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Background/purpose: The purpose of this study is to evaluate the function of the mechanically lengthened small intestine., Methods: A jejunal segment was separated from intestinal continuity in rats. A screw was inserted into its proximal end, and the distal end was oversewn. The screw was advanced into the jejunal segment by 5 mm every other day. The jejunal segments were retrieved after 2 weeks. The length, weight, muscular thickness, alkaline phosphatase, and lactase activities of the jejunal segments were determined. Comparisons were made among normal jejunum, isolated jejunal segments without lengthening, and lengthened jejunal segments., Results: Jejunal segments doubled in length after gradual mechanical stretching compared with the normal and isolated controls. The thickness of the muscular layer increased in both the isolated and lengthened groups. The total activity of alkaline phosphatase increased in jejunal segments that were lengthened, whereas the total lactase activity remained the same., Conclusions: Mechanical force is a viable method for increasing intestinal length while preserving the intestinal function. This phenomenon may provide a new method for the treatment of patients with short bowel syndrome.

Purpose: The adrenal cortex is a critical component of the hypothalamic-pituitary-adrenal/gonadal axis that coordinates the stress response and maintains homeostasis. The authors hypothesize that adrenal cortical cells can be transplanted in adrenal insufficiency states to regenerate the adrenal cortex., Methods: Murine adrenal glands were dissociated into adrenal cortical cells. Cells cultured in a collagen matrix were transplanted under the renal capsule. The implants were retrieved 1, 2, 4, and 8 weeks later. Total RNA was extracted from the retrieved specimens and was analyzed by real-time polymerase chain reaction., Results: All animals survived the surgical procedure. At implant retrieval, a distinct organoid could be visualized under the renal capsule. The expressions of adrenal-specific markers including Sf1, Dax1, Star, Cyp11a, Cyp11b1, and Cyp21 were detectable in the retrieved specimens up to 8 weeks posttransplantation., Conclusion: Primary adrenal cortical cells retained their gene expressions after heterotopic transplantation. Ex vivo gene transfer followed by adrenal cortical cell transplantation may lead to curative therapy for patients with adrenal insufficiency.

Giant omphalocele is associated with a high degree of visceroabdominal disproportion, which prohibits safe primary closure. Conventional treatment options include (1) topical therapy with epithelialization followed by secondary ventral hernia repair and (2) staged reduction using a SILASTIC(R) (Dow Corning, Midland, MI) chimney. The authors report a case in which staged reduction of a giant omphalocele was facilitated by the use of crescent-shaped tissue expanders positioned in the potential space between the internal oblique and transversus abdominis layers of the abdominal wall.

Purpose: Gastrointestinal (GI) dysmotility occurs frequently in full-term infants with gastroschisis (GS). Although controversial, preterm delivery of infants with GS has been advocated to prevent the development of GI dysmotility, and understanding the etiology of gestational-related bowel injury may lead to prenatal therapies. Using a fetal rabbit model, the authors assessed in vivo and in vitro GI motility in preterm GS fetuses., Methods: On gestation day 24 (term, 31), surgery was performed in maternal rabbits and GS induced in fetuses, whereas control fetuses underwent sham procedures. On gestation day 29, both groups of fetuses received ultrasound-guided intragastric injection of fluorescein and colored microspheres. Two hours after injection, fetuses were delivered by cesarean section and stomach and small intestine harvested intact. "GI motility" was calculated as the distance traveled by fluorescein divided by total length. In vitro studies of fetal gastric muscle strips contractility responses to bethanechol, a cholinergic agonist, were assessed in an organ bath system. Data were analyzed as paired and unpaired t tests and expressed as means +/- SEM., Results: GS reduced fetal body weight and intestinal length compared with controls (28.4 +/- 1.4 v. 33.5 +/- 1.5 g, 36.9 +/- 1.8 v. 25.9 +/- 1.2 cm; P <.05, respectively). Fetuses with GS showed markedly reduced in vivo GI motility (51.4 +/- 2.9 v 24.8 +/- 2.7%; P <.05) and in vitro gastric contractile tension (769 +/- 53 v 396 +/- 26 mNcm2; P <.05)., Conclusions: GI exposure to amniotic fluid reduces intestinal motility and gastric contractility functions in the preterm rabbit fetus. The results suggest that GS-associated impairment of GI neuromuscular functions occurs in utero, before term, and may be responsive to manipulation of amniotic fluid content or other therapeutic interventions.

Intestinal tissue engineering has the potential of developing new treatment strategies for patients with a deficit in intestinal surface area. The purpose of this study was to investigate the capacity of small intestine submucosa (SIS) to regenerate intestinal epithelia in a rodent model for a duodenal defect. A duodenotomy was created in 20 Sprague-Dawley rats and was repaired with a circular patch of SIS. The repaired sites were retrieved 1, 2, 4, and 12 weeks after implantation. The size of the residual mucosal defect was measured. The retrieved tissues were fixed in formalin and processed by standard histologic techniques. The animals tolerated the procedure well. The mean size of the mucosal defects significantly decreased with time. Complete epithelialization of the defects was noted within 4 weeks in three of five samples. Histologically, the defects were lined with crypts and villi, but the muscularis layer did not regenerate. In the rodent model, SIS can be used as a patch to repair a duodenotomy. Mucosal regeneration was observed in the area of the defect. Further studies will determine whether SIS may be used to preserve or increase mucosal surface area in patients whose bowel length is compromised.

Background/purpose: The administrative process for annual meetings is time consuming and increasingly costly when accomplished by traditional postal, fax, and telephone methods. The Pacific Association of Pediatric Surgeons introduced an all-electronic communication format for its 2002 annual meeting. Attendee acceptance and administrative and financial impact were evaluated., Methods: Interested physicians were directed to a Website containing detailed information and electronic forms. E-mail was used for the abstract selection and manuscript submission processes. Attendees were surveyed to evaluate the new format. Administrative costs for the new format were compared with estimated costs for a comparable traditionally managed meeting., Results: Attendance was similar to that at previous US meetings. Eighty-two percent of respondents approved of the all-electronic format, although 48% believed a choice should remain. None suggested a complete return to the traditional format. Abstract and manuscript processing time was reduced substantially as were administrative costs (79.43 dollars savings per physician registrant)., Conclusions: Adoption of an all-electronic annual meeting administrative process was associated with substantial cost reduction, increased efficiency, and excellent attendee satisfaction. This technology can help avoid increased registration fees while easing the burden on physician volunteers.

Purpose: Antegrade continence enemas (ACE) are an efficacious therapeutic option for patients with fecal incontinence. The authors review their institution's experience with a variation of the Monti-Malone ACE procedure using the left colon as a source of an intestinal conduit and enema reservoir., Methods: From 2000 to 2002, 18 patients with fecal incontinence or intractable constipation underwent left-colon ACE (LACE) procedure. Concomitant Mitrofanoff appendicovesicostomy was performed in 15 patients and bladder augmentation in 9. The majority of patients had neural tube defects. A segment of left colon was tubularized, tunneled into the muscular wall of the distal colon, and exteriorized through the left upper quadrant or midabdomen. Stomal catherization and enema installation were started one month postoperatively., Results: Fifteen patients (83%) achieved fecal continence, 2 remain incontinent of stool, and 1 experienced stomal closure (mean follow-up was 24 +/- 9 months). Two patients had stomal stenosis that required revision. The mean enema volume in patient's achieving continence was 360 +/- 216 mL, and the mean transit time was 18 +/- 12 minutes., Conclusions: LACE is an efficacious procedure for fecal incontinence that can be performed safely at the time of major urologic reconstruction. Administration of enemas into the left colon has several physiologic advantages that result in predictable bowel evacuation.

