What's New in Pediatric Surgery?

Marleta Reynolds, MD

The American College of Surgeons publishes yearly reviews of the contributions of leaders in each surgical specialty. The Advisory Council for Pediatric Surgery designated Dr. Reynolds to prepare this report for the year 2000. This summary is based upon her manuscript, published in the July 2001 issue of the Journal of the American College of Surgeons (formerly, Surgery, Gynecology & Obstetrics, or SG & O). Highlighted commentary notes the opinion and practice of the pediatric surgeons at Children's Memorial Hospital, where applicable.

Basic science and clinical research in this specialty are commonly presented at the principal pediatric surgical meetings, including those of the American Pediatric Surgical Association, the Surgical Section of the American Academy of Pediatrics, the Pediatric Surgical Forum at the American College of Surgeons, the Canadian Association of the Pediatric Surgery, and the British Association of Pediatric Surgery. The majority of this research is published in the Journal of Pediatric Surgery.[1]

CONGENITAL DIAPHRAGMATIC HERNIA

The salvage of neonates presenting with congenital diaphragmatic hernia and respiratory failure remains a clinical challenge. Two large clinical reviews have been completed. The Congenital Diaphragmatic Hernia Study Group1 included over 1,000 patients from multiple centers. Multivariate analysis of their data revealed that birth weight and 5-minute Apgar scores could separate the majority of patients into high, intermediate, and low risk groups. Muratore and associates[2] reviewed the records of 100 survivors treated from 1990 to 1999. Pulmonary morbidity continued long after hospital discharge. Increased morbidity was associated with the need for extracorporeal membrane oxygenation (ECMO) and synthetic patch repair of the diaphragm.

Early tracheal occlusion in the fetal lamb model of congenital diaphragmatic hernia has been shown to increase surfactant production and the numbers of type II pneumocytes. Wild and associates[3] studied the effects of occluding the trachea for only 2 weeks. Lung growth, as measured by total lung capacity and lung weight to body weight ratio, was not induced. Nevertheless, measurements of quasistatic compliance, pulmonary arterial pressure, and postductal blood gases documented correction of pulmonary hypertension and improvement in gas exchange in this experimental model. Using the nitrofen-induced (nitrofen, Wako Bioproducts, Richmond, Va.) rat model of congenital diaphragmatic hernia, Kitano and associates[4] demonstrated that tracheal occlusion was more effective late in gestation, possibly because of the more advanced stage of lung development with increased production of lung fluid.

Several growth factors have been implicated in fetal lung growth in experimental animals with congenital diaphragmatic hernia and following tracheal occlusion. McCabe and colleagues[5] demonstrated an upregulation of keratinocyte growth factor protein and gene expression in the lamb model. Separately, Moore and associates[6] demonstrated that Rho, a small GTPase, may play a role in the mechanism that allows mechanical forces to control lung development. They treated embryonic lung buds with a drug that inhibits Rho and found that the lung buds developed a dose-dependent reduction in the increase in number of terminal lung buds.

The results of some other investigations using the delivered fetal lamb model may prove to have clinical applications. Fauza and associates[7] harvested fetal myoblasts and constructed a tissue graft for the repair of the diaphragmatic defect after birth of the lamb. The engineered grafts were anatomically and histologically similar to normal skeletal muscle and may become an alternative to synthetic material in the future. This work becomes more intriguing in light of the report by Moss and colleagues[8] describing the high incidence (41%) of recurrent hernias in babies treated with prosthetic patch repair. McCabe and colleagues[9] demonstrated that myeloperoxidase activity was an indirect measure of postnatal lung injury created by hyperoxia and conventional ventilation in lambs. Antioxidant therapies, monitored with myeloperoxidase assay, may prove useful in preventing the iatrogenic injuries associated with respiratory support of infants with congenital diaphragmatic hernia.

The initial research on in-utero repair of congenital diaphragmatic hernia has lead to an explosion in the understanding of fetal wound healing and the fetal scarless wound. Liechty and colleagues[10] have developed a new murine model of syngenic wound repair to study the role of cytokines in fetal wound repair. They found that mice lacking interleukin (IL)-10 responded to wounding with scar formation. Hyaluronic acid (hyaluronan) is present in high levels in the fetus and may play a role in the scarless healing of the fetal dermis. Kennedy and associates[11] studied the differential effects of the proinflammatory cytokines interleukin 1B (IL-1B) and tumor necrosis factor–alpha (TNF-alpha) on hyaluronan (hyaluronic acid) and hyaluronan synethase in adult and fetal human fibroblasts. The muted response of fetal fibroblasts to cytokines may minimize inflammation associated with fetal repair.

