In this cohort, 9 of the 11 patients are presently alive (age range 0.7–12.5 years). The median follow-up is 5.3 (0.2–11.5) years. The median bowel length is 7.5 cm (range 3–9). No child underwent bowel-lengthening procedures because the residual bowel length is insufficient.
The last enrolled patient had 2 relevant comorbidities represented by the tracheoesophageal atresia and interventricular defect. The combination of the 2 malformations determined the ischemia of the superior mesenteric artery, and therefore the extensive necrosis of the gut.
One patient died while waiting for transplantation: he had been listed for combined intestinal and liver transplantation because of worsening liver disease, and his liver function deterioration and the difficult management of fluid balance contributed to his progressive deterioration. This child had multiple occlusive episodes after each attempt of re-establishing the intestinal continuity, which never could be completed. These episodes and the difficult management of fluid balance contributed to his progressive clinical deterioration. The second death was a child born at 27 weeks of gestational age and severe chronic bronchodysplasia, with U-SBS secondary to a midgut volvulus. His death was consecutive to the worsening of respiratory failure. Overall, the mortality rate in this cohort of U-SBS receiving long-term HPN was 18%.
One patient underwent ITx at 7 years of age; she is presently alive and fully orally fed. One patient is presently not receiving PN. The other 7 patients remained dependent on varying amounts of PN but all are advancing on oral/enteral nutrition. The caloric intake provided by PN ranges from 30% to 60% of the total energy intake. A total of 6 of the 7 patients received HPN 7 nights per week and only 1 received HPN 5 of 7 nights per week. Eight out of the 11 patients showed high value of conjugated bilirubin (>5.1 mg/dL) before they had been discharged on HPN. Four out of these were treated with Omegaven (Fresenius Kabi, Bad Homburg, Germany) supplementation at 1 g/kg and the remaining by modulating the soy-based lipid emulsions. Presently, none of the 9 surviving patients in this cohort has evidence of IFALD and none is listed for ITx. Three out of the 7 patients on HPN received SMOFlipid (Fresenius Kabi, Bad Homburg, Germany) and the remaining 4 patients ClinOleic (Baxter/Clintec Parenteral SA, Maurepas, France) received lipid formulation.
From a morbidity standpoint, the mean duration of inpatient hospital care ranged from 23 to 104 days/year of HPN, and therefore, from 6 to 28% of the overall HPN length. In all of the patients, the length of the inpatient care decreased during the study from 0 to 67 days (18% of the overall HPN days) in the last year of the study period (2012). Only 1 patient, presently receiving HPN, had a high amount of central line sepsis (3/1000 CVC days) and he required extensive inpatient hospital care (15% of the total length of HPN). If we exclude this patient, the number of CVC-related sepsis was ≤ 1/1000 CVC days.
The growth course in the 8 surviving patients with a length of HPN >1 year is reported in Fig. 1. The current anthropometric status is satisfactory and it shows growth channels for both weight and height maintained within the 3 standard deviations in 7 out of the 8 surviving patients.
There is plenty of information about the patients with SBS receiving HPN (14–25), but few studies (3–10) specifically addressing the outcomes of the children with U-SBS (remaining bowel length <10 cm). The prevalence of patients with U-SBS receiving HPN in the present series represents >25% of the HPN programs for patients with SBS. This high prevalence results from the fact that our hospital is the main reference center from central and southern Italy for the multidisciplinary treatment of IF.
In line with Pironi et al (2), we found that the outcomes of the patients with U-SBS receiving HPN do not differ significantly from those of patients with IF and other underlying diseases (14–19). Furthermore, according to a past report (11), this study confirms that of others, that these children benefit from a nontransplant approach within a multidisciplinary expert IF group.
With a median follow-up >5 years, the mortality rate was <20% in this cohort and the incidence of bloodstream infections was ≤1/1000 CVC days (with 1 exception, a single patient who developed 3/1000 CVC days septic episodes). The reports analyzing the long-term outcome of IF have mentioned a mortality rate ranging from 10% to 30% and a CVC-related bloodstream infection rate of 1.2 to 4/1000 CVC days (14–19). The bloodstream infections represent in our experience the main cause of a need for inpatient care after the discharge on HPN. Thus, as a strategy to decrease the risk of CVC line infections, we are starting the use of taurolidine locks in CVC lines in patients with recurrent infections, according to recent reports (26,27).