Numerous studies have described regulatory factors and sequences that control transcriptional responses in vitro. However, there is a paucity of information on the qualitative and quantitative regulation of heterologous promoters using transgenic strategies. In order to investigate the physiological regulation of human plasminogen activator inhibitor type-1 (hPAI-1) expression in vivo compared to murine PAI-1 (mPAI-1) and to test the physiological relevance of regulatory mechanisms described in vitro, we generated transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by the proximal -2.9 kb of the hPAI-1 promoter. Transgenic animals were treated with Ang II, TGF-beta1 and lipopolysaccharide (LPS) to compare the relative activation of the human and murine PAI-1 promoters. Ang II increased EGFP expression most effectively in brain, kidney and spleen, while mPAI-1 expression was quantitatively enhanced most prominently in heart and spleen. TGF-beta1 failed to induce activation of the hPAI-1 promoter but potently stimulated mPAI-1 in kidney and spleen. LPS administration triggered robust expression of mPAI-1 in liver, kidney, pancreas, spleen and lung, while EGFP was induced only modestly in heart and kidney. These results indicate that the transcriptional response of the endogenous mPAI-1 promoter varies widely in terms of location and magnitude of response to specific stimuli. Moreover, the physiological regulation of PAI-1 expression likely involves a complex interaction of transcription factors and DNA sequences that are not adequately replicated by in vitro functional studies focused on the proximal -2.9 kb promoter.

Objective: In the preterm human fetus, immaturity of gastrointestinal (GI) motility contributes to impairment of oral feeding and an increased risk of necrotizing enterocolitis. In view of the limited knowledge of fetal GI motility development, and the primary role of the muscarinic system in adult GI motility, we examined the development of GI muscarinic receptor subtypes associated with ileal motility., Study Design: Ovine term fetal, newborn, and pregnant adult ileal longitudinal muscle contractile responses to muscarinic agonists (bethanechol) and muscarinic nonspecific (atropine) and subtype specific-antagonists (M1-M4) were examined in organ baths. Immunohistochemical analysis of ileal muscle muscarinic receptor subtypes was correlated with contractile responses., Results: Bethanechol induced a concentration-dependent ileal contraction at all 3 age groups. Adult ileal maximal tension was 2-fold higher than that of the fetus and newborn, while 50% effective concentration (EC(50)) was similar at all ages. Atropine (10(-6)mol/L) inhibited contractility in fetal (67%+/-7%), newborn (82%+/-5%), and adult (97%+/-2%) in an age-dependent manner. The M3 antagonist exhibited robust inhibition at all age groups while the M2 antagonist demonstrated enhanced inhibition in the fetus. Immunohistochemical analysis indicated coexpression of subtype receptors in fetal, newborn, and adult ileal smooth muscle with increasing expression with advancing age., Conclusion: These results demonstrate a specific developmental pattern of muscarinic receptor subtype expression. Knowledge and/or alterations of GI motility regulation may aid in the treatment of the preterm fetus or newborn.

Introduction: Macaque species offer a valuable model for translational allo-transplantation and tolerance studies. Cardiac allograft vasculopathy in Macaca fascicularis is associated with elaboration of anti-donor antibodies. Since T-independent pathways of B cell activation have been described, and anti-B cell strategies have proven to be a fruitful tolerogenic adjunct in rodent and xenogenic models, here we investigate whether an anti-CD20 antibody (rituximab) would be useful to deplete B-cells in a pre-clinical allo-transplantation setting in macaques., Methods: Three cynomolgus macaques which had previously rejected a cardiac allograft and one with concurrent subacute vascular rejection were treated weekly with rituximab 20 mg/kg i.v. for 4 and 2 weeks, respectively. B-cell levels (CD19+ cells) were measured by flow cytometry in peripheral blood, spleen, lymph node and bone marrow cells at various intervals after initiation of treatment. B-cells and plasma cells were also analyzed by immunohistochemistry at necropsy in spleen, lymph node, tonsil and thymus tissue sections. Anti-donor antibody titers were measured by flow cytometry., Results: B-cells expressing CD19 were not detectable in the peripheral blood in any animal within 24 h after initial treatment, or over the ensuing month. At necropsy, the germinal centers in spleen and lymph node were completely depleted of CD20+ B-cells in 2 animals, leaving a hypocellular trabecular pattern around preserved plasma cell follicles. Substantial but incomplete depletion of B-cells was demonstrated in the other 2 animals, in each instance immunohistochemical findings in spleen and lymph node exhibiting higher sensitivity for residual B-cells compared to FACS. Anti-donor antibody titers exhibited kinetics similar to untreated animals over this short follow-up., Comment: Treatment with anti-CD20 very efficiently depletes peripheral and tissue B-cells but not plasma cells in this macaque species. Biopsy of lymph node is necessary and may be sufficient to assess B-cell clearance in secondary lymphoid organs in this model.

Laparoscopic Nissen fundoplication has been shown to improve overall quality of life (QOL) in patients with gastroesophageal reflux, but most studies have not addressed patients with atypical symptoms. We investigated the effect of laparoscopic Nissen fundoplication on QOL using the Gastrointestinal Quality of Life Index (GIQLI) survey modified to address both typical (heartburn, regurgitation, dysphagia) and atypical (hoarse voice, chronic cough, adult-onset asthma, vocal cord polyps) symptoms. One-hundred forty-eight patients underwent laparoscopic Nissen fundoplication for gastroesophageal reflux disease (GERD) at UCLA Medical Center from January 1, 1995 to May 1, 2002. Surveys evaluating pre- and postoperative QOL were administered after surgery: 55 per cent of patients responded (82/148). Forty-eight per cent of all patients (72/148) had atypical symptoms. Perioperative morbidity and mortality were 8.8 per cent and 0.7 per cent, respectively. Mean length of postoperative stay was 2.96 +/- 1.5 days. Mean follow-up for the entire cohort was 18.5 months. Postoperative dysphagia not present before surgery occurred in 4.7 per cent of patients. Eighty per cent of patients were medication-free following surgery. QOL scores for all participants increased significantly from 52.5 +/- 15.3 preoperatively to 72.0 +/- 14.9 postoperatively (P < 0.0001). Patients with atypical symptoms or typical symptoms alone showed significant mean QOL score increases from 48.3 +/- 17.6 preoperatively to 71 +/- 15.7 postoperatively (P < 0.0001) and from 55.7 +/- 12.6 to 72.8 +/- 14.4 (P < 0.0001), respectively. Laparoscopic Nissen fundoplication can effectively improve overall QOL for patients with GERD. Patients with atypical GERD symptoms can experience increases in QOL similar to those with only typical gastrointestinal symptoms.

Objective: In the fetal rabbit immediately prior to birth (day 30; 0.97 gestation), intragastric atropine suppresses upper gastrointestinal (GI) motility, indicating that cholinergic receptors are expressed and functional at birth. To explore the developmental timing of upper GI cholinergic receptor function, we assessed the effect of intragastric atropine administration in rabbit fetuses during the last 10% of gestation., Methods: Pregnant rabbits were studied at day 27, day 28 and day 29 of their normal 31-day gestation. In each litter, two fetuses were selected as study fetuses and two as control fetuses. Under ultrasound guidance, fluorescein and either atropine (0.04 microg/g fetal body weight) or normal saline were injected into the fetal stomach. Two hours after injection, fetuses were delivered and the small intestine was harvested. The per cent motility was calculated as the fluorescein travel distance, which was measured by ultraviolet light optical density, divided by the total small intestinal length., Results: Fetal body weight, small intestinal length and per cent motility increased from day 27 to day 29 (p < 0.01). There were no differences in fetal body weight and small intestinal length between atropine and control groups. Atropine significantly decreased per cent motility (versus control values) in fetuses at day 29 and day 28 (56.1 +/- 13.5 vs. 66.1 +/- 11.7% and 59.7 +/- 15.6 vs. 68.3 +/- 11.7%, respectively; p < 0.05), but not at day 27 (52.4 +/- 12.9 vs. 52.8 +/- 11.2%)., Conclusions: These results indicate that upper GI functional cholinergic receptors develop between 0.87 and 0.90 of rabbit gestation. Extrapolation to human development suggests that reduced GI motility in preterm human infants results, in part, from immature GI cholinergic receptors.

