- Email: [email protected]
Short bowel and long life: No longer mutually exclusive
all of us, but children are likely to be among the first and the hardest hit by environmental illness. As resources in this finite world become depleted and chemical, physical (eg, noise, ultraviolet radiation), and biological (eg, allergens, multidrug resistant pathogens) environmental hazards mount, children need adults to look creatively and with generosity to the future, to find ways to bequeath to them and their progeny a dynamic and resilient planet. What is critical to our children’s futures is how we respond now to this reality in our personal, professional, and political lives. Katherine M. Shea, MD, MPH Chapel Hill, NC 27514
REFERENCES 1. Reddy MM, Reddy MB, Reddy CF. Scientific advances provide opportunities to improve pediatric environmental health. J Pediatr 2004; 145:153-6. 2. United States Environmental Protection Agency. Terms of environment. Available at: http://www.epa.gov/ocepa111/OCEPAterms/. Last accessed: April 10, 2004.
3. National Library of Medicine. Specialized information services. Toxicology and environmental health. Click on ‘‘Toxicology Tutor.’’ Available at: http://sis.nlm.nih.gov/Tox/ToxMain.html. Last accessed: April 10, 2004. 4. Canfield RL, Henderson CR, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP, et al. Intellectual impairment in children with blood concentrations below 10 micrograms per deciliter. N Engl J Med 2003;348:1517-26. 5. Committee on the Toxicological Effects of Methylmercury, Board on Environmental Studies and Toxicology, National Research Council. Toxicological effects of methylmercury. Washington (DC): National Academy Press; 2000. 6. Organization for Economic Cooperation and Development. Cooperation in the investigation of existing chemicals. Available at: http:// www.oecd.org/about/0,2337,en_2649_34379_1_1_1_1_37407,00.html. Last accessed: April 10, 2004. 7. United States Environmental Protection Agency. National primary drinking water standard. Available at: http://www.epa.gov/safewater/consumer/mcl.pdf. Last accessed: April 10, 2004. 8. World Health Organization. A framework for the development of children’s environment and health action plan for Europe. Executive summary. Available at: http://www.who.dk/document/EEHC/4thigoprepmeet_BDS01.pdf. Last accessed: April 10, 2004.
SHORT BOWEL AND LONG LIFE: NO LONGER MUTUALLY EXCLUSIVE
ad a surgeon or pediatrician from the 1960s recapitulated Rip VanWinkle’s epic sleep and awakened in the 21st century, that person would be amazed at the many current practices employed to save children with short bowel syndrome (SBS) following intra-abdominal catastrophes. Among the most prominent is home total parenteral nutrition (TPN). TPN was first used by Sukarochana et al for undernourished postoperative patients,1 and soon thereafter studied in depth and popularized by Dudrick et al.2 Initially, TPN was thought to be too sophisticated a therapy for all but the most skilled medical practitioners to administer. However, by the late 1970s, hospitals and physicians faced a dilemma. Some patients receiving TPN succumbed to complications such as metabolic imbalance, sepsis, line complications, and cholestatic liver disease, but an ever growing number survived for months or even years while receiving TPN. These patients had ‘‘set up residence’’ in large teaching hospitals, draining resources. By the late 1970s, a few visionary physicians began training parents from all socioeconomic classes and educational levels to administer TPN to their children at home. Embraced by hospitals and the North American insurance industry because these patients could finally be discharged, this concept took root and is now the standard of care most health care providers in the developed world use for children with intestinal failure.
