高强度聚焦超声联合甲氨蝶呤在瘢痕子宫妊娠行宫腔镜微创清宫术中的应用效果分析

目的 探究采用高强度聚焦超声(HIFU)联合甲氨蝶呤(MTX)在瘢痕子宫妊娠行宫腔镜微创清宫术中的应用效果。方法 选择2018年5月—2019年5月在本院接受宫腔镜治疗的108例瘢痕子宫妊娠患者,依据随机数字表法分为研究组与对照组,每组各54例。对照组使用HIFU预处理,研究组则使用HIFU联合MTX的方式预处理,处理后两组均行宫腔镜辅助微创清宫术。通过随访分析比较两组的治疗效果及妊娠结局。结果 研究组术后7 d血清β-HCG水平为(28 598.38±2 176.52)U/L,低于对照组的(32 423.13±2 734.65)U/L,差异有统计学意义(t=8.042,P<0.001);研究组血清β-HCG转阴时间、月经恢复时间、住院时间分别为(21.33±3.78)d、(28.21±3.83)d、(6.53±2.12)d,分别短于对照组的(26.72±4.83)d、(33.82±4.91)d、(9.53±2.67)d,差异具有统计学意义(t=6.458、6.620、6.466,P均<0.001)。两组均随访≥24个月,宫内妊娠、未孕、流产、再次瘢痕子宫妊娠、异位妊娠比较,差异无统计学意义(χ2=1.895,P>0.05);宫内妊娠中足月分娩与早产比较,差异无统计学意义(χ2=0.131,P>0.05),研究组并发症发生率为22.58%,低于对照组的37.50%,差异有统计学意义(χ2=5.296,P=0.021)。结论 在宫腔镜辅助微创清宫术治疗瘢痕子宫妊娠前使用HIFU联合MTX预处理的效果优于单一使用HIFU预处理,可明显缩短患者血清β-HCG转阴时间、月经恢复时间与住院时间,但对女性的妊娠结局无影响,妇产科临床治疗前可结合患者需求择取最合适的预处理方案。     

Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review

BackgroundMultidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC.MethodsEligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included.ResultsIn total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide.ConclusionsRecent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

Successful Treatment of Necrotizing Retinitis with Epstein–Barr Virus-Positive Ocular Fluid by Intravitreal Methotrexate Injection

ABSTRACT

Purpose

To present a case of necrotizing retinitis with Epstein–Barr virus (EBV)-positive ocular fluid in a patient with sudden unilateral vision loss, which was successfully treated with intravitreal methotrexate (MTX) injections.     

Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study

BackgroundBecause primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC.Material and methodsWe conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated.ResultsBetween January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence.ConclusionBreast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence.     

Risk factors associated with delayed methotrexate clearance and increased toxicity in pediatric patients with osteosarcoma

High‐dose methotrexate (HD‐MTX; 12 g/m²) is part of standard therapy for pediatric osteosarcoma (OS). Risk factors associated with MTX toxicity in children with OS are not well defined. We investigated the association between peak MTX levels (four‐hour) and delayed MTX clearance or treatment toxicity. Information was retrieved from electronic medical records of 33 OS patients treated with HD‐MTX at Texas Children's Hospital from 2008 to 2015. We found that the four‐hour MTX level did not contribute to toxicity or delayed MTX clearance. We demonstrated that certain demographic characteristics are associated with delayed clearance and increased toxicity.     

急性淋巴细胞白血病患儿大剂量甲氨蝶呤给药后C44h对排泄延迟的预判价值

目的:探讨儿童急性淋巴细胞白血病(ALL)行大剂量甲氨蝶呤(HDMTX)化疗给药后C_44h对于排泄延迟的预判价值,为尽早采取有效措施减轻严重不良反应提供依据。方法:某院儿科住院接受HDMTX方案的ALL患儿42例,男27例,女15例,MTX剂量5 g·m^-2,24 h持续静滴,RP-HPLC法分别测定MTX给药后44 h和48 h血药浓度,按化疗药物常见不良反应事件评价标准(CTCAE v 4.02版)评定用药后MTX不良反应。结果:C_44h>0.5μmol·L^-1和C_44h≤0.5μmol·L^-12组不良反应发生率有明显差异,C_44h>0.5μmol·L^-1组血药浓度降低至安全阈值所需时间明显长于C_44h≤0.5μmol·L^-1组。结论:C_44h>0.5μmol·L^-1有预测MTX排泄延迟作用,有利于及时调整四氢叶酸(CF)解救方案。     

甲氨蝶呤及其代谢物血药浓度分析中细节问题的探讨

甲氨蝶呤（MTX）被广泛用于治疗骨肉瘤、急性淋巴细胞白血病、恶性淋巴瘤、类风湿性关节炎和炎性肠道疾病等。由于MTX个体差异大和不良反应较严重,同时其在体内代谢迅速,主要以多聚谷氨酸化代谢物的形式长期存在,因此,监测MTX及其代谢物的血药浓度显得尤为重要。本文对已发表的相关文献进行了分析,结合笔者在临床药物浓度监测实践中的经验和体会,从样品采集、样品保存、样品前处理方法、分离条件、检测方法等方面,探讨了MTX及其代谢物血药浓度测定中的细节问题,以期实现MTX的精准医疗,确保其用药安全性。