Effects of a membrane-permeable radical scavenger, Tempol, on healing of colonic anastomoses in the cecal ligation and puncture model of polymicrobial sepsis in rats

BACKGROUND: Tempol (Sigma-Aldrich, Steinheim, Germany) is a stable piperidine nitroxide of low molecular weight that permeates biologic membranes and scavenges superoxide anions in vitro. In recent animal studies, the delaying effect of intraperitoneal sepsis on the healing of colonic anastomoses has been shown. In this study we aimed to investigate the effects of Tempol on the healing of colonic anastomoses in the presence of polymicrobial sepsis. METHODS: Anastomosis of the left colon was performed on the day after cecal ligation and puncture (CLP) in 30 rats that were divided into 3 groups: sham-operated control (laparotomy and cecal mobilization, group I, n = 10), CLP (group II, n = 10), Tempol-treated group (30 mg/kg intravenously before the construction of colonic anastomosis, group III, n = 10). On postoperative day 6, all animals were killed and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of anastomotic hydroxyproline (HP) contents, perianastomotic myeloperoxidase (MPO) activity, malondialdehyde (MDA), and glutathione (GSH) levels. RESULTS: There was a statistically significant increase in MPO activity and MDA levels in the CLP group (group II), along with a decrease in GSH levels, anastomotic HP contents, and bursting pressure values when compared with controls (group I). However, Tempol treatment led to a statistically significant increase in anastomotic bursting pressure values, tissue HP contents, and GSH levels, along with a decrease in MPO activity and MDA levels in group III (P < .05). CONCLUSIONS: This study showed that Tempol treatment significantly prevented the delaying effect of CLP-induced polymicrobial sepsis on anastomotic healing in the left colon. Further clinical studies are needed to clarify whether Tempol may be a useful therapeutic agent to increase the safety of the anastomosis during particular surgeries in which sepsis-induced organ injury occurs.     

Segmental colonic transit studies: comparison of a radiological and a scintigraphic method

OBJECTIVE: Colonic transit studies are used to diagnose slow transit constipation (STC) and to evaluate segmental colonic transit before segmental or subtotal colectomy. The aim of the study was to compare a single X-ray radio-opaque marker method with a scintigraphic technique to assess total and segmental colonic transit in patients with STC. METHOD: Thirty-one female patients (median age 46 years) with severe constipation and a prolonged or borderline prolonged colonic transit time on radio-opaque marker study were included in the study. They were subsequently investigated with (111)Indium-DTPA colonic transit scintigraphy, with a median time between the investigations of 4(range 1-27) months. Normal values of healthy female controls were used for comparison. RESULTS: There was no difference between the two methods in terms of prolonged or normal total colonic transit time. Twenty-nine of 31 female patients had a prolonged transit time only in one or two segments on the marker study. On scintigraphy, the transit time was prolonged for patients in the left (P < 0.05 to P < 0.001), but not in the right colon. With respect to prolonged or normal segmental transit time, there was a significant difference between the two methods only in the descending colon (P = 0.02). However, the results varied considerably for individual patients. CONCLUSION: Segmental colonic delay was a common finding. The two methods gave similar results for groups of patients, except in the descending colon. The variation of the results for individuals suggests that a repeated transit test may improve the assessment of total and segmental transit.     

慢传输性便秘结肠阿片受体的病理生理改变

目的探讨慢传输性便秘(STC)的发病机制和病理生理改变。方法应用放射配体结合分析法,检测患者结肠mu、kappa阿片受体,观察其含量变化。结果STC患者结肠mu阿片受体的最大结合数(Bmax)和解离常数(KD)比正常对照组明显增加(Bmax400.950比96.304pmol,KD431.314比179.839pmol);kappa阿片受体含量检测亦有类似结果(Bmax:375.073比45.264pmol,KD485.407比141.016pmol)。结论STC患者阿片受体含量增加,内源性阿片肽活性增加。提示采用阿片受体拮抗剂可能是治疗STC的一个新途径。     

