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晚期结直肠癌在结直肠癌病人中占有较高比例,联合脏器切除手术是其惟一可能治愈的手段,R0切除是这类手术的核心,需要严格遵守手术适应证。多学科综合治疗模式是保证晚期结直肠癌病人获得最佳治疗的根本,已成为晚期结直肠癌治疗的标准模式。     

EGFR靶向药物西妥昔单抗在结直肠癌治疗中的应用进展

结直肠癌是最常见的恶性肿瘤,随着人类平均寿命的提高,生存环境及生活方式的改变,近年来结直肠癌的发病率呈逐年上升趋势,在发达国家及我国经济发达地区,结直肠癌的发病率已上升至恶性肿瘤的第2位.全球每年新增病例约100万,死亡病例约50万,结直肠癌已经成为全球恶性肿瘤导致死亡的主要原因之一.近年来分子靶向药物的出现使晚期结直肠癌患者的治疗得到了明显的改善,本文就结直肠癌靶向治疗的现状及研究进展做一综述.     

晚期结直肠癌的外科治疗进展

尽管结直肠癌的综合治疗有了很大的进展,但局部晚期(T3期和T4期)以及转移性结直肠癌的治疗仍然是具有挑战性的课题.新辅助放化疗、靶向治疗等研究取得了许多令人鼓舞的结果,但从外科处理的角度,仍然有诸多争议存在.包括对局部晚期结直肠癌多脏器切除的扩大根治指征、对结直肠癌肝转移和肺转移的最优化处理策略等.R0切除是转移病灶的首选处理策略,但仅适用于部分患者.利用化疗联合靶向药物的转化治疗策略将部分不可切除的转移肿瘤转化为可切除,也为进一步的外科治疗创造了机会.本文从局部晚期结直肠癌、结直肠癌肝和肺转移的外科治疗为切入点,简要阐述晚期结直肠癌的治疗进展.     

肿瘤细胞减灭术联合腹腔热灌注化疗在结直肠癌腹膜转移中的应用现状及前景

正结直肠癌是常见的消化道恶性肿瘤,在我国其发病率及死亡率仍呈上升趋势~([1])。腹膜转移是结直肠癌常见的转移形式,也是晚期结直肠癌病人死亡的主要原因之一。文献报道,结直肠癌确诊时同时合并腹膜转移的概率为5. 0%～15. 0%,而异时性腹膜转移的概率为20. 0%～50. 0%~([2-3])。传统观念认为,结直肠癌腹膜转移是疾病终末期,预后差,无外科手术治疗     

晚期结直肠癌术前评估及治疗策略

晚期结直肠癌主要分为局部晚期、术后局部复发及远处转移,远处转移主要包括腹膜转移及肝、肺等全身脏器的转移.手术切除是可能治愈晚期结直肠癌的惟一手段.术前以影像学评估为主,特别是对结直肠癌肝转移患者转移病灶可切除性的评估是外科治疗中尤其值得关注的问题.新辅助治疗及辅助治疗增加了晚期结直肠癌患者原发及转移病灶的手术切除率.近10年来,随着肿瘤外科的发展,多学科团队治疗模式的提出和实施,不仅使患者最大限度的受益,延长患者的生存时间,同时最大限度提高了患者的生命质量.     

手术切除和射频治疗孤立性结直肠癌肝转移的比较研究

孤立性结直肠癌肝转移行肝切除是一种可选择的治疗方法,近年来射频(RF)治疗结直肠癌已被较多采用,但确切治疗作用和疗效尚不明确,缺乏随机临床研究,本研究旨在对手术切除和RF治疗结直肠癌肝转移做一比较研究。病人和方法:共确诊45例结直肠癌肝转移病人,行肝切除20例,因手术禁忌     

直肠癌的早期诊断

随着生活习惯与饮食结构的变化,我国的直肠癌的发病日益增加,影响结直肠癌预后的首要指标是治疗时结直肠癌的分期~([1]),早期结直肠癌根治术后,病人5年存活率可达90%以上,而晚期癌5年存活率不足10%~([2]),但由于种种原因,大多数病人就诊时多已是中晚期,预后相对很差,若能早期就诊早期治疗,则相对很好,所以本文将就直肠癌早期症状及所需检查做一简单综述。     

结直肠癌外科手术的原则与进展

结直肠癌是人类常见的恶性肿瘤之一.早期诊断是改善结直肠癌患者预后的关键,对进展期及晚期肿瘤患者实施规范化的手术和综合治疗也能够改善治疗效果.基于结肠癌的淋巴结转移规律以及完整结肠系膜切除理论,结肠癌的手术治疗已经进入规范化和标准化的时代.而在全直肠系膜切除术(TME)金标准的基础上,直肠癌尤其是低位直肠癌手术方式更需考虑个体化.结直肠癌肝转移虽然是晚期疾病,但关于其治疗的研究非常活跃,对于可切除的结直肠癌肝转移肿瘤,肝切除是标准治疗方法,并且也是惟一可能根治的方法.因此,判断结直肠癌肝转移的可切除性显得尤为重要.外科医师是结直肠癌诊断治疗临床实践的最重要参与者,规范化的诊断与治疗是改善患者预后的关键所在.     

术前放化疗在局部晚期结直肠癌患者中的应用及敏感性预测研究进展

结直肠癌是常见胃肠道肿瘤之一,手术是其治疗的主要方法,但局部晚期结直肠癌患者手术耐受性较低,治疗风险以及复发可能性较大,一般通过化疗等进行治疗。术前放化疗通过有效缩小肿块、及早杀灭转移细胞从而为后续治疗提供有利条件,如今被广泛应用于临床。但术前放化疗并不适宜所有局部晚期结直肠癌患者,在临床的应用中还需根据患者自身情况进行个体化分析,需要确定其患者的敏感性。笔者对术前放化疗在局部晚期结直肠癌患者的应用研究以及敏感性预测新进展进行综述,对近年来国内外相关研究中存在的问题以及新治疗理念进行阐述,以期为临床治疗方案提供参考依据。     

循环肿瘤细胞的检测及其在结直肠癌中的研究进展

结直肠癌发病率逐年上升,转移和复发是结直肠癌死亡的主要原因。循环肿瘤细胞(CTCs) 的存在是肿瘤复发和远处转移的关键,与肿瘤患者的预后密切相关。CTCs 来源于肿瘤组织,主要存在于癌症患者的外周血中,已成为近年来研究的热点生物标志物。CTCs 检测在结直肠癌的早期诊断、评估结直肠癌术后预后、预测转移性结直肠癌的化疗反应、评估晚期结直肠癌的治疗反应和预后、筛选结直肠癌靶向治疗可能获益的患者方面具有重要意义。     

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 Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

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.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

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.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.