Background: Tracheal stenosis is a challenging surgical problem that can require reconstruction using autologous grafts or artificial stents. In this study, we evaluate the efficacy of Surgisis, a commercially available, biocompatible, acellular matrix, in the repair of a critical-size tracheal defect., Methods: A full-thickness defect (2 mm x 6 mm) was created in tracheal rings 4 through 6 in adult rats. A piece of 8-ply Surgisis (Cook; Bloomington, IN) was sutured to the edges of the defect with interrupted 8-0 polypropylene sutures. In control animals, the defect was closed primarily. The trachea was harvested at 4 weeks and prepared for histologic evaluation using conventional techniques. Cross-sectional area and perimeters were calculated using imaging software., Results: Tracheal defects without patch repair (n = 3) resulted in tracheal stenosis and immediate death. Animals that underwent Surgisis patch repair of tracheal defects (n = 10) tolerated the procedure well and had no audible stridor or evidence of respiratory distress. Eight of ten animals survived 4 weeks. The tracheal lumen was patent with no evidence of contracture or degradation of the Surgisis. Histologically, neovascularization of the Surgisis was noted with moderate inflammation. The surface of the Surgisis patch was covered ith a lining of ciliated epithelial cells., Conclusion: In the rodent model, Surgisis appears to be an efficacious method for the patch repair of partial circumferential tracheal defects. Surgisis appears to be a safe and promising means of facilitating neovascularization and tissue regeneration. The long-term use of Surgisis warrants further investigation.

Background: Robotic technology promises to have an important future in surgery, but few residency programs incorporate robotics into surgical training. We sought to compare the speed and accuracy with which junior residents could perform laparoscopic tasks using both a robotic surgical device (Zeus MicroWrist) and conventional laparoscopic instruments., Methods: Twelve residents performed exercises of progressive difficulty in an inanimate model using both the robot and conventional laparoscopy. Analysis of variance statistical analysis was used to compare task time and suturing accuracy scores., Results: Grasping and suturing exercises were performed significantly faster with conventional laparoscopic instruments than with the robot. However, no difference in task time was noted for intracorporeal knot tying. Accuracy scores for suturing were higher for the robot., Conclusions: Junior residents can be instructed easily and quickly in both robotic and conventional advanced laparoscopic skills. The utility of robotic surgical devices in resident training requires further investigation.

The July 2002 Case of the Month (COM). This 66-year-old Caucasian female presented with gradually increasing protrusion of her left eye over a one-year period. She complained of increased tearing and foreign body sensation. The physical examination revealed a visual acuity of 20/20, normal color testing, full vision field with motility of her left eye limited in lateral gaze. Pupils were round, symmetric, with no afferent pupillary defect noted. On external examination, her left eye was grossly proptotic with resistance to retropulsion. She had 4 mm proptosis of the left eye. Computed tomography and MR imaging demonstrated a left retro-orbital mass with gadolinium enhancement and focal remodeling of orbital bones. She underwent surgical resection of tumor with a diagnosis of solitary fibrous tumor, and postoperatively she was symptom free. The histopathological differential diagnoses of spindle cell neoplasms of the orbit are discussed. Five months after surgery, no evidence of tumor recurrence was seen on neuroimaging and her vision was 20/20.

Conjoined twins occur in approximately one of every 50,000 to 200,000 births. Atypical or parasitic conjoined twins result from the embryonic death of one twin, which leaves behind body parts vascularized by the primary twin. Omphalopagus refers to conjoined twins joined at the level of the umbilicus. The authors report a case of atypical omphalopagus involving an acardiac, acephalic, parasitic twin and a host twin with a large omphalocele, transposition of the great arteries, and aortic coarctation. The authors briefly review reported cases of parasitic omphalopagus and emphasize the role of intensive neonatal care, preoperative planning, and staged surgical intervention in the successful management of complicated variants., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Chronic wounds are associated with considerable morbidity and prolonged hospitalizations. The availability of recombinant growth factors and cytokines provides a new modality for treatment of recalcitrant wounds. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a growth protein for hematopietic cells, also enhances neutrophil and monocyte function and promotes keratinocyte proliferation. In three patients with inherited disorders associated with leukocyte dysfunction and non-healing wounds, topical application of GM-CSF resulted in complete wound closure within 1 to 4 weeks. A subcutaneous (s.c.) infusion pump for the local s.c. delivery of GM-CSF was also found to enhance healing. Local application of GM-CSF may thus promote wound closure in patients with impaired wound healing.

Background: Plasminogen activator inhibitor-1 (PAI-1) regulates fibrinolysis and has been reported to be an independent risk factor for ischemic cardiovascular events. This study describes the age-dependent development of spontaneous coronary arterial thrombi that are associated with evidence of subendocardial myocardial infarction in mice transgenic for human PAI-1., Methods and Results: We generated two independent transgenic mice founder lines that express a stable variant of active human PAI-1 under control of the murine preproendothelin-1 (mPPET-1) promoter. Backcrossed homozygous transgenic animals from founder line I had plasma PAI-1 levels of 23+/-12 ng/mL. PAI-1 transgenic animals younger than 4 months do not exhibit any evidence of arterial or venous thrombosis. Ninety percent of transgenic animals (n=10) older than 6 months developed spontaneous occlusions of typically multiple, penetrating coronary arteries, with histological evidence of subendocardial infarction identified in 50% of animals., Conclusions: This study shows that chronically elevated levels of PAI-1 are associated with age-dependent coronary arterial thrombosis in mice transgenic for human PAI-1. This is the first study of a murine model of coronary thrombosis that occurs in the absence of severe hypercholesterolemia or multiple genetic manipulations. These findings provide new evidence to support the hypothesis that PAI-1 excess contributes to the development of coronary arterial thrombosis.

Objective: At birth the newborn digestive tract must assume the responsibility of assimilating nutrients for survival. Immature gastrointestinal motility in the neonate may result in impaired feeding and nutrition. Newborn gastrointestinal motility development requires the expression and functional maturation of gastrointestinal receptors. To explore the timing of fetal responses to gastrointestinal cholinergic motility agents, we assessed the effect of the anticholinergic agent atropine in the late-gestation rabbit fetus., Methods: Seven pregnant New Zealand White rabbits were studied at day 30 of their normal 31-day gestation. In each litter, two fetuses were selected as study (n = 14) and two as control (n = 14). Under ultrasound guidance, a spinal needle was percutaneously inserted through the maternal uterus into the fetal stomach and 0.5 ml of gastric content was aspirated. Fluorescein, labelled with colored microspheres, and either atropine (0.04 microg/g fetal body weight) or normal saline were injected in a total volume of 0.5 ml. Two hours after injection, fetuses were delivered, the small intestine harvested, and the total small intestinal length and the distance the gastrointestinal fluorescein travelled were measured by ultraviolet light optical density. The fluorescein travelled distance and the per cent motility, defined as the length of fluorescein travelled divided by the total length of the small intestine, were calculated., Results: All fetuses survived the intragastric injection. Mean fetal body weight at delivery was 44.2 +/- 6.7 and 46.8 +/- 7.2 g in atropine and control fetuses, respectively. The fluorescein travelled distance (15.4 +/- 4.2 vs. 19.0 +/- 4.3 cm;. p < 0.01) and per cent motility (51.0 +/- 8.9 vs. 63.8 +/- 11.7%; p < 0.01) of atropine-treated fetuses were significantly lower than those of control fetuses., Conclusion: Fetal upper gastrointestinal motility is suppressed in response to intragastric atropine. These results indicate that fetal gastrointestinal cholinergic receptors are expressed and functional in the term (0.97 gestation) rabbit fetus. In utero administration of cholinergic agonists/antagonists may potentially modulate fetal gastrointestinal motility and absorption of amniotic fluid water and solutes.

Total parenteral nutrition (TPN) has made survival beyond infancy possible for many infants who have sustained small intestinal loss as a result of gastroschisis or omphalocele. The length and quality of life in these patients have often been limited by the development of late sequelae secondary both to the protracted use of TPN and the long-term complications of a shortened gut. This study was undertaken to determine what factors influence the morbidity and mortality of short-bowel syndrome (SBS) due to gastroschisis or omphalocele. A retrospective chart review of 850 infants who received TPN from January 1977 through December 1999 was carried out. All infants were treated at one academic medical center; those who had received > or =3 months of TPN were further segregated and their diagnosis, surgical procedures, length of bowel, ability to wean from TPN, follow-up weight and height, and developmental progress were recorded. Seventeen children were identified with SBS and either gastroschisis or omphalocele. Tight primary or secondary closure of the abdominal wall was believed to be a major cause of bowel necrosis and SBS in at least ten of the 17 patients. Overall survival was 76 per cent (13/17); survival was correlated with length of remaining bowel and was 86 per cent in patients having more than 15 cm of small bowel remaining but only 33 per cent in patients with less than 15 cm of small bowel remaining (P = 0.05). A longer length of residual small bowel resulted in a significantly shorter duration of TPN with a mean duration of 1.0 year for survivors having >38 cm and 10.0 years for survivors with <38 cm of bowel remaining (P = 0.03). Hepatic dysfunction with progressive failure resulting from TPN was related to death in three of the four nonsurvivors. The presence or absence of an ileocecal valve appeared unrelated both to the success of TPN weaning and to the length of time on TPN (P > 0.2). Eight of the 13 survivors have no ileocecal valve; five have undergone >50 per cent colonic resection. Nine of the survivors have adapted to enteral feedings (mean 36 +/- 60 months) during which time weaning from TPN occurred. The mean age of survivors is 7.9 +/- 5.1 years. Near-normal weights (defined as exceeding the fifth percentile for weight) were achieved for 92 per cent of the patients (12/13) with 46 per cent of the patients (6/13) exceeding the 50th percentile. Near-normal heights (exceeding the fifth percentile) were achieved for 77 per cent of the patients (10/13) with 15 per cent of the patients (2/13) exceeding the 50th percentile. Quality of life was measured on the basis of return to public school: nine of ten school-age survivors attend school and eight are normal without signs of developmental delay. Tight abdominal closure of gastroschisis or omphalocele may cause bowel necrosis and SBS. TPN has improved the long-term survival and quality of life in infants with SBS.

