The evaluation of the nutritional condition and the absorptive capacity in long-term follow-up of infants with short bowel syndrome

The nutritional conditions and absorptive capacity of nine infants with short bowel syndrome were investigated during a long follow-up period from one and half years to 14 years and 7 months. The length of the residual small intestine ranged between 13 and 90cm. The nine infants had normal meals at home and did not suffer from persistent diarrhea. Most of the infants were thin. Nutritional conditions, for example, serum protein, triglycerides, vitamins, trace elements and plasma amino acids, were kept relatively well, and there were no symptoms of deficiency. The results of D-xylose absorption test had gradually improved but the absorptive capacity of sugars and amino acids observed by potential differences were within the normal limits or slightly subnormal except one infant. This indicated that the absorptive capacity of sugars and amino acids per a given area of the residual small intestine did not increase. From our examination the critical length of intestine might be in the neighborhood of 50cm. The infants left with less than 50cm of small intestine seem to have grown up normally but malabsorption of fat, sugars and bile acids have continued for many years.     

Effects of transection and extrinsic denervation and a model of autotransplantation of the porcine jejunoileum on cholesterol biodynamics

Background/Purpose:

Small bowel transplantation impairs enteric function, necessitating transection, extrinsic denervation, and ischemia-reperfusion of the small intestine. The authors investigated how each of these nonimmunologic insides of the transplantation procedure modulates biodynamics of cholesterol and absorption of lipids.

Methods:

Twenty-three pigs with similar food, cholesterol, and fat intake underwent sham laparotomy (group 1), transection (group 2), extrinsic jejunoileal denervation (group 3), or a model of autotransplantation, including extrinsic jejunoileal denervation with in situ ischemia-reperfusion (group 4). Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis, and absorption, were measured after 2 and 8 weeks.

Results:

When compared with sham laparotomy and transection groups, denervation and autotransplantation significantly decreased weight gain and increased plasma cholesterol precursors and fecal excretion of bile acids. In relation to sham operated animals, transection alone modestly increased plasma plant sterols at 2 weeks and biliary secretion and mass absorption of cholesterol. The latter changes were not observed after denervation or autotransplantation, ie, fractional and total absorption of cholesterol were significantly decreased in autotransplanted pigs when compared with transected controls. As compared with all the other groups, autotransplantion significantly increased bacterial metabolites of neutral sterols in feces and net fecal elimination of cholesterol, mainly as bile acids.

Conclusions:

Extrinsic autonomic denervation of the jejunoileum, with or without synchronous ischemia-reperfusion, results in increased cholesterol synthesis, bile acid malabsorption, and decreased weight gain. Cholesterol malabsorption may develop gradually after intestinal autotransplantation, and even a short period of ischemia further impairs absorptive function of the denervated jejunoileum, resulting in increased fecal elimination of cholesterol mainly as bile acids.     

Nutritional and gastrointestinal complications of the use of bowel segments in the lower urinary tract

Almost all segments of the gastrointestinal tract have been used as urinary tract substitutes. The specific nutritional and gastrointestinal complications depend on the particular portion of bowel that is removed from the alimentary tract. The use of stomach theoretically may predispose the patient to hypergastrinemia and peptic ulcer disease, hypocalcemia, and iron deficiency or megaloblastic anemia. Resection of a large amount of jejunum causes malabsorption. Limited use of colon segments usually is well tolerated, but loss of large parts of the colon directly decreases available absorptive area, resulting in diarrhea. Resection of the ileum and ileocecal valve can lead to several disease states. One is mixed secretory-osmotic diarrhea. Decreased ileal reabsorption of bile salts results in fat malabsorption and steatorrhea. The presentation of increased amounts of bile salts and fatty acids to the colon decreases water absorption and stimulates active chloride and water secretion, producing a cholera-like high-volume secretory diarrhea. The loss of the ileocecal valve and ileum segment accelerates intestinal transit time, which does not allow for complete digestion and absorption of food. Water and electrolytes remain associated with undigested food particles and may overwhelm the absorptive capacity of the colon, resulting in an osmotic diarrhea. A second problem is vitamin B12 deficiency. Surgical reduction of sites in the terminal ileum for active and exclusive uptake of vitamin B12 might lead to hypovitaminosis. If this is unrecognized, patients may develop irreversible neurologic injury. A third problem is cholelithiasis. Derangements in bile salt metabolism can occur when as little as 10 cm of ileum is resected, and the propensity to form gallstones is increased. Pigment gallstones appear to be the predominant stone associated with ileal resections. The fourth possible problem is urolithiasis, the etiology of which is multifactorial in patients with ileal resections. With decreased availability of bile salts, fat malabsorption occurs. Fatty acids bind with calcium and magnesium to form soaps, resulting in increased levels of free oxalate available for absorption. Moreover, fatty acids directly increase colonic permeability to oxalate.(ABSTRACT TRUNCATED AT 400 WORDS)     

