BackgroundDetails of perioperative outcomes and survival after gastric cancer surgery in prior transplant recipients have received minimal research attention.MethodsWe performed an observational cohort study using the database of 20,147 gastric cancer patients who underwent gastrectomy at a single gastric cancer center in Korea. Forty-one solid organ recipients [kidney (n = 35), liver (n = 5), or heart (n = 1)] were matched with 205 controls using propensity score matching.ResultsOperation time, blood loss, and postoperative pain were similar between groups. Short-term complication rates were similar between transplantation and control groups (22.0% vs. 20.1%, P = 0.777). Transplantation group patients with stage 1 gastric cancer experienced no recurrence, while those with stage 2/3 cancer had significantly higher recurrence risk compared to the controls (P = 0.049). For patients with stage 1 cancer, the transplantation group had a significantly higher rate of non-gastric cancer-related deaths compared to the controls (19.2% vs. 1.4%, P = 0.001). For those with stage 2/3 cancer, significantly lower proportion of the transplantation group received adjuvant chemotherapy compared to the control group (26.7% vs. 80.3%, P < 0.001). The transplantation group had a higher (albeit not statistically significant) rate of gastric cancer-related deaths compared to the controls (40.0% vs. 18.0%, P = 0.087).ConclusionTransplant recipients and non-transplant recipients exhibited similar perioperative and short-term outcomes after gastric cancer surgery. From long-term outcome analyses, we suggest active surveillance for non-gastric cancer-related deaths in patients with early gastric cancer, as well as strict oncologic care in patients with advanced cancer, as effective strategies for transplant recipients. 相似文献
Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. Finally, antibody mediated rejection due to donor specific antibodies strongly affects allograft survival.Many drugs have been tested in the last decades, but very few have come to clinical use. The most recent one is CTLA4-Ig (belatacept), a costimulation blockade molecule that targets the second signal of T cell activation and is associated with a better long term kidney function than calcineurin inhibitors, despite an increased risk of acute cellular rejection.The research of new maintenance long-term immunosuppressive agents focuses on costimulation blockade. Agents inhibiting CD40-CD40 ligand interaction may enable a good control of both T cells and B cells responses. Anti-CD28 antibodies may promote regulatory T cells. Agents targeting this costimulation pathways are currently evaluated in clinical trials.Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology. 相似文献
Introduction: Interstitial lung disease (ILD) is the most serious complication of systemic sclerosis (SSc). There is no accepted guidance as to which clinical, radiological or physiological thresholds should prompt initiation or changes in treatment. Furthermore, some patients with extensive disease remain stable without the need for intervention whilst others with limited disease at the outset, experience a precipitous decline.
Areas covered: In this article, evidence for the integration of a number of disease-specific and patient-related domains are discussed and proposed. Introduction and maintenance of therapy requires a nuanced understanding of these factors and is crucial when weighing up the risks and benefits of immunomodulation. The evidence for the existing treatment modalities is discussed and the future directions for management of patients with SSc-ILD, which may include antifibrotic or biologic therapy, are explored.
Expert commentary: In the management of SSc-ILD, a multidisciplinary team approach which integrates physiology and radiology with the patient at the centre of the process is crucial for effective management and provision of the best outcomes. 相似文献
Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC).
Methods
We studied 118 kidney transplant recipients that initially received tacrolimus (TAC) and, at month-3, were converted or not to sirolimus (SRL).
Results
sCD30 serum levels gradually declined after transplantation, being the decline more pronounced in the SRL group. CD30 gene expression in PBMC was higher in the SRL group than in the TAC group. Patients with IF/TA?≥?I in the month-24 protocol biopsy had higher sCD30 levels than patients without IF/TA, in the SRL group (P?=?.03) and in the TAC group (P?=?.07). CD30+ cells were observed in three out of 10 biopsies with inflammatory infiltrate from the SRL group. In mixed lymphocyte cultures, SRL and TAC diminished the number of CD30+ T cells and the sCD30 levels in the supernatant, but the effect of SRL was stronger.
Conclusions
Overall, sCD30 levels are lower in SRL-treated patients, but the association between increased sCD30 levels and IF/TA at month-24 post-transplantation is stronger in SRL than in TAC-treated patients. 相似文献
Regulatory T cells (Tregs) are critical mediators of immune homeostasis and hold significant promise in the quest for transplantation tolerance. Progress has now reached a critical threshold as techniques for production of clinical therapies are optimised and Phase I/II clinical trials are in full swing. Initial safety and efficacy data are being reported, with trials assessing a number of different strategies for the introduction of Treg therapy. It is now more crucial than ever to elucidate further the function and behaviour of Tregs in vivo and ensure safe delivery. This review will discuss the current state of the art and future directions in Treg therapy. 相似文献
The primary challenge in organ transplantation continues to be the need to suppress the host immune system long-term to ensure prolonged allograft survival. Long-term non-specific immunosuppression can, however, result in life-threatening complications. Thus, efforts have been pursued to explore novel strategies that would allow minimization of maintenance immunosuppression, eventually leading to transplant tolerance. In this scenario, bone marrow-derived mesenchymal stromal cells (MSC), given their unique immunomodulatory properties to skew the balance between regulatory and memory T cells, have emerged as potential candidates for cell-based therapy to promote immune tolerance. Here, we review our initial clinical experience with bone marrow-derived MSC in living-donor kidney transplant recipients and provide an overview of the available results of other clinical programs with MSC in kidney and liver transplantation, highlighting hurdles and success of this innovative cell-based therapy. 相似文献