A comparison of histological findings in infants with necrotizing enterocolitis and intestinal...
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A760 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, NO. 4 • COMBINED LIVER/INTESTINAL VERSUS ISOLATED INTESTINAL TRANSPLANTATION IN CHILDREN. J.A. Vanderhoof, D.L. Antonson, S.S. Kaufman, D.R. Mack, B.W. Shaw, A.N. Langnas, Depts. of Pediatrics & Surgery, University of Nebraska Medical Center, Omaha, Nebraska Long-term home parenteral nutrition has been the mainstay of therapy for patients with intestinal failure, mostly due to short bowel syndrome. In children, the lifelong need for this expensive form of therapy coupled with the increased risk of paranteral nutrition-induced liver disease makes the usefulness of this therapy somewhat less attractive. Intestinal transplantation has frequently been discussed as an alternative for these patients but has been mostly utilized in combination with liver transplantation for parenteral nutrition dependent patients with irreversible end-stage liver disease. Over the past four years, we have performed a total of 15 intestinal transplantations in infants and children at the University of Nebraska Medical Center. Twelve have been combined liver/bowel transplants, all performed in patients with end- stage parenteral nutrition-induced liver disease. Three additional patients received isolated intestinal transplantations because of early liver disease, limited central venous access, or complications related to parenteral nutrition. After an initial experience with cyclosporine, the remaining 11 of 15 patients were immunosuppressed with oral tacmlimus (FK506) and supplemental corticosteroids. No induction therapy was utilized. All patients received monthly intravenous immunogiobulin and dally oral Acyclovir for the first year to prevent EBV-induced lymphoproliferative disease. Patients were fed Vivonex for the first month because of its low fat content, and feedings were subsequently liberalized. Recipient ages ranged from 6 months to 6 years. RESULTS: Seven of 12 combined liver/small bowel recipients are alive, the longest at 3 years, 5 months. Four are independent of parenteral nutrition. Two are in eady postop period (14 and 17 days). All 3 isolated intestinal transplant recipients are alive and well 8-12 months postoperative and al! are free of parenteral nutrition. All 3 were weaned from parenteral nutrition by 3 weeks postoperatively. Duration of hospitalizationwas dramatically less for the isolated than for the combined group, 19 vs87 days. No graft vs. host disease was observed, and only one case of mild lymphopmliferetive disease has been identified. Chylous ascites was a problem in only 1 patient, a combined liver/bowel recipient. CONCLUSIONS: Our data suggest that combined liver/small intestinal transplantation may be a viable therapeutic option for infants and children with end-stage paranteral nutrition-induced liver disease. However, our preliminary results suggest that, using these protOCOlS, isolated intestinal transplantation may be an attractive eadier option in patients likely to develop irreversible TPN liver disease. • EFFECTS OF DIETARY FATTY ACIDS AND VITAMIN E SUPPLEMENTATION ON LIPOPROTEIN OXIDATION IN CIGARETTE SMOKERS. Barbara S. VanDerWerken, Rachel A. Hopkins, Jane Stegner, and Richard B. Weinberg, Bowman Gray School of Medicine, Winston-Salem, NC. Background: Oxidation of plasma lipoproteins may play a role in the genesis of atherosclerosis. Previous studies of the effect of antioxidant vitamins on lipoprotein oxidation in cigarette smokers have neither controlled dietary fat, nor studied high density lipoproteln (HDL) oxidation. The aim of this study was to examine the effect of dietary fatty acids and vitamin E (VIT E) supplementation on low density lipoprotein (LDL) and HDL oxidation in cigarette smokers. Methods: I0 subjects who smoked 15-40 cigarettes/day were fed isocaloric diets (35%fat, 45% carbohydrate, 20g protein), in which the major source of fat was olive oil (monounsaturated, MONO), safflower oil (polyunsaturated , POLY), or safflower oil plus 800 IU VIT M/day. After 3 weeks on each diet fasting lipoprotein levels were measured, and the initial lag phase (min) and rate (units/min) of copper catalyzed oxidation were determined by fluorescence spectroscopy for LDL and HDL