超声造影引导迟发性脾破裂的诊治实验研究
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摘要
目的①在超声造影引导下建立迟发性脾破裂动物模型;②探讨超声造影引导下局部注射止血剂治疗迟发性脾破裂的应用价值;③超声造影引导下可注射性明胶基止血剂治疗脾脏外伤止血效果的动物实验研究。
     材料和方法①15只健康杂种犬常规麻醉,开腹制作脾脏血肿,72小时后以小型撞击器撞击实验犬腹壁造成血肿破裂,血肿破裂后前后均行常规超声、超声造影及增强CT检查。观察血肿破裂前后常规超声、超声造影表现,探讨其结果与增强CT的对照研究;②14只健康杂种犬常规麻醉,开腹制作迟发性脾破裂动物模型在超声造影引导下先后多点注射蛇毒凝血酶2ml和α-氰基丙烯酸酯1mL,分别在术后、第1天、第3天、第7天、第14天及第21天行常规超声和超声造影检查,观察脾脏损伤区域面积和腹腔积液情况,脾切除术后行病理学检查;③24只健康杂种犬常规麻醉,开腹后暴露脾脏,用止血钳在脾脏膈面制作长、宽、深分别为4cm、4cm、2.5cm的脾脏实质锐器伤。实验犬随机分为两组,治疗组在超声造影引导下注射4ml HIGM,阳性对照组注射4ml蛇毒凝血酶和α-氰基丙烯酸酯对创伤灶行局部注射治疗,通过超声造影观察即刻疗效,并在第1天、第3天、第7天、第14天及第21天行常规超声及超声造影分别观察记录腹腔积液和创伤灶面积,并于第21天行脾切除术,通过大体标本观察脾脏愈合情况并行组织病理学检查。
     结果①4只实验犬脾脏血肿面积明显缩小,72小时后血肿消失。11只实验犬脾脏血肿形成,常规超声对血肿边界显示不清晰,而超声造影可清晰显示血肿边界,大小,并观测到72小时后血肿面积明显增大。小型撞击器击打腹壁后,常规超声对创伤灶显示不清,可清晰显示腹腔积液,超声造影可清晰显示血肿破裂,部分血肿可见活动性出血。增强CT证实超声造影检查结果。②治疗组实验犬均存活。脾脏创伤灶经蛇毒凝血酶和α-氰基丙烯酸酯联合注射后,超声造影显示活动性出血消失,局部注射α-氰基丙烯酸酯处呈强回声。治疗后4个时间点观察,超声造影显示血肿面积明显缩小并未见活动性出血,常规超声显示腹腔积液减少。剖腹探查见大体标本显示创伤灶完全愈合,局部可见大网膜贴附,未见明确的并发症发生。③治疗组及阳性对照组所有实验犬均存活。治疗组在超声造影引导下注射HIGM后,损伤区域未见活动性出血,第1、3、7天创伤灶面积逐渐缩小,第14、21天所有实验犬(n=12)均未见创伤灶回声,阳性对照组实验犬于第1、3、7、14天可见创伤灶回声,第21天所有实验犬(n=12)未见创伤灶回声,且在第1、3、7天两组间创伤灶面积有显著统计学差异(p<0.05)。常规超声显示第3、7、14、21天治疗组未见腹腔积液,阳性对照组第14、21天未见腹腔积液,在第1、3、7天两组间腹腔积液测量值有明显统计学差异(p<0.05)。大体标本显示治疗实验犬脾脏组织愈合良好,未见粘连。第7、14、21天组织病理学检查未见明显异物及异物肉芽肿,可见红髓结构逐渐修复。
     结论在超声造影引导下成功建立迟发性脾破裂模型,针对其损伤区域在超声造影引导下注射止血剂止血,实现了迟发性脾破裂的快速、微创治疗。探讨研究了新型止血药物可注射性明胶基止血剂用于脾脏外伤止血治疗的应用价值,为临床治疗提供了初步的实验依据。
Objective:①To establish the animal model of delayed splenic rupture under theguidance of contrast-enhanced ultrasonography.②To explore the value of theappliance of hemostatic agents injected directly into injury site for delayed splenicrupture under the guidance of contrast-enhanced ultrasonography.③To evaluateefficacy and safety of hemostatics of injected gelatin matrix (HIGM) for treatingsplenic trauma in canine model.
