局部进展期胃癌动静脉结合的术前化疗——临床研究与存在的问题

正局部进展期胃癌的手术模式基本定型,疗效几近极限。化疗效果不理想,分子靶向药物、免疫治疗也难发挥重要作用。笔者针对局部进展期胃癌进行动静脉结合的术前化疗,临床实践与研究已达15年。采用现有药物,通过动静脉不同的给药途径,使时间依赖性药物与浓度依赖性药物的作用得到充分发挥,术前化疗效果得到大幅度提高。临床实践与研究中发现很多实际问题。如癌肿影像学形态的变     

静脉结合给药的FLEP法治疗难以切除的晚期胃癌

目的:为提高胃癌新辅助化疗的效果,观察动静脉结合的FLEP化疗方法对难以切除局部晚期胃癌的疗效.方法:2003年1月至2006年1月选择30例难以切除的晚期胃癌,以FLEP法化疗.FLEP方案:5-FU 370 mg/(m2·d),持续静脉滴注20h,第1～5天;四氢叶酸钙30mg/(m2·d),静脉滴注,第1～5天;...     

动静脉联合给药的FLEOX新辅助化疗加营养支持提高晚期胃癌可切除率

目的总结动静脉联合给药的FLEOX新辅助化疗加营养支持对以淋巴结转移为主的晚期胃癌的手术可切除率。方法对术前CT检查发现伴有严重的第3、7、9、12组淋巴结转移、或第14、16组淋巴结转移而难以切除的50例晚期胃癌患者进行新辅助化疗：氟尿嘧啶（5．FU）370mg／m^2，静滴，第1～5天；亚叶酸钙200mg静滴，第1～5天；足叶乙苷80mg／m^2与奥沙利铂120mg／m^2经动脉注射，第6、20天；每5周重复1次。其中12例伴有中、重度营养不良者酌情进行肠外、肠内营养支持，状况好转后进行化疗，以使患者获得手术切除的机会。结果50例晚期胃癌患者的影像学及组织学评价有效率（CR加PR）为84．0％；12例伴营养不良的病例在化疗结束、拟行手术前体重均较入院时明显增加，血清白蛋白等营养指标恢复正常。手术切除率为78．0％，全组均成功进行了胃次全切除、全胃或联合脏器切除和D2＋α、D3淋巴结清扫术。结论动静脉联合给药的FLEOX新辅助化疗加合理的营养支持对以淋巴结转移为主的晚期胃癌具有满意的治疗效果。     

胃癌新辅助化疗后的疗效评估研究进展

术前新辅助化疗作为局部进展期胃癌的标准治疗模式之一，能有效提高R0切除率和降低肿瘤复发率。目前影像学技术、临床生物学以及病理学指标已广泛用于胃癌新辅助化疗后的疗效评估，可为指导个体化新辅助化疗提供依据。该文就胃癌新辅助化疗后的疗效评估研究进展进行了综述，以期为临床实践提供参考。     

进展期胃癌新辅助化疗的研究进展

目的总结进展期胃癌新辅助化疗的研究进展。方法采用文献复习的方法,对有关进展期胃癌新辅助化疗研究进展的文献进行综述。结果进展期胃癌的新辅助化疗可显著提高R0切除率,提高远期生存率,降低死亡风险。对于无远处转移的局部进展期胃癌的新辅助化疗时间一般为6~9周,然后根据疗效评价结果决定是否进行手术治疗;进一步深入的临床研究及化疗敏感程度检测方法的改进有助于新辅助化疗标准的统一。结论进展期胃癌新辅助化疗的疗效已比较明确,但其在适应证、化疗方案、用药时限、疗效评价指标等方面尚无明确的统一标准,仍需要多中心、大型的临床试验进行深入的研究。     

新辅助化疗对进展期胃癌患者术后肺部感染的影响

目的探讨新辅助化疗对进展期胃癌患者术后肺部感染的影响。方法按随机数字表法将2009年1月至2011年1月间在南京军区南京总医院接受治疗的139例伴有淋巴结转移的胃癌病例（排除术前重度肺功能障碍者）,随机分为新辅助化疗组[69例,动静脉结合新辅助化疗（静脉用药：氟尿嘧啶、亚叶酸：动脉介入：奥沙利铂、表阿霉素、依托泊甙）1个半疗程后接受手术]和直接手术组（70例）,比较两组病例术后肺部感染的发生情况。结果两组病例术前一般情况的比较差异无统计学意义（均P〉0．05）。所有病例均顺利实施D2胃癌根治手术,术后新辅助化疗组和直接手术组分别有8例（11．6％）和9例（12．9％）患者出现肺部感染,差异无统计学意义（P〉0.05）。结论动静脉结合新辅助化疗不会增加胃癌患者术后肺部感染发生率,可安全应用。     

