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Pediatric Surgery at Hasbro Children's Hospital




Moise KJ Jr, Moldenhauer JS, Bennett KA, Goodnight W, Luks FI, Emery SP, Tsao K, Moon-Grady AJ, Moore RC, Treadwell MC, Vlastos EJ, Wetjen NM.
Current Selection Criteria and Perioperative Therapy Used for Fetal Myelomeningocele Surgery.
Obstet Gynecol. 2016 Mar;127(3):593-597.

OBJECTIVE: To determine the current maternal and fetal selection criteria and operative approaches used at centers performing fetal myelomeningocele surgery.
METHODS: The 17 principal investigators participating in the Fetal Myelomeningocele Consortium were asked to participate in an anonymous online survey regarding the current practice of maternal-fetal surgery for neural tube defect repair and results were tabulated. The 35-question survey related to diagnostic testing, inclusion and exclusion criteria, and clinical management.
RESULTS: Sixty-five percent (11/17) of principal investigators responded to the survey and not all centers responded to all 35 questions. All centers continue to use magnetic resonance imaging in their preoperative evaluation. Diagnostic testing from amniocentesis is varied: 5 of 11 (45%) require amniotic fluid α-fetoprotein, 4 of 10 (40%) amniotic fluid acetylcholinesterase, and 8 of 11 (73%) DNA microarray. There is also variation from the Management of Myelomeningocele Study with regard to body mass index (BMI) (1/11; 9% would offer surgery with BMIs higher than 35), maternal medical risk factors (surgery would be offered for controlled pregestational diabetes [3/10 (30%)]), hepatitis C with negative viral load (4/11 [36%]), and human immunodeficiency virus with an undetectable viral load (1/10 [10%] or an obstetric history [3/11 (27%)] would offer surgery with a history of preterm delivery on progesterone). Ten of 11 (91%) centers did not consider ventriculomegaly of 18 mm and 9 of 11 (82%) centers did not consider lack of leg movement as an exclusion criteria. Nuances in the perioperative and intraoperative management were also reported, including 5 of 11 (45%) use intraoperative echocardiography and alterations in postoperative tocolytics.
CONCLUSION: Variation in practice patterns for offering and performing maternal-fetal surgery for myelomeningocele repair exists among centers. Ongoing evaluation of inclusion and exclusion criteria as well as operative techniques is warranted to ensure continued safety, effectiveness, and beneficence.


Hartwich J, Luks FI, Watson-Smith D, Kurkchubasche AG, Muratore CS, Wills HE, Tracy TF Jr.
Nonoperative treatment of acute appendicitis in children: A feasibility study.
J Pediatr Surg. 2016 Jan;51(1):111-6.

PURPOSE: Nonoperative treatment of acute appendicitis appears to be feasible in adults. It is unclear whether the same is true for children.
METHODS: Children 5-18years with <48h symptoms of acute appendicitis were offered nonoperative treatment: 2 doses of piperacillin IV, then ampicillin/clavulanate ×1 week. Treatment failure (worsening on therapy) and recurrence (after completion of therapy) were noted. Patients who declined enrollment were asked to participate as controls. Cost-utility analysis was performed using Pediatric Quality of Life Scale (PedsQL®) to calculate quality-adjusted life month (QALM) for study and control patients.
RESULTS: Twenty-four patients agreed to undergo nonoperative management, and 50 acted as controls. At a mean follow-up of 14months, three of the 24 failed on therapy, and 2/21 returned with recurrent appendicitis at 43 and 52days, respectively. Two patients elected to undergo an interval appendectomy despite absence of symptoms. Appendectomy-free rate at one year was therefore 71% (C.I. 50-87%). No patient developed perforation or other complications. Cost-utility analysis shows a 0.007-0.03 QALM increase and a $1359 savings from $4130 to $2771 per nonoperatively treated patient.
CONCLUSION: Despite occasional late recurrences, antibiotic-only treatment of early appendicitis in children is feasible, safe, cost-effective and is experienced more favorably by patients and parents.


Chau DB, Ciullo SS, Watson-Smith D, Chun TH, Kurkchubasche AG, Luks FI.
Patient-centered outcomes research in appendicitis in children: Bridging the knowledge gap.
J Pediatr Surg. 2016 Jan;51(1):117-21.

