精氨酸促进短肠综合征肠道代偿及其机制的初步研究

目的研究肠内营养中添加精氨酸对广泛肠切除术后大鼠肠道代偿的影响。方法将30只SD大鼠随机分为Con组（假手术）、SB组（短肠对照）和SB—Arg组（短肠加用精氨酸）,各组大鼠于术后第2。14天分别给予等氮、等热量的肠内营养支持．其中SB-Arg组肠内营养中添加L-精氨酸（300mg·kg^-1·d^-1）。比较术后各组体质量、脂肪吸收率、血浆总游离脂肪酸及必需脂肪酸水平、小肠代偿指标、肠黏膜细胞增殖和凋亡的差异。结果SB组术后早期营养支持2周后,其体质量较Con组低,各项肠道代偿指标均明显升高（P〈0．05）。SB-Arg组大鼠脂肪吸收率[（84．9±3．2）％]、血浆游离脂肪酸水平[（650．0±86．5）mg／L]、回肠黏膜质量[（18．0±3．5）mg·cm^-1·100g^-1]、回肠DNA含量[（29．6±3．3）μg·cm^-1·100g^-1]、小肠蛋白质含量[空肠（65．5＋7．3）μg·cm^-1·100g^-1和回肠（39．2±2．3）μg·cm^-1·100g^-1]和小肠增殖指数（空肠31±4,回肠32±2）均高于SB组的[（81．3±3．9）％、（289．5±76．9）mg／L、（13．5±3．0）mg·cm^-1·100g^-1（26．0＋2．6）μg·cm^-1·100g^-1（59．8±6．2）μg·cm^-1·100g^-1、（35．4±2．3）μg·cm^-1·100g^-1、（22±3）及（25±3）,均P〈0．05];小肠超微结构亦观察到SB-Arg组大鼠小肠绒毛高度、隐窝深度及黏膜厚度均大于SB组大鼠（P〈0．05）。结论肠内营养中添加适量精氨酸能促进短肠综合征大鼠肠道结构及功能的代偿．其机制可能为促进肠黏膜细胞增殖、抑制其凋亡。     

The effect of growth hormone supplementation on late nutritional independence in pediatric patients with short bowel syndrome

Purpose

The use of growth hormone (GH) supplementation for intestinal adaptation among adult patients with short bowel syndrome (SBS) has provided mixed results. This report examines the effect of GH supplementation on SBS in pediatric patients.

Methods

Two girls with SBS from neonatal gastrointestinal catastrophes received exogenous GH at 0.3 mg/kg per week subcutaneously and concurrent glutamine supplementation, beginning at 6 and 6½ years of age. Changes in growth (height and weight) and changes in enteral and parenteral energy requirements were evaluated.

Results

Treatment duration was 8 and 2.5 years, respectively. Patient weights increased from the 5th to the 41st percentile and from the 17th to the 23rd percentile, respectively. Height increased from the 1st to the 57th percentile in the former patient and increased from less than the 1st to the 17th percentile in the latter. Both patients are independent of parenteral nutrition and take enteral nutrition alone. Tolerance for enteral diets was significantly improved in each girl, with only 2 stools per day maintained in one patient.

Conclusions

The data show that late exogenous treatment with GH and glutamine supplementation improved growth parameters in pediatric patients with SBS. Growth hormone and glutamine supplementation may be beneficial in promoting late intestinal adaptation in pediatric patients with SBS. These data also suggest that these adjuncts may be useful in the early phases of intestinal adaptation.     