Fetal wounds pass from scarless repair to healing with scar formation during gestation. This transition depends on both the size of the wound and the gestational age of the fetus. This study defines the transition period in the fetal rat model and provides new insight into scarless collagen wound architecture by using confocal microscopy. A total of 16 pregnant Sprague-Dawley rats were operated on. Open full-thickness wounds, 2 mm in diameter, were created on fetal rats at gestational ages 14.5 days (E14; n = 10), 16.5 days (E16; n = 42), and 18.5 days (E18; n = 42) (term = 21.5 days). Wounds were harvested at 24 (n = 18 per gestational age) and 72 hours (n = 24 per gestational age). Skin at identical gestational ages to wound harvest was used for controls. The wounds were fixed and stained with hematoxylin and eosin, antibody to type I collagen, and Sirius red for confocal microscopic evaluation. No E14 rat fetuses survived to wound harvest. Wounds created on E16 fetal rats healed completely and without scarring. E16 fetal rat hair follicle formation and collagen architecture was similar to that of normal, nonwounded skin. Wounds created on E18 fetal rats demonstrated slower healing; only 50 percent were completely healed at 72 hours compared with 100 percent of the E16 fetal rat wounds at 72 hours. Furthermore, the E18 wounds healed with collagen scar formation and without hair follicle formation. Confocal microscopy demonstrated that the collagen fibers were thin and arranged in a wispy pattern in E16 fetal rat wounds and in nonwounded dermis. E18 fetal rat wounds had thickened collagen fibers with large interfiber distances. Two-millimeter excisional E16 fetal rat wounds heal without scar formation and with regeneration of normal dermal and epidermal appendage architecture. E18 fetal rat wounds heal in a pattern similar to that of adult cutaneous wounds, with scar formation and absence of epidermal appendages. Confocal microscopy more clearly defined the dermal architecture in normal skin, scarless wounds, and scars. These data further define the transition period in the fetal rat wound model, which promises to be an effective system for the study of in vivo scarless wound healing.

Purpose: The aim of this study was to survey graduates of a university general surgical residency training program to determine factors that influenced their selection of a specialty field., Methods: A 39-item questionnaire was mailed to 86 graduates of a university general surgery program who matriculated from 1975 to 1989. The impact of lifestyle, technology, clinical opportunity, and mentor guidance in the residents' selection of a specialty field and eventual clinical practice was assessed. Results were analyzed using Fisher's Exact test with significance determined at P less than.05., Results: The response rate was 65% (56 of 86). Eighty percent of respondents identified the most important aspect influencing their choice of specialty was interest in that field; additional factors included perception of prestige, presence of clinical opportunity, mentor influence, and family priorities. Sixty-six percent of respondents chose the same career as their mentor, attributing this to the mentor's skill (n = 36, 68%), achievements (n = 35, 66%), and verbal recommendations about their specialty field (n = 24, 45%), p < 0.05., Conclusions: Surgical residents use many criteria in selecting a field of specialty with mentor guidance an important component. Knowledge of these influential areas should help training programs offer appropriate career guidance. J Pediatr Surg 36:1802-1804., (Copyright 2001 by W.B. Saunders Company.)

Purpose: Transforming growth factor beta (TGF-beta) bioactivity has been implicated as a potential regulator of the transition from scarless healing to scar formation in fetal wounds. Decorin is an extracellular matrix proteoglycan that regulates TGF-beta bioactivity and assists in collagen fibrillogenesis. To determine its role in scarless repair, the authors examined decorin expression in fetal fibroblasts, skin, and wounds., Methods: A single, full-thickness, 2-mm open wound was created on the dorsal surface of fetal rats at 16.5 days (E16) and 18.5 days (E18) gestational age (term, 21.5 days [E21]). Wounds were harvested at 24 and 72 hours (n = 12 wounds per time-point). Nonwounded fetal skin at E17, E19, and E21 was harvested for analysis of decorin expression during skin development and as controls for wounds. In addition, fetal (E14, E18) and adult dermal fibroblasts were cultured for in vitro analysis. Reduced-cycle, specific primer, reverse transcriptase polymerase chain reaction was performed to quantitate decorin expression., Results: Decorin expression increased rapidly with increasing gestational age in both fetal fibroblasts and skin. Expression was increased 22-fold in E18 fibroblasts (P <.002) and 300-fold in adult fibroblasts (P <.001) compared with E14 fibroblasts. In skin, expression increased 74% (P <.01) during the fetal wound healing transition period between E17 and E19. However, in E16 wounds (scarless), decorin expression decreased 59% (P <.006) at 24 hours and 45% (P <.02) at 72 hours. Decorin expression did not change in E18 (scar) wounds at 24 and 72 hours (P >.05)., Conclusions: Early gestation fetal fibroblasts and fetal skin express decorin at lower levels than late gestation fetal and adult fibroblasts and skin. Decorin expression is down-regulated in scarless (E16) compared with scar (E18) wounds. Thus, increased decorin expression is associated with both skin development and scar formation. Conversely, decreased decorin expression is associated with scarless repair., (Copyright 2001 by W.B. Saunders Company.)

Background/purpose: Although gene and protein transfer may potentiate the cure of genetic disease, current strategies involving fetal gene therapy remain nonfocal and confounded by the lack of imaging techniques and in vivo markers for precise gene transfer., Methods: Fourteen white Leghorn chick eggs were incubated for 48 to 56 hours postfertilization until they reached stages 11 to 16, about 3 mm in size. In 7 chick embryos, a glass needle was placed at the midbrain/hindbrain level and 1 x 10(7) pfu of an adenovirus containing the green fluorescent protein (GFP) reporter gene was injected into the lateral head. In another 7 chicken embryos, colored agarose beads coated with Sonic hedgehog (Shh) protein were implanted at the level of the hindbrain under direct microscopy. The eggs were then sealed, incubated at 37 degrees C for 24 hours, and reimaged using fluorescent microscopy and confocal laser microscopy., Results: At 24 hours postinjection, all embryos were alive and were imaged in vivo. Fluorescent microscopic imaging showed green fluorescence in the region of the injection site in all the embryos. In embryos that underwent bead placement, the beads were visualized under microscopy in the lateral hindbrain of all embryos, and the presence of the Shh protein was confirmed using fluorescein isothiocyanate (FITC)-conjugated secondary antibody., Conclusions: This study shows that embryonic 3-mm chick embryos survive adenoviral transduction or agarose bead implantation in a focal manner in vivo and that this delivery results in production of imageable levels of protein. This may be used in mammalian systems, including humans, to introduce genes and proteins., (Copyright 2001 by W.B. Saunders Company.)