LONG TERM NUTRITIONAL EFFECTS OF EXTENSIVE RESECTION OF THE SMALL INTESTINE

A nutritional study was carried out on 36 patients several years after major resection of the small intestine (100 to 330 cm). Thirty one of these resections had been performed for Crohn's disease and only patients who had been clinically free of disease for more than one year were studied. The group of patients were 15% below their ideal weight. Total body fat was 24% below the predicted normal value and total body protein was 10% below. Although deficiencies of iron, vitamin B₁₂ and folic acid were frequently found, only six patients were anaemic. Other vitamin and mineral deficiencies were common. Despite these abnormalities, two thirds of the patients were engaged in their normal occupation full time and were subjectively well. The others who did not regain their normal capacity for work, had a greater nutritional deficit and a shorter length of remaining small intestine. It is concluded that nutritional deficiencies are common following extensive small bowel resection and all patients need regular follow up and appropriate vitamin and mineral supplementation. However, major disturbances of body composition and severe protein energy malnutrition with a reduced capacity for work are restricted to a small number of patients with very short lengths of remaining small intestine.     

Long term prognosis after massive small bowel resection in children

Eight survivors after massive small bowel resection were reviewed for a period of 2 to 19 years to assess the long term prognosis of patients. The primary diseases of short bowel syndrome were congenital intestinal atresia (6) and midgut volvulus (2). The length of the residual small intestine ranged between 27 and 75 cm and ileocecal valve was also resected in 3 cases. All cases had been already weaned from parenteral nutrition and six children tolerate normal meals and two have still enteral formula at home now. Near normal somatic growth was achieved in cases which received intensive nutritional supports after operation. The D-Xylose absorption test revealed gradual improvement except one with the shortest intestine (27 cm) and fat absorption was disturbed in patients who had less than 45 cm residual intestine. Late metabolic complications, such as renal calculus, cholelithiasis and pathologic fractures were encountered in three cases.     

Biliary cholesterol and lithogeneity of bile in patients after ileal resection

For determination of the factors that regulate biliary cholesterol secretion and the lithogenity of bile in ileal dysfunction, plasma and biliary lipids and fecal excretion of bile acids were studied in 29 patients who had undergone ileal resection. Seven patients with ileal resection had normal bile acid excretion (less than 10 mg/kg/day), and 22 had various degrees of bile acid malabsorption. None of the patients had gallstones when examined with abdominal sonography. LDL cholesterol levels were decreased in bile acid malabsorption and demonstrated a positive correlation with the molar percentage of biliary cholesterol. Biliary cholesterol (mol percent) was inversely correlated with fecal bile acid excretion. This finding suggests that biliary cholesterol secretion decreases with increasing loss of bile acids to feces in ileal dysfunction, leading to an actual decrease in the lithogenic index and to hyposaturation of cholesterol in bile. The reduction in biliary cholesterol, regarded as protecting the gallbladder mucosa against the detergent properties of bile acids, may play an important role in the pathogenesis of increased gallstone formation in ileal dysfunction.     

The long-term effect of jejunoileal autotransplantation on intestinal function.

