缺血性肠炎是由于各种原因使肠壁血流灌注不良,导致缺血性损害的一种肠壁营养障碍综合征。结肠镜检查是诊断缺血性肠炎的金标准,然而,结肠镜检查本身也可诱发缺血性肠炎,尽管非常罕见。自1990年Weeldon等[1]首先报道以来,国外已有7篇,共11例报道[2-5]。国内李振磊等[6]也于2009年4月报道了3例病例。2009年2-10月,我院共发现结肠镜检查后并发缺血性肠炎患者4例,本文拟通过对这些患者的临床资料的分析,并结合国内外文献报道,探讨其发病机理,提高对该并发症的认识。例1 女,68岁,因反复便血10天行结肠镜检查,既往有高血压病史,肠镜发现乙状结肠及直肠息肉,余黏膜未见异常,遂行内镜下息肉电凝切除术,共耗时25 min,术后约12小时出现左下腹绞痛,随即出现解淡红色血水样黏液便,术后24小时再次行肠镜检查距肛门30 cm降结肠直肠黏膜节段性出现紫红色淤血水肿及黏膜下出血,散在糜烂灶,血管网结构消失,病变肠段与正常肠段界限清晰(图1),查体:左下腹轻压痛,无反跳痛,肠鸣音活跃,约10-15次/分,给予禁食,丹参及抗生素预防感染等治疗,5天后症状完全消失。图1:距肛门30cm肠镜下表现例2 男,55岁,因便秘行结肠镜检查,肠镜行至回肠末端,耗时10 min,肠镜检查顺利未见异常。术后26小时出现腹痛,便血。查体:左下腹轻压痛,无反跳痛,复查肠镜提示乙状结肠黏膜淤血水肿及黏膜下出血,散在糜烂灶,病变肠段长约15 cm,正常肠段界限清晰,给予禁食,丹参及抗生素预防感染等治疗,3天后症状完全消失。例3 男,70岁,因腹泻行结肠镜检查,行至回肠末端,耗时15min,肠镜检查未见异常。术后30小时出现腹痛,便血。查体:左下腹轻压痛,无反跳痛,肠镜提示乙状结肠黏膜淤血水肿及黏膜下出血,散在糜烂灶,病变肠段与正常肠段界限清晰,给予禁食,丹参及抗生素预防感染等治疗后2天后症状完全消失。例4 女,69岁,因直肠癌术后26年复查肠镜,行至回肠末端,耗时14min,肠镜检查未见异常,术后24小时出现下腹疼痛,血便。查体:腹部无压痛及反跳痛,肠镜提示乙状结肠黏膜淤血水肿及黏膜下出血,病变肠段与正常肠段界限清晰,给予禁食,丹参及抗生素预防感染等治疗,2天后症状完全消失。讨论:现有文献认为结肠镜后并发缺血性结肠炎的发生可能与下列因素相关:①存在高血压、糖尿病、结缔组织疾病等可引起血管狭窄和肠壁相对供血不足的基础疾病。②在结肠镜检查过程中过度的注气、牵拉以及镜身对结肠壁的机械作用。③检查时间过长导致肠黏膜长时间缺血缺氧,恢复肠道血流后肠黏膜缺血再灌注损伤。然而,在本院发现的病例中,仅1例有高血压病史,余3名无特殊疾病史,其中3例病人在15 min内完成了全部操作,说明其中任何一点的单独作用均不能成为这一并发症发生的主要原因,多因素的协同作用可能更值得加以重视。因此,对于预防结肠镜后并发缺血性结肠炎,加强结肠镜施术医师的操作水平,减少操作时间,在检查过程中手法轻柔,避免过度注气及对肠道过分牵拉显得尤为重要,特别是对于存在基础疾病的患者。目前,国内外文献报道中发现的所有结肠镜后并发缺血性结肠炎患者均为女性,但本院的4例病例中有2例为男性,是否此并发症确实多见于女性,尚需累积更多的病例数以兹分析。文献报道中病例的年龄在25~81岁,平均年龄在50岁左右,而本院发现的4例病人年龄则均在50岁以上。因此,我们认为,对高龄病人行结肠镜尤其需警惕缺血性结肠炎的发生。综合本院的发现及国内外文献报道,缺血性结肠炎多发生在结肠镜检查后24小时内,但也见有48小时后方发生者,因此,对结肠镜后3天内出现的腹痛,便血等症状的病人,均需留意其缺血性结肠炎发生的可能性。若肠镜下发现节段性黏膜紫红色淤血水肿及黏膜下出血,血管纹理消失,病变肠段和正常肠段界限清晰可明确诊断[7]。现有报道中绝大多数内科治疗均有效,本院的4例病人经早期禁食,扩血管,预防感染等治疗后均痊愈,提示结肠镜后并发的缺血性肠炎多为一过型[8],但治疗过程中仍需密切观察腹部体征,防止坏疽和穿孔等严重并发症的发生。参考文献1. Weeldon NM and G. MJ, Ischaemic colitis as a complication of colonoscopy. Br Med J, 1990. 