Abstract：
OBJECTIVE: To test the hypothesis that intraperitoneal instillation of a single bolus dose of l-alanyl-l-glutamine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans.
METHODS: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT).
METHODS: Tertiary care gynecology surgical centre.
METHODS: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL.
METHODS: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight.
METHODS: Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG.
RESULTS: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed.
CONCLUSIONS: Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG\'s known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.
METHODS: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT).
METHODS: Tertiary care gynecology surgical centre.
METHODS: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL.
METHODS: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight.
METHODS: Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG.
RESULTS: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed.
CONCLUSIONS: Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG\'s known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.
摘要：
目的：为了检验以下假设：腹膜内滴注1-丙氨酰-1-谷氨酰胺（AG）的单次推注剂量会降低发病率，子宫肌瘤切除术后粘连的程度和/或严重程度，并建立AG在人类中的初步安全性和耐受性。
方法：阶段1,2随机，双盲,安慰剂对照研究（DBRCT）。
方法：三级护理妇科手术中心。
方法：38名妇女在6-8周后通过腹腔镜检查（N=38；AG-19vs安慰剂-19）或剖腹手术（N=10；AG-5vs安慰剂-5）进行了子宫肌瘤切除术。腹腔镜臂中的32例患者完成了SLL。
方法:在腹腔镜端口缝合闭合之前立即腹膜内施用Bolus剂量的AG或生理盐水溶液对照(0.9%NaCl)。基于lg/kg体重的给药方案,平均剂量为170mLAG或对照。
方法：获得所有手术的数字录音。主要终点是发病率的降低，通过意向治疗（ITT）方法分析术后粘连的严重程度和程度。三个独立的,盲审核员评估了所有手术录像,以评估是否存在粘连.事后分析评估腹膜腔中是否存在粘连。次要终点评估AG的安全性和耐受性。
结果：服用AG降低了发病率，术后粘连的严重程度和/或程度（p=0.046）。AG组中粘连的存在低于对照组(p=0.041)。AG组中15个中的15个(100%)实现粘附性改善,而安慰剂组中17个中的5个(29.6%)实现粘附性改善。未报告严重不良事件。没有观察到安全参数的差异。
结论：腹膜内l-丙氨酰-l-谷氨酰胺可减少腹腔镜子宫肌瘤切除术后所有患者的粘连形成。在93％的患者中，所有腹部部位都完全没有粘连。结果证实了AG对粘连发生的细胞机制的已知作用，为新的粘连预防研究和治疗奠定了基础。
方法：阶段1,2随机，双盲,安慰剂对照研究（DBRCT）。
方法：三级护理妇科手术中心。
方法：38名妇女在6-8周后通过腹腔镜检查（N=38；AG-19vs安慰剂-19）或剖腹手术（N=10；AG-5vs安慰剂-5）进行了子宫肌瘤切除术。腹腔镜臂中的32例患者完成了SLL。
方法:在腹腔镜端口缝合闭合之前立即腹膜内施用Bolus剂量的AG或生理盐水溶液对照(0.9%NaCl)。基于lg/kg体重的给药方案,平均剂量为170mLAG或对照。
方法：获得所有手术的数字录音。主要终点是发病率的降低，通过意向治疗（ITT）方法分析术后粘连的严重程度和程度。三个独立的,盲审核员评估了所有手术录像,以评估是否存在粘连.事后分析评估腹膜腔中是否存在粘连。次要终点评估AG的安全性和耐受性。
结果：服用AG降低了发病率，术后粘连的严重程度和/或程度（p=0.046）。AG组中粘连的存在低于对照组(p=0.041)。AG组中15个中的15个(100%)实现粘附性改善,而安慰剂组中17个中的5个(29.6%)实现粘附性改善。未报告严重不良事件。没有观察到安全参数的差异。
结论：腹膜内l-丙氨酰-l-谷氨酰胺可减少腹腔镜子宫肌瘤切除术后所有患者的粘连形成。在93％的患者中，所有腹部部位都完全没有粘连。结果证实了AG对粘连发生的细胞机制的已知作用，为新的粘连预防研究和治疗奠定了基础。
