Nephrotoxicity From Molecularly Targeted Chemotherapeutic Agents

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胰腺癌术后辅助药物治疗的研究进展

胰腺癌是一种致死性极高的恶性肿瘤,其5年生存率不到8%。可行根治性手术的胰腺癌患者较未行手术者预后有显著差异,单纯的手术治疗仅能将胰腺癌5年生存率提高至10%左右,究其原因主要是单纯手术后复发、转移的几率仍然极高,且复发、转移后患者生活质量欠佳,预后极差,远期生存时间短。因此,寻求胰腺癌术后更加有效的辅助治疗药物或者方案,并进行规范、合理、综合的药物治疗,控制微转移,对防止和延迟复发意义重大,该研究领域也是近年来针对胰腺癌研究的重点方向。本文基于近年来胰腺癌术后治疗的研究进展做一综述。探索胰腺癌术后不同药物、不同治疗方案下的生存获益情况及胰腺癌术后治疗的药物发展趋势,为胰腺癌术后治疗提供有价值的参考。     

Development of a predictive score of axillary lymph node dissection based on targeted axillary dissection in patients with breast cancer diagnosis,affected lymph nodes,and neoadjuvant treatment

AimTo determine predictive factors of axillary lymph node dissection (ALND) results in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), and subsequent staging using Targeted Axillary Dissection (TAD).Material and methodCase-control study between January 2016 and August 2019. Patients with BC, cN1 staging, marked with a metallic clip prior to NACT, and subsequently staged with TAD and ALND were included. They were divided into 2 groups: ALND patients with or without metastatic involvement (group 1 and group 2, respectively). We carried out a univariate analysis comparing clinical, radiological, surgical and pathological variables, and a logistic regression, (dependent variable: positive result of ALND; independent variables: number of suspicious lymph nodes in diagnostic ultrasound, positive hormone receptors, HER2 positive, complete clinical-radiological response to NACT, positive TAD, and biopsy of ≤2 nodes in TAD). A score for prediction of a metastatic ALND was proposed, with an internal validation study.Results60 patients were included: Group 1: 33 (55.0%); Group 2: 27 (45.0%). Tumor size (Odds Ratio (OR) = 1.67; 95%CI 1.02–2.74), number of suspected nodes in ultrasound (OR = 2.20; 95%CI 1.01–4, 77), HER2 positive (OR 0.04; 95%CI 0.003–0.54), clinical-radiological response to NACT (OR = 0.07; 95%CI 0.01–0.75), and positive TAD (OR 15.48; 95%CI 1.68–142.78) were independent predictors of a positive result in ALND. We developed a “positive ALND predictive score”, with good calibration (Hosmer-Lemeshow test: p = 0.65), and discrimination (AUC = 0.93; 95% CI 0, 87–0.99), with highest Youden index (0.7) at cut-off point of 17% risk of positive ALND (sensitivity = 100%; specificity = 70%).ConclusionTumor size, number of suspected nodes, positive HER2, response to NACT, and metastatic TAD are independent predictors of ALND. The predictive score for positive ALND would be a good indicator to safely omit ALND.     

Association of serine/threonine kinase 11 mutations and response to programmed cell death 1 inhibitors in metastatic gastric cancer

Programmed cell death 1 (PD-1) inhibitors have shown therapeutic efficacy in metastatic gastric cancer (mGC). However, no predictive biomarkers have been established in mGC. Inactivating mutations in serine/threonine kinase 11 (STK11) are associated with poor response to PD-1 inhibitors in KRAS-mutant lung adenocarcinoma. Therefore, we hypothesized that STK11 inactivating mutations would be associated with inferior clinical response to PD-1 inhibitors in mGC. We analyzed 59 mGC patients who had been treated with PD-1 inhibitors and whose tumors had been analyzed by targeted high-throughput sequencing. STK11 mutations were identified in 30 (50.8%) patients, and were all missense mutations. Three patients (5.1%) had STK11 gene amplification and mutation, simultaneously. Patients with STK11 mutations had prolonged overall survival (median: 19.0 vs 11.6 months, p = 0.15), and progression-free survival (4.2 vs 1.9 months, p = 0.06) when treated with PD-1 inhibitors, but these differences were not statistically significant. Patients with STK11 inactivating mutations without STK11 gene amplification had significantly prolonged progression-free survival compared to patients with wild type STK11 or STK11 gene amplification (4.8 vs 1.0 months, p = 0.04). However, in multivariate Cox regression analysis with high microsatellite instability (MSI-H), the number of tumor mutations, PD Ligand-1 (PD-L1)+, Epstein-Barr virus positivity (EBV)+, and type of PD-1 inhibitor used (pembrolizumab vs nivolumab), only MSI-H and PD-L1+ were significantly associated with longer progression-free survival. In mGC, the presence of STK11 mutation was not predictive of the response to PD-1 inhibitors. Instead, patients with MSI-H or PD-L1+ tumors displayed superior clinical responses to PD-1 inhibitors.     

间歇性负压封闭引流联合自体皮瓣原位弹性绷带加压包扎对溃疡期压疮疗效分析

目的探讨间歇性负压封闭引流(VSD)联合自体皮瓣原位弹性绷带加压包扎对III~Ⅳ期溃疡期压疮疗效的影响。方法选择2009年4月~2014年3月我科住院治疗的溃疡性压疮患者40例作为观察组,采用间歇性VSD联合自体皮瓣原位弹性绷带加压包扎的治疗方法。选择同期我科住院治疗的III~Ⅳ期溃疡性压疮患者25例作为对照组,采用常规换药联合自体皮瓣原位弹性绷带加压包扎的治疗方法。观察两组感染发生率、愈合情况及住院时间,并进行比较。结果观察组感染率为0,对照组感染率为76%,两组比较有显著性差异(P0.05);观察组皮瓣修复术前住院时间、术后住院时间、总住院时间较对照组明显缩短,两组比较有显著性差异差异(P0.05)。两组皮瓣面积、一期愈合、复发情况比较无显著性差异(P0.05)。结论间歇性VSD联合自体皮瓣原位弹性绷带加压包扎,能阻止溃疡期压疮创面感染,促进创面愈合,改善预后。