PURPOSE: Patient-centered outcomes research (PCOR) aims to give patients a better understanding of the treatment options to enable optimal decision-making. As nonoperative alternatives are now being evaluated in children for acute appendicitis, we surveyed patients and their families regarding their knowledge of appendicitis and evaluated whether providing basic medical information would affect their perception of the disease and allow them to more rationally consider the treatment alternatives.
METHODS: Families of children aged 5-18 presenting to the Emergency Department with suspected appendicitis were recruited for a tablet-based interactive educational survey. One hundred subjects (caregivers and patients ≥15years) were questioned before and after an education session about their understanding of appendicitis, including questions on three hypothetical treatment options: urgent appendectomy, antibiotics alone, or initial antibiotics followed by elective appendectomy. Subjects were clearly informed that urgent appendectomy is currently the standard of care.
RESULTS: Only 14% of respondents correctly identified the mortality rate of appendicitis (17 deaths/year according to the 2010 US census) when compared with other extremely rare causes of death. Fifty-four and 31% thought it was more common than death from lightning (40/year) and hunting-associated deaths (44/year), respectively. Eighty-two percent of respondents believed it "likely" or "very likely" that the appendix would rupture if operation was at all delayed, and 81% believed that rupture of the appendix would rapidly lead to severe complications and death. In univariate analysis, this perception was significantly more prevalent for mothers (odds ratio, (OR) 5.19, confidence interval (CI) 1.33-21.15), and subjects who knew at least one friend or relative who had a negative experience with appendicitis (OR 5.53, CI 1.40-25.47). Following education, these perceptions changed significantly (53% still believed that immediate operation was necessary, and 47% believed perforation led to great morbidity and potential mortality, P<0.001). In a survey of potential appendicitis treatment options, urgent appendectomy was considered a "good" or "very good" option by 74% of subjects, compared with 68% for antibiotics only without appendectomy and 49% for initial antibiotic therapy followed by elective outpatient appendectomy.
CONCLUSION: There was a striking knowledge gap in the participant perception of appendicitis. Appropriate education can correct anecdotally supported misconceptions. Adequate education may empower patients to make better-informed decisions about their medical care and may be important for future studies in alternative treatments for appendicitis in children.

Fallon EA, Ha AY, Merck DL, Ciullo SS, Luks FI.
Interactive Instrument-Driven Image Display in Laparoscopic Surgery.
J Laparoendosc Adv Surg Tech A. 2015 Jun;25(6):531-5.

BACKGROUND: A significant limitation of minimally invasive surgery is dependence of the entire surgical team on a single endoscopic viewpoint. An individualized, instrument-driven image display system that allows all operators to simultaneously define their viewing frame of the surgical field may be the solution. We tested the efficacy of such a system using a modified Fundamentals of Laparoscopic Surgery™ (Society of American Gastrointestinal and Endoscopic Surgeons, Los Angeles, CA) bead transfer task.
MATERIALS AND METHODS: A program was custom-written to allow zooming and centering of the image window on specific color signals, each attached near the tip of a different laparoscopic instrument. Two controls were used for the bead transfer task: (1) a static, wide-angle view and (2) a single moving camera allowing close-up and tracking of the bead as it was transferred. Time to task completion and number of bead drops were recorded.
RESULTS: Thirty-six sessions were performed by surgical residents. Average time for bead transfer was 127.3±21.3 seconds in the Experimental group, 139.1±27.8 seconds in the Control 1 group, and 186.2±18.5 seconds in the Control 2 group (P=.034, by analysis of variance). Paired analysis (the Wilcoxon Signed-Rank Test) showed that the Experimental group was significantly faster than the Control 1 group (P=.035) and the Control 2 group (P=.028).
CONCLUSIONS: We have developed an image navigation system that allows intuitive and efficient laparoscopic performance compared with two controls. It offers high-resolution images and ability for multitasking. The tracking system centers close-up images on the laparoscopic target. Further development of robust prototypes will help transition this in vitro system into clinical application.

Maggio L, Carr SR, Watson-Smith D, O'Brien BM, Lopes V, Muratore CS, Luks FI.
Iatrogenic Preterm Premature Rupture of Membranes after Fetoscopic Laser Ablative Surgery.
Fetal Diagn Ther. 2015;38(1):29-34.