H
NEC SBS
Editorials
Necrotizing enterocolitis Short bowel syndrome
TPN
Total parenteral nutrition
That parents without formal education can be trained to successfully deliver TPN to their children ranks among the most important medical advances of the 20th century. Although long-term home TPN can now be provided to all children with intestinal failure, thoughtful clinicians question whether it should be provided because it is an expensive proposition. In an Oley Foundation survey from 1992, the cost of TPN for adults in the United States was almost $1000 per day.3 In Mexico, the annual cost was estimated to be $50,000 per year in the mid-1990s.4 Not only is the direct cost of TPN prodigious, but costs of repeated hospitalizations, loss of earning power by caregivers, and the chronic anxiety engendered by the ill health of the TPN recipient have overwhelmed many of the young parents giving birth to a child with SBS. It is not surprising that many families disintegrate as a result. Therefore, it is important to understand the TPN delivery strategies that will minimize See related article, p 157. its expense, the alimentation strategies that will maximize intestinal adaptation, and the Reprint requests: Samuel A. Kocoshis, patient characteristics that MD, Cincinnati Children’s Hospital mandate alternate treatments Medical Center, 3333 Burnet Ave, such as intestinal transplan- Cincinnati, OH 45229. J Pediatr 2004;145:147-8. tation for SBS. 0022-3476/$ - see front matter What Quiros-Tejeira Copyright ª 2004 Elsevier Inc. All rights et al have given to us in reserved. a report published in this 10.1016/j.jpeds.2004.05.036 147
issue of The Journal is a clearer focus on outcomes and therapeutic strategies for infants with SBS.5 Their retrospective analysis of outcomes in SBS covers a 25-year experience and includes nearly twice as many patients as any previous series. The authors can boast of outcomes much better than average, and they should be commended for their success. Of course, the astute reader may also infer that the surgeons who create surgical SBS and the neonatologists who manage the feedings of extremely premature infants also may have contributed to the outcomes reported. Surgeons who commit extremely premature infants with ultra-short bowel and multi-organ failure to TPN will guarantee early (but expensive) demise for those children, thereby skewing survival rates downward. It is notable that only 17 of the 78 patients in this series had ultra SBS, and only 16 of these patients had necrotizing enterocolitis (NEC). This represents about half the prevalence of NEC in some other series. One can question whether the incidence of NEC is low in Los Angeles or whether some of the sicker infants with NEC were allowed to die rather than being committed to a lifelong course of TPN. The relatively large proportion of ‘‘favorable risk’’ patients in this series does not at all diminish the authors’ remarkable dedication to their patients and their meticulous attention to detail in caring for them. Because outcomes from the UCLA program have remained relatively constant throughout three decades, during which the composition of formulas has changed, one may infer that the ‘‘continuous infusion’’ mode of delivering enteral nutrition is one of the more important variables facilitating gut adaptation. Some of us who care for such children have observed that the aesthetics of feces are less important for gut adaptation than is constant nutrient delivery to the gut. The authors are also to be commended for minimizing central line complications and maximizing the life span of central venous catheters. We have no information regarding the socioeconomic status or education level of the parents in this series, but we suspect that the success of UCLA’s home TPN program is due in large part to the ability of its staff to impart valuable insights regarding line care to the families of patients receiving TPN at home. Although the results of this series are impressive, they highlight the ongoing need for intestinal transplantation for patients with permanent intestinal failure. Obviously, those patients who experience persistent or deteriorating liver function should not be deprived of intestinal transplantation in the mistaken belief that transplantation is an experimental procedure. Likewise, early intestinal transplantation should be strongly considered for patients with ultra SBS. In the series by Quiros-Tejeira et al,5 only 3 of 17 patients with ultra SBS achieved full gut adaptation.