z. Results: below are means ± SD; values with different superscripts are significantly diffarent(p < 0.05): MONO POLY POLY + VlT E LDL (~/d~) 124 + 25a I18 + 26a 119 + 25a HDL (~/dL) 39 _+ 10a 35 + 8 b 36 _+ 9 b LDL ~-zas 62.4 ± 7.9 a 69.5 _+ 12.8 a 8L5 + 16.9 b HDL z ox-xas 24.7 +_ 4.0 a 30.4 ± 7.4 b 28.2 ± 10.6 ='b LDL O~-ra~* 4.1 + 0.7 = 4.8 + 1.2 a 3.9 -+ 2.5 = HDL z ox-ra~e 30.6 ± 9.0 a'b 21.9 ± 11.6 = 39.4 + 7.8b Plasma LDL and HDL levels decreased on the POLY diet , and did not change with subsequent addition of VIT E. VIT E increased the initial oxidation resistance (i.e., lag phase) of LDL, but paradoxically increased the rate of HDL 2 oxidation. Conclusions: In cigarette smokers VIT E protects LDL from oxidation, but functions as a pro-oxidant for HDLz. This suggests that POLY diets and VIT E may have an adverse impact on the anti-atherogenie actions of HDL in cigarette smokers. • A COMPARISON OF HISTOLOGICAL FINDINGS IN INFANTS WITH NECROTIZING ENTEROCOLITIS AND INTESTINAL ISCHEMIA. G.Veereman-Wauters*, N.Ectors', K.Geboes', F. Penninekx#, E.Eggermont*. Depts of Abdominal Surgery 0, Pathology" & Pediatrics*, University Hospitals Leuven, Leuven, Belgium. The etiology of necrotizing enterocolitis (NEC) remains incompletely understood. Current views are that intestinal prematurity may detemaine the risk for NEC. In order to identify a predisposing morphological substrate, we reviewed all intestinal samples prelevated over a 12 year period from infants with NEC and as a control from infants with intestinal isehemia. 21 specimens were obtained from 17 infants with NEC, 15 resected upon presentation, 6 at treatment for stenosis following conservative management (NEC group: 7M/10F, mean gestatiunal age: 34 weeks (w) (runge:25-41w), mean birth weight (bw): 2201g (range:550- 3934g), age at operation: 1day-4 months). For comparison, we reviewed 22 specimens from 20 infants with acute intestinal ischemia, 15 obtained at urgent laparotomy and 7 at reoperation for complications (control group:6M/14F,mean gestational age:31w (range: 26-40w), mean bw: 2318g (range: 500-3860g), age at operation: lday-12months). H&E stained slides were analysed without patient information, using light microscopy; different components of the intestinal wall were reviewed, inflammatory changes were graded semi-quantitatively. In infants with NEC, the epithelium appeared normal, demonstrating well developped villi in unaffected areas at the time of the acute insult and in material reseeted at a different time. As compared to infants with acute ischemia, biopsies with NEC showed a more pronounced and uniform inflammatory cell infiltrate, mainly composed of neutrophils and eosinophils, invading all compartments of the intestinal wall. Furthermore, the mucnsa associated lymphoid tissue (MALT) was not clearly underdevelopped in NEC and the ganglion cells in the plexus of Auerbach appeared more numerous and showed pale staining cytoplasm. Inflammatory cells (mainly eosinophils and mast cells) were admixed with or apposed to the neural structures. Pneumatosis intestinalis was not seen in the control group. Coneinsion: light microscopic analysis did not reveal features of intestinal prematurity in infants with NEC. The enteric nervous system in NEC showed inflammatory changes. These might be secundary but probably relate to the clinical aspect of ileus. GASTROESOPHAGEAL REFLUX AND THE DEVELOPMENT OF NORMAL FEEDING PATTERNS IN PREMATURE NEONATES. G. Veereman-Wauters2~, MM. Palmer1, A. Goeleven3, D. Lembrechts3, W. Vinck2, E. Eggermont2, MB Heymanl. Dept of Pediatric Gastroenterologyl, University of California San Francisco Medical Center, San Francisco, CA and Dept of Pediatrics2 & Ear Nose Throat3, University Hospitals Leuven, Leuven, Belgium. The Neonatal Oral-Motor Assessment Scale (NOMAS) 1 classifies dysfunctional, disorganized and normal feeders based upon observed feeding behavior. Disorganized feeders have abnormal rhythm and coordination of normal tongue and jaw movements. We hypothesized that neonates who present with disorganized characteristics of sucking on the NOMAS and whose feeding problems do not resolve by 44 weeks (w) post-conceptual age have significant gastroesophageal reflux (GER). 