Perioperative,short-, and long-term outcomes of gastric cancer surgery: Propensity score-matched analysis of patients with or without prior solid organ transplantation

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.     

New immunosuppressive agents in transplantation

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.     

吗替麦考酚酯治疗儿童复发性眼肌型重症肌无力的疗效

目的:探讨吗替麦考酚酯治疗儿童复发性眼肌型重症肌无力(OMG)的临床疗效及安全性。 方法:分析成都市妇女儿童 中心医院儿童神经内科 2017-2021 年收治的 5 例复发性 OMG 患儿应用吗替麦考酚酯治疗的临床资料及随访情况。 结果:5 例 患儿首次发病年龄 14~28 个月,使用吗替麦考酚酯前病程 21~94 个月,均在接受吗替麦考酚酯治疗前接受过激素、激素+溴吡 斯的明单用或联合治疗,均出现多次(≥2 次)复发。 最后一次复发时急性期均接受口服小剂量泼尼松及吗替麦考酚酯联合治 疗方案,病情稳定后,逐渐减停泼尼松,单用吗替麦考酚酯治疗。 随访时间 18 ~ 28 个月,随访期间无复发。 随访未发现明显药 物不良反应,且伴随激素减停,激素相关副作用逐渐缓解。 结论:吗替麦考酚酯是一种对儿童复发性 OMG 安全、有效的治疗药 物,但仍需大样本量的随机对照试验(RCT)进一步证实。     

Disease staging and sub setting of interstitial lung disease associated with systemic sclerosis: impact on therapy

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.     

Regulatory T cells for tolerance

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.     

Mesenchymal stromal cells for tolerance induction in organ transplantation

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.     

肾移植术后早期主动减少免疫抑制剂用量的前瞻性研究

目的探讨对肾移植术后受者早期主动减少免疫抑制剂用量的临床必要性和安全性。方法随机选择63例尸体肾移植受者为观察组,58例尸体肾移植受者为对照组,两组受者均采用环孢素(CsA)+麦考酚吗乙酯(MMF)+泼尼松三联免疫抑制方案。于术后第6周对观察组63例受者予以主动减少免疫抑制剂用量(将CsA血药谷浓度维持在200～250 ng/ml,MMF按受者体质量主动减药),术后4～6个月开始按个体状况将MMF用量调至减药前水平。对照组按常规免疫抑制方案治疗。观察两组受者术后6周至1年的血清肌酐(Scr)、血尿素氮(BUN)、CsA血药谷浓度、肺部感染发生率、急性排斥反应(AR)发生率。结果随访1年期间,观察组受者Scr、BUN基本稳定在同一水平,且与对照组比较差异无统计学意义(均为P>0.05)。观察组与对照组的AR发生率分别为8%与9%,比较差异无统计学意义(P>0.05)。两组的肺部感染率分别为8%(5/63)和14%(8/58),比较差异有统计学意义(P<0.05),对照组有2例发展为严重的肺部感染。结论肾移植术后早期主动减少免疫抑制剂用量能有效降低此阶段肺部感染发生率,且AR发生率并没有增加。