经直肠前列腺超声造影靶向活检诊断前列腺癌的可行性研究

目的评价超声造影对前列腺癌(PCa)的诊断价值,探讨PCa靶向活检(TB)的可行性。方法对164例前列腺特异度抗原(PSA)水平≥4ng/ml患者,在接受前列腺活检前行前臂静脉注射声诺维2.4ml (29.5μg),经直肠超声(TRUS)前列腺超声造影(CEUS)检查,评估CEUS的声像图表现。对92例CEUS显示前列腺异常灌注区行TB;并对260例PSA≥4ng/ml患者行前列腺系统活检(SB),然后对TB和SB的病理结果进行对比分析。结果 92例CEUS显示前列腺异常灌注区的患者于TRUS引导下行TB,平均每位患者取活检标本12.6条,病理诊断PCa阳性率66.3%(61/92),未见癌细胞33.7%(31/92);SB病理诊断PCa 19.6%(51/260),未见癌细胞199例76.5%(199/260),TB对PCa检出率明显高于SB的19.6%(优势比=3.3,P=0.002 7)。CEUS提示PCa的声像图表现多种多样:强对比增强、快速对比增强、血管灌注异常和低对比增强。结论 TRUS引导下CEUS靶向活检,可提高组织材料的质量,使患者避免不必要的穿刺,减少穿刺次数,从而提高PCa的诊断率,超声造影TB和SB结合,可以获得PCa较高的检出率,有较高的临床应用价值。     

超声靶向微泡破坏介导的纳米给药系统的研究进展

纳米给药系统是目前治疗多种疾病,尤其是肿瘤的一种很具前景的方法。基于纳米微泡结构的改变和修饰,超声靶向微泡破坏技术(UTMD)作为一种安全的物理靶向方法,可以增强组织渗透性和细胞膜通透性,帮助载药的纳米微泡进入靶组织和细胞内部,进而提高给药效率。本文就UTMD介导的靶向纳米超声造影剂(UCA)的最新研究进展进行综述。     

呼吸机相关性肺炎防控最佳护理实践 ——《导管相关感染防控最佳护理实践专家共识》系列解读之三

随着机械通气技术的广泛应用,呼吸机相关性肺炎的发生率也随之上升。呼吸机相关性肺炎的发生不仅增加治疗难度、延长住院时间、增加患者痛苦,还可致患者死亡。文章从呼吸机相关性肺炎的概念、流行病学及发病机制、危险因素及危害、重点环节的防控建议、目标性监测方面分享呼吸机相关性肺炎防控最佳护理实践,希望能为临床护理人员和抗击疫情一线人员预防与控制呼吸机相关性肺炎提供参考依据,以期指导和规范临床护理实践。     

Imatinib in advanced chordoma: A retrospective case series analysis

IntroductionImatinib showed activity in 50 chordoma patients treated within a Phase II study. In that study, 70% of patients remained with stable disease (SD), median progression free survival (PFS) was 9 months and median overall survival (OS) was 34 months. We now report on a retrospective series of PDGFB/PDGFRB positive advanced chordoma patients treated with imatinib as a single agent within a compassionate-use programme at Istituto Nazionale Tumori, Milan, Italy (INT) between August 2002 and November 2010, when the programme was closed.Methods48 patients were consecutively treated with imatinib 800 mg/d. All patients had inoperable and progressive disease before starting imatinib. Demographics, treatment duration, toxicity and response rate by Response Evaluation Criteria in Solid Tumors (RECIST) were retrospectively recorded.ResultsThe median duration of therapy was 7 months (1–46.5). No patient is on therapy at present. 46 patients were evaluable for response. No partial responses were detected. Best response was: stable disease 34 (74%), progressive disease 12 (26%). At a median follow-up of 24.5 months (0.5–117), median PFS was 9.9 months (95% confidence interval (CI) 6.7–13). Eight patients (16.5%) remained on therapy >18 months and 10 patients (21%) remained progression-free >18 months. Median OS was 30 months (95% CI 20–40), with 24 (50%) patients dead at the time of the present analysis.ConclusionsWe confirm the activity of imatinib in locally advanced and metastatic chordoma, in terms of >70% tumour growth arrest in previously progressive patients. Median duration of response lasted almost 10 months, with >20% of patients progression-free at 18+ months.     

双重打击淋巴瘤研究进展

双重打击淋巴瘤(DHL)通常是指发生MYC基因重排,同时伴有bcl-2和(或)bcl-6基因重排的大B细胞淋巴瘤.DHL侵袭性强,常规方案治疗预后差,目前尚无标准的一线治疗方案.文章就DHL在诊断、生物学行为、预后影响因素和治疗方面的研究进展进行综述,旨在加深对DHL的理解,优化治疗策略,以期改善其预后.     

Brentuximab Vedotin in Patients With Hodgkin Lymphoma and a Failed Allogeneic Stem Cell Transplantation: Results From a Named Patient Program at Four Italian Centers

Background.