12 infants, out of 27 observed, fulfilled entry criteria (disorganized feeding pattern, no gastrointestinal complications, permission for pH probe) and were scored weekly with the NOMAS. All infants received an initial 24h esophageal pH probe test; 6 refused foll0w-up pH study at 44 w. At w 1, the 12 infants were 0 - 14 w old (mean 8+6 SD), 34-41 w gestational age (37+3), and scored 3-7 (5+1) disorganized feeding characteristics on the NOMAS. At 44 w only 4/12infants developed a normal sucking pattern, 6/12 remained disorganized (score:5.+-2); 2/12 were disorganized at 40w (score:5) then lost to follow-up; none developed dysfunctional feeding characteristics. Of the 4 infants who normalized their sucking pattern, 1 had an abnormal initial and follow-up pH study with reflux index (RI) 35% and 21% respectively, 3 had initial normal studies 2, but the pH study was abnormal in 1 at 44w (RI:9.3%). Of the 8 infants who remained disorganized feeders, 4 had normal and 4 abnormal initial pH studies; 2 follow-up studies remained normal and I normalized. Conclusion: These studies show no relationship of GER and the development of feeding patterns in premature infants. Specifically these data do not support the widely held belief that GER inhibits normal oral motor development. 1. PalmerMM. J Per inatol 1993;23:28.~ 2. Vandenplas Y. J PediatrGasta'oenterol Hate" 1987;6:220.
Transcript of A comparison of histological findings in infants with necrotizing enterocolitis and intestinal...
A760 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, NO. 4
• COMBINED LIVER/INTESTINAL VERSUS ISOLATED INTESTINAL TRANSPLANTATION IN CHILDREN. J.A. Vanderhoof, D.L. Antonson, S.S. Kaufman, D.R. Mack, B.W. Shaw, A.N. Langnas, Depts. of Pediatrics & Surgery, University of Nebraska Medical Center, Omaha, Nebraska
Long-term home parenteral nutrition has been the mainstay of therapy for patients with intestinal failure, mostly due to short bowel syndrome. In children, the lifelong need for this expensive form of therapy coupled with the increased risk of paranteral nutrition-induced liver disease makes the usefulness of this therapy somewhat less attractive. Intestinal transplantation has frequently been discussed as an alternative for these patients but has been mostly utilized in combination with liver transplantation for parenteral nutrition dependent patients with irreversible end-stage liver disease. Over the past four years, we have performed a total of 15 intestinal transplantations in infants and children at the University of Nebraska Medical Center. Twelve have been combined liver/bowel transplants, all performed in patients with end- stage parenteral nutrition-induced liver disease. Three additional patients received isolated intestinal transplantations because of early liver disease, limited central venous access, or complications related to parenteral nutrition. After an initial experience with cyclosporine, the remaining 11 of 15 patients were immunosuppressed with oral tacmlimus (FK506) and supplemental corticosteroids. No induction therapy was utilized. All patients received monthly intravenous immunogiobulin and dally oral Acyclovir for the first year to prevent EBV-induced lymphoproliferative disease. Patients were fed Vivonex for the first month because of its low fat content, and feedings were subsequently liberalized. Recipien t age s ranged from 6 months to 6 years. RESULTS: Seven of 12 combined liver/small bowel recipients are alive, the longest at 3 years, 5 months. Four are independent of parenteral nutrition. Two are in eady postop period (14 and 17 days). All 3 isolated intestinal transplant recipients are alive and well 8-12 months postoperative and al! are free of parenteral nutrition. All 3 were weaned from parenteral nutrition by 3 weeks postoperatively. Duration of hospitalization was dramatically less for the isolated than for the combined group, 19 v s 8 7 days. No graft vs. host disease was observed, and only one case of mild lymphopmliferetive disease has been identified. Chylous ascites was a problem in only 1 patient, a combined liver/bowel recipient. CONCLUSIONS: Our data suggest that combined liver/small intestinal transplantation may be a viable therapeutic option for infants and children with end-stage paranteral nutrition-induced liver disease. However, our preliminary results suggest that, using these protOCOlS, isolated intestinal transplantation may be an attractive eadier option in patients likely to develop irreversible TPN liver disease.