301: p. 1080-1081.2. Versaci A, Macri A, and S. G, Ischemic colitis following colonoscopy in a systemic lupus erythematosus patient: report of a case. Dis Colon Rectum 2005. 48: p. 866-869.3. Yuksel O, B.A., Koklu S Ischemic colitis, an unusual complication of colonoscopy. . South Med J, 2008. 101: p. 972-973.4. Dong Q, Wang Q, and L. Y, Ischemic colitis after colonoscopy in a female patient. . Am J Gastroenterol, 2009. 104: p. 2123-2124.5. Cremers MI, O.A., Freitas J, Ischemic colitis as a complication of colonoscopy. . Endoscopy, 1998. 30: p. S54.6. 李振磊,刘明东, 结肠镜检查后并发缺血性结肠炎三例并文献分析. 中华消化内镜杂志, 2009. 26: p. 199-201.7. 杨秀兰,史维,吴立平, 缺血性结肠炎内镜及临床特点. 中国老年学杂志, 2007. 24: p. 2433-2434.8. 史维,赵聪,邱雄, 中老年人缺血性结肠炎. 中华消化内镜杂志, 2000. 17: p. 336-337.
内镜超声(EUS)是一种在传统内镜顶端连接有微型超声探头装置的新型组合式内镜系统。当EUS插入体腔后,通过内镜直接观察腔内的组织形态,同时又可进行实时超声扫描,以获得管道层次的组织学特征及周围邻近脏器的超声图像。EUS可以避开气体及腹壁对超声传播的影响并缩短探头和靶器官之间的距离,显著改善肝胆的超声显像。近年来,随着内镜医师操作水平的提高,EUS在肝胆疾病诊断和治疗中的价值也不断提高,现就此方面做如下综述。1.胆道疾病1.1胆总管结石EUS明显优于经腹壁超声(TUS)对胆总管下段的显示。Tse[1]等研究指出EUS诊断胆总管结石敏感性为0.94 (95% CI,0.93-0.96),特异性为 0.95 (95% CI,0.94-0.96)。因EUS可分辨出0.1 mm的结石,在微小结石及胆泥淤滞的诊断上优于ERCP及MRCP。 Frossard[2]对168例“特发性”胰腺炎行EUS,62%的患者发现了其原因,大多数由微结石,胆泥淤滞引起,EUS为这些病人提供了ERCP治疗的方向。ERCP (内镜下逆行胰胆管造影)被认为是诊断胆总管结石的金标准,但是其并发症发生率较高,约5% -10%,特别是会导致术后胰腺炎。周艳等[3]研究提示EUS对胆总管结石的诊断敏感性显著高于 ERCP (OR 2.02,95% CI = 1.01-4.03,P <0.05),特异性及准确性相似 (OR 0.49,95%CI = 0.12-1.99,P> 0.05),并且,EUS作为微侵入性操作目前研究尚无并发症的报道,其高敏感性能更有效的排除胆总管结石的诊断,避免不必要的诊断性ERCP。此外,EUS能够提供胰腺壶腹部及其它胰胆管周围组织结构的信息,有助于在排除胆石症后进一步的明确诊断。MRCP (胰胆管系统磁共振显象) 对胆总管结石诊断准确率也较高,报道在81-94%,McMahon[4]等的研究指出当MRCP扫描层厚<3mm时敏感性可达87%,相对于敏感性在90%的EUS,无创的高分辨MRCP似乎更具优势,应被作为诊断胆总管结石的首选方式。但是,在微小结石的诊断方面,EUS更胜一筹,对MRCP未发现结石而临床高度怀疑胆总管结石者,建议先行EUS明确诊断,避免不必要的诊断性ERCP。此外,对于有金属器件植入或伴有幽闭恐惧症的患者也可首选EUS。1.2胆道狭窄 胆管狭窄在临床上常见于胆管癌,胰头癌,肝门区肿瘤及炎性狭窄等。胆管癌的EUS表现为胆管附近的低回声团块或胆管壁的增厚,这和炎性增厚有时难以区别。胆道造影不能准确的区分良恶性狭窄,McMahon[5]研究指出在胆道狭窄的诊断方面EUS结合FNA(细针穿刺)特异性高于MRCP,分别为80%和65%。