Comparison of massive vs. repeated resection leading to short bowel syndrome

Short bowel syndrome can result from either a single massive intestinal resection or repeated lesser resections, which might have prognostic implications. The aim of this study was to compare patient populations and outcome of short bowel syndrome caused by massive and repeated resection. The records of 95 adult patients with short bowel syndrome evaluated over a 20-year period were reviewed. Massive resection was performed in 72 patients (76%) and repeated lesser resections in 23 patients (24%). Patients undergoing massive resection were more likely to be more than 70 years of age (26% vs. 9%, P <0.05). Mesenteric vascular disease was more prevalent among patients undergoing massive resection (39% vs. 9%, P <0.05), whereas Crohn’s disease was less prevalent (1% vs. 35%, P <0.05). Distribution of remnant length, presence of the ileocecal junction, and presence of a stoma were similar. Patients undergoing massive resection were more likely to require parenteral nutrition after the first year (56% vs. 23%, P <0.05). Patients with very short remnants (<60 cm) were more likely to receive parenteral nutrition after massive resection (95% vs. 60%, P <0.05). Thirty-day mortality was higher after massive resection (24% vs. 4%, P <0.05). However, those surviving 30 days had similar survival rates at 1 year and 5 years after massive and repeated resections. Patients undergoing massive vs. repeated resections are different with respect to age, underlying condition, and nutritional support needs. These factors may influence overall outcome in short bowel syndrome. The better nutritional prognosis of patients undergoing repeated resection given similar intestinal remnants may be related in part to enhanced intestinal adaptation. Presented at the Fortieth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Fla., May 16–19, 1999.     

短肠综合征的手术治疗进展

近年来随着小肠疾病发病率及诊断率的升高,短肠综合征的发病率也呈逐年上升趋势。手术是治疗短肠综合征的重要方法,其手术治疗方式主要包括治疗短肠综合征并发症、促进肠动力、延长食物停留时间、小肠缩窄与延长以及小肠移植术。     

Neonatal short bowel syndrome: a cohort study

Background

To date, our knowledge of morbidity and mortality in neonatal short bowel syndrome (SBS) is based on individual case series. Shortcomings of the published literature include long patient recruitment time, selection bias, variable SBS definitions, failure to account for gestational age, and incomplete follow-up. By applying more rigorous methodology, our aim was to determine outcomes of SBS neonates compared with a control group of neonates without SBS.

Methods

A cohort study of all neonates with abdominal pathology requiring laparotomy between January 1, 1997, and December 31, 1998, with observation through July 1, 2001. Short bowel syndrome was defined as patients requiring parenteral nutrition for more than 42 days or residual small bowel length of less than 25% predicted by gestational age. Student's t test, Mann-Whitney U test, and χ² were used where appropriate. Kaplan-Meier curves were used to determine cumulative survival. Covariates important in the development of SBS were examined using forward step-wise logistic regression.

Results

There were 175 patients (with SBS = 40, without SBS = 135) with a mean gestational age of 30.7 ± 4.6 weeks vs 35.9 ± 4.8 weeks, respectively (P < .0005). The patients with SBS suffered significantly more morbidity than the group without SBS in all categories of investigation (surgical complications, septic events, central venous line complications, duration to adaptation and parenteral nutrition independence, cholestasis and liver failure, and duration of hospitalization). The case fatality rate was 37.5% in patients with SBS vs 13.3% in patients without SBS (P = .001). Most of the deaths were caused by liver failure or sepsis and occurred within 1 year from the date of surgery. Presence of an ileostomy (exp(B) = 12.29; P < .0005) and a residual small bowel length less than 50% of the original length (exp(B) = 26.84; P < .0005) were the only 2 variables in a logistic regression analysis found to be independently associated with the development of SBS.

Conclusion

This cohort study clearly illustrates the tremendous morbidity experienced by infants with SBS relative to other surgical neonates. Accurate estimates of the morbidity associated with SBS enables clinicians to appropriately counsel parents, allocate resources and initiate therapeutic trials.     

Citrulline levels following proximal versus distal small bowel resection

Purpose

Citrulline, a nonprotein amino acid synthesized by enterocytes, is a biomarker of bowel length and the capacity to wean from parenteral nutrition. However, the potentially variant effect of jejunal versus ileal excision on plasma citrulline concentration [CIT] has not been studied. This investigation compared serial serum [CIT] and mucosal adaptive potential after proximal versus distal small bowel resection.

Methods

Enterally fed Sprague-Dawley rats underwent sham operation or 50% small bowel resection, either proximal (PR) or distal (DR). [CIT] was measured at operation and weekly for 8 weeks. At necropsy, histologic features reflecting bowel adaptation were evaluated.

Results

By weeks 6–7, [CIT] in both resection groups significantly decreased from baseline (P < 0.05) and was significantly lower than the concentration in sham animals (P < 0.05). There was no difference in [CIT] between PR and DR at any point. Villus height and crypt density were higher in the PR than in the DR group (P ≤ 0.02).