In the present series, 2 patients died, and a single death was because of the IF. This patient was affected by multiple intestinal atresias and he developed a severe IFALD. He had permanent stomies because of recurrent occlusive episodes at each attempt to reestablish the gut continuity. This case highlights that IFALD (20) and digestive continuity can strongly affect the clinical course of SBS (21).
The IFALD occurred in >70% of the patients of this cohort; the use of Omegaven and soy-based lipid restricted regimens failed to reverse the liver function in only 1 case. This patient had a progressive worsening of his liver disease, in spite of the HPN regimen, including Omegaven and Clinoleic as lipid formulations. Presently, in our center, in patients with IFALD and minimal potential for enteral feeding advancement, the inpatient PN program includes the use of Omegaven and in the HPN program the use of the SMOFlipid. All of the patients with SBS received enteral feeding independently of how much residual bowel was present, as part of a management strategy that could optimize the process of intestinal adaptation and reverse the IFALD (22–24).
The early reestablishment of intestinal continuity in patients with SBS has been recommended as a means to maximize the intestinal absorptive surface (21,25). In the present cohort, >90% of the patients underwent procedures to reestablish continuity over a period ranging from 0 to 150 days. The lack—or the late—reestablishment of digestive continuity were both associated with a poor prognosis. As other teams have done with similar patients (11), no child was proposed to undergo a bowel-lengthening procedure in this series. Bowel-lengthening procedures are a part of our intestinal rehabilitation program; however, in this particular subgroup of patients, as similarly reported by other teams (11), we agree that, given the shortness of the residual small bowel, the gain of length after any procedure will not significantly improve absorption. Because in these children the adaptation process is mainly related to the colon, we suggest that surgical approaches involving this part of the intestine will provide valid therapeutic options.
From a social point of view, the 8 surviving patients had a good quality of life and all of them attended school regularly, although 6 of them were dependent on PN. The number of days of inpatient care decreased in all of the patients except for 1 who had repeated episodes of CVC line infections. All of the patients also received outpatient clinic visits scheduled at once every month in the patient with high bloodstream infections to twice every year in the oldest patient, who lived a long distance from our center. The remaining patients had clinical controls scheduled once every 2 or 3 months. Furthermore, all of the patients in this cohort received home visits by the nurses involved in the HPN programs, scheduled once every month. All of the 9 surviving patients had oral intake; 4 of them were also fed by gastrostostomy.
The American Society of Transplantation (1) had considered patients with U-SBS (gastrostomy, duodenostomy, residual small bowel <10 cm in infants, and <20 cm in adults), along with those with intraabdominal invasive desmoid tumors and with congenital mucosal disorders as candidates for a preemptive/rehabilitative ITx owing to the high risk of death attributable to the underlying disease. Pironi et al (2), however, found that among the 80 candidates to a preemptive/rehabilitative intestinal transplantation, 5-year survival was 83% in the 67 who remained on HPN, and 78% in the 13 who underwent ITx. In the present study, the 5-year survival on HPN was 90%, confirming the data (2). The outcome is likely to be even better for infants with U-SBS born today given the recent advances in management of IF, thus increasing the possibility of weaning from PN without the long-term complications of an ITx and the consequent immunosuppression.
This study has 2 main limitations that are the small size of the cohort (9 patients alive) and the short follow-up (5 years); however, the literature is so poor on children with U-SBS that despite these limitations, it may be useful to clarify the outcomes of this disease.
The present series of the patients with U-SBS receiving HPN, death related to IFALD was 9%. Although IFALD was frequent, it had been well managed in most patients and avoided liver function deterioration, but in a single complex case in whom it led to death. The overall survival results were similar to that seen in other categories of IF. The multidisciplinary management warranted to these patients to approach school age, to grow, and to maintain various amounts of oral intake in all of the cases. Furthermore, the need of inpatient care decreased over time. The main causes of morbidity were the CVC-related sepsis that led us to start a new protocol based on the use of taurolidine to more efficaciously prevent these complications. To better understand and to manage the specific comorbidities associated with their long-term survival, it is necessary to develop national and international collaborations to promote multicentric cohorts of children with HPN.
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Keywords:© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
intestinal failure; intestinal failure associated liver disease; intestinal transplantation; pediatric; short bowel syndrome