• EFFECTS OF DIETARY FATTY ACIDS AND VITAMIN E SUPPLEMENTATION ON LIPOPROTEIN OXIDATION IN CIGARETTE SMOKERS. Barbara S. VanDerWerken, Rachel A. Hopkins, Jane Stegner, and Richard B. Weinberg, Bowman Gray School of Medicine, Winston-Salem, NC.
Background: Oxidation of plasma lipoproteins may play a role in the genesis of atherosclerosis. Previous studies of the effect of antioxidant vitamins on lipoprotein oxidation in cigarette smokers have neither controlled dietary fat, nor studied high density lipoproteln (HDL) oxidation. The aim of this study was to examine the effect of dietary fatty acids and vitamin E (VIT E) supplementation on low density lipoprotein (LDL) and HDL oxidation in cigarette smokers. Methods: I0 subjects who smoked 15-40 cigarettes/day were fed isocaloric diets (35%fat, 45% carbohydrate, 20g protein), in which the major source of fat was olive oil (monounsaturated, MONO), safflower oil (polyunsaturated , POLY), or safflower oil plus 800 IU VIT M/day. After 3 weeks on each diet fasting lipoprotein levels were measured, and the initial lag phase (min) and rate (units/min) of copper catalyzed oxidation were determined by fluorescence spectroscopy for LDL and HDL z. Results: below are means ± SD; values with different superscripts are significantly diffarent(p < 0.05):
MONO POLY POLY + VlT E LDL (~/d~) 124 + 25 a I18 + 26 a 119 + 25 a HDL (~/dL) 39 _+ 10 a 35 + 8 b 36 _+ 9 b
LDL ~-zas 62.4 ± 7.9 a 69.5 _+ 12.8 a 8L5 + 16.9 b HDL z ox-xas 24.7 +_ 4.0 a 30.4 ± 7.4 b 28.2 ± 10.6 ='b
LDL O~-ra~* 4.1 + 0.7 = 4.8 + 1.2 a 3.9 -+ 2.5 = HDL z ox-ra~e 30.6 ± 9.0 a'b 21.9 ± 11.6 = 39.4 + 7.8 b
Plasma LDL and HDL levels decreased on the POLY diet , and did not change with subsequent addition of VIT E. VIT E increased the initial oxidation resistance (i.e., lag phase) of LDL, but paradoxically increased the rate of HDL 2 oxidation. Conclusions: In cigarette smokers VIT E protects LDL from oxidation, but functions as a pro-oxidant for HDL z. This suggests that POLY diets and VIT E may have an adverse impact on the anti-atherogenie actions of HDL in cigarette smokers.
• A COMPARISON OF HISTOLOGICAL FINDINGS IN INFANTS WITH NECROTIZING ENTEROCOLITIS AND INTESTINAL ISCHEMIA. G.Veereman-Wauters*, N.Ectors' , K.Geboes', F. Penninekx #, E.Eggermont*. Depts of Abdominal Surgery 0, Pathology" & Pediatrics*, University Hospitals Leuven, Leuven, Belgium.
