碘伏胸膜固定术与胸腔镜滑石粉胸膜固定术治疗恶性胸腔积液的对比研究

目的:对乳腺癌胸腔转移的恶性胸腔积液的患者,通过使用胸腔镜滑石粉喷洒和通过胸导管注入聚合碘行胸膜固定术,比较两种方法的有效性、安全性及成功率。方法:42个乳腺癌胸腔转移的恶性胸腔积液的患者纳入了此项前瞻性随机对照研究。所有患者都有中度至重度呼吸困难(MRC呼吸困难量表Ⅲ-Ⅴ级)。22个患者完成胸腔镜滑石粉胸膜固定术(A组),而20例(B组)在床旁完成胸腔注入聚合碘。比较两组患者胸膜固定的成功率,呼吸困难缓解情况,住院时间以及胸痛、发热等并发症发生情况。结果:胸膜固定术成功率两组无明显差异(91%vs 85%,P=0.9),术后并发症两组均较低。手术后,因胸膜炎性胸痛需要止痛处理的A组明显高于B组(18%vs 0,P=0.2)。手术后48小时内,A组患者中有4个病人(18%),B组中1个患者(5%)出现发热(38℃)。治疗后两组呼吸困难症状得到了较好的控制,呼吸困难程度为(Ⅰ-Ⅱ),但两组之间无统计学差异(P0.05)。没有患者在医院内死亡。术后B组患者的住院时间更短(P=0.009)。平均症状无进展时间隔为6.6(范围3-15)月。随访中胸腔积液复发需要从新干预的A组有2例,B组3例。结论:对于乳腺癌转移性胸腔积液,聚合碘可作为胸腔镜滑石粉胸膜固定术外不错的选择。聚合碘容易获得,便宜且安全,可通过胸腔引流管给药,如果必要可以重复操作。     

信息管理系统下胸腔镜胸膜固定术治疗恶性胸腔积液

目的:分析基于信息管理系统的胸腔镜滑石粉胸膜固定术控制恶性胸腔积液患者术后的并发症,死亡率及生存时间。方法:2011年9月至2014年10月,一共400个患者完成了胸腔镜辅下滑石粉胸膜固定术。对手术前后的患者的并发症,死亡率,成功率和中位生存时间进行评价。结果:中位随访时间为40个月(范围4-61月)。所有患者的呼吸困难症状都得到明显缓解。围手术期死亡率为0。患者对这一手术的耐受性良好,没有观察到明显的副作用。院内死亡率为2%,胸膜固定的成功率为85%。较差的KS评分及胸腔积液诊断到完成胸膜固定术之间的时间延误与院内死亡的发生明显相关。乳腺癌的生存情况最好,其次为卵巢癌,淋巴瘤和胸膜间皮瘤。结论:胸腔镜滑石粉胸膜固定术是一项安全有效的操作,胸膜固定的成功率较高,呼吸困难会能够得到长期有效的控制。     

血清和胸水中CA125在结核性和癌性胸水中的表达及临床意义

目的:探讨血清和胸水中CA125在结核性和癌性胸水中的表达及鉴别诊断意义。方法:抽选我院确诊的结核性胸水病人85例(结核组)和癌性胸水病人71例(癌症组),检测两组患者血清和胸水中CA125表达,并以胸水/血清中CA125比值10(p-CA125/s-CA12510)为临界值,观察其对癌性胸水的鉴别特异度、灵敏度及准确性。结果:癌症组胸水中CA125表达及p-CA125/s-CA125比值均显著高于结核组(P0.05);但血清中两组CA125表达比较差异无显著性(P0.05);两组胸水中,以35U/ml为临界值,两组患者阳性率92.9%(79/85)、100%(71/71)比较差异无显著性(X2=7.0718,P=0.0078)。癌症组中p-CA125/sCA125比值10的比率(84.5%VS 17.6%)明显高于结核组(X2=66.6244,P=0.0000);并以其为诊断癌性胸水的临界值,鉴别诊断特异度、灵敏度及准确性分别为82.3%、84.5%、83.3%。结论:血清和胸水中CA125表达对于鉴别结核性或者是癌性胸水的临床意义不大,但是p-CA125/s-CA125比值对于鉴别结核性和癌性胸水具有一定临床价值。     

Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis

Background

Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion.

Methods

PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model.

Results

In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90–0.96), specificity of 0.91 (95% CI: 0.86–0.95), positive likelihood ratio of 10.9 (95% CI: 6.4–18.6), negative likelihood ratio of 0.07 (95% CI: 0.04–0.12), and diagnostic odds ratio of 157 (95% CI: 57–430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86–0.95), with a specificity of 0.88 (95% CI: 0.77–0.94), positive likelihood ratio of 7.8 (95% CI: 3.7–16.3), negative likelihood ratio of 0.10 (95% CI: 0.06–0.16), and diagnostic odds ratio of 81 (95% CI: 27–241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies.