     Material and methods:①A total15mongrel dogs were anesthetized andlaparotomized. The hematoma was formed on the spleen using external force. Thehematoma was ruptured by beating the abdominal wall after72hours. Conventianalultrasound and CEUS were used to detect traumatic lesions of spleen before and afterimpacting. The results of CEUS were compared with those of CECT.②A total14mongrel dogs were anesthetized and laparotomized. The hematoma was formed onthe spleen. Hemocoagulase2mL combined with α-cyanoacrylate1mL were injecteddirectly into injury sites under the guidance of CEUS in splenic trauma. Conventianalultrasound and CEUS were used to detect the injury area and ascites at1st,3rd,7th,14th,21thday. The spleen was harvested on the21thday for gross and pathologicalexamination.③A total of24commercial hybrid dogs underwent celiotomy with creationof uniformly blunt splenic trauma lesion of4cmx4cmx2.5cm (length, width, depth,respectively) by hemostatic clamp. Subjects were prospectively randomized into2groups.The treatment group were treated with HIGM under the guidance of CEUS, the positivecontrol group received thrombin solution. Conventional ultrasound and CEUS wereperformed to record the ascites and the splenic lesion areas at1st,3rd,7th,14th,21thday. Thefine needle biopsy and splenectomy were performed for histopathologic examination.
     Result:①In4dogs, the hematoma showed by CEUS was gradually reduced during72hours. The CEUS results showed that the splenic hematoma in11canine wasformed continuously during a72hours period and the hematoma area graduallyincreased. The hematoma was ruptured after impacting the abdominal wall.Conventional ultrasound showed that the hamatoma was ill-defined and ascites wasclearly recorded. CEUS results showed that the hematoma was ruptured and activebleeding in the injury site. These conditions were demonstrated via CTscanning.②All animals survived.After injection of hemocoagulase combined withα-cyanoacrylate under the guidance of CEUS, CEUS exam demonstrated that activebleeding disappeared. At4time points, CEUS showed that the aera of hematoma wassignificantly decreased without active bleeding. Conventional ultrasound showed thatthe ascites was decreased. Pathologic examination revealed that the injury site treatedwas covered with glue membrane and no hematoma was observed.③All animals in2groups survived. All dogs succeed stopping hemorrhage after injection of HIGM underCEUS guidence. The area of injury site was gradually reduced at1st,3rd,7thday and all dogs(n=12) were not found splenic lesion at14thand21thday in HIGM group. The splenic lesionwas found in the postive group at1st,3rd,7th, and14thday and all dogs (n=12) were notfound splenic lesion at21thday. At1st,3rdand7thday post-injection, lesion areas werestatistically significant between2groups (p<0.05, all).F ree intraperitoneal fluid was notfound by conventional ultrasound at3rd,7th,14thand21thday in HIGM group. The samecondiction in postive group was14thand21thday. At1st,3rdand7thday post-injection, freeintraperatitoneal fluid were statistically significant between2groups (p<0.05, all).Histopathologic examination showed that there was no no foreign body and foreign bodygranuloma present and the structure of red pulp was repair at7th,14thand21thday. Grossanatomy showed that the splenic injury site was recoved completely without complications.
     Conclusion: A delayed splenic rupture canine model was established successfullyunder the guidance of CEUS. The hemostatic agents injection therapy for splenictruama under the guidance of CEUS is effective, safe and no adverse effect, whichcarry out the minimal invasive treatment of splenic trauma. This study explored the value of HIGM for hemostasis of splenic trauma, and provided a preliminary experimentalevidence for clinical treatment.
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    5Lorimer WS Jr.Occult rupture of the spleen.Arch Surg,1964,89:434-440
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    7Burd RS, Helikson MA. Delayed splenic rupture following low impact activity. JPediatr Surg,2000,35(10):1529.
    8Deva AK, Thompson JF. Delayed rupture of the spleen5.5years afterconservative management of traumatic splenic injury. Aust N Z J Surg,1996,66(6):494-495.
    9Simpson RA, Ajuwon R. Occult splenic injury: delayed presentation manifestingas jaundice. Emerg Med J,2001,18(6):504-505.
    10Hammond JC, Canal DF, Broadie TA. Nonoperative management of adult blunthepatic trauma in municipal trauma center. Am Surg,1992,58(9):551-555.