胃癌新辅助化疗疗效临床评价方法及进展

目的研究胃癌新辅助化疗疗效临床评价方法及进展。方法对有关胃癌新辅助化疗疗效临床评价方法的文献进行综述分析,比较CT、EUS、MRI及PET的评价结果与术后病理、预后结果的符合度。结果CT、EUS是目前临床中常用的疗效评价方法,但是其评价指标和标准不统一,胃癌套用现有的实体瘤疗效评价标准似乎并不适用;采用磁共振扩散加权成像(DWI)评价胃癌新辅助化疗疗效还有待进一步研究;PET在早期准确筛选出化疗无效病例方面具有优势。结论胃癌新辅助化疗疗效临床评价尚缺乏统一标准,各种影像学方法的综合应用可能有利于提高评价的准确性。     

胃癌新辅助化疗前后多药耐药基因的表达及其与化疗敏感性的关系

目的 探讨6种多药耐药基因:G谷胱甘肽S转移酶(GST-π)、肺耐药相关蛋白(LRP)、多药耐药相关蛋白(MRP)、拓扑异构酶Ⅱ(Topo Ⅱ)、多药耐药基因蛋白(P-gP)、胸苷酸合成酶(TS)在胃癌新辅助化疗前后的表达及其与化疗敏感性的关系,寻求建立化疗敏感性的预测指标.方法 采用免疫组化方法评价35例胃癌新辅助化疗前后6种多药耐药基因的表达情况,分析各耐药基因表达与化疗疗效的关系.对所有患者均行FOLFOX4方案化疗,以WHO实体瘤疗效评价标准评价疗效.结果 本组35例患者中1例完全缓解(3%),15例部分缓解(43%),16例病情稳定(46%),3例病情进展(9%),新辅助化疗有效率为46%.35例患者肿瘤标本中6种多药耐药基因的表达情况:GST-π阳性率为40%,LRP阳性率为69%,MRP阳性率为34%,TopoⅡ阳性率为37%,P-gp阳性率为86%,TS阳性率为40%.GST-π、LRP、MRP、Topo Ⅱ、P-gP的表达与化疗敏感性无关(P>0.05),TS的表达与化疗敏感性有关(P=0.0048).结论 FOLFOX4方案新辅助化疗不影响6种多药耐药基因GST-π、LRP、MRP、Topo Ⅱ、P-gP及TS的表达;TS的表达与化疗敏感性有关,有可能成为评估胃癌化疗敏感性的重要指标.     

胃癌新辅助化疗与康莱特的近期临床和病理研究

目的：观察新辅助化疗加中药康莱特注射液治疗胃癌的疗效。方法：８１例胃癌病人行新辅助化学，其中２２例行加中药康莱特注射液的经疗，观察临床症状变化、病理变化和Ｔ淋巴细胞亚群的变化。结果：临床太改善率７５．３％，组织病理学有效率６８．９％，列达到显效（ｈｉｓＣＲ）。结论：胃癌的新辅助化疗能提高胃癌的综合治疗疗效，加用小剂量中药康莱特注射液对改善化疗后的免疫功能下降无效。提示对化疗后的免疫功能下和应引起重     

区域动脉灌注化疗在进展期胃癌短程新辅助化疗中的应用

目的 探讨短程新辅助化疗应用于进展期胃癌的可行性,并比较不同化疗方式短程新辅助化疗的临床疗效.方法 回顾性分析2008年1月至201 1年12月间在南京中医药大学附属医院接受短程（1个周期）EOF方案（表柔比星、奥沙利铂、氟尿嘧啶加亚叶酸钙）新辅助化疗的310例进展期胃癌患者的临床资料.比较全身静脉化疗方案与区域动脉灌注化疗方案的临床疗效.结果 310例患者均完成了1个周期的短程EOF方案新辅助化疗,无一例因化疗毒副反应而终止.术后病理缓解率为33.9％（105/310）,其中5例（1.6％）获病理完全缓解.接受区域动脉灌注化疗者的病理缓解率为42.4％（72/170）,明显高于全身静脉化疗者的23.6％ （33/140） （P=0.001）.Logistic多因素回归分析证实,化疗方式是影响进展期胃癌短程新辅助化疗后病理缓解率的独立危险因素（HR=1.827; 95％ CI：1.006～3.316; P=0.048）.结论 进展期胃癌短程新辅助化疗病理缓解率总体较低;区域动脉灌注化疗能提高进展期胃癌短程新辅助化疗的术后病理缓解率。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

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.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Intrathecal administration of sameridine to patients subjected to arthroscopic knee joint surgery

Background: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i. e. in patients subjected to arthroscopic knee joint surgery.
Method: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group.
Results: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5–Th7, was reached within 30 min with a median duration of 3.6–3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i. v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33).
Conclusion: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.     

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.