Conclusions

BNP, NT-proBNP, and MR-proANP, either in blood or PF, are effective tools for diagnosis of HF. Additional studies are needed to rigorously evaluate the diagnostic accuracy of PF and blood MR-proANP and BNP for the diagnosis of HF.     

腺苷脱氨酶在结核性胸膜炎和恶性胸腔积液的对比临床分析

目的：探究腺苷脱氨酶在结核性胸腔积液和恶性胸腔积液中的含量规律。方法：回顾分析自2010年3月至2012年5月于本院胸心外科住院的胸腔积液患者,对穿刺获得的胸腔积液,用比色法测定胸腔积液中腺苷脱氨酶的水平。测量血中腺苷脱氨酶的水平进行对比。结果：结核性胸膜炎组患者胸腔积液ADA测定值为89．67±47．85IU／L,癌性胸腔积液组水平为24．56±11．491U／L,胸腔积液ADA水平在结核性胸膜炎与癌性胸腔积液组之间存在显著性差异（P〈0．05）;以ADA〉45IU／L诊断结核性胸膜炎：则敏感性为（48／51）94．1,特异性为（48／52）88．9％,以ADA〈45IU／L一诊断恶性胸腔积水：则敏感性（（51／55）89．4％,特异性为（51／54）94．4％;结核性胸膜炎中胸腔积液ADA／血清中ADA比值为2．25±0．72,癌性胸腔积液组水平0．43＋0．1,结核性胸膜炎与癌性胸腔积液组之间存在显著性差异（P〈0．05）;以胸腔积液ADA／血清中ADA比值〉1．0为界诊断结核性胸膜炎：则敏感性为（46／51）90．1,特异性为（45／55）81．8．％,以胸腔积液ADA／血清中ADA比值〈1．0诊断恶性胸腔积水：则敏感性（47／57）82．4％,特异性为（47／53）88．7％。结论：腺苷脱氨酶在结核性胸膜炎和恶性胸腔积液中的含量有明显差异。     

香菇多糖与金葡素治疗恶性胸腔积液的临床研究

目的:恶性胸腔积液是晚期非小细胞肺癌常见的并发症,严重影响患者的生活质量及预后。治疗恶性胸腔积液的方法虽多,但疗效有限,且目前尚无统一的治疗规范。本研究通过向胸腔内注入香菇多糖和金葡素,观察其治疗恶性胸腔积液的疗效和安全性。方法:60例恶性胸腔积液患者随机分成两组,每组30例:A组(香菇多糖组),B组(金葡素组)。通过胸腔闭式引流术排净胸腔积液后,分别向胸腔内注入香菇多糖、金葡素,评价两组的有效率和毒副反应。结果:两组疗效显著:香菇多糖组CR 11例,PR 12例,NC 3例,PD 4例,治疗有效率为76.7%,金葡素组CR 14例,PR 11例,NC 4例,PD 2例,治疗有效率为83.3%,两组疗效比较无显著性差异(x2=0.42,P0.05);两组毒副反应轻微,主要为骨髓抑制、胃肠道反应和发热,两组毒副反应比较无显著性差异(x2=0.58,P0.05),全组无毒性相关死亡。结论:胸腔内注入香菇多糖和金葡素可有效杀灭肿瘤细胞、促进胸膜粘连,显著缓解症状,提高机体免疫功能,改善生活质量和预后。二者疗效相当,不良反应轻微,值得临床大力推荐应用。     

Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis

Aim

The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome.

Methods

We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis.

Results

Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score ≥4). Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77). In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71), while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28). The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99). The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17). In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37). Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups.

Conclusions

TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS.     

Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials

BackgroundMethotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse.ObjectiveIn order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods).ResultsIn terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1–60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5–5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1–14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time.LimitationsMeta-analyses for efficacy and safety, respectively, employed non-identical selection criteria.ConclusionsThese meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes.     

Recombinant Human Endostatin Endostar Suppresses Angiogenesis and Lymphangiogenesis of Malignant Pleural Effusion in Mice

Background

Malignant pleural effusion (MPE) is a common complication of lung cancer. One widely used treatment for MPE is Endostar, a recombined humanized endostatin based treatment. However, the mechanism of this treatment is still unclear. The aim of this study was to investigate the effects of Endostar in mice with MPE.