    11范康川,郭吉生,周惠彬,脾破裂延迟性出血.现代诊断与治疗,1992:(1):29-30.
    12FAST Consensus Conference Committee. Focused assessment with sonographyfor trauma (FAST): results from an international consensus conference. J Trauma,1999,46:466-4721.
    13Poletti PA, Kinkel K, Vermeulen B, et al. Blunt abdominal trauma: should US beused to detect both free fluid and organ injuries? Radiology April,2003,227(1):95-103.
    14李国杰,周永昌.急诊超声对钝性腹部创伤的内脏破裂出血的研究.中国超声医学杂志,2002,18(1):29-33.
    15Siniluoto TM, P iv nsalo MJ, Lanning FP, et al. Ultrasonography in traumaticspleen rupture. Clin Rediol,1992,46(6):391-396.
    16吕发勤,唐杰,罗渝昆,李志艳,李俊来,黎檀实,超声造影在腹部实质脏器创伤快速分类治疗中的价值[J/CD].中华超声学杂志:电子版:2009:6(1):25-29.
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    22夏穗生,我国脾脏外科的发展回顾.中国实用外科杂志,2004,24(12):705-707
    23范士志,蒋耀光,现代创伤治疗学.人民军医出版社,2009:334-336
    24吕发勤,唐杰,张惠琴,等.超声造影引导经皮注射治疗严重脾破裂出血.中华超声影像学杂志,2008:17(7):598-600.
    25谭敏,辻羲彦,吴志棉,等.腹腔镜技术在脾切除术中的应用.中华外科杂志,2001,39(8):599-601.
    26祝智军,李大伟,郑蓉蓉.手助腹腔镜脾切除术治疗外伤性脾破裂.中华创伤杂志,2003,19(10):583-584.
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    32鞠新华,赵海英,于宏,等.微波在保脾手术中的临床应用(附5例报告).肝胆外科杂志,2003,11(1):57-58.
    33Tabuse K. Basic knowledge of a microwave tissue and its clinical applications. JHepatobiliary Pancreat Surg,1998,5(5):560-563.
    34乔海泉,代文杰,刘冰,等.脾损伤的脾保留手术-10年经验总结.中华肝胆外科杂志,2002,8(6):343-345.
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    61Parithivel VS, Sajja SB, Basu A, et al. Delayed presentation of splenic injury: stilla common syndrome. Int Surg,2002,87(2):120-124
    62陈维鹏,脾外科学,山东:山东科学技术出版社,1989:108-11
    63杨春明,李纪仑.延迟性脾破裂的诊治问题(附17例报告).实用外科杂志,1986,6(8):411-412.
    64Lorimer WS Jr.Occult rupture of the spleen.Arch Surg,1964,89:434-440
    65Spacek V, Jandik P, Smejkal K. Delayed splenic rupture: an unusual cause ofacute surgical abdomen. Acta Medica,2002,45(1):45-46.
    66Burd RS, Helikson MA. Delayed splenic rupture following low impact activity. JPediatr Surg,2000,35(10):1529.
    67Deva AK, Thompson JF. Delayed rupture of the spleen5.5years afterconservative management of traumatic splenic injury. Aust N Z J Surg,1996,66(6):494-495.
    68Simpson RA, Ajuwon R. Occult splenic injury: delayed presentation manifestingas jaundice. Emerg Med J,2001,18(6):504-505.
    69Hammond JC, Canal DF, Broadie TA. Nonoperative management of adult blunthepatic trauma in municipal trauma center. Am Surg,1992,58(9):551-555.
    70范康川,郭吉生,周惠彬,脾破裂延迟性出血.现代诊断与治疗,1992:3(1):29-30.
    71FAST Consensus Conference Committee. Focused assessment with sonographyfor trauma (FAST): results from an international consensus conference. J Trauma,1999,46:466-4721.
    72Poletti PA, Kinkel K, Vermeulen B, et al. Blunt abdominal trauma: should US beused to detect both free fluid and organ injuries? Radiology April,2003,227(1):95-103.
    73李国杰,周永昌.急诊超声对钝性腹部创伤的内脏破裂出血的研究.中国超声医学杂志,2002,18(1):29-33.
    74Siniluoto TM, P iv nsalo MJ, Lanning FP, et al. Ultrasonography in traumaticspleen rupture. Clin Rediol,1992,46(6):391-396.