MINIMAL ACCESS SURGERY

The techniques of minimal access surgery are accepted alternatives in many procedures performed by pediatric surgeons. Cost, associated morbidity and long-term results are the focus of clinical research. Kawahara and colleagues[12] studied the motor function and lower esophageal sphincter in children following laparoscopic Nissen fundoplication. While there was no abnormality of esophageal motor function, they documented increased residual lower esophageal pressure at the nadir of relaxation of the lower esophageal sphincter. The high zone pressure may be the cause of dysphagia following laparoscopic Nissen and might need to be controlled to improve the long-term results of this technique.

Progressive operative experience and advances in instrumentation have advanced the practice of laparoscopic splenectomy in many centers. Esposito and colleagues[13] from 3 European countries have reported a 5-year experience with this approach. Operating time was still longer than with the open technique and the extraction of the splenic tissue was more complex. Danielson and colleagues[14] report similar operating times (a mean of 125 vs 140 minutes) but have instituted variations in their technique to facilitate the procedure, especially the extraction phase. In a 2-year period, none of their patients required transfusion or conversion to open splenectomy. Hospital charges appeared to be approaching those for the open technique.

This approach has been used at Children's Memorial Hospital for the last several years with excellent results.

Video-assisted thoracic surgery (VATS) has been used extensively in adults for a variety of pulmonary and mediastinal procedures. Subramanian and associates[15] compared their prior experience with open thoracotomy for empyema in childhood with their recent experience using VATS exposure. They found that open thoracotomy was only necessary for lung resection or control of bronchopleural fistula. Patients were referred earlier and blood transfusion, analgesic requirement, postoperative length of hospital stay, time to normothermia, and time to removal of chest tubes were all less in children treated with VATS. These findings should encourage increased utilization of minimally invasive approaches.

Since the 1970s, we have promoted a thorough debridement of the infected pleural cavity through an open approach, but using a very small incision — a "mini-thoracotomy." The VATS technique offers an additional option for minimizing the size of the incision. However, this approach may require more operative time and expense.

In 1998, the "Nuss Procedure" was introduced as an alternative to the Ravitch procedure for correction of the pectus excavatum deformity. The depressed lower sternum is elevated by pressure exerted from a steel bar, which is guided under the sternum blindly or using thoracoscopic visualization. Dr. Nuss reported good early results and few complications. However, other surgeons have seen more problems. Moss and associates16 reported the experience of 3 different institutions. Complications of the Nuss procedure included thoracic outlet syndrome (symptomatic neurovascular compression at the thoracic outlet) in 3 patients, pericarditis and empyema in 1 patient, and cardiac perforation in 1 patient. Molik and colleagues[17] compared their experience with the Ravitch and Nuss procedures in 100 children. The Nuss procedure required less operating room time. Complication rates were higher in the Nuss procedure (43% vs 20%) although this difference was not statistically significant. Length of hospital stay, narcotic requirement for pain control, and rate of re-operation were higher in children after the Nuss procedure.

This approach has been used at Children's Memorial Hospital with limited success. Although the technique initially appears attractive, a clear advantage over the open operation has not been demonstrated. Perioperative pain may be greater that with the open technique. We can recommend this operation only for selected patients.

Canty and associates[18] have compared over 1,000 appendectomies for simple and complicated appendicitis using the open and laparoscopic techniques. They have shown laparoscopic techniques to be as safe and effective as the open technique, and in the past 4 years, the laparoscopic technique has been their technique of choice. Experience has led to a decrease in operating time with fewer complications.

In general, the laparoscopic approach offers no advantage when operating upon younger, slender children. Length of operation and days of hospitalization are about the same with both techniques. The complication of abdominal abscess has been reported more frequently in adults with the laparoscopic technique.

