Plasma citrulline as marker of bowel adaptation in children with short bowel syndrome

Purpose  

The aim of this study is to determine if prospective determinations of citrulline could be predictive of the bowel adaptation in children with short bowel syndrome (SBS).     

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.     

短肠综合征的肠内营养支持

目的探讨短肠综合征患者肠内营养支持的临床意义、疗效及注意事项。方法回顾性总结1999至2005年收治的40例短肠综合征患者的临床资料。所有患者均存活至今,并随访2年以上。统计分析其肠内营养用量、费用、脱离肠外营养时间及目前营养状况。结果40例患者平均残存小肠（50．8±29．4）cm,脱离肠外营养平均时间为（29．1±9．2）个月。肠内营养用量为（3284．0±1408．8）kJ／d,其费用显著低于肠外营养（P〈0．01）。目前本组患者平均体质指数为（17．8±3．2）kg,／m^2,血红蛋白（113．3±14．8）g／L,血清白蛋白（35．0±4．1）g／L。平均大便次数为（3．4±1．7）次／d,平均大便量为（720．2±350．3）ml／d。结论肠内营养对于维持短肠综合征患者营养状况、减少并发症具有重要意义,但在具体实施时需掌握方法。     

Small bowel necrosis related to enteral nutrition after duodenal surgery

Nutritional support is the key to the successful recovery of any patient. Small bowel necrosis is described in patients being fed with enteral nutrition after surgery. Five patients with small bowel necrosis after surgery will be discussed and an etiology proposed. A retrospective review of patient data was performed. Data was collected on the type of surgical procedures performed, the enteral nutrition given to the patient, basic laboratory data, the length of stay, and discharge status. A total of five patients' charts were reviewed. Three patients had pancreaticoduodenectomy for a pancreatic mass and two required pyloric exclusion secondary to gunshot wounds. All five patients were fed with a fiber-based enteral nutrition. All patients subsequently had small bowel necrosis requiring reoperation. Four of the five patients had inspissated tube feeding within the necrotic small bowel. Two patients died and three survived with prolonged hospital courses. We propose that the combination of duodenal surgery and fiber-based enteral nutrition contribute to the development of small bowel necrosis postoperatively.     

Five-year outcomes after serial transverse enteroplasty in children with short bowel syndrome

AimThe aim of this study is to report 5-year outcomes in patients who have received serial transverse enteroplasty (STEP) using clinical and biochemical assessments of intestinal function.MethodsThirty-one STEP procedures have been performed at our institution. Twelve patients who received STEP before January 2005 were analyzed. Clinical and biochemical outcomes were performed pre-STEP and post-STEP on an annual basis. Paired t tests were used to compare post-STEP outcomes to pre-STEP values (P < .05 was significant).Main ResultsThere were 12 patients (3 females; median age, 5.5 months). Serial transverse enteroplasty resulted in mean increase in length of dilated bowel segment of 89% ± 26% and increase in total small bowel length of 46% ± 40%. Two patients received liver-intestinal transplants post-STEP (at 4 and 5 months), and 2 patients died of liver failure at 3 and 8 months. The remaining 8 of 12 patients all show stable intestinal absorptive capacity (data not shown). Of 8 patients, 7 were weaned off parenteral nutrition by 4 years. No patient has required repeat STEP or bowel tapering. Two patients developed staple line leak, and 1 patient developed gastrointestinal bleed from staple line ulcers.ConclusionThis report represents the largest series of STEP patients followed up beyond 5 years. Long-term clinical, biochemical, and radiologic outcomes appear to be robust.     

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.     

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。     

精氨酸促进短肠综合征肠道代偿及其机制的初步研究

/L、(13.5±3.0) mg﹒cm-1·100 g-1、(26.0±2.6) μg·cm-1·100 g-1、(59.8±6.2) μg·cm-1·100 g-1、(35.4±2.3) μg·cm-1·100 g-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.     