Conclusion

[CIT] effectively differentiates animals undergoing major bowel resection from those with preserved intestinal length. The region of intestinal resection was not a determinant of [CIT]. The remaining bowel in the PR group demonstrated greater adaptive potential histologically. [CIT] is a robust biomarker for intestinal length, irrespective of location of small intestine lost.     

Evaluation of intestinal absorption after longitudinal intestinal lengthening for short bowel syndrome

Purpose

The aim of this study was to answer if the longitudinal intestinal lengthening and tailoring (LILT) by Bianchi, modified by Aigrain, can allow the child to be weaned from parenteral nutrition (PN) and if the length of the bowel after the procedure can influence the results of the absorption test such as Schilling or d-xylose test.

Patients and Methods

We reviewed the files of 7 children who have had LILT from 1980 to 2003. We performed to explore 2 intestinal function tests: the d-xylose and the Schilling tests. Both were performed early (during the first year after the procedure) and late (during the second year) after the LILT. We used the χ² and Bartlett's correlation tests for statistical analysis.

Results

There were 6 boys and 1 girl. The surgical indication was short bowel syndrome with parenteral nutrition owing to multiple intestinal atresia (2 cases), severe necrotizing enterocolitis with volvulus (1 case), necrotizing enterocolitis (1 case), intestinal atresia with gastroschisis (2 cases), and volvulus owing to malrotation (1 case). The length of the bowel was significantly different before and after LILT (P < .0001). After LILT, the length of the bowel was significantly correlated with the percentage of PN on energy at 6 months (P = .02) and at 12 months (P = .001). Moreover, the length of the bowel after the procedure was significantly correlated with the results of the d-xylose test during the first year (P = .002) but not with the results after the second year. The length after lengthening influenced neither the results of the Schilling test during the first nor those of the second year after. Four patients were weaned from the PN 21 months in average after the LILT (57%); 1 was not because we had only a 2-month follow-up. The average follow-up was 111 (5 months; range, 4- 206).

Conclusion

Longitudinal intestinal lengthening and tailoring for short bowel syndrome is a good option to allow children to be weaned from the PN. The length of the bowel after the procedure can influence the absorption test such as d-xylose during the first postoperative year but not during the second and does not influence the Schilling test. We think it is not necessary to perform these tests during the follow-up of these patients.     

Ostomy in continuity: A novel approach for the management of children with complex short bowel syndrome

Introduction

Despite medical and surgical management, a subset of children with short bowel syndrome (SBS) who have discrepancy between proximal small bowel and distal colon have persistent feeding intolerance. We propose the use of an Ostomy in Continuity (OIC) (Bishop-Koop or Santulli) as a salvage procedure to decompress the proximal bowel while still maintaining maximal intestinal length, in these patients.

短肠综合征病人的营养支持及肠道代偿治疗

目的探讨短肠综合征病人的营养支持以及肠道代偿、康复治疗体会。方法回顾性分析1986~2005年复旦大学附属中山医院64例短肠综合征病人治疗过程及随访情况,其中26例联合应用生长激素[GH,每天(0.10±0.06)mg/kg]和谷氨酰胺[GLN,每天(0.30±0.17)g/kg]进行肠道促代偿治疗。结果64例病人中死亡6例,存活58例,存活时间3个月至19年,平均(6.6±9.4)年。9例长期接受家庭肠外营养(HPN),13例接受部分PN或肠内营养(EN)支持,完全摆脱PN者36例,平均摆脱PN的时间为(8.6±14.2)个月。26例接受GH GLN治疗的SBS病人,其中9例(34.6%)治疗后近期内完全摆脱PN;8例(30.8%)经治疗后明显减少了PN用量[从每周需要PN支持(6.5±1.0)d下降至(4.2±1.0)d,每周PN需要量从(13.6±5.2)L降至(8.2±3.3)L];9例(34.6%)在治疗后仍依赖PN支持。64例共发生286次各种并发症。结论经过适宜的营养支持和肠道促代偿治疗,大多数短肠综合征病人的残留肠道可充分代偿,完全摆脱PN或减少PN用量,长期健康存活。     