CANCER

Several centers have concentrated on a variety of novel experimental studies of neuroblastoma. Survivin, a cell cycle-regulated inhibitor of apoptosis (regulated cell death), is expressed in neuroblastoma cell lines. Azahata and associates[19] have shown that survivin appears to be a better prognostic indicator than n-myc. Survivin expression was associated with n-myc amplification, a greater neuroblastoma cell proliferation rate and a greater resistance to activation-induced apoptosis. Kim and colleagues[20] demonstrated expression of gastrin-releasing peptide receptors (GRPRs) in neuroblastoma cell lines. GRPRs were shown to stimulate growth of the neuroblastoma cells. New therapies for neuroblastoma may involve agents that block GRPRs or inhibit their expression. Scott and colleagues[21] have developed a tumor vaccine using a model of murine neuroblastoma. Neuro-2A/Fas-L cells were created and injected with or without cpG-1826 adjuvant. The immune-stimulating properties of cpG-1826 improved the antitumor effect of the Fas-L transduced cells. The vaccine destroyed the innoculated neuro-2A cells and generated immunity to subsequent challenge with wild type tumor and inhibited growth of a preestablished tumor at a remote site.

Experimental studies related to Wilms' tumor now focus on fine-tuning current treatment regimens and developing novel therapies that might decrease treatment morbidity. Naraghi and associates[22] found that 3 growth factor receptor tyrosine kinase (GFR-TK) inhibitors suppress growth of rhabdoid tumor of the kidney and Wilms' tumor cell lines. A specific isoform of the vascular endothelial growth factor (VEGF165) is found in Wilms' tumor. Huang and colleagues[23] found that an anti-VEGF165 aptamer suppressed Wilm's tumor growth in an experimental animal. Takamizawa and associates[24] studied the expression of surviving, which is expressed in some Wilms' tumors, and the prognostic value of the survivin:fas ratio in renal tumors. They found the survivin:fas mRNA ratio was of prognostic value in predicting recurrent disease. A ratio of greater than 1.6 predicted recurrent disease irrespective of clinical stage or pathology.

Anaplastic Wilms' tumors are poorly responsive to conventional therapy. Delatte and colleagues[25] have delivered a p553 tumor suppression gene to anaplastic Wilms' tumors by an adenoviral vector. The gene replacement technique reduced cell proliferation by 97% and 99.8% after 5 days. This new therapy option may be possible for children with anaplastic Wilms' tumor.

germ cell tumor

Rescorla and associates[27] reported the findings based upon the same Intergroup Study focusing on 74 children with tumors arising in the sacrococcygeal region. Surgical resection was completed before chemotherapy in 29 patients and following chemotherapy in 42. Three children never had surgical resection; 1 died from infection, 1 died of tumor progression prior to completion of chemotherapy and 1 child had no evidence of disease after chemotherapy. Four-year survival was 90%. Delay of surgical resection until after chemotherapy did not adversely affect outcome. There was no statistical difference between chemotherapy regimens, although there was a trend in favor of the high-dose cisplatin arm.

Lymphatic mapping with sentinel node biopsy may guide biopsy of specific pathological nodes and limit unnecessary extensive nodal dissection in children with cancer. Neville and associates[28] reviewed the care of 13 children who had undergone sentinel node biopsy after lymphatic mapping with technetium-labeled sulfur colloid and lymphazurin blue. The procedures were accurate in identifying involved nodes. These children were being treated for malignant melanoma (8), peripheral nerve sheath tumor (1), alveolar soft part sarcoma (1), and rhabdomyosarcoma (3). As in adults, these procedures are most useful in patients with malignant melanoma. The utility of the diagnostic procedure in other childhood malignancies will need to be further studied.

LaQuaglia and colleagues[29] reviewed the course of 327 children treated for differentiated thyroid carcinoma with distant metastasis at diagnosis. In this group, 100% of the children received adjuvant iodine-131 therapy. Overall survival of 10 years was 100%. Progression-free survival rate was 76% at 5 years and 66% at 10 years from diagnosis. Distant metastasis found by preoperative chest CT or the presence of clinical features associated with distant metastasis is an indication for total or subtotal thyroidectomy with removal of involved regional lymph nodes. This surgical plan will facilitate radioiodine imaging and treatment.

TRAUMA

Beta glucan collagen matrix (BGC) is a combination of a complex carbohydrate and collagen combined in a meshed wound dressing. This mesh is an easily applied temporary dressing for partial thickness burns or other superficial injuries. Delatte and associates[30] report their 2-year experience applying BGC to clean debrided wounds that did not involve face, fingers, toes, genitalia, or major joints. The BGC was attached with steristrips and covered with gauze and elastic bandages. After 24 hours, the outer dressing was removed to assure attachment. A light dressing was reapplied when appropriate for the patient. Partial thickness burns healed without the need for painful dressing changes or prolonged hospitalization.