Background/purpose: Reports of clinical trials often lack adequate descriptions of design and analysis; recent attention has focused on improving this omission so readers can properly assess the strength of the findings and draw their own conclusions. Similar analysis of study design and methodologic standards associated with quality reporting has not been carried out for pediatric surgery journals., Methods: All studies (n = 642) published in 1998 in Journal of Pediatric Surgery (JPS) and Pediatric Surgery International (PSI), were reviewed for demographic data and study design. The frequency of reporting of 11 basic elements of design and analysis was evaluated in randomized clinical trials (RCT), nonrandomized clinical trials (NRCT), and retrospective cohorts (RC) from JPS by consensus of 2 assessors., Results: Of the 642 studies, 17% of articles (111 of 642) were classified as clinical studies. Sixty-three were comparative studies and consisted of RC (n = 48), NRCT (n = 12), and RCT (n = 3). Two-thirds of articles published were either case reports or case series (431 of 642), and 16% were basic science articles. Demographic analysis showed a wide range of topics addressed, 4 authors per article, and multiple country of origin of authors. More than 66% of all RCT in JPS reported on eligibility criteria, admission before allocation, random allocation, method of randomization, patients' blindness to treatment, treatment complications, statistical analyses, statistical methods, loss to follow-up, and statistical methods; 2 elements of design and analysis, however, were poorly reported: blind assessment of outcome (33%) and power (17%)., Conclusions: There were few randomized, controlled trials in pediatric surgery journals, and further attention should be given to evaluate the causal factors. Nine elements of quality reporting were well reported; however, 2 others were poorly reported; this may improve if editors of pediatric surgical journals provide authors with guidelines on how to report clinical trial design and analysis., (Copyright 2001 by W.B. Saunders Company.)

We present an analysis of the A0(+)(6(3)P(1))-->X0(+)(6(1)S(0)) bound-bound and bound-free fluorescence spectrum, and of the A0(+)(6(3)P(1))<--X0(+)(6(1)S(0)) and B1(6(3)P(1))<--X0(+)(6(1)S(0)) bound-bound excitation spectrum of the HgKr van der Waals molecule. The A-->X fluorescence spectrum, which was observed for the first time, as well as the excitation spectra were recorded using a pulsed supersonic molecular beam crossed with a pulsed dye laser beam. An analysis of the A(v')<--X(v"), B(v')<--X(v"), and A(v'=8)-->X(v") bound-bound bands indicates that a Morse function combined with a long-range approximation represents the interatomic potential energy curve of the A, B, and X states below the dissociation limit. In the simulation of the A(v'=8)-->X bound-free spectrum the Morse, Lennard-Jones (n-6), and Maitland-Smith (n(0), n(1)) functions were tested, and the Maitland-Smith (11.39, 10.50) potential was found to be a good representation of the repulsive part of the X-state PE curve above the dissociation limit, over the internuclear separation range R=2.85-3.55 Å. The spectroscopic characteristics for the A, B, and X states obtained in this work are compared with other available experimental and theoretical results. Copyright 2001 Academic Press.

Stretch-activated ion channels have been identified as transducers of mechanoelectric coupling in the heart, where they may play a role in arrhythmogenesis. The role of the cytoskeleton in ion channel control has been a topic of recent study and the transmission of mechanical stresses to stretch-activated channels by cytoskeletal attachment has been hypothesized. We studied the arrhythmogenic effects of stretch in 16 Langendorff-perfused rabbit hearts in which we pharmacologically manipulated the microtubular network of the cardiac myocytes. Group 1 (n=5) was treated with colchicine, which depolymerizes microtubules, and Group 2 (n=6) was treated with taxol, which polymerizes microtubules. Stretch-induced arrhythmias were produced by transiently increasing the volume of a fluid-filled left ventricular balloon with a volume pump driven by a computer-controlled stepper motor. Electrical events were recorded by a contact electrode which provided high-fidelity recordings of monophasic action potentials and stretch-induced depolarizations. The probability of eliciting a stretch-induced arrhythmia increased (0.22+/-0.11 to 0.62+/-0.19, p=0.001) in hearts treated with taxol (5 microM), whereas hearts treated with colchicine (100 microM) showed no statistically significant change. We conclude that proliferation of microtubules increased the arrhythmogenic effect of transient left ventricle diastolic stretch. This result indicates a possible mode of arrhythmogenesis in chemotherapeutic patients and patients exhibiting uncompensated ventricular hypertrophy. The data would indicate that the cytoskeleton represents a possible target for antiarrhythmic therapies.

Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation (Tx) can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal Tx include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Because a critical shortage of donor organs exists, waiting times for intestinal Tx are prolonged. Therefore, it is essential that children with life-threatening complications of intestinal failure and parenteral nutrition therapy be identified comparatively early, i.e. in time to receive suitable donor organs before they become critically ill. Children with liver dysfunction should be considered for isolated intestinal Tx before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present. Death resulting from complications of liver failure is especially common during the wait for a combined liver and intestinal transplant, and survival following combined liver and intestinal Tx is probably lower than following an isolated intestinal transplant. The incidence of morbidity and mortality following intestinal Tx is greater than that following liver or kidney Tx, but long-term survival following intestinal Tx is now at least 50-60%. It is probable that outcomes shall improve in the future with continued refinements in operative technique and post-operative management, including immunosuppression.

Low doses of diquat cause massive liver necrosis and death of selenium-deficient rats within a few hours. Protection against this injury by selenium correlates with the presence of selenoprotein P, an extracellular selenoprotein that associates with endothelial cells. Selenium-deficient rats were injected with diquat (10 mg/kg) and their livers were removed for light and electron microscopy at times up to 120 minutes after injection. Selenium-replete animals were studied before and 120 minutes after the same dose of diquat. With selenium deficiency, diquat caused injury to centrilobular endothelial cells. This injury was evident 20 minutes after diquat injection and progressed to cell loss at 60 minutes after diquat injection. At 120 minutes, endothelial cells were virtually absent from the centrilobular regions and hepatocytes in those areas were undergoing necrosis. Portal and midzonal areas remained normal in selenium-deficient livers, as did the entire liver lobule of selenium-replete rats. These findings indicate that the initial liver lesion in selenium-deficient rats given diquat is injury of the endothelial cells in the centrilobular region. After detachment of the endothelial cells, centrilobular hepatocytes undergo necrosis. We postulate that selenoprotein P protects the centrilobular endothelial cells against injury by oxidant molecules that result from diquat administration.

Purpose: Renal failure occurs in children with moderate frequency. Surgical aspects of establishing and maintaining dialysis access in small infants are exceptionally challenging. The purpose of this review is to evaluate the authors' experience with dialysis access for infants less than 10 kg, particularly with respect to the surgical care required., Methods: A retrospective review was conducted between 1991 and 1999 of all pediatric dialysis patients weighing 10 kg or less (n = 29). Age at start of dialysis, duration of dialysis, modes of dialysis, and complications specific to peritoneal (PD) and hemodialysis (HD) were examined., Results: The mean age at start of dialysis was 10.4 months and continued for an average duration of 16.3 months. Seventy-two percent of all patients required both modes of dialysis. HD and PD duration averaged 7.8 and 10.5 months, respectively. Catheter durability was 3.1 and 4.5 months per catheter for HD and PD, respectively. There was no significant difference in complications when comparing HD and PD. Patients who weighed 5 to 10 kg had significantly longer PD catheter durability than patients 0 to 5 kg (P = .001). Forty-one percent of patients terminated dialysis after transplantation, whereas 24% died awaiting transplantation., Conclusion: Despite a large number of operations required, infants less than 10 kg can be bridged successfully, by surgical intervention and subsequent dialysis, to transplantation.

Extracorporeal membrane oxygenation (ECMO) has been used for pediatric cardiac support in settings of expected mortality due to severe myocardial dysfunction. We reviewed the records of 34 children (<18 years) placed on ECMO between March 1995 and May 1999. Demographic, cardiac, noncardiac, and outcome variables were recorded. Data were subjected to univariate analysis to define predictors of outcome. Eighteen patients were placed on ECMO after cardiac surgery (Group A); seven of 18 were weaned off ECMO, and four survived to discharge (22%). Thirteen patients were placed on ECMO as a bridge to cardiac transplantation (Group B), six of 13 received a heart transplant, one recovered spontaneously, and six survived to discharge (46%). Three patients were placed on ECMO for failed cardiac transplantation while awaiting a second transplant (Group C); one recovered graft function, two received a second heart transplant, and two of three survived (66%). The primary cause of death was multiorgan system failure (68%). Group A patients supported on ECMO for more than 6 days did not survive. Mediastinal bleeding complications and renal failure requiring dialysis were associated with nonsurvival. We conclude that ECMO as a bridge to cardiac transplant was more successful than ECMO support after cardiotomy. Mediastinal bleeding and renal failure were associated with poor outcome. Recovery of cardiac function occurred within the first week of ECMO support if at all. Longer support did not result in survival without transplantation.