INTRODUCTION: To describe the incidence and risk factors for iatrogenic premature preterm rupture of membranes (iPPROM) after fetoscopic laser surgery for the twin-to-twin-transfusion syndrome.
MATERIALS AND METHODS: This is a retrospective review of all patients who have undergone fetoscopic laser surgery at a single fetal treatment center since 2000. We defined iPPROM as spontaneous rupture of membranes before the onset of labor prior to 34 weeks of gestation. The iPPROM cohort was compared to the cohort without iPPROM for several preoperative, operative, and delivery characteristics.
RESULTS: Ninety-two consecutive patients were reviewed. The overall rate of iPPROM was 18.5% (n = 17). The rates of iPPROM within 1 and 4 weeks were 5.4 and 10.9%, respectively. The median interval from surgery to delivery was significantly shorter in the iPPROM group (21 vs. 62 days, p = 0.01). The mean gestational age at delivery (27.0 vs. 31.1 weeks, p = 0.02) was lower in the iPPROM group. No other characteristics studied differed significantly between the groups.
DISCUSSION: The incidence of iPPROM was substantially lower than in recent multicenter reports; however, no risk factors of iPPROM could be identified. Whether this is related to variations in surgical or anesthetic management will require further investigation.

Duron VP, Day KM, Steigman SA, Aidlen JT, Luks FI.
Maintaining low transfusion and angioembolization rates in the age of nonoperative management of pediatric blunt splenic injury.
Am Surg. 2014 Nov;80(11):1159-63.

Nonoperative management of hemodynamically stable blunt splenic injury (BSI) is the gold standard in children. Recent studies from nonpediatric surgery-specialized trauma centers have demonstrated a rise in transfusion and angioembolization associated with decreased splenectomy rates. We investigate the rate of splenectomy and nonsurgical interventions (angioembolization, blood transfusion) for BSI in a pediatric surgery-specialized trauma center. We conducted a retrospective review of children (0 to 18 years) treated between September 2001 and September 2011 at a children's hospital. Analyzed data included presenting vital signs, nadir hemoglobin, splenic injury grade, Revised Trauma Score, and Injury Severity Score (ISS). Measured outcomes included transfusion, angioembolization, and splenectomy rates. The study period was divided into three time periods to identify possible trends and compared with national averages. There were 180 patients, 91 with multiple injuries (50.6%) and 89 (49.4%) with isolated BSI. Seventy-six per cent of patients were male, average age was 12.8 years, and average ISS was 14.7. The overall splenectomy rate was 1.7 per cent (1.1% for isolated splenic injury). Our angioembolization rate was 0.6 per cent compared with 7.4 to 16 per cent nationally. Our transfusion rate was 14.4 per cent overall and 5.6 per cent for isolated splenic injury compared with 9.5 to 24.9 per cent nationally. Intervention rates remained unchanged over the study period. Splenectomy rates have remained low at our institution without an increase in angioembolization or transfusion. Children with splenic injuries treated at dedicated pediatric hospitals can be successfully managed nonoperatively without angioembolization or blood transfusion.

Ventetuolo CE, Muratore CS.
Extracorporeal life support in critically ill adults.
Am J Respir Crit Care Med. 2014 Sep 1;190(5):497-508.

Extracorporeal life support (ECLS) has become increasingly popular as a salvage strategy for critically ill adults. Major advances in technology and the severe acute respiratory distress syndrome that characterized the 2009 influenza A(H1N1) pandemic have stimulated renewed interest in the use of venovenous extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal to support the respiratory system. Theoretical advantages of ECLS for respiratory failure include the ability to rest the lungs by avoiding injurious mechanical ventilator settings and the potential to facilitate early mobilization, which may be advantageous for bridging to recovery or to lung transplantation. The use of venoarterial ECMO has been expanded and applied to critically ill adults with hemodynamic compromise from a variety of etiologies, beyond postcardiotomy failure. Although technology and general care of the ECLS patient have evolved, ECLS is not without potentially serious complications and remains unproven as a treatment modality. The therapy is now being tested in clinical trials, although numerous questions remain about the application of ECLS and its impact on outcomes in critically ill adults.