Isoperistaltic bowel lengthening for short bowel syndrome in children

BACKGROUND: Short bowel syndrome, secondary to a variety of causes, can be lethal in infancy and childhood. Isoperistaltic bowel lengthening, performed by longitudinal division of dilated small bowel with end-to-end anastomosis, has shown early promise but long-term outcome is unknown. METHODS: Sixteen infants and children (aged 3 months to 14 years) had short bowel syndrome from necrotizing enterocolitis (8), gastroschisis (4), atresia (2), and volvulus (2). All of these patients were partially or totally dependent on parenteral nutrition and have undergone isoperistaltic bowel lengthening for short bowel syndrome (length <100 cm). Bowel length was increased by 22% to 85% (mean 42%) with the procedure. Studies of intestinal function were performed preoperatively and postoperatively. RESULTS: Isoperistaltic bowel lengthening resulted in significant improvement in stool counts, intestinal transmit time, intestinal clearance of barium, D-xylose absorption, and fat absorption at 6 months and 12 months postoperatively. Fourteen of 16 patients (88%) have been weaned from parenteral nutrition. CONCLUSIONS: These data show that isoperistaltic bowel lengthening can be an effective operation for short bowel syndrome in children, improving absorption and motility, and allowing weaning from parenteral nutrition.     

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。     

Cognitive deficits in school-age children with severe short bowel syndrome

BACKGROUND/PURPOSE: Improved therapies for the management of short bowel syndrome (SBS) have resulted in the prolonged survival of many children. By early childhood, the physiological sequelae of severe SBS include delayed physical development and metabolic imbalances. However, little is known about how SBS affects brain development. Although many parents report school problems, no controlled study has evaluated the integrity of the central nervous system in SBS children. The purpose of this study was to investigate the neuropsychological status of school-aged SBS children to determine if there were characteristic cognitive impairments that might be amenable to early therapeutic intervention. METHODS: SBS children (n = 8; mean age, 116.9 +/- 21 months) were compared with an age-matched cystic fibrosis (CF) control group (n = 8; mean age, 118.1 +/- 14 months). Groups did not differ in age, grade, or absences. Neuropsychological tests with established sensitivity to CNS integrity compared performance over 6 cognitive domains. Emotional status also was measured. Analyses were completed with 2-tailed t tests. RESULTS: Groups did not differ on tests of intellectual ability and emotional function. Language, memory and learning, and problem-solving testing results indicated no significant group differences. However, the SBS group performed more poorly on measures assessing visual-spatial ability, with P values ranging from .002 to .045. In a subset of subjects, we noted significantly slower left-handed, but not right-handed, performance on measures of finger dexterity and psychomotor speed. CONCLUSIONS: Although emotional status did not differ from that of children with CF, SBS patients showed visual-spatial deficits in the company of preserved language, attention and memory, and executive skills. The specificity and consistency of these findings suggests that right hemisphere CNS changes may occur in children with SBS. This unexpected finding, coupled with the indication of left-sided psychomotor slowing in right-handed subjects, raises the possibility that actual brain impairment, rather than developmental delay accompanying slowed physical growth, accounts for these findings. Longitudinal studies are needed to further clarify this issue. The educational significance of the results is discussed.     

Results of growth trophic therapy in children with short bowel syndrome

Purpose

In addition to the structural, ultrastructural, and functional changes that occur after extensive enterectomy or in utero bowel loss that results in short bowel syndrome (SBS), a complex array of humoral responses take place that may also affect adaptation of the remaining small intestine as well as nutritional status or growth. These include alterations in the levels of circulating hormones and trophic substances such as growth hormone (GH) and insulinlike growth factors (IGF-1 and IGFBP-3). The purpose of this investigation is to report on the management/treatment of 3 children with SBS (>4 years in duration) and growth failure.

Methods

Serum measures of growth factors and the response to GH stimulation after an arginine insulin tolerance test (AITT) were determined. Weight and height z-scores as well as linear growth velocity were calculated annually pre- and postinitiation of medication therapy.

Results

Patient 1 (boy, 8.5 years old, midgut volvulus, 18-cm bowel) was found to be GH deficient, whereas patients 2 (girl, 12.5 years old, gastroschisis, 70-cm bowel) and 3 (boy, 9 years old, jejunal atresia, 21 cm bowel) were found to have limited GH responsiveness. Subsequently, treatment with GH (1) and growth releasing factor (GRF; 2 & 3) was prescribed. Z-scores for both weight and height improved over time. Positive linear growth velocity was observed from initiation of therapy (<0.5 cm/yr for all) to more than 3 years of treatment (mean 1, 4.7 cm/yr; 2, 8.7 cm/yr; 3, 5.0 cm/yr [age adjusted normals >4.5, >8.5, and >4.9 cm/yr, respectively]). All patients received a regular diet with oral supplements, whereas 2 received parenteral nutrition support for about 1 year.

