Koffeman Geert Iede, Hulscher Jan B F, Schoots Ivo G, van Gulik Thomas M, Heij Hugo A, van Gemert Wim G
Department of Pediatric Surgery, Pediatric Surgical Center Amsterdam AMC/VUmc, Amsterdam, The Netherlands; Department of Surgery, St Lucas Andreas Hospital, Amsterdam, The Netherlands.
Department of Pediatric Surgery, University Medical Center Groningen, Groningen, The Netherlands.
J Surg Res. 2015 May 15;195(2):433-43. doi: 10.1016/j.jss.2014.12.024. Epub 2014 Dec 29.
Treatment of short bowel syndrome (SBS) remains difficult, entailing severe morbidity and mortality. Accepted surgical treatment modalities for SBS are the Bianchi intestinal lengthening procedure and reversed-segment procedure. We seek to investigate the short-term effects regarding growth, nutrition, and microscopic and functional adaptation after the intestinal lengthening and RS procedures in a piglet SBS-model.
Twenty-four piglets (Sus scrofa, ±30 kg) were divided into four groups (n = 6 each) as follows: sham, SBS, Bianchi lengthening procedure (BIA), and reversed-segment (RS). At day one either sham laparotomy (sham) or 75% small bowel resection (SBS, BIA, and RS) was performed. After 2 wk sham laparotomy (sham and SBS), BIA, or RS procedure was performed. After 8 wk all animals were terminated. During the experimental time course, the following parameters were assessed: body weight, intestinal length, diameter, and weight, fat absorption, and biochemical parameters from serum and urine. Citrulline was used as a marker of absorptive enteral mass to demonstrate massive functional bowel loss. Intestinal biopsies were obtained for histologic analysis and electrophysiological measurements to analyze glucose absorptive capacity.
Eight weeks after bowel resection, piglet growth was reduced in SBS, BIA, and RS piglets as demonstrated by reduced weight (51 ± 4 kg, 47 ± 2 kg, and 53 ± 1 kg, respectively) compared with sham (69 ± 3 kg; P < 0.01), with no demonstrable difference between SBS and treatment groups. Malabsorption and malnutrition occurred in SBS, BIA, and RS piglets reflected by increased fecal fat loss per 24 h (35 ± 4%, 30 ± 2%, and 32 ± 4%, respectively versus 18 ± 1% in sham; P < 0.01) and reduced serum albumin levels (24 ± 1 g/L, 22 ± 1 g/L, and 24 ± 1 g/L, respectively versus sham 33 ± 1 g/L; P < 0.01), but there was no significant difference between SBS and treatment groups. Serum citrulline levels reflected massive functional bowel loss (SBS 36 ± 7 μmol/L, BIA 23 ± 1 μmol/L, and RS 24 ± 2 μmol/L) compared with sham (64 ± 5 μmol/L; P < 0.01). Electrophysiological measurements demonstrated reduced glucose absorption after intestinal resection, which did not return to base levels within the experimental time course. However, the intestine of BIA and RS piglets adapted more profoundly than SBS piglets, as reflected by a greater crypt depth (490 ± 25 μm and 492 ± 21 μm versus 388 ± 20 μm; P < 0.01); and BIA piglets showed greater villus length (884 ± 58 μm) than RS or SBS piglets (715 ± 30 μm and 737 ± 64 μm, respectively; P < 0.01) after 8 wk.
Despite increased histologic intestinal adaptation, neither intestinal lengthening nor RS procedure demonstrated significantly improved absorption, nutrition, or weight gain for the treatment of SBS during the study period. Reduced glucose uptake on electrophysiology measurements and persistent low levels of citrulline may indicate reduced small bowel enterocyte functioning during the initial phase of intestinal adaptation.
短肠综合征(SBS)的治疗仍然困难,会导致严重的发病率和死亡率。公认的SBS手术治疗方式为比安基肠道延长术和肠段倒置术。我们试图在仔猪SBS模型中研究肠道延长术和肠段倒置术后对生长、营养以及微观和功能适应性的短期影响。
24只仔猪(猪,体重约30千克)分为四组(每组n = 6):假手术组、SBS组、比安基延长术(BIA)组和肠段倒置(RS)组。在第1天,对假手术组进行假剖腹手术,对SBS组、BIA组和RS组进行75%小肠切除术。2周后,对假手术组(假手术组和SBS组)、BIA组或RS组进行假剖腹手术、BIA手术或RS手术。8周后,处死所有动物。在实验过程中,评估以下参数:体重、肠长度、直径和重量、脂肪吸收以及血清和尿液中的生化参数。瓜氨酸用作吸收性肠质量的标志物,以证明大量功能性肠丢失。获取肠道活检组织进行组织学分析和电生理测量,以分析葡萄糖吸收能力。
肠切除术后8周,SBS组、BIA组和RS组仔猪的生长减缓,与假手术组(69±3千克)相比体重降低(分别为51±4千克、47±2千克和53±1千克;P<0.01),SBS组与治疗组之间无明显差异。SBS组、BIA组和RS组仔猪出现吸收不良和营养不良,表现为每24小时粪便脂肪损失增加(分别为35±4%、30±2%和32±4%,假手术组为18±1%;P<0.01)以及血清白蛋白水平降低(分别为24±1克/升、22±1克/升和24±1克/升,假手术组为33±1克/升;P<0.01),但SBS组与治疗组之间无显著差异。与假手术组(64±5微摩尔/升;P<0.01)相比,血清瓜氨酸水平反映出大量功能性肠丢失(SBS组为36±7微摩尔/升,BIA组为23±1微摩尔/升,RS组为24±2微摩尔/升)。电生理测量表明,肠切除术后葡萄糖吸收减少,在实验过程中未恢复到基础水平。然而,BIA组和RS组仔猪的肠道比SBS组仔猪适应性更强,表现为隐窝深度更深(分别为490±25微米和492±21微米,SBS组为388±20微米;P<0.01);8周后,BIA组仔猪的绒毛长度(884±58微米)比RS组或SBS组仔猪(分别为715±30微米和737±64微米)更长(P<0.01)。
尽管组织学上肠道适应性增强,但在研究期间,肠道延长术和肠段倒置术均未显示出对SBS治疗的吸收、营养或体重增加有显著改善。电生理测量中葡萄糖摄取减少和瓜氨酸水平持续较低可能表明在肠道适应的初始阶段小肠肠上皮细胞功能降低。