Brentuximab vedotin (BV) has demonstrated an extraordinary efficacy in heavily pretreated classical Hodgkin lymphoma (cHL) patients, targeting CD30-positive cells; however, limited data have been reported on the efficacy of BV in cHL patients failing allogeneic stem cell transplantation (allo-SCT). The aim of this study was to retrospectively evaluate the efficacy and safety of BV in a multicenter setting of cHL relapsing or progressing after allo-SCT.

Methods.

Sixteen BV-naïve patients with recurrent cHL after allo-SCT were included in a compassionate use program and treated with intravenous BV at the dose of 1.8 mg/kg of body weight every 3 weeks for a maximum of 16 cycles.

Results.

The objective response rate was 69%. Five patients (31%) had complete remission, and 6 (37%) had partial remission. Stable disease was observed in 4 patients (25%), and progressive disease was observed in 1 (6%). After median follow-up of 26 months (range: 5–30 months), median progression-free survival (PFS), overall survival (OS), and duration of response were 7, 25, and 5 months, respectively. The 2-year PFS and OS were 20% and 61%, respectively. Grade 3–4 hematological adverse events included anemia (15%), thrombocytopenia (12%), and neutropenia (18%). Grade 3 peripheral sensory neuropathy occurred in 2 patients (12%).

Conclusion.

BV therapy is an effective and safe approach for achieving transient disease control in cHL patients with failed allo-SCT. To improve disease control, future studies should explore the combination of BV with targeted agents.     

小细胞肺癌的靶向治疗

小细胞肺癌（SCLC）靶向治疗药物包括血管生成抑制剂、酪氨酸激酶抑制剂和信号通路抑制剂等。研究表明血管生成抑制剂如贝伐珠单抗疗效并不显著;酪氨酸激酶抑制剂如舒尼替尼等可能更适合单药治疗;信号通路抑制剂如 Amuvatinib、LDE225等正在进行Ⅰ、Ⅱ期临床试验。目前认为 SCLC对于靶向治疗不敏感,或更具有选择性和针对性,有待于进一步研究。     

A Prospective,Blinded Comparison of Magnetic Resonance (MR) Imaging–Ultrasound Fusion and Visual Estimation in the Performance of MR-targeted Prostate Biopsy: The PROFUS Trial

Background

Increasing evidence supports the use of magnetic resonance (MR)–targeted prostate biopsy. The optimal method for such biopsy remains undefined, however.

Objective

To prospectively compare targeted biopsy outcomes between MR imaging (MRI)–ultrasound fusion and visual targeting.

Design, setting, and participants

From June 2012 to March 2013, prospective targeted biopsy was performed in 125 consecutive men with suspicious regions identified on prebiopsy 3-T MRI consisting of T2-weighted, diffusion-weighted, and dynamic-contrast enhanced sequences.

Intervention

Two MRI–ultrasound fusion targeted cores per target were performed by one operator using the ei-Nav|Artemis system. Targets were then blinded, and a second operator took two visually targeted cores and a 12-core biopsy.

Outcome measurements and statistical analysis

Biopsy information yield was compared between targeting techniques and to 12-core biopsy. Results were analyzed using the McNemar test. Multivariate analysis was performed using binomial logistic regression.

Results and limitations

Among 172 targets, fusion biopsy detected 55 (32.0%) cancers and 35 (20.3%) Gleason sum ≥7 cancers compared with 46 (26.7%) and 26 (15.1%), respectively, using visual targeting (p = 0.1374, p = 0.0523). Fusion biopsy provided informative nonbenign histology in 77 targets compared with 60 by visual (p = 0.0104). Targeted biopsy detected 75.0% of all clinically significant cancers and 86.4% of Gleason sum ≥7 cancers detected on standard biopsy. On multivariate analysis, fusion performed best among smaller targets. The study is limited by lack of comparison with whole-gland specimens and sample size. Furthermore, cancer detection on visual targeting is likely higher than in community settings, where experience with this technique may be limited.

Conclusions

Fusion biopsy was more often histologically informative than visual targeting but did not increase cancer detection. A trend toward increased detection with fusion biopsy was observed across all study subsets, suggesting a need for a larger study size. Fusion targeting improved accuracy for smaller lesions. Its use may reduce the learning curve necessary for visual targeting and improve community adoption of MR-targeted biopsy.     

Phase 2 Trial of Neoadjuvant Axitinib in Patients with Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma

Background

Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery.

Objective

To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC).

Design, setting, and participants

This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible.

Intervention

Patients received axitinib 5 mg for up to 12 wk. Axitinib was continued until 36 h prior to surgery. Patients underwent partial or radical nephrectomy after axitinib therapy.

Outcome measurements and statistical analysis

The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST).

Results and limitations

A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers.

Conclusions

Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC.

Patient summary

In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use.

Trial registration

This clinical trial was registered with clinicaltrials.gov (NCT01263769).