新辅助化疗后乳腺癌组织中survivin和Ki-67的表达及意义

目的 探讨CTF方案新辅助化疗后乳腺癌组织survivin和Ki-67的表达及其临床意义.方法 应用免疫组化SABC法检测60例行新辅助化疗和60例未行新辅助化疗的乳腺癌组织中survivin 和Ki-67的表达水平.结果 新辅助化疗组survivin和Ki-67阳性率分别为36.7%和38.3%,明显低于对照组的71.7%和61.7%(均P＜0.05);新辅助化疗组survivin的表达与Ki-67表达呈正相关(r=0.47,P＜0.05).新辅助化疗组总有效率73.3%;化疗后部分缓解者survivin阳性率为18.2%,明显低于无效者的81.3%(P＜0.01);化疗后部分缓解者Ki-67阳性率为47.7%,低于无效者的56.3%(P＞0.05).结论 应用CTF方案新辅助化疗缓解率高,近期疗效明显.CTF化疗药物,可能通过抑制乳腺癌survivin表达而抑制肿瘤的增殖.     

表阿霉素联合多西紫杉醇新辅助化疗治疗三阴乳腺癌的疗效及预后评价

目的探讨三阴乳腺癌(TNBC)与非三阴乳腺癌(non-TNBC)接受表阿霉素联合多西紫杉醇方案(ET方案)的化疗敏感性及预后方面的差别。方法对接受ET新辅助化疗方案治疗的249例乳腺癌患者进行回顾性分析。依据免疫组化雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体2(HER2)表达水平将乳腺癌分为三阴乳腺癌及非三阴乳腺癌两类,分析三阴与非三阴乳腺患者接受ET新辅助化疗方案后,二者病理疗效及远期生存的差别。结果 249例患者中,54(21.7%)例为三阴乳腺癌,195(78.3%)例为非三阴乳腺癌。三阴乳腺癌的病理完全缓解(pCR)率为25.9%,明显高于非三阴乳腺癌的12.3%(P=0.019)。三阴乳腺癌患者,特别是新辅助化疗后仍有癌残留的患者,其5年无病生存率(DFS)及5年的总生存率(OS)均明显低于非三阴乳腺癌(P值均<0.05)。获得pCR的乳腺癌患者5年的DFS和OS均明显高于化疗后仍有癌残留的患者(P值均<0.05)。获得pCR的三阴乳腺癌与非三阴乳腺癌患者的DFS(P=0.837)及OS(P=0.398)均无统计学差异。结论本研究结果表明,相比于非三阴乳腺癌患者,三阴乳腺癌患者具有更高的病理完全缓解率,但预后却较差。     

表阿霉素联合多西紫杉醇新辅助化疗治疗三阴、非三阴乳腺癌的疗效及预后评价

目的比较表阿霉素联合多西紫杉醇新辅助化疗方案(ET方案)对三阴乳腺癌(TNBC)和非三阴乳腺癌(non-TNBC)的临床疗效及预后差别。方法回顾性分析接受ET新辅助化疗方案治疗的198例乳腺癌患者的临床资料,依据免疫组化结果将乳腺癌分为TNBC及non-TNBC两组,对两类乳腺患者接受ET新辅助化疗方案后的病理疗效及预后的差别进行分析比较。结果 198例乳腺癌患者中,TNBC43例,non-TNBC155例。所有患者的临床总有效率(cOR)为76.8%,其中完全缓解率24.7%,部分缓解率48.5%;TNBC患者的临床有效率84.2%,病理完全缓解率(pCR)27.9%;non-TNBC患者临床有效率70.4%,病理完全缓解率12.9%。TNBC患者与非TNBC患者5年无病生存率(DFS)分别为52.9%和70.9%(P<0.05);TNBC患者与非TNBC患者5年总体生存率分别为59.1%和80.5%(P<0.05)。结论表阿霉素联合多西紫杉醇新辅助化疗方案治疗三阴乳腺癌患者能够获得较好的临床效果。     