Aidlen JT, Glick S, Silverman K, Silverman HF, Luks FI.
Head-motion-controlled video goggles: preliminary concept for an interactive laparoscopic image display (i-LID).
J Laparoendosc Adv Surg Tech A. 2009 Aug;19(4):595-8.

BACKGROUND: Light-weight, low-profile, and high-resolution head-mounted displays (HMDs) now allow personalized viewing, of a laparoscopic image. The advantages include unobstructed viewing, regardless of position at the operating table, and the possibility to customize the image (i.e., enhanced reality, picture-in-picture, etc.). The bright image display allows use in daylight surroundings and the low profile of the HMD provides adequate peripheral vision. Theoretic disadvantages include reliance for all on the same image capture and anticues (i.e., reality disconnect) when the projected image remains static, despite changes in head position. This can lead to discomfort and even nausea. MATERIALS AND METHODS: We have developed a prototype of interactive laparoscopic image display that allows hands-free control of the displayed image by changes in spatial orientation of the operator's head. The prototype consists of an HMD, a spatial orientation device, and computer software to enable hands-free panning and zooming of a video-endoscopic image display. The spatial orientation device uses magnetic fields created by a transmitter and receiver, each containing three orthogonal coils. The transmitter coils are efficiently driven, using USB power only, by a newly developed circuit, each at a unique frequency. The HMD-mounted receiver system links to a commercially available PC-interface PCI-bus sound card (M-Audiocard Delta 44; Avid Technology, Tewksbury, MA). Analog signals at the receiver are filtered, amplified, and converted to digital signals, which are processed to control the image display. RESULTS: The prototype uses a proprietary static fish-eye lens and software for the distortion-free reconstitution of any portion of the captured image. Left-right and up-down motions of the head (and HMD) produce real-time panning of the displayed image. Motion of the head toward, or away from, the transmitter causes real-time zooming in or out, respectively, of the displayed image. CONCLUSIONS: This prototype of the interactive HMD allows hands-free, intuitive control of the laparoscopic field, independent of the captured image.


Luks FI, Carr SR, Muratore CS, O'Brien BM, Tracy TF.
The pediatric surgeons' contribution to in utero treatment of twin-to-twin transfusion syndrome.
Ann Surg. 2009 Sep;250(3):456-62.

OBJECTIVE: To evaluate the outcome of twin-to-twin transfusion syndrome (TTTS) treated using a combination of endoscopic fetal surgery-specific techniques and surgical restraint. SUMMARY BACKGROUND DATA: TTTS is a condition of identical twins that, if progressive and left untreated, leads to 100% mortality. The best treatment option is obliteration of the intertwin placental anastomoses, but fetal surgery carries significant maternal and fetal risks. Even if successful, percutaneous endoscopic laser ablation of placental vessels (LASER) causes premature rupture of membranes (PROM) in 10% to 20% of pregnancies. Patient selection is particularly critical because the progression of the disease is unpredictable. This has prompted many to intervene early, yielding survival rates of >=1 twin of 75% to 80%. METHODS: We developed a minimally invasive approach to fetal surgery, a unique membrane sealing technique and a conservative algorithm that reserves intervention for severe TTTS. Pregnancies with TTTS (stages I-IV) managed in the last 8 years were reviewed. LASER was offered in stage III/IV only. RESULTS: Ninety-eight cases of TTTS were managed in a pediatric surgery/maternal-fetal medicine collaborative Fetal Treatment Program-39 were observed (40%) and 59 underwent LASER (60%). Survival of >= twin was seen in 82.7%, and overall survival was 69.4%. These survival rates are similar to, or better than, other comparable series with similar stage distribution (low:high stage ratio 1:1) in which all patients underwent LASER. PROM rate was 4%. CONCLUSIONS: Reserving LASER treatment for severe TTTS results in outcomes similar to, or better than, LASER for all stages. Applying fetal surgery-specific endoscopic techniques, including port-site sealing, reduces postoperative complications.


Muratore CS, Harty MW, Papa EF, Tracy TF Jr.
Dexamethasone alters the hepatic inflammatory cellular profile without changes in matrix degradation during liver repair following biliary decompression.
J Surg Res. 2009 Oct;156(2):231-9. Epub 2009 May 14.