EUS-FNA除了能观察胆管形态,胆道周围结构,还能同时取得病理学证据,对胆管狭窄的诊断敏感性明显增加。对于由局部肿块引起的狭窄,EUS-FNA准确率也较高,文献报道平均达80-90%[6]。 对于胆道狭窄的诊断,EUS-FNA较现有的方式(如MRCP,ERCP)准确性更高,是目前最佳的诊断手段,但其对于仅胆管壁局部增厚者的诊断敏感性仍较低,Rosch[7]对50例胆管狭窄的研究显示EUS-FNA的敏感性仅43%。如何提高其敏感性仍需进一步研究,如穿刺次数及穿刺部位的选择等。1.3胆囊息肉 大部分胆囊息肉为良性,但一些早期肿瘤也会表现为息肉样变,目前对于其重要性及治疗的选择仍存在争议。一般认为,大于1cm的胆囊息肉因其恶变风险高,建议行手术切除。Young等[8]回顾性研究了94例经手术切除的小于2cm的胆囊息肉,EUS诊断准确率明显高于经皮超声(TUS),分别为80.9%及63.9% (P < 0.05),但对于小于1cm的息肉诊断正确率明显低于大于1cm的息肉(分别为40%和88.9%)。Sadamoto等[9]对70例手术切除的5-15mm的息肉分别从瘤体最大直径,内部回声类型及高回声光点三方面进行EUS评分,评分大于12分的胆囊息肉诊断为恶性的敏感性,特异性及准确性分别为77.8 %,82.7 % 及 82.9 %。因此,通过评分系统进行综合评定能有效地提高其准确性。1.4胆道梗阻的治疗ERCP下胆道支架安置术对约10-15%的患者因十二指肠乳头通路被阻断(如肿瘤浸润,压迫等)或因十二指肠局部解剖结构改变而无法成功。这种情况下,临床上还可以选择PTCD(经皮肝胆管穿刺造影及引流)或外科胆管搭桥术,但PTCD对于存在严重凝血障碍,血小板减少,大量腹水等合并症的情况不宜采用,其并发症发生率达10-30%,同时还存在长期胆汁外引流不符合生理状态而引起生活质量下降等问题;外科手术对这类患者干扰太大,死亡率达32%,术后并发症发生率也高达66%。因此,新的胆汁引流术被不断推出,EUS在这方面的应用获得了广泛关注。自1996年Wiersema等[10]首次报道EUS介导下的胆管穿刺以来,一系列关于EUS介导下的穿刺及引流技术相继被报道[11]。EUS能很好的显示肝内胆管(特别是胆道梗阻后扩张胆管)及胆总管,为建立肝内胆管与胃以及胆总管与十二指肠之间的联系提供了可靠的影像学支持。利用EUS建立胆道与胃肠道之间的胆汁流出通路解决胆道梗阻的方法目前倍受瞩目。现有的方法有EUS-guided choledochoduodenostomy(EUS介导下胆总管十二指肠吻合术);EUS-guided hepaticogastrostomy(EUS介导下肝胃吻合术);EUS-guided rendezvous techniques (EUS介导下会师技术, 即EUS辅助ERCP插管)等。EUS介导下胆总管十二指肠吻合术即在十二指肠球部利用针形电刀切开肠壁, 将细针插入胆总管中,吸出胆汁后注入造影剂行胆道成像,之后将导丝通过针道插入,拔出针刀后沿导丝放入塑料或金属支架,至今已有25例报道。其技术成功率92%,并发症包括2例局限性胆汁性腹膜炎,3例气腹,尚无严重并发症发生。EUS介导下肝胃吻合术其步骤与胆总管十二指肠吻合术相仿,不过穿刺部位为贲门或胃小弯侧,建立左肝胆管与胃之间的分流。至今共有约20例报道,技术成功率为90-100%,临床缓解率75-100%,并发症包括胆汁瘤,支架移位,胆管炎等。Kahaleh等[12]认为肝内途径进行穿刺引流较胆总管穿刺引流更安全。胆汁漏发生率低,可能与扩张的胆总管管壁弹性下降有关。同时,对于壶腹部肿瘤所致胆道梗阻,远离肿瘤安置引流管可避免肿瘤生长压迫引流道。EUS介导下会师技术是通过经肝内或肝外途径将导丝送入胆管,若导丝能够沿胆管顺行穿过狭窄部穿出乳突部,则将EUS替换为十二指肠镜,通过圈套器抓住穿出乳突部的导丝,沿导丝放入胆管支架从而达到引流胆汁的目的。Mallery等[13]首次报道了2例经肝外途径完成的会师技术,均取得成功。因这种技术是通过自然腔道引流胆汁,其风险及并发症是3种方式中最小,所以在经肝外或肝内途径置管减黄前,均应尝试是否能将导丝通过梗阻部位,完成会师技术。以往胆道梗阻若失去ERCP治疗指征的只有选择风险极大的PTCD或外科手术,EUS介导的胆汁引流术为这类病人提供了另一种更符合生理需求的解决方案。