Original Articles: Gastroenterology
Advances in nutritional therapy have contributed to an improved quality of life and long-term survival of patients with cystic fibrosis (CF) (1,2). Children with established CF-associated liver disease (CFALD) are at a greater risk of poor nutrition, which has been demonstrated in a case-control study (3). Once oral intake and pancreatic enzyme replacement have been optimized, further nutritional support is only possible with nasogastric or gastrostomy placement and overnight supplemental feeding. Nasogastric feeding is generally used as a short-term measure with gastrostomy, the preferred intervention for nutritional supplementation (4). Gastrostomy placement in children with CF has been shown to significantly improve body mass index (BMI) percentile and lung function (forced expiratory volume in 1 second [FEV1] %predicted) independent of the level of lung function at placement (5); however, gastrostomy placement in patients with cirrhosis has been considered a relative contraindication because of an increased risk for the development of stomal varices and life-threatening haemorrhage. In individuals with ascites, there is the potential for tube dislodgement and peritonitis (6,7).
The primary aim of this study was to report our experience with gastrostomy placement in children with CFALD and portal hypertension and, in particular, the development of stomal varices. Secondary outcomes included assessment of nutritional and pulmonary outcomes after gastrostomy placement.
The CF database at the Royal Children's Hospital (Melbourne, Australia) was reviewed to identify all children ages 0 to 18 years with CFALD and portal hypertension, who underwent gastrostomy insertion between 1991 and 2011. All patients had CF according to international guidelines (8). Patients were classified as pancreatic insufficient by 3-day faecal fat balance or the presence of fat globules on faecal microscopy in conjunction with a history of steatorrhea. Gastrostomy placement was recommended by consensus of treating physicians and followed published guidelines (9).
The diagnosis of liver disease was based on clinical assessment, and the presence of persistently elevated transaminases after other causes of liver disease were excluded as per the CF Foundation Hepatobiliary Disease Consensus Statement guidelines (10). The diagnosis of portal hypertension was based on clinical findings of a hard liver edge 2 to 3 cm beyond the right costal margin, with firm splenomegaly and ultrasound findings that confirmed splenic enlargement.
Weight, height, and respiratory function tests were measured, and weight-for-age z-score (WAZ), height-for-age z-score (HAZ), and BMI z-score were calculated using the epidemiological software program EpiInfo 2000 (Centers for Disease Control and Prevention, Atlanta, GA) (11). Spirometry measurements were obtained from all patients 5 years and older, and the FEV1 was expressed as percentage predicted after adjustment for weight, height, and sex (12). All patients were asked to use their gastrostomy tube for supplemental feeding 5 to 6 nights per week. Patients were prescribed dietary supplements providing 30 to 40 kcal/kg (125–170 kJ/kg) per day, which were administered by continuous overnight infusion. Pancreatic enzymes are administered at the commencement and completion of gastrostomy feeds. The nutritional and lung function measurements were collected for each patient at insertion and then at 12 and 24 months after gastrostomy placement. Short-term (1 month) and long-term complications from the gastrostomy were documented. Data collected on short-term complications included any immediate procedure-related mortality and morbidity, for example, variceal bleeding during insertion, and postprocedure complications, for example, infection, cellulitis, peritonitis, and tube dislodgement. Long-term complications screened for included the development of varices at the stomal site and gastrointestinal haemorrhage. The study was approved by the Ethics in Human Research Committee at the Royal Children's Hospital.
Normally distributed data were presented as mean ± standard deviation, or as median and interquartile range for skewed data. To allow longitudinal comparisons of growth and lung function, the study was divided into 3 time points, that is, insertion, 1 year, and 2 years after gastrostomy placement. Data on each patient, at each time point after gastrostomy placement, were compared with the time of insertion using the 2-sample t test. All of the data analyses were performed using GraphPad Prism 5 software (GraphPad Software, La Jolla, CA).
