Ricardo O. Castillo

Risk factors for small bowel bacterial overgrowth in cystic fibrosis

Objectives:The purpose of this study was to determine the prevalence of small bowel bacterial overgrowth in patients with pancreatic-insufficient cystic fibrosis (CF) compared with age-matched controls and to identify potential risk factors for small bowel bacterial overgrowth. Patients and Methods:Fifty patients, 25 pancreatic-insufficient CF study patients (mean age, 17 y) and 25 gastrointestinal clinic control patients (mean age, 15 y), completed a glucose-hydrogen breath test after an overnight fast. Study patients completed a quality-of-life questionnaire modified from the Cystic Fibrosis Questionnaire. The medical history of each patient was compared with breath test results. A positive breath test was defined as a fasting hydrogen ≥15 ppm or a rise of ≥10 ppm hydrogen over baseline during the test. Results:The prevalence of positive breath tests was higher in the CF study group (56%) than in the control group (20%) (P = 0.02). The mean fasting hydrogen levels of patients in the study and control groups were 22 and 5 ppm (P = 0.0001). The mean questionnaire scores were not significantly different between breath test–positive and –negative study patients. The use of azithromycin was associated with an increased risk of a positive breath test. Use of laxatives and inhaled ipratropium was associated with a decreased risk of a positive breath test. Conclusions:Patients with CF were more likely to have elevated fasting hydrogen levels compared with controls. This suggests a high prevalence of small bowel bacterial overgrowth in CF patients. Medications commonly used by CF patients may influence intestinal health.

Long-term outcomes in pediatric liver recipients: Comparison between cyclosporin A and tacrolimus

Cao S, Cox KL, Berquist W, Hayashi M, Concepcion W, Hammes GB, Ojogho OK, So SKS, Frerker M, Castillo RO, Monge H, Esquivel CO. Long‐term outcomes in pediatric liver recipients: Comparison between cyclosporin A and tacrolimus. Pediatr Transplantation 1999: 3: 22–26.

Outcomes of transplantation in children with primary hepatic malignancy

Abstract:  HBL and HCC are the most common hepatic malignancies in children. The role of OLT in children with HCC is still a matter of debate. The aim of this study was to review our experience of OLT for HCC. Medical records of patients (< 18 yr) who underwent OLT for HCC were reviewed and compared to children who underwent OLT for HBL and for indications other than malignancy. There were 25 patients: HCC (10 cases) and HBL (15 cases). The actuarial patient survival for HCC at one and five yr was 100% and 83.3%, for the HBL group the survival was 86.7% at both one and five yr, and for indications (n = 377) other than malignancy the patient survival for pediatric OLT at our center was 87.7% and 84.7% at one and five yr, respectively. The actuarial recurrence free survival at five yr was 83.3% for HCC and 66.8% for HBL. In conclusion, OLT is a good therapeutic modality for children with HCC and HBL.

Management of esophageal strictures in children with recessive dystrophic epidermolysis bullosa.

Background Recessive dystrophic epidermolysis bullosa is a rare, genetically transmitted skin disorder characterized by blister formation and scarring in response to minor trauma. One of the most debilitating features of the disease is the development of esophageal strictures, which produces profound dysphagia, exacerbating an already highly compromised nutritional status common to these patients. Due to the extreme fragility of epithelial surfaces, the optimal therapeutic approach to esophageal strictures in this setting has not been established. Methods We have developed an approach to treatment of esophageal strictures in children with epidermolysis bullosa combining upper endoscopy using small caliber endoscopes, endotracheal intubation, and fluoroscopically assisted balloon dilatation. We report our experience using this technique in 22 children who have undergone a total of 109 dilatations. Results Upper endoscopy, endotracheal intubation, and balloon dilatation were well tolerated by even very young children with epidermolysis bullosa. Dysphagia was markedly reduced post-procedure, permitting resumption of normal diet for age, including solids, within six hours of the procedure. Post-procedure recovery has been rapid and does not require admission to the hospital. Complications have been infrequent, minor, and limited to the first year of our experience. The mean interval between dilatations for all children is 11 months. All children have gained weight, and have not required steroids or phenytoin. Conclusions Balloon dilatation is a safe and effective therapy for esophageal strictures in children with recessive dystrophic epidermolysis bullosa. Limited upper endoscopy and endotracheal intubation are well tolerated by these children. This approach should be considered as primary therapy in this clinical setting.

Oral Correction of Essential Fatty Acid Deficiency in Cystic Fibrosis

A combination of pancreatic insufficiency and inadequate caloric intake may produce essential fatty acids (EFA) deficiency in patients with cystic fibrosis. Seventy-five percent of the adolescents and young adults with poor weight gain in our clinic were EFA-deficient by total plasma linoleic acid criteria. Twenty of these patients were placed on an oral hyperalimentation regimen containing 230% of calories required for basal energy expenditure, 40% as fat. Forty percent of these (8/20) achieved normal EFA levels on this diet. Eight of the nonresponding patients were given an additional 5% of their caloric intake as linoleic acid monoglyceride. All who maintained caloric intake achieved normal EFA levels. Normalization of EFA levels was associated with a number of clinical benefits including increase in weight and activity and, in five teenage girls, regulation of menses. The 16 control patients who received standard pancrelipase therapy and nutritional supplements remained fatty acid deficient. We conclude that oral hyperalimentation can restore EFA levels in cystic fibrosis patients if adequate calories are available to provide energy needs.

Analysis of clinical variables associated with tolerance in pediatric liver transplant recipients.

