AEs) and significantly more dose modifications, interruptions, or discontinuations due to an AE were reported with TAC/MMF. Study withdrawal due to leucopenia was significantly higher with TAC/MMF (0.0% vs. 1.7%. Por=2 fasting plasma glucose values >or=7.0 mmol/L) were low at 9.5% (TAC/DAC) and 11.0% (TAC/MMF).Both TAC-based regimens allowed optimization of immunoprophylaxis while eliminating some of the negative consequences associated with steroids. Efficacy outcomes were comparable; however, TAC monotherapy after DAC induction was associated with significantly less leucopenia and less bacterial infection than a dual regimen incorporating MMF.
Long-term T-cell memory is dependent on the maintenance of memory T cells in the lymphoid tissues, and at the surface interfaces that provide entry routes for pathogens. However, much of the current information on human T-cell memory is based on analyzing circulating T cells. Here, we have studied the distribution and age-related changes of memory T-cell subsets in samples from blood, mesenteric LNs, spleen, and ileum, obtained from donors ranging in age from 5 days to 67 years of age. Our data show that the main reservoir of polyclonal naive cells is found in the LNs, and the resting memory subsets capable of self-renewal are also prominent there. In contrast, nondividing but functionally active memory subsets dominate the spleen, and especially the ileum. In general, the replacement of naive cells with memory subsets continues throughout our period of observation, with no apparent plateau. In conclusion, the analysis of lymphoid and nonlymphoid tissues reveals a dynamic pattern of changes distinct to each tissue, and with substantial differences between CD4+ and CD8+ compartments.