Disturbed intestinal absorption has been demonstrated almost uniformly early after intestinal autotransplantation. Our aim was to study the long-term effects of autotransplantation on intestinal absorptive function. Studies of nutritional status and absorptive function were performed on groups of dogs at three intervals after autotransplantation: I (less than 6 months; n = 4), II (6 to 12 months; n = 4), and III (12 to 18 months; n = 4). At death samples of intestinal fluid were obtained for bacteriologic analysis, and studies of morphology and in vitro absorption were performed on intact and autotransplanted intestine. Similar studies were performed on a group of five control animals. Although body weight and serum albumin levels remained stable in dogs that had undergone autotransplantation and initial diarrhea improved, stool moisture was persistently elevated and late defects in fat and D-xylose absorption developed (4.8% +/- 3.2% stool fat at 12 months vs 2.1% +/- 0.6% before surgery and 3.4 +/- 2.0 x 10(-2) mmol/L xylose/hr at 12 months vs 8.8 +/- 5.4 x 10(-2) mmol/L xylose/hr before surgery; p less than 0.05). In vitro glucose uptake and villus height were similar in autotransplanted and adjacent intact intestine at death. Compared with control animals, animals that had undergone autotransplantation demonstrated significant overgrowth of fecal flora in jejunum and ileum (14/18 segments greater than 10(5) bacteria vs 6/15 segments; p less than 0.05). Thus delayed defects in intestinal absorption of fat and D-xylose occurred more than 12 months after autotransplantation. Because intestinal structure and function of the autotransplanted intestine were similar to those of adjacent intact intestine, this malabsorption may be related to bacterial overgrowth or other in vivo factors.     

Massive small bowel resection in neonates—Is weaning from parenteral nutrition the final goal?

Eight surviving cases from an original 15 pediatric patients who underwent massive small bowel resection during their neonatal period were reviewed for a period of 2–19 years to assess long-term prognosis. the primary diseases were congenital intestinal atresia in 6 cases and midgut volvulus in 2. The length of the residual small intestine ranged from 27–75 cm and the ileocaecal valve had been resected in 3 cases. All cases were able to be weaned from parenteral nutrition and at present, 6 of the children can tolerate normal meals but 2 are still receiving enteral nutrition, in the form of a low residue diet at home. Near normal somatic growth was achieved in the most recent 5 cases who received intensive nutritional treatment in the immediate postoperative period, whereas 3 who did not receive nutritional management exhibited growth retardation. The D-Xylose absorption test revealed gradual improvement and finally normal absorption in all except one case with the shortest remaining intestine (27 cm). However, the fat absorption test revealed abnormal absorption in cases with a residual intestine of less than 45 cm. Late metabolic complications such as renal calculi, cholelithiasis and pathologic fractures were encoutered in 3 cases.     

Application of a potential difference to evaluate the absorptive faculty in the small intestine. The changes in potential differences, uptake of sugars and amino acid and electrical transmural resistance in injured intestine

Since there was no effective method for evaluating the absorptive capacity in the small intestine, we devised a test for evaluating the absorptive capacity with potential difference. Potential difference is provided by electrical resistance of intestine and flux of substances. Previously, we reported that the electrical resistance of the small intestine in the guinea pigs had changed very slightly throughout the entire life, and that sugars and neutral amino acids have been transported completely activity from the birth. In addition, potential difference of glycyl-glycine reflected the uptake of the intestine after the period of weanling. We experimentally studied the electrical transmural resistance and absorptive capacity of the small intestine with various damages to the small intestine by 5-Fu, ischemia and long fasting. Histologically, swelling of nucleus, intracellular edema, dilatation of capillary vein, dropping of epithelial cells, etc., were seen in these models. But the electrical resistance was slightly changed in 10% of the cases. Potential differences by sugars or neutral amino acid ingestion accurately reflected their real flux. These facts suggest that the potential differences deficiently reflect the uptake of sugars and amino acids in the small intestine under conditions with malabsorption.     