Conclusions

In children with medically refractory SBS, it is not only important to offer trophic factors but also essential that sufficient nutrient substrate be provided to achieve adequate growth.     

Adverse effects of liver dysfunction and portal hypertension on intestinal adaptation in short bowel syndrome in children

BACKGROUND: The effects of liver dysfunction and portal hypertension on intestinal adaptation in short bowel syndrome are generally unknown. The presence of these disorders may adversely affect the ability to wean these patients from parenteral nutrition. METHODS: Forty-two infants with short bowel syndrome were placed in one of three Child's classifications, depending on serum bilirubin, prothrombin time, ascites, albumin, and liver biopsy, and compared for time to diet tolerance, time required for parenteral nutrition, and survival. A subgroup of these patients also underwent portal pressure measurement, which was combined with liver biopsy results to compare three groups for the same parameters. RESULTS: Survival was Child's class A 100%, B 84%, C 61%, while time to feeding tolerance was A 16.3 days, B 20.0 days, C 28 days, and total parenteral nutrition time was A 80.0 days, B 98.0 days, C 100.0 days. In the groups that underwent portal pressure measurement, the survival was group I (normal biopsy and pressure) 100%, group II (abnormal biopsy and normal pressure) 90%, group III (abnormal biopsy and pressure) 66%, while time to feeding tolerance was I 15.0 days, II 18.0 days, III 24.0 days, and total parenteral nutrition time was I 72.0 days, II 94.0 days, III 184.0 days. CONCLUSIONS: Cholestatic liver disease, especially associated with portal hypertension adversely affects bowel adaptation in short bowel syndrome.     

谷氨酰胺和生长激素对短肠综合征患者肠道代偿作用

目的探讨谷氨酰胺和生长激素对短肠综合征(SBS)患者的肠道代偿作用。方法26例短肠综合征患者残余小肠长度为0～100(中位数42.5)cm,手术后接受肠外营养(PN)支持3-52个月,联合应用生长激素(GH)(0.10±0.06)mg·kg-1·d-1和谷氨酰胺(GLN)(0.30±0.17)g·kg-1·d-1进行肠道促代偿治疗。结果26例接受GH加GLN治疗的SBS患者,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(6.0±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维持。结论经过合适的营养支持和肠道促代偿治疗,大多数短肠综合征患者残留肠道能充分代偿,完全摆脱PN或减少PN用量,长期健康生存。     

Differential sugar absorption as a marker for adaptation in short bowel syndrome

PURPOSE: There are no reliable monitoring methods for following up with patients with short bowel syndrome (SBS). This study examines the use of inert sugar markers (mannitol and lactulose) as indicators of the surface area increases occurring with adaptation. METHODS: Juvenile male rats underwent either transection with intestinal reanastomosis or resection with removal of the proximal 90% of the small bowel, leaving 10 cm of terminal ileum (n = 8 in each group). Animals were studied in vivo, measuring absorption of mannitol and lactulose on day 7, 14, and 28 and killed with the representative histological samples taken on day 7, 14, and 28. RESULTS: Resected animals showed significant increases in intestinal length (initial bowel length 10 cm, final length 17.8 +/- 1.4 cm, while transected showed no significant changes (101 +/- 2 cm): resection also increased intestinal circumference (initial circumference 0.5 cm +/- 0.1 cm, final circumference 1.1 cm +/- 0.2 cm in resected animals, while transected animals remained unchanged). Resected animals also showed significant increases in villus height (0.7 +/- 0.06 mm initially, 0.9 +/- 0.09 mm at day 28), and but a decrease in villus density (116 +/- 20 villi/mm2 initially, 78 +/- 20 villi/mm2 at day 28), again controls showed no changes. This resulted in a significant increase in intestinal surface area in resected animals over the study; surface area initially calculated at 640 +/- 80 cm2 increasing to 1,440 +/- 360 cm2, while controls showed no significant change in surface area. There was also an increase in mannitol absorption, which went from 1.8 +/- 0.6% on day 7 to 2.56 +/- 0.6% on day 28 in resected animals, while permeability actually decreased over time. (All data mean +/- SD, with P<.05 by Student's t test). Mannitol absorption correlated well with intestinal surface area (R2 = 0.82). CONCLUSION: These results suggest that inert sugar markers, such as lactulose and mannitol, may be useful in following adaptation in patients who have short bowel syndrome.     