Background: Conflicting reports exist regarding the permanence of improved gastric emptying (GE) after fundoplication for gastroesophageal reflux in children., Methods: Changes in gastric volume (GV) and GE of a radiolabeled mixed meal induced by a Nissen fundoplication (NF) were compared with those with a NF plus pyloroplasty (NF + P). GE was measured preoperatively, 15 and 30 days postoperation, in 24 Sprague-Dawley rats; 12 had NF alone, and 12 had NF + P Results were expressed as percent gastric retention at 90 minutes (GR90). GV was measured at the same time periods in 20 additional rats., Results: NF rats had enhanced GE with reduction of preoperative GR90 from 37.6% to 23.7% at 15 days (P < .05); however, at 30 days the GR90 increased to 34.3%. NF + P rats had enhanced GE with reduction in GR90 from 37.2% to 20.8% at 15 days (P< .05), which persisted at 30 days (20.4%). Mean GV decreased from (1.36 mL/100 g body weight) preoperation to 0.86 at 15 days (P< .05) at 15 days in the NF group, and returned to 1.29 at 30 days. Mean GV decreased from 1.36 to 0.91 at 15 days in the NF + P rats and persisted at 0.90 at 30 days., Conclusion: In the rat model, NF enhances GE transiently, whereas NF + P produces long-term enhancement of GE.

Objective: To compare the effects of 35% hepatic cryoablation with a similar degree of radiofrequency ablation (RFA) on lung inflammation, nuclear factor kappaB (NF-kappaB) activation, and production of NF-kappaB dependent cytokines., Summary Background Data: Multisystem injury, including acute lung injury, is a severe complication associated with hepatic cryoablation of 30% to 35% or more of liver parenchyma, but this complication has not been reported with RFA., Methods: Sprague-Dawley rats underwent 35% hepatic cryoablation or RFA and were killed at 1, 2, and 6 hours. Liver and lung tissue were freeze-clamped for measurement of NF-kappaB activation, which was detected by electrophoretic mobility shift assay. Serum concentrations of tumor necrosis factor alpha and macrophage inflammatory protein 2 were measured by enzyme-linked immunosorbent assay. Histologic studies of pulmonary tissue and electron microscopy of ablated liver tissue were compared among treatment groups., Results: Histologic lung sections after cryoablation showed multiple foci of perivenular inflammation, with activated lymphocytes, foamy macrophages, and neutrophils. In animals undergoing RFA, inflammatory foci were not present. NF-kappaB activation was detected at 1 hour in both liver and lung tissue samples of animals undergoing cryoablation but not after RFA, and serum cytokine levels were significantly elevated in cryoablation versus RFA animals. Electron microscopy of cryoablation-treated liver tissue demonstrated disruption of the hepatocyte plasma membrane with extension of intact hepatocyte organelles into the space of Disse; RFA-treated liver tissue demonstrated coagulative destruction of hepatocyte organelles within an intact plasma membrane. To determine the stimulus for systemic inflammation, rats treated with cryoablation had either immediate resection of the ablated segment or delayed resection after a 15-minute thawing interval. Immediate resection of the cryoablated liver tissue prevented NF-kappaB activation and lung injury; however, pulmonary inflammatory changes were present when as little as a 15-minute thaw interval preceded hepatic resection., Conclusions: Hepatic cryoablation, but not RFA, induces NF-kappaB activation in the nonablated liver and lung and is associated with acute lung injury. Lung inflammation is associated with the thawing phase of cryoablation and may be related to soluble mediator(s) released from the cryoablated tissue. These findings correlate the clinical observation of an increased incidence of multisystem injury, including adult respiratory distress syndrome (ARDS), after cryoablation but not RFA.

Objective: To review the surgical experience with pectus excavatum chest deformities at UCLA Medical Center during a 30-year period., Background: Pectus excavatum is a relatively common malformation that is often symptomatic; however, children's physicians often do not refer patients for surgical correction., Methods: Hospital records from 375 patients who underwent repair of pectus excavatum deformities between 1969 and 1999 were reviewed. Decrease in stamina and endurance during exercise was reported by 67%; 32% had frequent respiratory infections, 8% had chest pain, and 7% had asthma. The mean pectus severity score (width of chest divided by distance between posterior surface of sternum and anterior surface of spine) was 4.65 (normal chest = 2.56). All patients had marked cardiac deviation into the left chest. Repair was performed with subperiosteal resection of the abnormal cartilages, transverse wedge osteotomy of the anterior sternum, and internal support with a steel strut for 6 months. Repair was performed on 177 children before age 11 years; 38 adults with severe symptoms underwent repair., Results: The mean hospital stay was 3.1 days. With a mean follow-up of 12.6 years, all patients with preoperative respiratory symptoms, exercise limitation, and chest pain experienced improvement. Vital capacity increased 11% (mean) within 9 months in 35 patients evaluated. There were no deaths. Complications included hypertrophic scar formation (35), atelectasis (12), pleural effusion (13), recurrent sternal depression (5), and pericarditis (3). More than 97% had a very good or excellent result., Conclusion: Pectus excavatum deformities can be repaired with a low rate of complications, a short hospital stay, and excellent long-term physiologic and cosmetic results.

Objectives: To study changes in PaCO2 and PaO2 during intratracheal pulmonary ventilation (ITPV) and hybrid intratracheal pulmonary ventilation (h-ITPV) compared with conventional mechanical ventilation (CMV) in a rabbit model of respiratory failure, and to define the technique of h-ITPV that combines conventional mechanical ventilation and ITPV., Design: Prospective, interventional study., Subjects: Twelve adult New Zealand White rabbits., Interventions: Surfactant deficiency was induced by saline lavage, and rabbits were randomized to either ITPV or h-ITPV. The study consisted of four phases: phase 0, CMV after saline lavage, ventilator rate 30 breaths/min; phase I, ITPV or h-ITPV initiated at the same pressure and rate as in phase 0; phase II, ITPV or 1.0 L/min h-ITPV bias flow, with peak inspiratory pressure (PIP) decreased and ventilator rate increased to achieve the lowest tidal volume while maintaining adequate gas exchange; and phase III, animals returned to CMV., Measurements and Main Results: In phase I, no difference in PaCO2 was observed between ITPV, h-ITPV, or CMV. There was a decrease in PaO2 when switching from CMV to ITPV but not to h-ITPV. In phase II, it was possible to decrease PIP (average of 37% for ITPV and 36% for h-ITPV) and tidal volume (average of 64% for ITPV and 53% for h-ITPV) without compromising gas exchange (p < .05). Oxygenation tended to improve from phase 0 to the end of phase II. In phase III, PaCO2 increased (average of 71% for ITPV and 79% for h-ITPV) and pH decreased (p < .05). Normocapnia was achieved using significantly higher PIP and tidal volume, compared with phase 0 (p < .05)., Conclusions: ITPV and h-ITPV can effectively ventilate and oxygenate rabbits with surfactant-deficient lungs at tidal volumes and therefore pressures lower than required with CMV. Maximum benefit appears to occur at high ventilator rates. These findings suggest that both modes of ventilation may represent powerful new tools in the management of patients with acute respiratory failure. (Crit Care Med 2000; 28:774-781)

Purpose: Stage IV-S neuroblastoma is a metastatic disease associated with spontaneous regression and good survival, but 10% to 20% of infants die from early complications. The purpose of this study was to evaluate outcome and prognostic factors in infants with stage IV-S neuroblastoma treated prospectively with supportive care only or, in symptomatic patients, with low-dose cytotoxic therapy., Patients and Methods: Eighty eligible infants were studied for response and survival with supportive care or, for symptomatic patients, cyclophosphamide 5 mg/kg/d for 5 days with or without hepatic radiation of 4.5 Gy over 3 days. Staging was reviewed centrally, and MYCN gene copy number, Shimada histopathologic classification, serum ferritin levels, and bone marrow immunocytology were determined., Results: Stage IV-S and International Neuroblastoma Staging System stage 4S were 98% concordant. MYCN was not amplified in any of the tumors tested (n = 58), and Shimada histopathologic classification was favorable in 96% (n = 68/71). The 5-year event-free survival (EFS) rate for all infants was 86% and the survival rate was 92%. Supportive care was the only treatment provided for 44 (55%) of 80 infants, and their 5-year survival rate was 100%, compared with 81% survival for those requiring cytotoxic therapy for symptoms (P =.005). Five of six deaths were in infants younger than 2 months of age at diagnosis and were due to complications of extensive abdominal involvement with respiratory compromise or disseminated intravascular coagulation. Although age