Serial transverse enteroplasty for short bowel syndrome: a case report

The patient is a 2-year-old boy born with gastroschisis and midgut volvulus that left him dependent on total parenteral nutrition (TPN). At 11 months of age, a Bianchi procedure was performed increasing the total length of bowel from 72 cm to 130 cm. Although he appeared to have sufficient bowel length, he continued to have malabsorption and could only tolerate 10% of his caloric requirement enterally. A barium study found significant dilatation of the lengthened small bowel. At 23 months, we performed a novel bowel lengthening procedure that we have reported previously in an animal model. The serial transverse enteroplasty (STEP) operation increased the 83 cm of dilated and previously lengthened bowel to 147 cm, making the total small bowel length 200 cm. The patient tolerated the procedure well and began to have semisolid bowel movements. Small intestinal absorptive capacity measured by D-xylose absorption showed a substantial increase from 5 to 12 mg/dL (normal range, >20), implying improved but not completely normal small bowel function. This case shows that the STEP procedure increases intestinal length, can be used after a prior Bianchi, and may result in improved intestinal absorptive capacity. The STEP procedure should be considered a surgical option for children with short bowel syndrome.     

Growth hormone selectively improves intestinal cholesterol absorption after jejunoileal autotransplantation in pigs

Background/Purpose

Small bowel transplantation impairs enteric function and causes malabsorption of cholesterol and bile acids. Growth hormone stimulates intestinal absorptive function. The authors hypothesized that long-term growth hormone therapy could improve absorption of bile acids and cholesterol after autotransplantation of the jejunoileum.

Methods

Sixteen pigs with similar food, cholesterol, and fat intake underwent either sham laparotomy or a model of jejunoileal autotransplantation, including extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia. Five randomly chosen autotransplanted animals received daily growth hormone treatment for 8 weeks. Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Mucosal morphometrics, proliferation, and enzyme activities were determined. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks.

Results

After jejunoileal autotransplantation, growth hormone treatment significantly increased body weight gain, cholesterol absorption efficiency from 45.1% to 62.1%, plasma campesterol to cholesterol proportions, and biliary secretion of cholesterol. With or without growth hormone treatment, autotransplantation significantly increased fecal bile acid excretion, plasma cholesterol precursors, fecal bacterially modified neutral sterols, mucosal thickness of the ileum (but not jejunum), and intestinal transit time when compared with sham-operated animals. Crypt cell proliferation, mucosal enzyme activities, and microvilli showed no differences between the groups.

Conclusions

These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum.     

Postobstructive enteropathy in infants with transient enterostomy: its consequences on the upper small intestinal functions.

Repeated or prolonged organic obstruction of the small intestine in the neonatal period can lead to severe refeeding problems, despite a transient ostomy. These problems are thought to result from a postobstructive enteropathy (POE) of the apparently normal small intestine segment above the obstruction. Ten infants with a POE, characterized by limited oral caloric and carbohydrate intakes and increased ostomy effluent, were compared with 8 controls with an enterostomy and a normal postoperative refeeding pattern. There was no statistical difference in the histomorphometric appearance of the mucosa or its digestive or absorptive capacity (brush-border hydrolases, glucose transport) between the two groups. The effluent and duodenal floras of the two groups were similar. However, all POE patients showed significant abnormal peristalsis characterized by barium and carmin transit times. This suggests that repeated or prolonged obstruction in the neonatal period could lead to a POE, caused by chronic motricity abnormalities of the small intestine above the obstruction. Although this POE is more frequent after small bowel atresia, it may also occur with other conditions causing prenatal and postnatal intestinal obstruction.     

The effects of ileal resection with cholecystectomy on bile salt metabolism in the prairie dog

The adverse effects of ileal resection on bile salt metabolism may be aggravated by cholecystectomy. Female prairie dogs had either sham laparotomy, cholecystectomy, distal 50% small bowel resection, or cholecystectomy and distal 50% small bowel resection. After 4 weeks the common bile duct was cannulated and bile collected for up to 12 hr. Bile salt pool size and synthetic rate were measured from the washout curve. Bile salt, phospholipid, and cholesterol concentrations were determined. Bile salt pool size was reduced after cholecystectomy and after ileal resection. Cholecystectomy plus ileal resection further lowered the pool size, increased the synthetic rate, and increased the proportion of secondary bile salts. Cholecystectomy increased the synthesis and the concentration of bile salts in hepatic bile and altered the proportions of biliary lipids. Ileal resection decreased the concentration of hepatic bile salts with the formation of noncholesterol stones. The drastic reduction in pool size with the combined operation might be expected to lead to fat malabsorption. The higher concentration of bile salts after the combined operation compared with ileal resection alone reflects a possible beneficial effect of cholecystectomy.     