虽然仍处于试验阶段,尚有各种并发症发生,但其优势是显而易见的。未来对这项技术在操作,支架设计上的改进必将使其具有更大的应用前景。2.肝脏疾病2.1肝脏活检肝脏活检是诊断肝脏疾病的重要手段。传统方法包括经皮肝穿,经静脉肝穿,腹腔镜手术活检等。活检准确性与样本大小及所包含的完整汇管区数量有关,充足的样本量至少长度在15mm以上,包含5个完整的汇管区[14]。 随着EUS技术的发展,使用EUS进行的活检已有报道。DeWitt J[15]报道21例EUS活检,平均需要3次穿刺,长度9mm,包含2个完整及3个部分汇管区,90%获得病理学诊断。因此,EUS相对于传统的经皮肝穿并无优势,取材部位局限,取材量不充足限制了其实际应用。2.2肝脏占位病变的诊断由于超声探头的深度及局部解剖位置的影响,EUS对肝脏的扫描成像局限在肝左叶,尾叶,部分肝右叶,但EUS能发现<1cm的肿块,因此在肝脏占位病变的诊断中,也已有系列病例报道。Pankaj等[16] 对比了17例肝细胞癌,TUS,CT,MRI,EUS的诊断准确性分别为38%,69%,92%和94%。因EUS能发现极小的病灶,对于肝转移性肿瘤的监测具有重要意义。Pankaj等[17]对132例消化系统肿瘤患者分别行CT及EUS检查,发现26例肝转移,两者诊断准确率分别为92%和98%,并且EUS能发现更多、更小的转移灶,7/8例CT无法确定性质的病灶通过EUS-FNA明确诊断。EUS对转移性肝癌的检查是否应作为常规检查仍有争论,虽然EUS能辨别微小病灶,但其侵入性性质及费用限制了应用。目前认为对于消化道肿瘤(如食道癌)或纵隔肿瘤,EUS进行检查的同时完成肝脏的扫描,排除肝转移具有更高的经济效益比。2.3肝脏的EUS介入治疗目前对肝脏肿瘤介入治疗方法包括局部注射抗肿瘤物质(如酒精,乙酸),RFA射频消融,冷冻疗法,激光热疗,高强聚焦超声(HIFU),经动脉化疗栓塞等。因其大部分可以通过经皮或经肝动脉完成,EUS仅作为定位手段对在CT或TUS下难以达到的部位进行操作,其意义不及胰腺治疗方面。Barclay等[18]报道了一例行EUS介导下对转移性肝癌(病变位于肝尾叶)注射无水酒精治疗, 共注射7次, 瘤体明显缩小,无并发症发生。对肝脏脓肿的EUS介入治疗目前仅有个案报道,Stefan等[19]报道了一例肝左叶巨大脓肿EUS下穿刺置管引流, 操作顺利, 无并发症发生。对于脓肿位于肝左叶或尾叶的患者,EUS肝穿相对于经皮途径具有减少穿入到脓肿的距离,可通过实时多普勒超声避开血管等优势。EUS对肝脏血管的介入治疗,包括有门静脉造影及测压[20,21],门静脉栓塞[22]以及EUS介导下肝内门体分流[23]等,这方面的研究大多仍停留在动物实验阶段。EUS的优点在于能更好的显示肝内外血管, 达到血管的超选,使治疗更精准,但出血及感染问题仍是目前研究的瓶颈,需要进一步探索。综上所述,EUS在肝胆疾病的诊断和治疗中正发挥着越来越重要的作用,相信在不久的将来,肝胆疾病的早期诊断及治疗水平会随着EUS的发展而显著提高。参考文献:1. 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Captopril is an effective antihypertensive drug. Recent studies revealed its promoting effects in stem cell transplantation treatment. However, some researches implied its opposite effects in certain cases. Because of the pluripotent differentiation ability and the convenience to amplify, mesenchymal stem cell (MSC) is commonly used in tissue engineering and pharmacological researching. In our study, we added captopril in different doses into isolated and cultured