148
Editorials
Far more encouraging are the survival figures reported for small bowel transplantation using a recipient preconditioning regimen employed at centers such as Cincinnati Children’s Hospital Medical Center, The University of Pittsburgh Medical Center,6 and the University of Miami Medical Center.7 Preliminary findings have reported 2-year survival up to 100%, as well as full intestinal autonomy within days of transplantation using this regimen.6,7 The principle governing recipient preconditioning is recipient lymphocyte and/or monocyte ablation immediately before the transplant.7 A polyclonal T-cell or monocyte antibody is given to the recipient just before allograft reperfusion. This strategy has produced better short-term allograft acceptance, a decreased need for immunosuppression, and fewer opportunistic infections for recipients receiving transplants in these medical centers.6,7 Ultimately, the paper by Quiros-Tejeira et al teaches us that long life is indeed possible for infants with SBS.5 These infants, when managed in a center of excellence with an active home TPN program, have a strong likelihood of survival. For the subset incapable of ever achieving gut adaptation, small bowel transplantation has finally evolved enough to promise complete emancipation from TPN for the vast majority of these unfortunate children. Samuel A. Kocoshis, MD Cincinnati Children’s Hospital Medical Center Cincinnati, OH 45229
REFERENCES 1. Sukarochana K, Motal Y, Slim M, Shepard R, Kiesewetter WB. Postoperative protein metabolism in pediatric surgery. Surg Gynecol Obstet 1965;121:79-80. 2. Dudrick SJ, Wilmore DW, Vars HM, Rhoades JE. Long-term parenteral nutrition with growth, development and positive nitrogen balance. Surgery 1968;64:134-42. 3. Howard L, Malone M. Current status of home parenteral nutrition. Transplant Proc 1996;28:2691-8. 4. Varela-Fascinetto G, Greenawalt SR, Villegas-Alvarez F. Short bowel syndrome in patients studied at the National Institute of Pediatrics in Mexico: care, cost, and perspectives. Arch Med Res 1998;29:88-95. 5. Quir´os-Teijeira RE, Ament ME, Reyen L, Herzog F, Merjanian M, Olivares-Serrano N, et al. Long-term parenteral nutritional support and intestinal adaptation in children with short bowel syndrome: a 25-year experience. J Pediatr 2004;145:157-63. 6. Nakao A, Nalesnik MS, Azhipa O, Ishikawa T, Abu-Elmagd K, Starzl TE, et al. Immunomodulation of intestinal transplantation: antilymphocyte serum donor pretreatment vs. ex vivo graft irradiation. Transplant Proc 2002;34:986-7. 7. Garcia M, Weppler D, Mittal N, Nishida S, Kato T, Tzakis A, et al. Campath-1H immunosuppressive therapy reduces incidence and intensity of acute rejection in intestinal and multivisceral transplantation. Transplant Proc 2004;36:323-4. 8. Starzl TE, Murase N, Abu-Elmagd K, Gray EA, Shapiro R, Eghtesad B, et al. Tolerogenic immunosuppression for organ transplantation. Lancet 2003;361:1502-10.
The Journal of Pediatrics August 2004
REFERENCES 1. Reddy MM, Reddy MB, Reddy CF. Scientific advances provide opportunities to improve pediatric environmental health. J Pediatr 2004; 145:153-6. 2. United States Environmental Protection Agency. Terms of environment. Available at: http://www.epa.gov/ocepa111/OCEPAterms/. Last accessed: April 10, 2004.
3. National Library of Medicine. Specialized information services. Toxicology and environmental health. Click on ‘‘Toxicology Tutor.’’ Available at: http://sis.nlm.nih.gov/Tox/ToxMain.html. Last accessed: April 10, 2004. 4. Canfield RL, Henderson CR, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP, et al. Intellectual impairment in children with blood concentrations below 10 micrograms per deciliter. N Engl J Med 2003;348:1517-26. 5. Committee on the Toxicological Effects of Methylmercury, Board on Environmental Studies and Toxicology, National Research Council. Toxicological effects of methylmercury. Washington (DC): National Academy Press; 2000. 6. Organization for Economic Cooperation and Development. Cooperation in the investigation of existing chemicals. Available at: http:// www.oecd.org/about/0,2337,en_2649_34379_1_1_1_1_37407,00.html. Last accessed: April 10, 2004. 7. United States Environmental Protection Agency. National primary drinking water standard. Available at: http://www.epa.gov/safewater/consumer/mcl.pdf. Last accessed: April 10, 2004. 8. World Health Organization. A framework for the development of children’s environment and health action plan for Europe. Executive summary. Available at: http://www.who.dk/document/EEHC/4thigoprepmeet_BDS01.pdf. Last accessed: April 10, 2004.