The etiology of necrotizing enterocolitis (NEC) remains incompletely understood. Current views are that intestinal prematurity may detemaine the risk for NEC. In order to identify a predisposing morphological substrate, we reviewed all intestinal samples prelevated over a 12 year period from infants with NEC and as a control from infants with intestinal isehemia. 21 specimens were obtained from 17 infants with NEC, 15 resected upon presentation, 6 at treatment for stenosis following conservative management (NEC group: 7M/10F, mean gestatiunal age: 34 weeks (w) (runge:25-41w), mean birth weight (bw): 2201g (range:550- 3934g), age at operation: 1day-4 months). For comparison, we reviewed 22 specimens from 20 infants with acute intestinal ischemia, 15 obtained at urgent laparotomy and 7 at reoperation for complications (control group:6M/14F,mean gestational age:31w (range: 26-40w), mean bw: 2318g (range: 500-3860g), age at operation: lday-12months). H&E stained slides were analysed without patient information, using light microscopy; different components of the intestinal wall were reviewed, inflammatory changes were graded semi-quantitatively. In infants with NEC, the epithelium appeared normal, demonstrating well developped villi in unaffected areas at the time of the acute insult and in material reseeted at a different time. As compared to infants with acute ischemia, biopsies with NEC showed a more pronounced and uniform inflammatory cell infiltrate, mainly composed of neutrophils and eosinophils, invading all compartments of the intestinal wall. Furthermore, the mucnsa associated lymphoid tissue (MALT) was not clearly underdevelopped in NEC and the ganglion cells in the plexus of Auerbach appeared more numerous and showed pale staining cytoplasm. Inflammatory cells (mainly eosinophils and mast cells) were admixed with or apposed to the neural structures. Pneumatosis intestinalis was not seen in the control group. Coneinsion: light microscopic analysis did not reveal features of intestinal prematurity in infants with NEC. The enteric nervous system in NEC showed inflammatory changes. These might be secundary but probably relate to the clinical aspect of ileus.
G A S T R O E S O P H A G E A L R E F L U X AND THE DEVELOPMENT OF NORMAL FEEDING PATTERNS IN PREMATURE NEONATES. G. Veereman-Wauters2~, MM. Palmer1, A. Goeleven3, D. Lembrechts3, W. Vinck2, E. Eggermont2, MB Heymanl. Dept of Pediatric Gastroenterologyl, University of California San Francisco Medical Center, San Francisco, CA and Dept of Pediatrics2 & Ear Nose Throat3, University Hospitals Leuven, Leuven, Belgium.
The Neonatal Oral-Motor Assessment Scale (NOMAS) 1 classifies dysfunctional, disorganized and normal feeders based upon observed feeding behavior. Disorganized feeders have abnormal rhythm and coordination of normal tongue and jaw movements. We hypothesized that neonates who present with disorganized characteristics of sucking on the NOMAS and whose feeding problems do not resolve by 44 weeks (w) post-conceptual age have significant gastroesophageal reflux (GER). 12 infants, out of 27 observed, fulfilled entry criteria (disorganized feeding pattern, no gastrointestinal complications, permission for pH probe) and were scored weekly with the NOMAS. All infants received an initial 24h esophageal pH probe test; 6 refused foll0w-up pH study at 44 w. At w 1, the 12 infants were 0 - 14 w old (mean 8+6 SD), 34-41 w gestational age (37+3), and scored 3-7 (5+1) disorganized feeding characteristics on the NOMAS. At 44 w only 4/12infants developed a normal sucking pattern, 6/12 remained disorganized (score:5.+-2); 2/12 were disorganized at 40w (score:5) then lost to follow-up; none developed dysfunctional feeding characteristics. Of the 4 infants who normalized their sucking pattern, 1 had an abnormal initial and follow-up pH study with reflux index (RI) 35% and 21% respectively, 3 had initial normal studies 2, but the pH study was abnormal in 1 at 44w (RI:9.3%). Of the 8 infants who remained disorganized feeders, 4 had normal and 4 abnormal initial pH studies; 2 follow-up studies remained normal and I normalized. Conclusion: These studies show no relationship of GER and the development of feeding patterns in premature infants. Specifically these data do not support the widely held belief that GER inhibits normal oral motor development. 1. Palmer MM. J Per inatol 1993;23:28.~ 2. Vandenplas Y. J Pediatr Gasta'oenterol Hate" 1987; 6:220.