Antithrombin III prevents deleterious effects of remote ischemia-reperfusion injury on healing of colonic anastomoses

BACKGROUND: Antithrombin III is known as the most important natural inhibitor of thrombin activity and has been shown to attenuate local harmful effects of ischemia-reperfusion injury in many organs. In recent animal studies, delaying effect of remote organ ischemia-reperfusion injury on healing of intestinal anastomoses has been demonstrated. In this study, we investigated whether antithrombin III reduces deleterious systemic effects of ischemia-reperfusion injury on healing of colonic anastomoses in rats. METHODS: Anastomosis of the left colon was performed in 24 rats that were divided into three groups: sham operated control (group I, n = 8), 30 minutes of intestinal ischemia-reperfusion by superior mesenteric artery occlusion (group II, n = 8), antithrombin III treated group (250 U/kg before and after the ischemia-reperfusion, group III, n = 8). On postoperative day 6, all animals were sacrificed, and bursting pressure and tissue hydroxyproline content of the anastomoses were assessed and compared. RESULTS: On postoperative day 6 the mean bursting pressures were 149.6 +/- 4.8, 69.8 +/- 13.5, and 121.8 +/- 8.7 mm Hg for groups I, II, and III, respectively (P = 0.000). Mean tissue hydroxyproline concentration values were 389.5 +/- 29.6, 263.1 +/- 10.0, and 376.0 +/- 33.8 microg/mg for groups I, II, III respectively (P = 0.005). CONCLUSIONS: This study showed that, antithrombin III treatment significantly prevented the delaying effect of remote organ ischemia-reperfusion injury on anastomotic healing in the colon. Further clinical studies are needed to clarify whether antithrombin may be a useful therapeutic agent to increase the safety of the anastomosis during particular operations where remote organ ischemia-reperfusion injury takes place.     

γ-氨基丁酸B型受体对结肠癌HCT116细胞周期的影响

目的利用人结肠癌细胞株HCT116细胞为研究模型,探究γ-氨基丁酸B型受体（GABABR）/糖原合成激酶3β（GSK-3β）/核转录因子（NF-κB）信号通路对结肠肿瘤细胞HCT116周期的影响,明确GABABR调控结肠癌细胞增殖的机制。 方法使用人结肠癌细胞株HCT116细胞为模型,构建针对GABABR的shRNA,流式细胞仪检测不同刺激条件下HCT116细胞周期分布,四甲基偶氮唑盐微量酶反应比色法（MTT）、5-溴脱氧尿嘧啶核苷（Brdu）法检测细胞的增殖能力变化。 结果GABABR可调控HCT116细胞的增殖。GABABR激动剂巴氯芬将HCT116细胞滞留在G1期,GSK-3β激动剂wort能逆转巴氯芬对结肠癌的该作用;GSK-3β抑制剂SB216763处理后,HCT116细胞增殖得到抑制,而NF-κB激动剂PMA可以阻断此作用;NF-κB激动剂PDTC能够回救敲低GABABR所引起的HCT116细胞增殖抑制,Akt抑制剂MK-2206 2HCl能逆转巴氯芬、SB216763对HCT116细胞增殖的抑制作用。 结论GABABR/GSK-3β/NF-κB信号通路可以调控结肠癌细胞增殖,通过抑制GSK-3β的活性,抑制NF-κB信号通路的激活,将HCT116细胞滞留在G1期。GABABR/GSK-3β/NF-κB信号通路可以作为临床预防和治疗结肠癌的潜在药物靶点之一。     

腹腔镜右半结肠癌扩大切除术意义的纷争

随着全结肠系膜切除(CME)及扩大淋巴结清扫(D3)理念在结肠癌手术中的推广,CME及D3淋巴结清扫上取得了良好的肿瘤学和手术结果,提高生存率及无病生存率,降低局部复发率。CME手术与直肠癌术中直肠系膜全切除相似,是切除肿瘤引流区域的所有淋巴、血管和神经组织以及完整的肠系膜,腹膜和包围的筋膜。而D3淋巴结清扫也是基于相似的原则。但是,目前有证据表明CME和D3淋巴结清扫的预后获益受限于方法缺陷和一些潜在的混杂因素,需要大宗病例的前瞻随机对照临床实验进一步验证。     