Purpose: To determine prospectively whether surgery alone is sufficient therapy for Evans stages I and II neuroblastoma and to define biologic and clinical features having prognostic potential for this group., Patients and Methods: Between June 1989 and August 1995, 374 eligible children (age range, 0 to 18 years) with newly diagnosed stage I (n = 141) and stage II (n = 233) neuroblastoma were registered onto Children's Cancer Group trial 3881. Surgical resection was the only primary therapy except in cases with spinal cord compression, where radiation therapy was allowed. Event-free survival (EFS) and overall survival (OS) were analyzed by life-table methods according to clinical and biologic features., Results: EFS and OS (mean +/- SE) for all stage I patients were 93% +/- 3.0% and 99% +/- 1.0%, respectively, compared with 81% +/- 4.0% and 98% +/- 2. 0%, respectively, for stage II patients. The significantly higher recurrence rate among stage II patients was managed successfully in 38 of 43 children with either surgery or multimodality treatment. There was one death among stage I patients and six among stage II. For stage II patients tumor MYCN gene amplication, unfavorable histopathology, an age greater than 2 years, and positive lymph nodes predicted a lower OS (P <.05)., Conclusion: Children with stages I and II neuroblastoma have 98% survival with surgery alone as primary therapy. Supplemental treatment was necessary in only 10% of stage I patients and 20% of stage II patients. In children with localized neuroblastoma, a subset of patients that are at higher risk for death can be defined as those with stage II disease who have tumor MYCN amplification or who are >/= 2 years of age with either unfavorable histopathology or positive lymph nodes.

Background: We evaluated whether a humanized anti-CD154 antibody (hu5c8) prolongs primate cardiac allograft survival., Methods: Heterotopic cardiac allografts were performed between MHC class II-mismatched cynomolgus monkeys. Survival was compared between groups treated with a perioperative dosing of hu5c8 (group 1; n=6), sustained dosing with hu5c8 (group 2; n=3), and control regimens (n=4). All recipients received fresh donor-specific transfusions during surgery., Results: Median graft survival was 49 days (range 14 to 56) in group 1 and 106 days (range 56 to 245) in group 2, compared with 5 days (range 5 to 6) for controls (P<0.05 for all comparisons). Lymphocytic infiltrates were often present in hu5c8-treated grafts with stable contractility. Donor-specific mixed lymphocyte reaction was generally preserved. Vasculitis and cellular intimal proliferation were prevalent in rejected grafts but occurred later and were less prevalent in group 2., Conclusions: Anti-CD154 antibody markedly prolongs the survival of cardiac allografts in primates and is well tolerated. Sustained dosing with hu5c8 yielded improved survival and may be associated with a lower incidence of vascular pathology. We conclude that hu5c8 therapy is an effective approach for inhibiting acute cardiac allograft rejection in primates.

Background: Vascular smooth muscle cell growth factors are postulated to contribute to cardiac allograft vasculopathy (CAV). Few data quantitatively address the timing, location, or stimuli for growth factor expression and relationship to CAV., Methods and Results: Acidic fibroblast growth factor (aFGF) mRNA expression was determined in serial endomyocardial biopsies during the first year after transplantation. Patients with high levels of aFGF mRNA and elevations after the early posttransplant period had significantly more severe CAV than patients with low aFGF and no late elevations., Conclusions: Parenchymal aFGF expression varies between patients and in the same patient over time and correlates with development of CAV.

Background: Esophageal replacement is associated with significant morbidity that may lead to operative interventions. This study reviews the management and outcome of children who underwent reoperation after esophageal replacement., Methods: Eighteen patients who underwent esophageal replacement from 1985 to 1997 were reviewed retrospectively. Ten patients underwent reoperation. Patient management, perioperative morbidity, and the dietary intake at follow-up were recorded for each patient., Results: Of the reoperated patients, 7 had esophageal atresia, 2 had caustic ingestion, and 1 had achalasia. Nine patients received a colon interposition, and 1 received a reverse gastric tube as the initial esophageal replacement. Seven patients required revision of the anastomoses. Three patients required complex esophageal reconstruction: 1 underwent gastric transposition, 1 underwent free jejunal graft, and 1 underwent gastric transposition combined with free jejunal graft. Seven patients were eating well at follow-up. Two patients still required partial gastrostomy tube feeding. One patient died 6 months postoperatively from aspiration pneumonia., Conclusions: Esophageal replacement continues to be a challenging operation associated with significant complications. Most reoperative procedures were directed toward strictures and persistent fistulae. Complete graft failure can be managed by gastric transposition or free jejunal graft. Despite the perioperative morbidity, most patients have good functional outcome.

Background/purpose: Postoperative ileus after abdominal operations is thought to be related to the degree of surgical trauma, and it has been shown that the simple act of opening the peritoneum can decrease gastrointestinal motility. Accordingly, some investigators have shown a reduction in the duration of postoperative ileus after laparoscopic procedures. It is not clear, however, if this reduction is secondary to less manipulation of the viscera or to the lack of an abdominal incision. The aim of this study was to determine the effect of intraabdominal insufflation with CO2 on postoperative gastrointestinal transit., Methods: Twenty-eight male mice weighing between 25 and 30 g were divided randomly into 4 groups: Control (unoperated), Incision (conventional laparotomy), Cecal (laparotomy plus cecal manipulation), and Insufflation (abdominal insufflation with CO2). Postoperative gastrointestinal motility was assessed by weighing total fecal output over the first 15 postoperative hours., Results: Fecal pellet output over 15 hours in the untreated control group was 1.20 +/- 0.12 g. In mice subjected to peritoneal incision alone, fecal pellet output was significantly decreased to 0.82 +/- 0.11 g (P < .05). However, in mice subjected to abdominal insufflation with CO2, fecal pellet output was not significantly different from untreated controls (1.2 +/- 0.05 g; not significant). Fecal pellet output was markedly reduced by incision combined with cecal manipulation (0.24 +/- 0.02 g, P < .01)., Conclusions: The current study findings show that abdominal insufflation, in a procedure similar to that used during laparoscopic surgery, had no measurable effect on gastrointestinal transit in awake mice. This suggests that the lack of an abdominal incision can contribute to a reduced postoperative ileus after abdominal surgery.

The survival of infants with tracheoesophageal fistula was stratified by David J. Waterston et al. in 1962. This classification has been used as a guide to direct the timing of operative intervention in these infants. This study examines the current applicability of this classification system. The hospital records of 64 infants with esophageal atresia and/or tracheoesophageal fistula were reviewed. The survival rate was analyzed as a function of the infants' risk stratification, birth weight, and additional anomalies. Twenty-three infants were in Waterston Group A, 20 infants in Group B, and 21 infants in Group C. The survival of all infants was 81 per cent. Six infants died after recognition of severe anomalies and withdrawal of care, four infants died of cardiopulmonary arrest, and two infants died of sepsis. The survival of infants in both Groups A and B was 100 per cent, in contrast to 43 per cent survival in Group C. Only infants who weighed <1800 g or had severe additional anomalies were at risk of dying. Therefore, the classification of infants with esophageal atresia and/or tracheoesophageal fistula may be simplified by combining Waterston's Groups A and B into a single risk stratum.

We compared different hybrid mode ITPV (h-ITPV) flow rates, and h-ITPV with intratracheal pulmonary ventilation (ITPV) with respect to CO2 clearance and oxygenation. Surfactant deficiency was induced in six adult rabbits with saline lavage. The study consisted of three phases. Phase 0: Stabilization on conventional mechanical ventilation (CMV). Phase I: Bias flow initiated at same pressure and respiratory rate as Phase 0. Flow rates of 25%, 50%, 75% h-ITPV, and ITPV were initiated. Animals were transitioned from CMV to 25% h-ITPV proceeding sequentially to ITPV or vice versa. Phase II: Animals were returned to CMV. Statistical analysis included the two-way analysis of variance (ANOVA) and repeated measures ANOVA with Tuckey's test. No difference in PaCO2 was observed among all h-ITPV flow rates or between h-ITPV and ITPV. After bias flow was introduced (transition from Phase 0 to Phase I), PaCO2 decreased by 37%. PaCO2 increased by 119% during Phase II. Oxygenation improved in all animals, particularly in those transitioned to 25% h-ITPV and proceeding to ITPV. No difference in CO2 clearance between ITPV and h-ITPV was observed. Even at low bias flows, excellent CO2 clearance was achieved. Oxygenation was superior when animals were transitioned from CMV to h-ITPV. Hybrid-ITPV offers some advantages over ITPV and may represent a powerful tool in the management of acute respiratory distress syndrome (ARDS).