Patel and associates[31] reviewed data collected on cervical spine injury by the National Pediatric Trauma Registry, 1988 through 1998. This Registry includes cases of over 75,000 children. Cervical spine injury occurred in only 1.5% of injured children, with upper cervical spine injuries equally distributed along all age groups. Lower spine injuries were more frequent in children over 8 years of age. Mortality was 6 times higher in children with upper cervical spine injuries. Neurological injury was present in one third of the children studied, although only one half had radiological abnormalities. Neurological deficit was complete in only 24% of the children. Initial evaluation and management must focus on prevention of further injury to the spinal cord, which may have incomplete deficits. Use of the large database allows the authors to alert pediatric surgeons to the needs of children with this rare injury.

Pediatric surgeons and pediatricians, as children's advocates, must play a more aggressive role in injury prevention efforts. Wesson and associates[32] have documented the positive effects of an educational campaign and a new bicycle helmet law on bicycle-related head injuries.. Over the 1-year study period, bicycle helmet use increased from 4 to 67%. The total number of bike-related head injuries fell by more than 50%.

GASTROINTESTINAL CONDITIONS

Cholelithiasis

Ultrasonography is used now to evaluate children with a variety of abdominal complaints and cholelithiasis is diagnosed more frequently. Bruch and associates[33] studied 74 children whose nonpigmented gallstones were found by ultrasonography. They recommend cholecystectomy for all patients with typical biliary symptoms (right upper quadrant pain or epigastric pain, nausea and vomiting, or food intolerance). Children with atypical symptoms could be followed and treated with dietary adjustment, reserving operation for those who remained symptomatic. Safford and colleagues[34] described a population of children in their bone marrow transplant program who had cholelithiasis. Abdominal ultrasonography was performed for evaluation of jaundice, sepsis, abdominal pain, or metastasis. Cholelithiasis was more prevalent in children treated for a bone marrow failure than for malignancy. Only 15% (3 of 20 patients) had signs of acute cholecystitis and underwent cholecystectomy. Sonographic resolution of gallstones occurred in 25% of the remaining 17 patients, and the others either died of their original disease or were still being followed without operation. The authors concluded that bone marrow transplant patients have a high incidence of cholelithiasis, especially those with bone marrow failure. Nonoperative management was safe in the asymptomatic patient.

Short Bowel Syndrome

Intestinal adaptation occurs after extensive bowel resection but the mechanisms involved are not completely understood. Stern and colleagues[35] studied the effect of serum taken from mice after a 50% bowel resection on rat intestinal epithelial cells. They could demonstrate that the serum contained a growth factor that induced cell growth in vitro. They also found that caspase-3 activity, a marker for apoptosis, was suppressed. Alavi and associates[36] studied the effects of leptin, a cytokine expressed in a number of tissues, on intestinal mucosal mass and absorption. The increase in mucosal mass and increase in absorptive function that resulted was dose-dependent and implicated leptin as a growth factor for the intestine.

Small Bowel Transplantation

Intestinal transplantation is being offered to more children as survival improves and morbidity decreases. Iyer and associates[37] reported a 6-year experience with small bowel and liver-small bowel transplantation for intestinal pseudo-obstruction with exclusion of stomach and colon. Indications for transplantation included lack of vascular access for total parenteral nutrition (TPN) (2), recurrent or life-threatening line infections (3), and TPN-associated end stage liver disease (3). Median follow-up was 40 months with a median transplant graft survival of 15 months. Nine children underwent 6 small bowel and 3 liver-small bowel transplants, 1 patient had 2 small bowel transplants. Two children died, 1 of postoperative complications and the other from autoimmune hemolysis 1 year after transplant. Five children have functioning grafts, 4 have had their ileostomies closed, and 3 have normal bowel movements. All receive full enteral feedings, and 3 of the 5 enjoy a regular diet by mouth. Gastric paresis was a problem in the early post-transplant period but resolved in most over time.

Bueno and colleagues[38] reported their experience with 27 children with short-gut syndrome who were TPN-dependent and had undergone intestinal lengthening procedures. Only 9 patients increased their caloric intake following the lengthening procedure and only 1 patient could be weaned off TPN. None of the patients with liver dysfunction at the time of the lengthening procedure recovered. Most of these patients had multiple episodes of sepsis following the lengthening procedure. The authors have recommended that an intestinal lengthening procedure should be avoided in the neonatal period, especially in those patients with liver dysfunction and when the intestinal length is less than 50 cm.