腹腔镜右半结肠癌CME切除术——尾侧中间联合入路

手术遵循完整结肠系膜切除原则。手术过程包括：探查腹腔;自尾侧从末端回肠系膜根部黄白交界线打开系膜,进入右结肠后间隙,向头侧,外侧拓展该间隙,至十二指肠水平;回到传统中间入路,回结肠血管下方打开结肠系膜,与尾侧方向打开的间隙会师;解剖并高位结扎切断回结肠血管、打开肠系膜上静脉血管鞘,清扫外科干,高位结扎切断右结肠血管、中结肠血管右支,继续拓展分离右结肠后间隙、横结肠后间隙,直至胰腺下缘并进入小网膜囊;打开胃结肠韧带,游离结肠肝曲;打开右侧腹膜,完成肠段游离,体外切除标本、重建消化道。     

腹腔镜右半结肠切除中间入路与侧方入路的前瞻性随机对照研究

目的 对比中间入路法与传统侧方入路法在右半结肠癌行腹腔镜右半结肠切除术中的效果.方法 于2007年1月至2009年7月,将入院拟行手术治疗的48例右半结肠癌患者按随机数字表法前瞻性随机分为两组（各24例）,分别行中间入路和侧方入路腹腔镜右半结肠切除术,对比两组手术时间、术中出血量、淋巴结清扫情况、术中及术后并发症及术后住院时间.结果中间入路法与侧方入路法两组患者手术时间分别为（122.5±25.8）min及（162.9±30.9）min（P=0.01）;术中出血量分别为（55.8±36.2）ml及（104.6±58.2）ml（P=0.01）;差异均有统计学意义.两组术中并发症分别为4.2%和8.3%,术后并发症分别为8.3%和16.7%,淋巴结清扫数分别为（17.4±3.2）枚和（17.8±3.4）枚,术后住院时间分别为（7.8±2.2）d和（8.0±3.6）d,差异均无统计学意义（P＞0.05）.结论 中间入路法较传统的侧方入路法在腹腔镜右半结肠切除术中可明显缩短手术时间,减少术中出血量.     

结肠镜联合钛夹定位法对结肠肿瘤手术切口选择的作用

目的 探讨肠镜联合钛夹定位法进行结肠肿瘤定位诊断对选择手术切口的指导意义.方法 30例结肠肿瘤患者在术前行结肠镜检查,于肿瘤处使用钛夹进行标记,摄腹部立、平卧位腹平片确定其体表投影部位并进行切口选择.结果本组患者在肠镜下有9例患者（30%）出现定位错误或无法准确判定;联合钛夹定位后,所有患者术前均明确肿瘤部位,以此指导手术切口选择,100%手术切口选择正确,获得良好的术野暴露.结论 肠镜对于结肠肿瘤定位困难,有一定误差率,肠镜联合钛夹标记法进行肿瘤定位,有助于准确定位并选择最佳的手术切口.     

结肠镜联合钛夹定位法对结肠肿瘤手术切口选择的作用

目的 探讨肠镜联合钛夹定位法进行结肠肿瘤定位诊断对选择手术切口的指导意义.方法 30例结肠肿瘤患者在术前行结肠镜检查,于肿瘤处使用钛夹进行标记,摄腹部立、平卧位腹平片确定其体表投影部位并进行切口选择.结果本组患者在肠镜下有9例患者(30%)出现定位错误或无法准确判定;联合钛夹定位后,所有患者术前均明确肿瘤部位,以此指导手术切口选择,100%手术切口选择正确,获得良好的术野暴露.结论 肠镜对于结肠肿瘤定位困难,有一定误差率,肠镜联合钛夹标记法进行肿瘤定位,有助于准确定位并选择最佳的手术切口.