Talisetti A, Hurwitz M, Sarwal M, Berquist W, Castillo R, Bass D, Concepcion W, Esquivel CO, Cox K. Analysis of clinical variables associated with tolerance in pediatric liver transplant recipients. Pediatr Transplantation 2010: 14: 976–979.

Intestinal maturation in the rat: the role of enteral nutrients

In order to investigate the role of enteral nutrients in intestinal maturation, an animal model was developed consisting of provision of intravenous nutrient infusions to immature suckling rats over the period of weaning. Age- and litter-matched controls were provided identical amounts of the parenteral solution by entered cannula using the same model. At the end of the period of weaning, animals were killed and the intestines removed for measurement of morphologic parameters and disaccharidase, DNA, and protein levels. The absence of enteral nutrients during weaning resulted in striking inhibition of intestinal growth, diminution in mucosal cell mass, and delayed development of lactase. Although the appearance of sucrase was not affected by the lack of enteral nutrients, sucrase levels rose to only one-third of control levels. Jejunoileal gradients were not present in animals deprived of enteral nutrients but were present in animals receiving enteral nutrients. These results are distinct from adult animals treated in identical experimental fashion and indicate that major parameters of intestinal maturation are altered by the absence of intraluminal nutrients. A critical role for intraluminal nutrients in regulation of intestinal development is therefore suggested. The animal model developed for these studies is well suited for investigation of the interactions of the intraluminal environment with intestinal maturation.

Factors affecting survival to intestinal transplantation in the very young pediatric patient.

Background. Very young pediatric patients awaiting intestinal transplantation have a high mortality rate due to long waiting times, scarcity of appropriate size donor organs, and mortality due to sepsis and liver failure. To investigate specific risk factors impacting survival to intestinal transplantation, we performed a 4-year institutional retrospective study comparing children who received grafts by age 18 months with children 18 months or younger who died while on the waiting list. Patients and Methods. Twelve children comprised the transplanted group and had the underlying diagnoses: necrotizing enterocolitis, gastroschisis, Hirschsprung’s disease, and omphalocele. Ten children comprised the deceased group and had the underlying diagnoses: intestinal atresia, necrotizing enterocolitis, gastroschisis, and midgut volvulus. Multiple risk factors were assessed in these groups. Results. No differences in residual small bowel length, presence of the colon, number of line infections, or number of central lines were found. The average body weight of the transplanted group trended higher, whereas the deceased group had more impairment of hepatic function. Intestinal atresia was the most common diagnosis in the deceased group while none of the transplanted group carried this diagnosis. Ileocecal valve was retained in 80% of the deceased group and in none of the transplanted group. Conclusions. In children younger than 18 months, risk factors affecting survival to intestinal transplantation include small body size and advanced liver disease. A primary diagnosis of intestinal atresia and the presence of the ileocecal valve may confer additional risk to these very young children.

Paediatric liver transplantation: Indications, timing and medical complications

Newer surgical techniques and immunosuppressive therapies have resulted in paediatric liver transplantation being available for most children with end‐stage liver disease and has resulted in a greater than 80% 5‐year survival rate. The most common indications for paediatric liver transplantation are biliary atresia (43%), metabolic disease (13%) and acute hepatic necrosis (11%). For approximately 75% of children with acute hepatic failure, the cause is unknown. Timing of liver transplantation not only affects survival rate, but may influence neurodevelopmental outcome. Fortunately, numerous types of donors, such as reduced‐sized, living related or unrelated and blood‐type mismatched, have reduced the mortality of children who are waiting for liver transplantation. However, the mortality and morbidity before and after liver transplantation remain high for children who have fulminant hepatic failure or are less than 5 months of age at the time of transplantation. The principle medical complications after liver transplantation are rejection and infection. Although use of newer immunosuppressive regimens has reduced the rate of rejection, Epstein–Barr virus infection with associated lymphoproliferative disorder remains the principle cause for morbidity and mortality after the initial 3 months post‐liver transplant.

Regulation of intestinal ontogeny by intraluminal nutrients.

Major events in gastrointestinal ontogeny occur in the infant rat in association with weaning, resulting in striking alterations in small intestinal structure and function. Although the dietary changes attendant to weaning are not essential for the initiation of these events, dietary nutrients have been shown to participate in the maturation of some intestinal parameters. In order to define more precisely the role of intraluminal nutrients in the regulation of small intestinal ontogeny, a longitudinal study was conducted using a unique animal model in which intraluminal nutrients were excluded from the intact maturing intestine in vivo throughout the entire weaning period without major compromise in nutritional status. The absence of intraluminal nutrients over the weaning period resulted in diminished lengthening and accretion of mucosal mass, suggesting a slower rate of intestinal growth. Lower mucosal DNA, protein, and mitotic indices in intestines of animals receiving no intraluminal nutrients suggested that the lack of intraluminal nutrients resulted in the blunting of the striking increases in cellular proliferation normally exhibited by the developing intestinal mucosa at this time. Maturation of intestinal lactase-phlorizin hydrolase and maltase-glucoamylase was not affected by the absence of intraluminal nutrients. Although the appearance of sucrase-isomaltase was not altered by the absence of intraluminal nutrients, activity levels rose to only 50% of control levels. These data suggest that during this period of rapid intestinal maturation, intestinal growth is more dependent upon intraluminal nutrients than are the characteristic enzymic alterations normally expressed during this period. The lack of alteration in patterns of intestinal maturation in animals receiving intraluminal nutrients in elemental form compared with normally weaned animals suggests that intraluminal nutrients regulate intestinal maturation by mechanisms that do not depend upon nutrient form.