Background/purpose: It has been proposed that preterm and prelabor cesarean section may improve the outcome of infants with gastroschisis. The purpose of this study is to examine the impact of gestation and delivery method on infants with gastroschisis., Methods: The medical records of 60 infants with gastroschisis treated at a tertiary care center from 1985 through 1995 were reviewed retrospectively. The gestational age, the mode of delivery, the type of operative repair, and the length of hospital stay were recorded for each patient., Results: Infants born vaginally were more likely to require silo stage repair than those delivered by cesarean section (21 of 29 v. 11 of 31, P<.01). Infants born vaginally also had longer hospital stay than those delivered by cesarean section (53 v. 39 days, P = .19). Infants born before 33 weeks' of gestation stayed longer in the hospital than those born after 33 weeks. After 33 weeks' gestation, infants had similar hospital stay regardless of the gestational age., Conclusions: Cesarean section delivery was beneficial for infants with gastroschisis. Preterm delivery did not shorten the length of hospital stay. The role of elective cesarean section delivery at term should be considered for infants with gastroschisis diagnosed antenatally.

Inflammatory myofibroblastic tumours (IMTs) or inflammatory pseudo-tumours are uncommon lesions of unknown aetiology. The majority of the cases are reported in the lungs of young patients. Extra-pulmonary anatomic locations include the abdomen and pelvis, but rare cases have been described in the breast. We describe an IMT in an 86-year-old female, presenting as a well-circumscribed palpable mass in the left breast. Histologically the remarkable feature was the presence of giant vacuolated cells intermixed with spindle cells and a prominent plasma cell infiltrate immersed in a fibrous hyalinized stroma. Immunohistochemical and electron microscopy studies demonstrated the myofibroblastic nature of the giant vacuolated cells and the spindle cells, and the polyclonal nature of the plasma cells. The morphologic and immunohistochemical findings supported the diagnosis of IMT. The biological behaviour of IMT in this age group is unknown and surgical excision with close mammographic follow-up is considered to be appropriate treatment for this lesion in the breast.

Purpose: The goal of this study was to determine the incidence of metastatic sites in neuroblastoma and the extent to which metastatic sites correlate with age, tumor biology, and survival., Patients and Methods: All 648 patients with stage IV and IVS neuroblastoma registered on Children's Cancer Group protocols 3881 and 3891 were analyzed. Metastatic site data were provided by treating institutions and reviewed in patients with central nervous system (CNS), intracranial, lung, or "other" metastases., Results: The incidence of metastatic sites at diagnosis was 70.5% in bone marrow, 55.7% in bone, 30.9% in lymph nodes, 29.6% in liver, 18.2% in intracranial and orbital sites, 3.3% in lung, and 0.6% in CNS. Event-free survival (EFS) was decreased in patients with bone, bone marrow, CNS, intracranial/ orbital, lung, and pleural metastases, and improved in those with liver and skin metastases. In infants, MYCN amplification and unfavorable Shimada histopathology correlated with increased frequencies of bone and intracranial or orbital metastases. In older patients, MYCN amplification correlated with increased frequencies of intracranial or orbital, liver, and lung metastases. Multivariate analysis revealed that metastatic site is not an independent prognostic factor., Conclusions: Metastatic pattern in neuroblastoma differs with age and correlates with tumor biological features and EFS. These correlations could reflect changes in host or tumor biological features with age resulting in differences in metastatic capacity or tumor affinity for specific sites.

Pigmented schwannomas of the spinal canal are rare entities. We present a case of such in an unusual, ventral intradural, extramedullary location in a 27-year-old man. Imaging and histopathologic findings, including electron microscopy, showed an intradural, extramedullary pigmented schwannoma, densely adherent to the leptomeninges of the anterior median septum. This lesion is demonstrative of the neuroectodermal origin of these lesions and represents a rare location of these tumors.

Purpose: The aim of this study was to analyze the indications and results of fundoplication in 110 infants under 3 months of age., Methods: A retrospective review was conducted on the charts of all infants operated on for gastroesophageal reflux disease (GERD) at the UCLA Medical Center from January 1980 to December 1997. There were 59 boys and 51 girls. Recurrent emesis was the indication for operation in 62 of 110 infants, and respiratory symptoms in 85 of 110, with 54 of 110 having both. Neurological impairment was present in 32%. Prematurity was present in 21%; 35% had associated anomalies. Overall, 81 of 110 infants (73.6%) had one or more associated major malformations or disorders. Reflux was confirmed by upper gastrointestinal series findings in 63 of 78, esophageal pH monitoring in 60 of 62, and endoscopy in five of seven., Results: Mean age at operation was 1.8+/-0.1 months and mean weight was 3,686+/-90.2 g. A Nissen fundoplication was performed on 104 children, and six underwent a Thal procedure. Thirty-one had a gastric emptying procedure for delayed gastric emptying. Complications occurred in 7 infants. Emesis was controlled in 57 of 62 patients, aspiration in 38 of 48, and apneic spells in 54 of 57. Follow-up greater than 6 months was available for 73 patients. There were nine late deaths, all related to severe associated malformations. Seven patients required a redo fundoplication for recurrent reflux., Conclusions: Nissen fundoplication can be performed safely in symptomatic infants under 3 months of age with low mortality and morbidity rates and with resolution of the presenting symptoms in 79% of infants.

Neuroblastoma is one of the most intensely studied solid malignancies that affect the pediatric age groups; its clinical presentation, treatment strategies and ultimate prognosis vary greatly. The biologic and genetic character of each tumor has an important impact on disease behavior, and clinical staging now incorporates these factors to generate an overall therapy plan. The clinical presentation of neuroblastoma is related to primary tumor location, production of metabolically active substances, and the presence of metastatic disease. There are also prognostically important associated syndromes including opsoclonus-myoclonus, Horner's syndrome, neurofibromatosis, and a variety of other neurocristopathies. The histologic features of the tumor are of prognostic significance and are utilized in treatment stratification. The International Neuroblastoma Staging System (INSS) has unified classic clinical staging. Features at diagnosis and those determined by initial operation are combined with biologic prognostic factors to achieve risk group assignment for virtually all patients. There are groups of children in which limited therapy is curative and intermediate-risk situations where standard multimodality treatment provides favorable outcomes. Unfortunately, there are many patients with high-risk disease that require intensive strategies, but success is still limited. It is in these most resistant patients that innovative approaches are being undertaken and novel strategies are being investigated.

Breast carcinoma presents rarely (<5% of cases) as an axillary mass without an obvious primary tumor. The value of mammography in detecting an occult breast carcinoma is low, with a sensitivity of 29 per cent and specificity of 73 per cent. MRI and positron emission tomography (PET) are potentially more sensitive in this setting. We present a case recently seen at the Vanderbilt University Hospital, a 63-year-old woman with a 2-cm painless mass in the right axilla. Mammography was negative, and fine needle aspiration revealed atypical cells suspicious for malignancy. An excisional biopsy of the right axillary lymph node revealed metastatic adenocarcinoma, most likely breast primary. A PET showed increased uptake of 18-fluorodeoxyglucose and 99m Technetium in the right axilla and the right lateral breast. The patient underwent right modified radical mastectomy. The final pathological report revealed a 0.9-cm primary tumor in the upper inner quadrant of the breast and 1 of 41 nodes positive for tumor. This case confirms that mammography has low sensitivity in identifying the primary tumor in occult breast carcinoma and illustrates the usefulness of PET in identifying the primary tumor. We advocate an aggressive approach to evaluation of the breast in women presenting with metastatic adenocarcinoma in the axillary nodes. This evaluation should include clinical examination and mammography in all cases, and PET and MRI in selected cases. PET and MRI may be particularly useful when considering a breast-conserving surgical procedure.