短肠综合征的营养康复治疗

短肠综合征的治疗主要为营养支持和小肠移植,但两种疗法都有其限制和不足之处。作者总结了３例短肠综合征患者联合应用重组人生长激素、谷氨酰胺、纤维素行营养康复治疗的经验,３例患者残存小肠的长度分别为６５、７５、３０ｃｍ,治疗后患者残存肠管的吸收功能和营养状况均有明显改善。作者认为营养康复疗法为短肠综合征提供了一个新的有效的治疗选择。     

The effect of cholesterol feeding and alterations in bile acid homeostasis on de novo sterologenesis in diabetic rats

Previous studies have demonstrated that de novo cholesterol synthesis is increased two- to threefold in the intestines of diabetic animals. This increase is due to a stimulation of cholesterogenesis in both the small and large intestine but, quantitatively, the small intestine is primarily responsible for the observed increase. The present study examined the effect of cholesterol feeding and alterations of bile acid homeostasis on de novo sterol synthesis in intact normal and diabetic animals. Cholesterol feeding in the control animals did not affect sterol synthesis in the small intestine, but in diabetic animals cholesterol feeding markedly inhibited small intestinal sterologenesis. The threefold stimulation of small intestinal sterol synthesis observed in diabetic animals is completely obliterated by cholesterol ingestion. Moreover, this inhibition of sterol synthesis by cholesterol feeding in the small intestine of diabetic animals occurred very rapidly (within 36 h). In the large intestine, cholesterol feeding did not influence sterol synthesis in either the diabetic or control animals. In the liver, cholesterol feeding markedly inhibited sterol synthesis to similar degrees in the diabetics and controls. Colestipol feeding and biliary drainage, procedures that reduce bile acid pool size, stimulated sterol synthesis in the liver and small intestine of both diabetic and control animals. However, reductions in bile acid pool size increased sterologenesis in the large intestine in control animals but had no effect in the diabetics. Bile acid ingestion did not alter either small or large intestinal sterologenesis in the diabetic or control animals. In conclusion, the present study demonstrates the sterol synthesis is enhanced in the small and large intestine of diabetic animals and, moreover, both the cholesterol- and bile acid-mediated regulation of cholesterol synthesis in the intestines of the diabetic animals is altered from normal.     

Hyperphagia alters cholesterol dynamics in diabetic rats

Rats with streptozotocin-induced diabetes stop growing and start eating more chow. These two events elicit an interacting series of changes in cholesterol dynamics. Hyperphagia increases dietary cholesterol intake and cholesterol synthesis by the small intestine. These increases are balanced by a decrease in cholesterol synthesis in the rest of the body so that total cholesterol input is normal. With growth failure, utilization of cholesterol for formation of new tissue ceases. This decrease is balanced by an increase in bile acid synthesis by the liver. The bile acid pool in the contents of the small intestine is enlarged by hyperphagia. Despite these changes, fecal sterol excretion and total utilization of cholesterol are normal. During the course of changes in growth and food intake and the attendant changes in cholesterol flux, the total tissue cholesterol pool does not change. Therefore influx equals efflux and the systems regulating cholesterol and bile acid synthesis are responding appropriately and are themselves unperturbed by insulin deficiency. However, plasma cholesterol level increases threefold. This elevation is due to increased influx of cholesterol from the small intestine and decreased synthesis in the rest of the body, so that a larger portion of total body cholesterol influx passes through the blood.     

Short bowel syndrome]

Short bowel syndrome (SBS) is defined in adults as a malabsorption disorder as a result of shortening the bowel to <200 cm. The severity of symptoms is less dependent on the amount of residual intestine than on the anatomical position of the resected bowel, the type of operative reconstruction, and the type and quality of nutritional, medical, and surgical treatment. Numerous complications and deficiency symptoms are associated with SBS. The extent of deficient nutrition should be determined. The need to create accesses for enteral and parenteral delivery, to supply supplementation as needed, perform pharmacological therapy, and in individual cases surgical treatment all necessitate a broad knowledge of nutritional medicine. The goals of therapy are correction and prevention of malnourishment, restoration of a normal nutritional status, and the normal thriving of children. Complications should be avoided, particularly those problems associated with parenteral nutrition. The frequency of diarrhea should be reduced. Overall, the aim is to achieve an optimized quality of life.     