Early and late acute rejection continues to be a major stumbling block in small bowel transplantation. Guo and colleagues[39] studied the role of CD4+ and CD8+ T cells in early and late rejection of small bowel transplants in a rat model. Survival of the intestinal graft was significantly prolonged when activation of CD4+ cells was suppressed by FK 506-based immunosuppression. At late acute rejection, the CD4+ and CD8+ T cells remained at low-level activation status, suggesting that even at low levels, the resistant T-cell activation is enough to cause late acute rejection. Therapeutic strategies targeting these cells are needed for long-term engraftment.

REFERENCES

1. The Congenital Diaphragmatic Hernia Group. Estimating disease severity of congenital diaphragmatic hernia in the first 5 minutes of life. J Pediatr Surg 2001;36(1): 41–145.

2. Muratore CS, Kharasch V, Lund DP, et al. Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia in a multidisciplinary clinic. J Pediatr Surg 2001;36(1): 33–140.

3. Wild YK, Piasecki GJ, DePaepe ME, Luks FI. Short-term tracheal occlusion in fetal lambs with diaphragmatic hernia improves lung function, even in the absence of lung growth. J Pediatr Surg 2000;35(5):775–779.

4. Kitano Y, Kanai M, Davies P, et al. Lung growth induced by prenatal tracheal occlusion and its modifying factors: a study in the rat model of congenital diaphragmatic hernia. J Pediatr Surg 2001;36(2):251–259.

5. McCabe AJ, Carlino V, Holm BA, Glick PL. Upregulation of keratinocyte growth factor in the tracheal ligation lamb model of congenital diaphragmatic hernia. J Pediatr Surg 2001;36(1):128–132.

6. Moore KA, Kong Y, Huang S, et al. Treatment with Rho-kinase inhibitor Y27632 results in decreased lung branching morphogenesis. Surg Forum 2000; L1:544–546.

7. Fauza DO, Marler JJ, Koka , et al. Fetal tissue engineering: diaphragmatic replacement. J Pediatr Surg 2001;36(1):146–151.

8. Moss RL, Chen CM, Harrison MR. Prosthetic patch durability in congenital diaphragmatic hernia: a long-term follow up study. J Pediatr Surg 2001;36(1):152–154.

9. McCabe AJ, Downy M, Holm BA, Glick PL. Myeloperoxidase activity as a lung injury marker in the lamb model of congenital diaphragmatic hernia. J Pediatr Surg 2001;36(2): 34–337.

10. Leichty KW, Kim HB, Adzick NS, Crumbleholme TM. Fetal wound repair results in scar formation in interleukin-10 deficient mice in a syngenic murine model of scarless fetal wound repair. J Pediatr Surg 2000;35(6):866–873

11. Kennedy CI, Diegelmann RF, Hayes JH, Yager DR. Proinflammatory cytokines differential regulate hyaluronan synthase isoforms in fetal and adult fibroblasts. J Pediatr Surg 2000;35(6):874–879.

12. Kawahara H, Imura K, Nakajima K et al. Motor function of the esophagus and the lower esophageal sphincter in children who undergo laparoscopic Nissen fundoplication. J Pediatr Surg 2000;35(11):1666–1671.

13. Esposito C, Schaarschmidt KI, Settimi A, Montupet Ph. Experience with laparoscopic splenectomy. J Pediatr Surg 2001;36(2):309–311.

14. Danielson PD, Shaul DB, Phillips D, et al. Technical advances in pediatric laparoscopy have had a beneficial impact on splenectomy. J Pediatr Surg 2000;35(11):1578–1581.

15. Subramaniam R, Joseph VT, Tan GM, et al. Experience with video-assisted thoracoscopic surgery in the management of complicated pneumonia in children. J Pediatr Surg 2001;36(2):316–319.

16. Moss RL, Albanese CT, Reynolds M. Major complications after minimally invasive repair of pectus excavatum: case reports. J Pediatr Surg 2001;36(1):155–158.

17. Molik KA, Engum SA, Rescorla FJ, et al. Pectus excavatum repair: experience with standard and minimal invasive techniques. J Pediatr Surg 2001;36(2):324–328.