    75吕发勤,唐杰,罗渝昆,李志艳,李俊来,黎檀实,超声造影在腹部实质脏器创伤快速分类治疗中的价值[J/CD].中华超声学杂志:电子版:2009:6(1):25-29.
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    77梁峭嵘,黄春燕,梁彤,等.超声造影在脾外伤评估分级诊断中的临床应用[J/CD]..中华超声医学杂志:电子版,2008:5(2):288-294.
    78Impellizzeri P, Cutrupi A, Chirico MR, et al.Conservative treatment of pediatricspleen trauma, Twenty years of experience.Pediatr Med Chir,2007,29(1):38-43.
    79Rydberg J, Buckwalter KA, Caldemeyer KS, et al. Multisection CT: scanningtechniques and clinical applications. Radiographics,2000,20(6):1787-1806.
    80Becker CD, Spring P, Gl ttli A, et al. Blunt splenic trauma in adults: can CTfindings be used to determine the need for surgery? AJR Am JRoentgenol,1994,162(2):343-347
    81夏穗生,我国脾脏外科的发展回顾.中国实用外科杂志,2004,24(12):705-707
    82范士志,蒋耀光,现代创伤治疗学.人民军医出版社,2009:334-336
    83吕发勤,唐杰,张惠琴,等.超声造影引导经皮注射治疗严重脾破裂出血.中华超声影像学杂志,2008:17(7):598-600.
    84谭敏,辻羲彦,吴志棉,等.腹腔镜技术在脾切除术中的应用.中华外科杂志,2001,39(8):599-601.
    85祝智军,李大伟,郑蓉蓉.手助腹腔镜脾切除术治疗外伤性脾破裂.中华创伤杂志,2003,19(10):583-584.
    86张耘,宋建宁,宋林学,等.腹腔镜切除治疗外伤性脾破裂.中国微创外科杂志,2005,(11):886-887.
    87徐迎讯.脾动脉栓塞治疗外伤性脾破裂28例临床疗效观察[J/CD].中华普通外科学文献:电子版,2007,1(4):228-229.
    88陆永良,韩春蕃,吴平,郑少俊,顾凤元,脾动脉栓塞止血治疗外伤性脾破裂,中华外科杂志,1997,35(1):31-32.
    89Hagiwara A, Yukioka T, Ohta S.Nonsurgical management of patients with bluntsplenic injury: efficacy of transcatheter arterial embolization. Am J Roentgenol,1996,167(1):159-166.
    90刘强,李铎,李建新,等.选择性脾动脉栓塞与脾修补术治疗外伤性脾破裂的比较.中华肝胆外科杂志,2005,11(11):752-754.
    91鞠新华,赵海英,于宏,等.微波在保脾手术中的临床应用(附5例报告).肝胆外科杂志,2003,11(1):57-58.
    92Tabuse K. Basic knowledge of a microwave tissue and its clinical applications. JHepatobiliary Pancreat Surg,1998,5(5):560-563.
    93乔海泉,代文杰,刘冰,等.脾损伤的脾保留手术-10年经验总结.中华肝胆外科杂志,2002,8(6):343-345.
    94Moore EE, Cogbill TH,Jurkovich G J, et al.Organ injury scaling: spleen andliver (1994revision). J Trauma,1995,38(3):323-324.
    95Federle MP, Jeffrey RB Jr. Hemoperitoneum studied by computed tomography.Radiology,1983,148(1):187-192.
    96Godley CD, Warren RL, Sheridan RL, et al. Nonoperative management of bluntsplenic injury in adults: age over55years as a powerful indicator for failure. JAm Coll Surg,1996;183(2):133-139.
    97Hawkins ML, Wynn JJ, Schmacht DC, et al. Nonoperative management of liverand/or splenic injuries: effect on resident surgical experience. Am Surg,1998,64(6):552-556.
    98Goan YG, Huang MS, Lin JM. Nonoperative management for extensive hepaticand splenic injuries with significant henoperitoneum in adults. JTrauma,1998,45(2):360-364.
    99张牧,姜洪池.保脾措施今日观.中国实用外科杂志,2009,29(5):377-378.
    100Richardson JD. Changes in the management of injuries to the liverand spleen. JAm Coll Surg,2005,200(5):648-669.
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