Low-fat diet impairs postresection intestinal adaptation in a rat model of short bowel syndrome

Background: Low-fat diets (LFD) are utilized frequently in patients with short bowel syndrome (SBS). The purpose of this study was to investigate the effects of LFD on intestinal adaptation, enterocyte proliferation, and enterocyte cell death in a rat model of SBS.Methods: Adult male Sprague-Dawley rats were divided into 3 experimental groups: Sham-NC rats underwent bowel transection and reanastomosis and were fed normal chow (NC), SBS-NC rats underwent 75% small bowel resection and were fed NC, and SBS-rats were fed a low-fat diet (SBS-LFD). Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 14 after operation.Results: SBS-NC rats showed a significant increase (v Sham-NC) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. A significant 67% increase in crypt cell proliferation rate and 265% increase in villus enterocyte apoptosis was seen in the ileum of SBS-NC rats compared with control animals (P < .05). SBS-LFD animals showed lower ileal mucosal weight (29%; P < .05), jejunal crypt depth (20%; P < .05), and ileal villus height (21%; P < .05). A significant decrease in villus apoptosis in jejunum (74%; P < .05) and ileum (67%; P < .05) and a decrease in cell proliferation in ileum (35%; P < .05) was seen also after exposure to LFD compared with SBS-NC.Conclusions: In a rat model of SBS, early LFD appears to inhibit parameters of intestinal adaptation. A possible mechanisms for this effect may be decreased cell proliferation. Decreased enterocyte loss via apoptosis, found in this study, may reflect a reduced number of enterocyte.     

Improved survival in a multidisciplinary short bowel syndrome program

Purpose

Pediatric short bowel syndrome (SBS) remains a management challenge with significant mortality. In 1999, we initiated a multidisciplinary pediatric intestinal rehabilitation program. The purpose of this study was to determine if the multidisciplinary approach was associated with improved survival in this patient population.

Methods

The Center for Advanced Intestinal Rehabilitation includes dedicated staff in surgery, gastroenterology, nutrition, pharmacy, nursing, and social work. We reviewed the medical records of all inpatients and outpatients with severe SBS treated from 1999 to 2006. These patients were compared to a historical control group of 30 consecutive patients with severe SBS who were treated between 1986 and 1998.

Results

Fifty-four patients with severe SBS managed by the multidisciplinary program were identified. Median follow-up was 403 days. The mean residual small intestinal length was 70 ± 36 vs 83 ± 67 cm in the historical controls (P = NS). Mean peak direct bilirubin was 8.1 ± 7.9 vs 9.0 ± 7.4 mg/dL in controls (P = NS). Full enteral nutrition was achieved in 36 (67%) of 54 patients with severe SBS vs 20 (67%) of 30 patients in the control group (P = NS). The overall survival rate, however, was 89% (48/54), which is significantly higher than in the historical controls (70%, 21/30; P < .05).

Conclusions

A multidisciplinary approach to intestinal rehabilitation allows for fully integrated care of inpatients and outpatients with SBS by fostering coordination of surgical, medical, and nutritional management. Our experience with 2 comparable cohorts demonstrates that this multidisciplinary approach is associated with improved survival.     

短肠综合征康复治疗的实验研究和临床应用

目的观察应用重组人生长激素、谷氨酰胺和膳食纤维行康复治疗的实验动物及短肠综合征患者的治疗效果。方法 30只大鼠分为对照组、短肠组和生长激素 (growthhormone ,GH)组 ,短肠组和GH组切除 80 %小肠 ,GH组术后第 1天开始注射GH 1U·kg-1·d-1,共 2 8d ;9例患者残存小肠长度为 (4 4± 2 4)cm ,其中 3例无完整结肠。结果S期细胞比率系数、增殖指数和增殖细胞核抗原表达的增强表明外源性GH可明显促进残存小肠粘膜的增殖 ,GH的作用机理可能与原癌基因C jun表达的改变有关。康复治疗后 9例患者营养状况和残存肠管吸收功能均明显改善 ,8例患者进行了随访 ,75 %的患者完全脱离肠外营养 ,2 5 %的患者需间断肠外营养补充。结论康复治疗为短肠综合征提供了一个新的有效的治疗方法     

Intermediate outcomes after serial transverse enteroplasty in children with short bowel syndrome

Background

Serial transverse enteroplasty (STEP) is a novel intestinal lengthening procedure introduced in 2003. To date, no human studies exist that report objective assessment of intestinal absorptive capacity. The aim of this study was to report intermediate outcomes in patients who have received the STEP at our institution using clinical and biochemical assessment of intestinal function.