Methods and Materials

Lewis lung carcinoma (LLC) cell line expressing enhanced green fluorescent protein (EGFP) was injected into pleural cavity to establish MPE mice model. Mice were randomly divided into four groups. High dose of Endostar (30 mg/kg), low dose of Endostar (8 mg/kg), normal saline, or Bevacizumab (5 mg/kg) was respectively injected into pleural cavity three times with 3-day interval in each group. Transverse computed tomography (CT) was performed to observe pleural fluid formation 14 days after LLC cells injection. Mice were anesthetized and sacrificed 3 days after final administration. The volume of pleural effusion n was measured using 1 ml syringe. Micro blood vessel density (MVD), Lymphatic micro vessel density (LMVD), the expression level of vascular endothelial growth factor A (VEGF-A) and VEGF-C were observed by immunohistochemistry (IHC) staining.

Results

The volume of pleural effusion as well as the number of pleural tumor foci, MVD and the expression of VEGF-A were significantly reduced in high dose of Endostar treat group. More importantly, LMVD and the expression of VEGF-C were markedly lower in treat group than those in the other three control groups.

Conclusion

Our work demonstrated that Endostar played an efficient anti-cancer role in MPE through its suppressive effect on angiogenesis and lymphangiogenesis, which provided a certain theoretical basis for the effectiveness of Endostar on the MPE treatment.     

Beneficial Impact of CCL2 and CCL12 Neutralization on Experimental Malignant Pleural Effusion

Using genetic interventions, we previously determined that C-C motif chemokine ligand 2 (CCL2) promotes malignant pleural effusion (MPE) formation in mice. Here we conducted preclinical studies aimed at assessing the specific therapeutic potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous delivery of lung (LLC) or colon (MC38) adenocarcinoma cells. Human lung adenocarcinoma cells (A549) were used to induce MPEs in severe combined immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three days. We found that high doses of CCL2/12 neutralizing antibody treatment (50 mg/kg) were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and CCL12 neutralization was also effective against MC38-induced MPE and prolonged the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was associated with inhibition of immune and vascular MPE-related phenomena, such as inflammation, new blood vessel assembly and plasma extravasation into the pleural space. We conclude that CCL2 and CCL12 blockade are effective against experimental MPE induced by murine and human adenocarcinoma in mice. These results suggest that CCL2-targeted therapies may hold promise for future use against human MPE.     

Effects of Intracavitary Administration of Endostar Combined with Cisplatin in Malignant Pleural Effusion and Ascites

This study evaluated the efficacy and safety of intracavitary administration of recombinant human endostatin (Endostar) combined with cisplatin chemotherapy in treating malignant pleural effusion and ascites. Forty-five patients with malignant pleural effusion and ascites were divided into the EP group (n = 23), who received Endostar and cisplatin intracavitarily, and P group (n = 22), who were intracavitarily treated with cisplatin only. Pleural effusion and ascites were completely drained before treatments. The treatment was administered once a week; two treatments were considered as one course. The outcome quality of life as well as toxicity were evaluated. The objective overall response and disease control rates were, respectively, 78.3 % (18/23) and 87.0 % (20/23) in EP group. In contrast, these parameters were significantly (p < 0.05) lower in P groups: 40.9 % (9/22) and 59.1 % (13/22), respectively. The improvement rate of Karnofsky Performance Status was 87.0 % (20/23) in EP group versus 59.1 % (13/22) in P group (p < 0.05). All patients tolerated the combined treatment well, and no severe adverse effects were observed. Intracavitary injection of Endostar combined with cisplatin is effective and safe to treat malignant pleural effusion and ascites.     

Clinical Efficacy and Safety of Nerve-Sparing Radical Hysterectomy for Cervical Cancer: A Systematic Review and Meta-Analysis

Backgroud and Objective

Nerve-sparing radical hysterectomy (NSRH) may be associated with lower postoperative morbidity than radical hysterectomy (RH). We aimed to compare the clinical efficacy and safety of abdominal or laparoscopic NSRH and RH for treating cervical cancer through systematic review and meta-analysis.

Methods

PubMed, EMBASE, The Cochrane Library and the Chinese National Knowledge Infrastructure databases were systematically searched for all relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to compare intra- and postoperative outcomes for the two techniques.

Results

A total of 17 clinical trials were identified. Meta-analysis showed that although operating time was significantly longer for abdominal or laparoscopic NSRH than for RH, NSRH based on laparotomy or laparoscopy proved more effective for postoperative recovery of bladder function. NSRH was also associated with lower bladder dysfunction morbidity and fewer postoperative complications. Two abdominal trials and one laparoscopic study further suggested that NSRH was associated with shorter time to recovery of anal/rectal function. In contrast, RH and NSRH based on laparotomy or laparoscopy were similar in terms of extent of resection, recurrence rate, survival rate, blood loss and frequency of intraoperative complications. The meta-analysis showed that abdominal NSRH was not significantly different from RH in length of hospital stay, while one trial suggested that length of hospital stay was shorter after laparoscopic NSRH than after the corresponding RH.