18. Canty TG, Collins D, Losasso B et al. Laparoscopic appendectomy for simple and perforated appendicitis in children: The procedure of choice? J Pediatr Surg 2000;35(11):1582–1585.

19. Azahata T, Scott D, Takamizawa S, et al. Survivin: expression and function in neuroblastoma. Surg Forum 2000; L1:529–531.

20. Kim S, Chung DH, Escalon J, et al. Expression and functional regulation of the gastrin-releasing peptide (GRP) receptor in the neuroblastoma cell line IMR-32. Surg Forum 2000; L1:532–534.

21. Scott D, Takamizawa S, Wen J, et al. A novel murine neuroblastoma vaccine strategy. Surg Forum 2000; L1:534–535.

22. Naraghi S, Khoshyomn S, DeMattia JA, Vane DW. Receptor tyrosine kinase inhibition suppresses growth of pediatric renal tumor cells in vitro. J Pediatr Surg 2000;35(6):884–890.

23. Huang J, Moore J, Soffer S, et al. Highly specific anti-angiogenic therapy is effective in suppressing growth of experimental Wilms' tumor. J Pediatr Surg 2001;36(2):357–361.

24. Takamizawa S, Scott D, Wen J, et al The survivin:fas ratio in pediatric renal tumors. J Pediatr Surg 2001;36(1):37–42.

25. Delatte SJ, Hazen-Martin D, Re GG, et al. Restoration of p53 function in anaplastic Wilms' tumor. J Pediatr Surg 2001;36(1):43–50.

26. Billmire D, Vinocur C, Rescorla F, et al. Malignant mediastinal germ cell tumors: An intergroup study. J Pediatr Surg 2001;36(1):18–24.

27. Rescorla F, Billmire D, Stolar C, et al. The effect of cisplatin dose and surgical resection in children with malignant germ cell tumors at the sacrococcygeal region: A Pediatric Intergroup Trial (POG 9049/CCG 8882). J Pediatr Surg 2001;36(1):12–17.

28. Neville HL, Andrassy RJ, Lally KP. Lymphatic mapping with sentinel node biopsy in pediatric patients. J Pediatr Surg 2000;35(6):961–964.

29. LaQuaglia MP, Black T, Holcomb III GW, et al. Differentiated thyroid cancer: clinical characteristics, treatment, and outcome in patients under 21 years of age who present with distant metastases. A Report from the Surgical Discipline Committee of the Children's Cancer Group. J Pediatr Surg 2000;36:955–960.

30. Delatte SJ, Evans J, Hebra A, et al. Effectiveness of beta-glucan collagen for treatment of partial-thickness burns in children. J Pediatr Surg 2001;36(1):113–118.

31. Patel JC, Tepas JJ, Mollitt DL, Pieper P. Pediatric cervical spine injuries: defining the disease. J Pediatr Surg 2001;36(2):373–376,.

32. Wesson D, Spence L, Hu X, Parkin P. Trends in bicycling-related head injuries in children after implementation of a community-based bike helmet campaign. J Pediatr Surg 2000;35(5):688–689.

33. Bruch SW, Ein SH, Rocchi C, Kim PCW. The management of nonpigmented gallstones in children. J Pediatr Surg 2000;35(5):729–732.

34. Safford SD, Safford KM, Martin P, et al. Management of cholelithiasis in pediatric patients who undergo bone marrow transplantation. J Pediatr Surg 2001;36(1):86–90.

35. Stern LE, Erwin CR, O'Brien DP. Serum from mice after small bowel resection enhances intestinal epithelial cell growth. J Pediatr Surg 2001;36(1):184–189.

36. Alavi K, Schwartz MZ, Prasad R, Funanage VL. Leptin: a new growth factor for the small intestine. Surg Forum 2000;L1: 527–529.

37. Iyer K, Kaufman S, Sudan D, et al. Long-term results of intestinal transplantation for pseudo-obstruction in children. J Pediatr Surg 2001;36(1):174–177.

38. Bueno J, Guiterrez J, Mazariegos GV, et al. Analysis of patients with longitudinal intestinal lengthening procedure referred for intestinal transplantation. J Pediatr Surg 2001;36(1):178–183.

39. Guo WH, Tian L, Chan KL, et al. Role of CD4+ and CD8+ T cells in early and late acute rejection of small bowel allograft. J Pediatr Surg 2001;36(2):352–356.

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