new born rabbit MSC. The cell’s viability and the morphological characteristics were observed for exploring the dose-response relationship between captopril and MSC. The new born laboratory Japanese white rabbits were purchased from Medical Experimental Animal Center, Sichuan Province. Bone marrow MSC was isolated in sterile conditions. After passaged for 3 times, the MSC as trypsinized and re-suspended by α-MEM medium. 5×104/100 ul cells were injected into each hole of a 96-hole plate. 20 ug/mL to 2400 ug/mL captopril was added into the holes in triple. After 48 h cultured, the cell viability was detected by MTT method and the morphological characteristics were observed. MSC isolated from new born rabbit bone marrow grew well. At the end-point, more cells suspended morphologically in high dose captopril group, and each group presented obviously different in color 4 h after MTT addition. The supernatant was sucked up at uncentrifuged and 5 min 500 g centrifuged conditions and dimethyl sulfoxide was added in respectively. Then, the absorbance values were compared at 570 nm. The results showed that high dose captopril can promote the proliferation of MSC, instead of cell attachment. Dose 100-300 ug/mL may be able to guarantee the normal physiological function and proliferation of MSC. The effect of captopril on MSC is still in debates. In our research, the dose of captopril may be one of the answers to the divergences. Though dose 100-300 ug/mLseems to be the better choice in culture condition, it’s too high to be got in practical situation. We have reasons to believe that as long as keeping in allowable scope, the higher the captopril dose is, the better the promoting effects of captopril on the MSC are. Due to the convenience, rabbit MSC shares the same value in exploring and solving similar problems.