ABSTRACT
PURPOSE: The aim of this study was to understand the long-term outcome of near-total intestinal aganglionosis (NTIA). METHODS: The study was an institutional review of all patients with NTIA between 1974 and 1999, inc!usive. Seven full-term babies were identified (4 boys, 3 girls). Mean birth weight was 3.2 kg (range, 2.7 to 4.1). Patients included 1 pair of siblings and 1 Down's syndrome baby. All 7 had obstruction within 5 days of life. One patient experienced bowel perforation. All 7 had NTIA diagnosed within the first 2 months of life. In 2 of 7, aganglionosis began 10 cm distal to the ligament of Treitz (LOT). The longest segment of normal small bowel was 130 cm from the LOT. Five of 7 babies underwent a stoma between day of life (DOL) 1 and 15. RESULTS: Two of three "long-term" survivors (>2 years) had corrective surgery by 13 months. The first received extended jejuno-ileal myotomy and myectomy with multiple postoperative problems. She died at 8 years of age of complications of total parenteral nutrition (TPN). The second underwent myotomy, resection and patch graft to jejunum, and several jejunostomy revisions. All of the involved bowel eventually was resected. The 3 of 7 who lived more than 1 year all took some nutrition orally. Three died, between 3 months and 8 years of age, of complications of TPN. There are 2 survivors at 3 and 7 years of age. Survival has not correlated with the length of aganglionic bowel. CONCLUSIONS: Aganglionosis involving most of the bowel has a high morbidity and mortality rate. Since 1990 a more aggressive surgical approach has resulted in improved survival rates but with significant morbidity. For children surviving beyond 3 months of age, outcome was less dismal. Some patients may benefit from extended jejunal myotomy or myectomy. However, postoperative complications are the rule, not the exception.
Subject(s)
Abnormalities, Multiple/diagnosis , Hirschsprung Disease/diagnosis , Intestinal Obstruction/diagnosis , Down Syndrome/diagnosis , Female , Follow-Up Studies , Hirschsprung Disease/mortality , Hirschsprung Disease/surgery , Humans , Ileostomy , Infant, Newborn , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intestinal Perforation/diagnosis , Intestinal Perforation/etiology , Jejunostomy , Male , Quebec , Retrospective Studies , Severity of Illness Index , Survival RateABSTRACT
The infusion of anti-CD3-activated murine T cells plus interleukin-2 (IL-2) exerts antitumor effects against several tumors in murine immunotherapy models. This study compares the therapeutic efficacy of anti-CD3-activated CD4+ or CD8+ T-cell subsets, when given with cyclophosphamide (Cy) and liposome-encapsulated IL-2 (L-IL2) in a murine model. C57BL/6 mice bearing subcutaneous (S.C.) MC-38 colon adenocarcinoma, 3LL Lewis lung carcinoma, or 38C13 lymphoma for 7 to 14 days were pretreated with low-dose intraperitoneal (I.P.) Cy before intravenous (I.V.) injection of anti-CD3-activated T cells or T-cell subsets. Cell administration was followed by I.P. administration of L-IL2 for 5 days. Mice receiving activated CD4+ T cells showed significantly reduced tumor growth or complete remissions with prolonged disease-free survival in MC-38, 3LL, and 38C13. The timing of Cy doses in relation to adoptive transfer was critical in obtaining the optimal antitumor effect by CD4+ cells. Injecting Cy 4 days before the infusion of CD4+ cells greatly enhanced the antitumor effect of the CD4+ cells and improved survival of the mice compared with other Cy regimens. C57BL/6 mice cured of MC-38 after treatment with CD4+ T cells developed tumor-type immunologic memory as demonstrated by their ability to reject rechallenges with MC-38, but not 3LL. Similarly, mice cured of 3LL tumors rejected rechallenges of 3LL, but not MC-38. The immunologic memory could be transferred with an I.V. injection of splenocytes from mice cured of MC-38 or 3LL. No cytotoxic T-lymphocyte activity was detected in T cells or T-cell subsets from mice cured of MC-38 or 3LL. Increased IL-2 and interferon-gamma (IFN-gamma) production was observed from CD4+ subsets in cured animals when stimulated in vitro with the original tumor, but not with an unrelated syngeneic tumor. These results suggest that tumor-specific immunity can be achieved in vivo with anti-CD3-stimulated CD4+ T cells in this cellular therapy model.