Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

1. Download : Download high-res image (268KB)
2. Download : Download full-size image

     

China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.     

脊柱后路内固定术后硬膜外血肿的预防与护理体会

目的 探讨脊柱后路内固定术后硬膜外血肿的预防与护理体会。方法 遵照回顾性分析法选择我院2013年2 月～2018 年2 月纳入的60 例脊柱后路内固定术患者，依照不同理疗方式进行分组。其中30 例给予常规药物治疗作为对照组，另30 例除了常规治疗之外实施综合护理作为研究组，记录两组硬膜外血肿、腰椎术后血肿及颈椎术后血肿发生率，分别在干预前后进行生活质量评分（QOL）调查，出院时发放满意度调查问卷表，对比两组干预结果。结果 研究组血肿发生率为6.67%，明显低于对照组的20.00%（P＜0.05）。干预前两组的食欲、精神、睡眠、疼痛及日常生活评分相比差异无统计学意义（P＞0.05），干预后研究组的各项评分均高于对照组（P＜0.05）。研究组对干预效果的满意度为90.00%，明显高于对照组的76.67%（P＜0.05）。结论 护理干预运用于脊柱后路内固定中效果显著，能够有效减少硬膜外血肿的发生率，提升生活质量，促进病情稳定，患者满意度较高，可维持良好医患关系。     

Intrathecal catheterisation after observed accidental dural puncture in labouring women: update of a meta-analysis and a trial-sequential analysis

BackgroundOur meta-analysis from 2013 showed that inserting a catheter intrathecally after an observed accidental dural puncture can reduce the need for epidural blood patch in labouring women requesting epidural analgesia. We updated our conventional meta-analysis and added a trial-sequential analysis (TSA).MethodsA systematic literature search was conducted to identify studies that compared inserting the catheter intrathecally with an epidural catheter re-site or with no intervention. The extracted data were pooled and the risk ratio (RR) and 95% confidence interval (95%CI) for the incidence of post-dural puncture headache (PDPH) was calculated, using the random effects model. A contour-enhanced funnel plot was constructed. A TSA was performed and the cumulative Z score, monitoring and futility boundaries were constructed.ResultsOur search identified 13 studies, reporting on 1653 patients, with a low risk of bias. The RR for the incidence of PDPH was 0.82 (95%CI 0.71 to 0.95) and the RR for the need for epidural blood patch was 0.62 (95%CI 0.49 to 0.79); heterogeneity of both analyses was high. The TSA showed that the monitoring or futility boundaries were not crossed, indicating insufficient data to exclude a type I error of statistical analysis. Contour-enhanced funnel plots were symmetric, suggesting no publication bias.ConclusionsConventional meta-analyses showed for the first time that intrathecal catheterisation can reduce the incidence of PDPH. However, TSA did not corroborate this finding. Despite increasing use in clinical practice there is no firm evidence on which to base a definite conclusion.     

全麻复合硬膜外在高龄患者腹腔镜直肠癌根治术中的应用

目的:研究全麻复合硬膜外在高龄患者腹腔镜直肠癌根治术中的应用效果。方法:选择60岁以上择期行腹腔镜直肠癌根治术患者60例,随机分为G组和GA组,每组各30例。G组患者为单纯全麻组,GA组患者为硬膜外复合全麻组。GA组患者在诱导前取L1~2硬膜外穿刺置管,予0.5%罗哌卡因5 ml,术中每小时追加5~7 ml。两组患者诱导方法相同:即,咪哒唑仑0.04 mg/kg、舒芬太尼0.3~0.4μg/kg、顺阿曲库铵0.15~0.20 mg/kg、依托咪酯0.2~0.3 mg/kg。监测并记录患者血压(BP),心率(HR),心电图(ECG),术中全麻药用量及术后患者苏醒情况。结果:GA组患者气腹后、拔管前BP、HR明显低于G组(P<0.05),且全麻药用量明显低于G组(P<0.05)。结论:全麻复合硬膜外应用于老年腹腔镜直肠癌手术较单纯全麻用药量减少,术中循环更加稳定,是腹腔镜直肠癌根治术比较安全可行的麻醉方法。     

CTLA4 antagonists in phase I and phase II clinical trials,current status and future perspectives for cancer therapy

Introduction: In cancer, the immune response to tumor antigens is often suppressed by inhibitors and ligands. Checkpoint blockade, considered one of the most promising frontiers for anti-cancer therapy, aims to stimulate the immune anti-cancer response. Agents such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) inhibitors offer prolonged survival with manageable side effects.

Areas covered: We summarize the recent clinical successes of CTLA-4 inhibitors and place a strong emphasis on those in early phase clinical trials, often in combination with other immune check-point inhibitors, i.e., programmed cell death protein 1 (PD-1) and BRAF/mitogen-activated protein kinase inhibitors.

Expert opinion: Recent phase I and phase II clinical trials confirm the efficacy of anti-CTLA-4 therapy for treatment of cancers such as renal cell carcinoma. These studies also indicated increased efficacy with combined immune checkpoint blockade with PD-1 or Ras/Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) inhibitors. Researchers must search for new immune targets that may enable more effective and safe immune checkpoint blockade and cancer therapy. This goal may be achieved by next-generation combination therapies to overcome immune checkpoint therapy resistance.     

Dural puncture epidural versus conventional epidural block for labor analgesia: a systematic review of randomized controlled trials

IntroductionDural puncture epidural (DPE) analgesia is a modification of conventional epidural analgesia that involves the intentional puncture of the dura with a spinal needle through the needle placed in the epidural space, without a medication being injected intrathecally. There have been contradictory findings regarding better analgesia and better block quality.MethodsA systematic literature search was done to identify randomized controlled trials (RCT) comparing DPE with epidural analgesia. The risk of bias was assessed with the Cochrane tool. Risk ratio and 95% confidence intervals were calculated.ResultsFive RCTs including 581 patients were identified. One RCT on caesarean section was excluded. Single studies suggested slightly better analgesia by finding a median time to achieve sufficient analgesia of two minutes less in the DPE group, a higher number of women having a pain score <10/100 at 20 min, a reduction in the number of epidural top-ups and better sacral spread. The studies did not show a difference between DPE and epidural analgesia for catheter replacement or manipulation rates, the incidence of intravascular placement or unilateral block.ConclusionThere is a lack of clear evidence on either the benefits or the risks of the DPE technique, such that a recommendation for or against its routine use is premature. Two of the three studies showing a beneficial effect of DPE came from the same institution and replication of the findings by other groups is warranted.     

Failure of ivalon to provide permanent hepatic arterial occlusion

Ivalon (polyvinyl alcohol) is a commonly used embolic agent, generally considered to be permanent. In a patient with the carcinoid syndrome, embolization of hepatic metastases with Ivalon failed to produce permanent occlusion, and recurrent tumor was supplied by many of the same small arteries identified on the original arteriogram. Occasionally, Ivalon may have only a temporary occlusive effect. A possible explanation for this phenomenon is proposed.