Methods

All 14 patients who received the STEP since May 2003 were reviewed. Clinical (weight gain, enteral tolerance, stool frequency) and biochemical (citrulline levels, d-xylose absorption, alpha-1 antitrypsin clearance, and fecal fat content) outcomes were performed pre-STEP and post-STEP at 1, 6, and 12 months, respectively. Data are presented as means with standard deviation. Paired t tests were used to compare post-STEP outcomes with pre-STEP values (P < .05 was significant). Three patients had a STEP as a newborn and are analyzed separately.

Main Results

There were 14 patients (3 females; mean age, 24.8 months; range, 1 day-14 years). Serial transverse enteroplasty resulted in a mean increase in length of dilated bowel segment of 94% ± 30% and increase in total small bowel length of 49% ± 42% with mean application of 16 ± 9 cartridges and cost of Can$2878.51 ± 1406.22. Patients demonstrated improvement in both clinical parameters, as well as intestinal absorptive function. Complications included 2 patients with staple line leak and 1 patient with gastrointestinal bleeding from staple line ulcers. Three patients died (2 from liver failure and 1 from sepsis and congenital heart disease). Two patients received liver-intestinal transplants at 4 and 5 months post-STEP. Mean follow-up was 23 ± 9 months, with 7 patients followed more than 2 years. Of 8 patients with post-STEP follow-up of more than 1 year, 7 have weaned from parenteral nutrition.

Conclusion

Clinical and objective biochemical outcomes of intestinal function after the STEP procedure show promise after intermediate follow-up.     

���ܵ��������ƶ̳��ۺ��������ۣ���6�����棩

目的 总结6例短肠综合征病人肠管倒置手术失败的教训，强调合理选择手术适应证的重要性和必要性，提出短肠综合征合理的治疗策略，方法 回顾性分析6例短肠综合征病人，均在外院接受肠管倒置手术，除1例为结肠倒置外，其余均为小肠倒置，倒置肠管长度从10～50cm不等，5例小肠倒置手术均在广泛肠切除的同时进行，术后1例出现吻合口瘘，4例出现肠梗阻。结果 1例病人因肝功能衰竭于术后5年死亡，1例病人放弃治疗，1例行肠瘘及倒置小肠切除治愈，2例行倒置肠管切除治愈，1例行倒置肠管复位治愈。治愈病人依靠普通饮食和部分肠内营养支持维持正常营养状况。结论 短肠综合征病人应首选肠康复治疗和小肠移植。只有极少数病人适宜进行肠倒置手术，手术时倒置肠管不应超过10cm，手术时机应在广泛肠切除2年以后进行．手术时应注意倒置肠管的血液供应，避免肠缺血。     

Intestinal adaptation in short bowel syndrome

Regaining enteral autonomy after extensive small bowel resection is dependent on intestinal adaptation. This adaptational process is characterized by hyperplastic growth of the remaining gut, which is accompanied by both an increase of cell division at the level of the crypt cells and by an increased rate of programmed cell death (apoptosis). Apart from the absorptive function, the small bowel also has a barrier function and plays an important role in interorgan metabolism. Also, these functions are greatly affected by a massive intestinal resection and subsequent recovery by intestinal adaptation. This review aims to give an overview of the debilitating effects of massive intestinal resection on gut function and subsequently discusses intestinal adaptation and possible factors stimulating adaptation.     