Between 1991 and 2011, 60 patients with CF had gastrostomy tubes inserted for nutritional support. We identified 7 children who had CFALD and portal hypertension at the time of gastrostomy placement. All were pancreatic insufficient and had failed to maintain adequate nutrition despite pancreatic enzymes and the consumption of energy-dense foods. Four were boys and the mean age at gastrostomy insertion was 10.6 ± 4.3 years. The mean BMI percentile at insertion was 20.9 ± 18.7. Six of the 7 patients had a percutaneous endoscopic gastroscopy because they did not have varices (oesophageal or gastric) at the time of insertion, and the position and size of the spleen did not preclude a percutaneous approach. One had an open surgical placement because of preexisting esophageal varices. No patients had ascites or coagulation abnormalities.
No one had bleeding from varices at insertion. One patient had minimal cellulitis in the postoperative phase and there were no deaths associated with the procedure. The median length of follow-up after gastrostomy was 4 years (interquartile range 2.6–8 years) and there were 35.1 patient-years of follow-up. During this time, no patients developed stomal varices but 3 patients developed oesophageal varices. Two patients died 7 years after gastrostomy placement because of advanced pulmonary disease.
Complete data were available for 6 patients (Table 1). There was improvement in mean BMI z-score from −1.07 ± 0.87 to −0.58 ± 0.81 (n = 6), P = 0.05 at 2 years after insertion. Similar changes were seen in the WAZ score, which improved from −2.00 ± 0.80 at insertion to −1.19 ± 1.04 (n = 7) by 2 years postinsertion P = 0.02. There were no significant changes in HAZ scores. Lung function FEV1 %predicted data were available for 6 patients (1 <5 years old). There was significant improvement from 49.5 ± 12.6 to 62.3 ± 20.3, P = 0.04 at 2 years postinsertion (Fig. 1).
This case series demonstrates that gastrostomy placement in children with CFALD and portal hypertension is safe and does not result in the development of stomal varices or other substantial complications of portal hypertension, despite the fact that 4 of 7 patients either had or developed esophageal varices during the follow-up period. There were significant long-term improvements in nutrition and lung function. Another point is that in most cases, splenomegaly was not massive, precluding a percutaneous approach; however, if this were the case, either a standard surgical approach or a combined laproscopic/endoscopic approach would be sensible.
The risks of developing stomal varices at a gastrostomy site in patients with CFALD and portal hypertension is unknown; however, it has been reported to be as high as 31% in patients with another cholangiopathy, primary sclerosing cholangitis, who have undergone a colectomy and have had a colostomy or ileostomy fashioned (6). The chance of a life-threatening haemorrhage from such a stoma is estimated to be 3% to 4% (14). In our small case series, none of the children developed stomal varices around the gastrostomy or had any bleeding. We have previously reported adverse events that occurred as a result of gastrostomy placement in a subset of our study cohort of patients with CF without CFALD and portal hypertension (13). In a cohort of 37 patients, 11 developed a mild stomal leak and 6 had at least 1 episode of cellulitis. The findings in this cohort were somewhat better.
In addition to demonstrating the safety of gastrostomy placement in patients with CF with portal hypertension, we also showed the long-term nutritional benefits as measured by WAZ and BMI z-score 2 years after the procedure. In addition, lung function also improved in the second year. This is somewhat unexpected, but has been reported before in patients with CF (15). The authors proposed that this finding may be the result of initial weight gain being secondary to an increase in fat and that perhaps it is only later that it leads to an increase in lean body mass, which correlates more closely with FEV1.
A significant limitation to this study is the small cohort of patients with CFALD and subsequent gastrostomy placement. Another limitation is the retrospective nature of the study and lack of controls. The study includes data for a 20-year period when changes in CF management that may affect both BMI percentile and FEV1 %predicted have occurred; however, the effect of these changes is limited by using each patient as his or her own control (5).
In conclusion, this case series demonstrates that gastrostomy placement in patients with CF with liver disease and portal hypertension is safe and leads to improved nutrition and lung function.
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Keywords:© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
cystic fibrosis; gastrostomy; liver disease; nutrition; outcome; portal hypertension