Kurzdarmsyndrom

Short bowel syndrome (SBS) is defined in adults as a malabsorption disorder as a result of shortening the bowel to <200 cm. The severity of symptoms is less dependent on the amount of residual intestine than on the anatomical position of the resected bowel, the type of operative reconstruction, and the type and quality of nutritional, medical, and surgical treatment. Numerous complications and deficiency symptoms are associated with SBS. The extent of deficient nutrition should be determined. The need to create accesses for enteral and parenteral delivery, to supply supplementation as needed, perform pharmacological therapy, and in individual cases surgical treatment all necessitate a broad knowledge of nutritional medicine. The goals of therapy are correction and prevention of malnourishment, restoration of a normal nutritional status, and the normal thriving of children. Complications should be avoided, particularly those problems associated with parenteral nutrition. The frequency of diarrhea should be reduced. Overall, the aim is to achieve an optimized quality of life.     

Problems and difficulties in adapting period in infants and children after massive intestinal resection

In the period of intestinal adaptation following massive resection of intestine, patients have several difficulties and problems. This study was done in 17 survivals of 31 infants and children received massive intestinal resection (residual intestine; less than 75 cm) between 1966-1987 to define these problems and difficulties. 1) Postoperative hepatic dysfunction occurred in 11 of the 17 survivals. The relationship between relapsing frequency of hepatic dysfunction and length of remaining ileal segment suggested that the reduced ileal length may be one of the etiologic factors of the hepatic dysfunction. 2) Evaluation of serum bile acid levels suggested that the disturbance of bile acid reabsorption and its rapid turn over might still remain even after catch-up growth of these patients. 3) Abnormal levels of serum minerals (Ca, InP, Mg, Zn and Cu) were observed in 4 cases during TPN, and these abnormalities disappeared by discontinuation of parenteral nutrition and beginning of oral feeding. 4) Serum vitamin levels (Vit.A, Vit.E, 25-OH-D3, and Vit.B12) still remained in abnormal even after the patients reached school age. These results suggested that very long-term nutritional cares, especially in lipid and vitamin nutrition, are necessary for the children with massive intestinal resection.     

Effect of hypocholesterolemia on cholesterol synthesis in small intestine of diabetic rats

Studies by our and other laboratories have demonstrated that cholesterol synthesis is increased in the small intestine of insulinopenic diabetic animals. In normal animals, many factors have been shown to regulate cholesterol synthesis in the small intestine, including changes in plasma cholesterol levels. The purpose of this study was to determine the effect of lowering plasma cholesterol levels on small intestine cholesterol synthesis in streptozocin-induced diabetic rats. In diabetic rats, 4-aminopyrazolo[3,4-d]pyrimidine (4-APP)-induced hypocholesterolemia (plasma cholesterol levels less than 20 mg/dl) resulted in a 2.5-fold increase in small intestine cholesterol synthesis, which was most marked in the distal small intestine, decreasing proximally. In the distal small intestine the incorporation of 3H2O into cholesterol was 0.28 +/- 0.04 mumol.h-1.g-1 in diabetic rats versus 1.60 +/- 0.38 in diabetic rats administered 4-APP (P less than .01). This stimulation of cholesterol synthesis occurred in the upper villus, middle villus, and crypt cells isolated from the middle intestine of the 4-APP-treated diabetic animals. In agreement with these observations, "functional hypocholesterolemia" due to Triton WR-1339 administration also stimulated cholesterol synthesis 2.5-fold in the small intestine of normal and diabetic animals. In the distal small intestine, cholesterol synthesis was 0.43 +/- 0.10 mumol.h-1.g-1 in the diabetic rats versus 1.08 +/- 0.21 in diabetic rats treated with Triton WR-1339 (P less than .05). In both the 4-APP and Triton WR-1339 experiments, the response of the diabetic rats was similar to that observed in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)