短肠综合征患者血清游离氨基酸水平的改变

目的研究短肠综合征患者血清游离氨基酸水平的变化规律,指导短肠患者的营养支持。方法对17例短肠综合征患者于入院时检测17种血游离氨基酸水平,并选择15例健康志愿者为对照组。结果 17种氨基酸中,短肠综合征患者血清缬氨酸、亮氨酸、异亮氨酸、赖氨酸、蛋氨酸、丝氨酸、胱氨酸、组氨酸水平显著低于对照组(P<0．05),短肠综合征患者支链氨基酸水平(381± 124)μmol／L、必需氨基酸水平(1895±460)μmol/L及必需氨基酸／非必需氨基酸比值(0．4±0．1)均显著低于对照组(P<0．05)。结论短肠综合征患者氨基酸及必需氨基酸均缺乏,在营养支持时需增加必需氨基酸的给予。     

Current short bowel syndrome management: An era of improved outcomes and continued challenges

Prior to the late 1960s, pediatric short bowel syndrome was a frequently fatal disease. Currently, pediatric interdisciplinary bowel rehabilitation centers report very high survival rates. The mortality trends, up-to-date definitions, incidence, causes, and clinical manifestations of short bowel syndrome are reviewed. Emphasis is placed upon the nutritional, medical, and surgical advances that have contributed to the dramatic improvement in outcomes for pediatric short bowel syndrome patients. Recent findings and remaining challenges are highlighted.     

短肠综合征患儿血清微量营养素状况评价

目的评价短肠综合征患儿不同状态下的血清微量营养素状况。方法收集并分析2004年4月至2006年7月间收治并获随访的17例短肠综合征患儿的临床资料。结果本组患儿年龄为3个月至18岁。其中完全脱离肠外营养（PN）11例，6例仍靠部分PN支持；保留回盲瓣11例，无回盲瓣6例；剩余小肠在75cm以上者5例，小于或等于75cm者12例。采用高效液相法测定血清维生素A、E和β-胡萝卜素水平。11例已脱离PN的患儿中有9例测定了血清铁、锌和铜。维生素低于参考值的发生率：维生素A占23．5％，维生素E占35．3％，β-胡萝卜素占58．8％。在未脱离PN、无回盲瓣和剩余小肠小于或等于75cm的患儿中，维生素A和β-胡萝卜素低于参考值的发生率较高。在脱离PN和剩余小肠大于75cm的患儿，维生素E低于参考值发生率较高。而在有或无回盲瓣患儿中，上述的发生率差异无统计学意义。3例血清锌浓度低于正常．1例血清铁浓度低于正常。结论短肠综合征患儿无论在PN支持时还是恢复正常饮食时，均可能发生微量营养素缺乏，应密切随访并补充有关微量营养素。     

Preservation of intestinal motility after the serial transverse enteroplasty procedure in a large animal model of short bowel syndrome

Introduction

Serial transverse enteroplasty (STEP) has been shown to improve bowel function in short bowel syndrome. The effect of the STEP procedure on intestinal motility is not known, but some have hypothesized that it could disrupt bowel innervation and thus impair intestinal motility.

Methods

Growing Yorkshire pigs (n = 7) underwent 3 operations at 6-week intervals: (1) reversal of 50 cm of jejunum, (2) 90% bowel resection ± STEP to the proximal dilated bowel (4 STEP, 3 control), and (3) implantation of serosal strain gauges. At each operation, baseline and post-octreotide small intestinal motility was studied with continuously perfused manometry catheters using non-anticholinergic anesthesia. In addition, awake monitoring was performed using strain gauge analysis 1 week after the third operation. Characteristics of phase III of the migrating motor complex (MMC) were compared between and within groups using t test, χ², and analysis of variance, with significance set at P < .05.

Results

Manometry data from the third surgery revealed no differences between groups or compared with baseline within groups for the presence and characteristics of phase III of the MMC. Specifically, the mean amplitude and frequency of phase III after octreotide, and both the mean baseline and mean octreotide-stimulated motility indices were equivalent. The duration of phase III after octreotide stimulation was significantly increased in the STEP animals, suggesting a potential benefit of the STEP procedure. Strain gauge analysis, performed in awake animals, confirmed no differences between the groups for basal and octreotide-stimulated characteristics of phase III of the MMC.

Conclusions

These preliminary data suggest that the STEP procedure in a porcine model of short bowel syndrome does not interfere with baseline or hormonally stimulated motility within the small bowel. These findings further support the STEP procedure as a safe option for the surgical management of short bowel syndrome.