Conclusion

NSRH may be a reliable technique for treating early cervical cancer. Available evidence suggests that it is better than RH for postoperative recovery of pelvic organ function and postoperative morbidity, while the two techniques involve similar clinical safety and extent of resection. These results should be considered preliminary since they are based on a relatively small number of controlled trials, most of which were non-randomized. The findings should be verified in larger, well-designed studies.     

Efficacy and Safety of Deep Anterior Lamellar Keratoplasty vs. Penetrating Keratoplasty for Keratoconus: A Meta-Analysis

Purpose

To evaluate difference in therapeutic outcomes between deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PKP) for the clinical treatment of keratoconus.

Methods

A comprehensive search was conducted in Pubmed, EMBASE, Cochrane Library, and Web of science. Eligible studies should include at least one of the following factors: best corrected visual acuity (BCVA), postoperative spherical equivalent (SE), postoperative astigmatism and endothelial cell count (ECC), central corneal thickness (CCT), graft rejection and graft failure, of which BCVA, graft rejection and graft failure were used as the primary outcome measures, and postoperative SE, astigmatism, CCT and ECC as the secondary outcome measures. Given the lack of randomized clinical trials (RCTs), cohort studies and prospective studies were considered eligible.

Results

Sixteen clinical trials involving 6625 eyes were included in this review, including 1185 eyes in DALK group, and 5440 eyes in PKP group. The outcomes were analyzed using Cochrane Review Manager (RevMan) version 5.0 software. The postoperative BCVA in DALK group was significantly better than that in PKP group (OR = 0.48; 95%CI 0.39 to 0.60; p<0.001). There were fewer cases of graft rejection in DALK group than those in PKP group (OR = 0.28; 95%CI 0.15 to 0.50; p<0.001). Nevertheless the rate of graft failure was similar between DALK and PKP groups (OR = 1.05; 95%CI 0.81 to 1.36; p = 0.73). There were no significant differences in the secondary outcomes of SE (p = 0.70), astigmatism (p = 0.14) and CCT (p = 0.58) between DALK and PKP groups. And ECC in DALK group was significantly higher than PKP group (p<0.001). The postoperative complications, high intraocular pressure (high-IOP) and cataract were analyzed, fewer cases of complications occurred in DALK group than those in PKP group (high-IOP, OR 0.22, 95% CI 0.11–0.44, P<0.001) (cataract, OR 0.22; 95% CI 0.08–0.61, P = 0.004). And no cases of expulsive hemorrhage and endophthalmitis were reported.

Conclusion

The visual outcomes for DALK were not equivalent to PKP. The rate of graft failure was similar between DALK and PKP. Fewer postoperative complications occurred in DALK group, indicating that compared with PKP, DALK has lower efficacy but higher safety.     

The Malignant Pleural Effusion as a Model to Investigate Intratumoral Heterogeneity in Lung Cancer

Malignant Pleural Effusions (MPE) may be useful as a model to study hierarchical progression of cancer and/or intratumoral heterogeneity. To strengthen the rationale for developing the MPE-model for these purposes, we set out to find evidence for the presence of cancer stem cells (CSC) in MPE and demonstrate an ability to sustain intratumoral heterogeneity in MPE-primary cultures. Our studies show that candidate lung CSC-expression signatures (PTEN, OCT4, hTERT, Bmi1, EZH2 and SUZ12) are evident in cell pellets isolated from MPE, and MPE-cytopathology also labels candidate-CSC (CD44, cMET, MDR-1, ALDH) subpopulations. Moreover, in primary cultures that use MPE as the source of both tumor cells and the tumor microenvironment (TME), candidate CSC are maintained over time. This allows us to live-sort candidate CSC-fractions from the MPE-tumor mix on the basis of surface markers (CD44, c-MET, uPAR, MDR-1) or differences in xenobiotic metabolism (ALDH). Thus, MPE-primary cultures provide an avenue to extract candidate CSC populations from individual (isogenic) MPE-tumors. This will allow us to test whether these cells can be discriminated in functional bioassays. Tumor heterogeneity in MPE-primary cultures is evidenced by variable immunolabeling, differences in colony-morphology, and differences in proliferation rates of cell subpopulations. Collectively, these data justify the ongoing development of the MPE-model for the investigation of intratumoral heterogeneity, tumor-TME interactions, and phenotypic validation of candidate lung CSC, in addition to providing direction for the pre-clinical development of rational therapeutics.