SHORT BOWEL AND LONG LIFE: NO LONGER MUTUALLY EXCLUSIVE
ad a surgeon or pediatrician from the 1960s recapitulated Rip VanWinkle’s epic sleep and awakened in the 21st century, that person would be amazed at the many current practices employed to save children with short bowel syndrome (SBS) following intra-abdominal catastrophes. Among the most prominent is home total parenteral nutrition (TPN). TPN was first used by Sukarochana et al for undernourished postoperative patients,1 and soon thereafter studied in depth and popularized by Dudrick et al.2 Initially, TPN was thought to be too sophisticated a therapy for all but the most skilled medical practitioners to administer. However, by the late 1970s, hospitals and physicians faced a dilemma. Some patients receiving TPN succumbed to complications such as metabolic imbalance, sepsis, line complications, and cholestatic liver disease, but an ever growing number survived for months or even years while receiving TPN. These patients had ‘‘set up residence’’ in large teaching hospitals, draining resources. By the late 1970s, a few visionary physicians began training parents from all socioeconomic classes and educational levels to administer TPN to their children at home. Embraced by hospitals and the North American insurance industry because these patients could finally be discharged, this concept took root and is now the standard of care most health care providers in the developed world use for children with intestinal failure.
H
NEC SBS
Editorials
Necrotizing enterocolitis Short bowel syndrome
TPN
Total parenteral nutrition
That parents without formal education can be trained to successfully deliver TPN to their children ranks among the most important medical advances of the 20th century. Although long-term home TPN can now be provided to all children with intestinal failure, thoughtful clinicians question whether it should be provided because it is an expensive proposition. In an Oley Foundation survey from 1992, the cost of TPN for adults in the United States was almost $1000 per day.3 In Mexico, the annual cost was estimated to be $50,000 per year in the mid-1990s.4 Not only is the direct cost of TPN prodigious, but costs of repeated hospitalizations, loss of earning power by caregivers, and the chronic anxiety engendered by the ill health of the TPN recipient have overwhelmed many of the young parents giving birth to a child with SBS. It is not surprising that many families disintegrate as a result. Therefore, it is important to understand the TPN delivery strategies that will minimize See related article, p 157. its expense, the alimentation strategies that will maximize intestinal adaptation, and the Reprint requests: Samuel A. Kocoshis, patient characteristics that MD, Cincinnati Children’s Hospital mandate alternate treatments Medical Center, 3333 Burnet Ave, such as intestinal transplan- Cincinnati, OH 45229. J Pediatr 2004;145:147-8. tation for SBS. 0022-3476/$ - see front matter What Quiros-Tejeira Copyright ª 2004 Elsevier Inc. All rights et al have given to us in reserved. a report published in this 10.1016/j.jpeds.2004.05.036 147
issue of The Journal is a clearer focus on outcomes and therapeutic strategies for infants with SBS.5 Their retrospective analysis of outcomes in SBS covers a 25-year experience and includes nearly twice as many patients as any previous series. The authors can boast of outcomes much better than average, and they should be commended for their success. Of course, the astute reader may also infer that the surgeons who create surgical SBS and the neonatologists who manage the feedings of extremely premature infants also may have contributed to the outcomes reported. Surgeons who commit extremely premature infants with ultra-short bowel and multi-organ failure to TPN will guarantee early (but expensive) demise for those children, thereby skewing survival rates downward. It is notable that only 17 of the 78 patients in this series had ultra SBS, and only 16 of these patients had necrotizing enterocolitis (NEC). This represents about half the prevalence of NEC in some other series. One can question whether the incidence of NEC is low in Los Angeles or whether some of the sicker infants with NEC were allowed to die rather than being committed to a lifelong course of TPN. The relatively large proportion of ‘‘favorable risk’’ patients in this series does not at all diminish the authors’ remarkable dedication to their patients and their meticulous attention to detail in caring for them. Because outcomes from the UCLA program have remained relatively constant throughout three decades, during which the composition of formulas has changed, one may infer that the ‘‘continuous infusion’’ mode of delivering enteral nutrition is one of the more important variables facilitating gut adaptation. Some of us who care for such children have observed that the aesthetics of feces are less important for gut adaptation than is constant nutrient delivery to the gut. The authors are also to be commended for minimizing central line complications and maximizing the life span of central venous catheters. We have no information regarding the socioeconomic status or education level of the parents in this series, but we suspect that the success of UCLA’s home TPN program is due in large part to the ability of its staff to impart valuable insights regarding line care to the families of patients receiving TPN at home. Although the results of this series are impressive, they highlight the ongoing need for intestinal transplantation for patients with permanent intestinal failure. Obviously, those patients who experience persistent or deteriorating liver function should not be deprived of intestinal transplantation in the mistaken belief that transplantation is an experimental procedure. Likewise, early intestinal transplantation should be strongly considered for patients with ultra SBS. In the series by Quiros-Tejeira et al,5 only 3 of 17 patients with ultra SBS achieved full gut adaptation.