ET方案新辅助化疗对乳腺癌组织中CXCR4表达的影响及临床意义

目的探讨ET方案新辅助化疗对乳腺癌组织中CXCR4表达的影响及临床意义。方法回顾性分析我院2005年4月至2009年3月期间59例接受3周期ET(紫杉醇+表阿霉素)方案新辅助化疗的Ⅱ期、Ⅲ期乳腺癌患者的临床资料,应用免疫组化方法检测乳腺癌组织中CXCR4的表达情况,分析其与临床病理特征的关系。结果 CXCR4在乳腺癌组织中的表达阳性率为94.9%(56/59),在癌旁正常组织中不表达。CXCR4表达水平与淋巴结转移(P=0.019)及肿瘤TNM分期有关(P=0.040),与患者年龄、肿瘤大小、组织学分级、ER和PR状态以及HER2表型无关(P0.05)。新辅助化疗后CXCR4表达水平下降,但CXCR4的表达水平及化疗后下降的比例与化疗疗效无关(P0.05)。CXCR4的表达分布状态中呈簇状分布者化疗疗效好于呈散在分布者(P=0.015)。结论 ET方案新辅助化疗后乳腺癌组织中CXCR4的表达水平下降比例与化疗疗效无关,但其表达的分布状态可作为新辅助化疗疗效的参考指标。     

P53和Ki-67的表达变化与三阴性乳腺癌pCR的关系研究

目的探讨三阴性乳腺癌新辅助化疗前后P53和Ki-67的表达变化,及其与病理完全缓解率(pCR)间的关系。方法选取2016-01-2018-12间就诊的73例三阴性乳腺癌患者的病史及病理资料,均经空心针穿刺病理确诊,并接受表柔比星联合多西他赛新辅助化疗。8周期化疗后行乳腺癌改良或保乳根治术。探讨新辅助化疗前后P53和Ki-67表达变化及其与pCR间的关系。结果73例患者总体pCR为30.1%(22/73),其中P53阳性组pCR为38%(19/50)、Ki-67高表达组pCR为39.2%(20/51)、Ki-67高表达且P53阳性组pCR高达48.6%(17/35),明显高于其他组。化疗后P53阳性表达率及Ki-67表达率均明显下降,其中P53阳性组有21例转为阴性组,pCR达71.4%。结论结合化疗前后P53及Ki-67的表达变化有助于预测三阴性乳腺癌新辅助化疗的pCR。     

应变力超声弹性成像预测乳腺癌患者新辅助化疗后病理完全缓解

目的评估应变力超声弹性成像(SUE)技术预测乳腺癌患者新辅助化疗(NAC)后病理完全缓解(pCR)的效能。方法收集乳腺癌患者60例,采用SUE评估NAC前肿瘤的弹性评分和弹性应变率比值,记录肿瘤穿刺活检的免疫组化结果,术后病理参照Miller-Panye分级法评估病理反应性,采用Logistic回归分析获得影响NAC后pCR的独立影响因素。绘制不同指标预测pCR结局的ROC曲线,并计算曲线下面积(AUC),Z检验比较不同指标的AUC。结果高弹性评分是pCR的独立影响因素。弹性应变率比值的预测效能最佳,AUC为0.92±0.03,且与Ki-67(0.60±0.08)的AUC比较差异有统计学意义(P0.01);而弹性应变率比值与弹性评分(0.89±0.05)的AUC差异无统计学意义(P=0.36)。结论 SUE评估乳腺癌硬度可预测NAC后pCR结局,在乳腺癌的个体化精准治疗中有重要作用。     

ET与CEF新辅助化疗方案的临床疗效比较

目的比较ET与CEF两种不同新辅助化疗方案治疗乳腺癌的疗效及不良反应。方法收集130例Ⅱa-Ⅲc期乳腺癌患者，分为两组，分别接受ET组（多西紫杉醇加表阿霉素）和CEF组（环磷酰胺加表阿霉素加5-Fu）化疗方案治疗。其中ET组64例，CEF组66例，化疗21天为1个周期。所有的患者均完成2—4个周期新辅助化疗后评价疗效。结果乳腺癌新辅助化疗总有效率（ORR）ET组为85．9％（57／64），CEF组为71．2％（47／66）。主要不良反应是脱发、乏力、恶心、呕吐、腹泻，两组间不良反应无显著性差异。ET组3度以上粒细胞缺乏、粒细胞缺乏性发热、外周性水肿、关节痛、肌痛、神经感觉异常发生率较CEF组高（P〈0．05），但不良反应均可耐受。结论两组新辅助化疗方案对乳腺癌的原发肿瘤均有效。ET组的疗效及不良反应均高于CEF组。     