Use of an ethanol lock to prevent catheter-related infections in children with short bowel syndrome

Background

Children with short bowel syndrome (SBS) requiring central venous catheters (CVCs) may experience frequent catheter-related infections (CRIs). Treatment strategies include antibiotic- and ethanol-containing locks, with CVC removal if the CRI cannot be cleared. Ethanol lock therapy has been reported for CRI treatment in children but not for CRI prevention.

Methods

Medical records of children with SBS receiving cycled home parenteral nutrition via a silicone CVC and who received a daily 70% ethanol lock at some time during their therapy were reviewed retrospectively.

Main Results

Ten patients had 26 CVCs for a total of 3556 catheter-days and received a daily ethanol lock for 4 to 14 hours during a total of 3018 catheter-days. Before ethanol lock therapy (n = 5), there were 6 CRIs in 538 catheter-days (rate, 11.15 per 1000 catheter-days). During ethanol lock therapy in the same 5 patients, the CRI rate decreased to 2.06 per 1000 catheter-days (4 CRIs in 1936 catheter-days). In the 5 patients with no ethanol lock-free period, the CRI rate was 1.85 per 1000 catheter-days. Overall, CRI rate with ethanol lock therapy was 1.99 per 1000 catheter-days (2 CRIs in 1081 catheter-days). Four patients developed 6 CRIs during ethanol lock therapy. Four of these CRIs were cleared with systemic anti-infective and ethanol lock therapy; 2 CVCs were removed owing to infection. No adverse reactions were reported during ethanol instillation.

Conclusion

A daily 70% ethanol lock for CRI prevention was safe and effective in a series of 10 patients with SBS.     

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生物赖营养得以生存,人的营养主要来自于对食物的消化吸收.消化系统的肝、胆、胃肠等均直接参与人体的代谢与组织合成,肠道更是消化吸收的首要器官,一旦功能障碍,营养难以获得补充.若大部分小肠丧失（剩余肠段不足70cm）,在20世纪70年代前,静脉营养尚不能满足人体的营养需要,难以吸收营养;70年代以后,全肠外营养应用于临床使部分病人获得了存活的时间,肠功能得以代偿,恢复从肠道吸收部分或大部营养的功能,或是全赖肠外营养维持营养的需要量.     

短肠综合征患者的肠道代偿及康复治疗

目的 总结短肠综合征(SBS)的治疗经验。方法 分析38例SBS患者的治疗过程,随访其目前饮食情况,肠外营养(PN)或肠内营养(EN)的时间,了解并发症情况,对部分患者作有关检测,并联合应用生长激素(GH)和谷氨酰胺(GLN)治疗,采用稳定核素示踪检测残余肠道对单糖、脂肪酸及氨基酸的吸收情况。结果 本组患者死亡5例;存活33例,存活时间为6个月～17年,平均(5.9±4.3)年。目前有3例长期接受家庭PN,6例需部分或间歇性接受PN或EN补充,完全摆脱PN的有24例,其平均摆脱PN的时间为(9.5±6.6)个月。GH加GLN治疗只能在短时间内促进残余肠道对营养物质的吸收能力。结论 经过合适的肠道康复治疗,大多数SBS患者残留肠道能充分代偿,可完全摆脱PN或减少PN用量,长期健康地生存。     

Direct re-instillation through endotracheal intubation tubes during enteral nutrition for short bowel syndrome

Case report of a 65-year-old man, operated on for small bowel infarction. Only the initial 40 cm of the jejunum, and the last 10 cm of the ileum were vital and could be kept. The ileo-caecal valve and the colon were not resected. Two stomas were carried out: a left-sided jejunostomy, and a right-sided ileostomy. Enteral nutrition was attempted, but jejunal outflow increased. It was therefore decided to attempt re-instillation of jejunal juices directly to the ileum using two 33 CH endotracheal tubes connected with soft chest drain tubing. A bag was placed over the jejunal tube to collect any leakage. Semi-elemental enteral nutrition could then be successfully carried out, and parenteral feeding stopped. With this simple appliance, the patient was able to lead as normal a life as possible. After 42 days of such feeding, the patient had only lost 2 kg in body weight, and intestinal continuity was re-established.