148
Editorials
Far more encouraging are the survival figures reported for small bowel transplantation using a recipient preconditioning regimen employed at centers such as Cincinnati Children’s Hospital Medical Center, The University of Pittsburgh Medical Center,6 and the University of Miami Medical Center.7 Preliminary findings have reported 2-year survival up to 100%, as well as full intestinal autonomy within days of transplantation using this regimen.6,7 The principle governing recipient preconditioning is recipient lymphocyte and/or monocyte ablation immediately before the transplant.7 A polyclonal T-cell or monocyte antibody is given to the recipient just before allograft reperfusion. This strategy has produced better short-term allograft acceptance, a decreased need for immunosuppression, and fewer opportunistic infections for recipients receiving transplants in these medical centers.6,7 Ultimately, the paper by Quiros-Tejeira et al teaches us that long life is indeed possible for infants with SBS.5 These infants, when managed in a center of excellence with an active home TPN program, have a strong likelihood of survival. For the subset incapable of ever achieving gut adaptation, small bowel transplantation has finally evolved enough to promise complete emancipation from TPN for the vast majority of these unfortunate children. Samuel A. Kocoshis, MD Cincinnati Children’s Hospital Medical Center Cincinnati, OH 45229
REFERENCES 1. Sukarochana K, Motal Y, Slim M, Shepard R, Kiesewetter WB. Postoperative protein metabolism in pediatric surgery. Surg Gynecol Obstet 1965;121:79-80. 2. Dudrick SJ, Wilmore DW, Vars HM, Rhoades JE. Long-term parenteral nutrition with growth, development and positive nitrogen balance. Surgery 1968;64:134-42. 3. Howard L, Malone M. Current status of home parenteral nutrition. Transplant Proc 1996;28:2691-8. 4. Varela-Fascinetto G, Greenawalt SR, Villegas-Alvarez F. Short bowel syndrome in patients studied at the National Institute of Pediatrics in Mexico: care, cost, and perspectives. Arch Med Res 1998;29:88-95. 5. Quir´os-Teijeira RE, Ament ME, Reyen L, Herzog F, Merjanian M, Olivares-Serrano N, et al. Long-term parenteral nutritional support and intestinal adaptation in children with short bowel syndrome: a 25-year experience. J Pediatr 2004;145:157-63. 6. Nakao A, Nalesnik MS, Azhipa O, Ishikawa T, Abu-Elmagd K, Starzl TE, et al. Immunomodulation of intestinal transplantation: antilymphocyte serum donor pretreatment vs. ex vivo graft irradiation. Transplant Proc 2002;34:986-7. 7. Garcia M, Weppler D, Mittal N, Nishida S, Kato T, Tzakis A, et al. Campath-1H immunosuppressive therapy reduces incidence and intensity of acute rejection in intestinal and multivisceral transplantation. Transplant Proc 2004;36:323-4. 8. Starzl TE, Murase N, Abu-Elmagd K, Gray EA, Shapiro R, Eghtesad B, et al. Tolerogenic immunosuppression for organ transplantation. Lancet 2003;361:1502-10.
The Journal of Pediatrics August 2004