Ⅱ期和ⅢA期可手术乳腺癌新辅助化疗的疗效观察

目的 探讨Ⅱ期和ⅢA期(仅指T3N1M0)可手术乳腺癌新辅助化疗的效果,评价新辅助化疗在Ⅱ、ⅢA期乳腺癌治疗中的价值;初步探讨肿瘤大小与病理完全缓解的关系;初步分析新辅助化疗的应用选择.方法 回顾分析北京友谊医院普外科收治的可手术乳腺癌临床病例共408例,分为A组(新辅助化疗组)及B组(对照组),A组Ⅱ期106例、ⅢA期112例,B组Ⅱ期92例、ⅢA期98例,A组应用新辅助化疗4个周期,随后进行手术,术后辅助化疗、放疗.B组不做任何形式的术前辅助治疗,手术和术后其他治疗与A组相同,比较两组的近期疗效、术式选择、局部控制率和5年生存率.结果 A组Ⅱ期可保乳率由23.6％提高到49.1％ (P=0.000),两组Ⅱ期5年总生存率和无瘤生存率差异无统计学意义(P =0.939、0.858);A组ⅢA期患者5年总生存率(59.8％)和无瘤生存率(51.8％),均高于B组(35.7％、27.6％)(P=0.000、0.000);3年局部复发转移率A组(7.9％)低于B组(18.4％)(P＜0.05);肿瘤小于3.0 cm易达到病理完全缓解(P =0.001),预后情况好(P=0.000).结论 新辅助化疗可提高Ⅱ、ⅢA期可手术乳腺癌患者的保乳率、降低局部复发转移率;可提高ⅢA期乳腺癌患者的5年生存率;新辅助化疗能达到临床和病理完全缓解患者5年总生存率和无瘤生存率更高;肿瘤大小是影响乳腺癌新辅助化疗病理完全缓解的独立因素,病灶小易达到完全缓解.     

TAC与TC新辅助化疗方案治疗局部晚期乳腺癌疗效比较

目的 比较TAC与TC新辅助化疗方案治疗局部晚期乳腺癌的临床疗效和不良反应.方法 经病理等检查确诊局部晚期乳腺癌患者257例,随机分为TAC组(130例)及TC组(127例),分别给予TAC方案、TC方案化疗4个周期.TAC组129例、TC组124例化疗结束2周后行乳腺癌改良根治术.比较TAC组、TC组疗效和不良反应,治疗前、后TNM分期变化及术后并发症.结果 临床疗效比较TAC组优于TC组,其差异有统计学意义(P＜0.05);TNM分期较新辅助化疗前降低(P＜0.05),不良反应比较差异无统计学意义(P＞0.05);术后并发症比较差异无统计学意义(P＞0.05).结论 TAC及TC新辅助化疗方案对局部晚期乳腺癌均有效,TAC方案优于TC方案.     

局部晚期乳腺癌新辅助化疗预后因素分析

目的 探讨术前接受长春瑞滨联合表柔比星(VE)方案治疗的局部晚期乳腺癌的预后影响因素.方法 回顾分析2001年9月至2006年5月术前接受3个周期VE方案化疗的119例局部晚期乳腺癌患者的临床病理资料.所有患者均经术前空心针活检证实为浸润性乳腺癌,新辅助化疗后接受手术治疗.术后根据新辅助化疗的临床疗效,再继续接受3个周期VE或标准的环磷酰胺+表柔比星+氟尿嘧啶(CEF)方案辅助化疗及局部区域放射治疗和相应的内分泌治疗.分析新辅助化疗前及术后临床病理资料与预后的关系.结果 新辅助化疗后临床完全缓解27例(22.7%),部分缓解78例(65.5%);肿瘤原发灶病理完全缓解(pCR)22例(18.5%).本组115例(96.6%)获得随访,随访时间9～76个月,中位时间63.4个月.无局部复发转移患者共72例(60.5%).5年无病生存率为58.7%,5年总生存率为71.3%.多因素分析显示,新辅助化疗前Ki-67(pre-Ki-67)高表达(P=0.012)、化疗后Ki-67(post-Ki-67)高表达(P=0.045)、化疗后病理未完全缓解(P=0.034)与无病生存时间的降低有关;pre-Ki-67高表达(P=0.017)、post-Ki-67高表达(P=0.001)、pre-ER阴性(P=0.002)、化疗后病理未完全缓解(P=0.034)与总生存时间的降低有关.结论 pre-Ki-67、post-Ki-67及pre-ER的表达水平和新辅助化疗后肿瘤原发灶病理状况是接受术前3个周期VE新辅助化疗局部晚期乳腺癌的独立预后因素.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.