BACKGROUND: Biliary atresia is characterized by extrahepatic bile duct obliteration along with persistent intrahepatic portal inflammation. Steroids are standard in the treatment of cholangitis following the Kasai portoenterostomy, and were advocated for continued suppression of the ongoing immunologic attack against intrahepatic ducts. Recent reports, however, have failed to demonstrate an improved patient outcome or difference in the need for liver transplant in postoperative patients treated with a variety of steroid regimes compared with historic controls. In the wake of progressive liver disease despite biliary decompression, steroids are hypothesized to suppress inflammation and promote bile flow without any supporting data regarding their effect on the emerging cellular and molecular mechanisms of liver repair. We have previously shown in a reversible model of cholestatic injury that repair is mediated by macrophages, neutrophils, and specific matrix metalloproteinase activity (MMP8); we questioned whether steroids would alter these intrinsic mechanisms. METHODS: Rats underwent biliary ductal suspension for 7 d, followed by decompression. Rats were treated with IV dexamethasone or saline at the time of decompression. Liver tissue obtained at the time of decompression or after 2 d of repair was processed for morphometric analysis, immunohistochemistry, and quantitative RT-PCR. RESULTS: There was a dramatic effect of dexamethasone on the inflammatory component with the initiation of repair. Immunohistochemistry revealed a reduction of both ED1+ hepatic macrophages and ED2+Kupffer cells in repair compared with saline controls. Dexamethasone treatment also reduced infiltrating neutrophils by day 2. TNF-alpha expression, increased during injury in both saline and dexamethasone groups, was markedly reduced by dexamethasone during repair (day 2) whereas IL-6, IL-10, and CINC-1 remained unchanged compared with saline controls. Dexamethasone reduced both MMP8 and TIMP1 expression by day 2, whereas MMP9, 13, and 14 were unchanged compared with sham controls. Despite substantial cellular and molecular changes during repair, collagen resorption was the same in both groups CONCLUSION: Dexamethasone has clear effects on both the hepatic macrophage populations and infiltrating neutrophils following biliary decompression. Altered MMP and TIMP gene expression might suggest that steroids have the potential to modify matrix metabolism during repair. Nevertheless, successful resorption of collagen fibrosis proceeded presumably through other MMP activating mechanisms. We conclude that steroids do not impede the rapid intrinsic repair mechanisms of matrix degradation required for successful repair.

Harty MW, Papa EF, Huddleston HM, Young E, Nazareth S, Riley CA, Ramm GA, Gregory SH, Tracy TF Jr.
Hepatic macrophages promote the neutrophil-dependent resolution of fibrosis in repairing cholestatic rat livers.
Surgery. 2008 May;143(5):667-78.

BACKGROUND: Cholestatic liver injury from extrahepatic biliary obstruction is well characterized by inflammatory and fibrogenic mechanisms. Little is known, however, about mechanisms required to reverse injury and effect liver repair. We sought to determine the cellular and molecular requirements for repair after biliary decompression, focusing on the role of hepatic macrophages in regulating inflammation and matrix resolution. METHODS: Male Sprague-Dawley rats underwent bile duct obstruction for 7 days followed by ductular decompression. Rats were treated with gadolinium chloride (GdCl(3)) to deplete the macrophage populations 24 or 48 hours before decompression. Liver tissue obtained at the time of decompression or after 2 days of repair was processed for morphometric analysis, immunohistochemistry, quantitative RT-PCR and in situ hybridization. RESULTS: GdCl(3) treatment for either 24 or 48 hours before decompression reduced the numbers of ED2(+) Kupffer cells and ED1(+) inflammatory macrophages in obstructed livers; only 48 hours of pretreatment, however, reduced the neutrophil counts. Furthermore, 48-hour GdCl(3) pretreatment blocked matrix degradation. Quantitative polymerase chain reaction demonstrated decreased cytokine-induced neutrophil chemoattractant-1 (CINC-1; CXCL1) and intercellular adhesion molecule-1 mRNA expression after GdCl(3) treatment and the elimination of hepatic macrophages. Immunohistochemistry and in situ hybridization revealed that neutrophils and CINC-1 mRNA localize within regions of fibrotic activity during both injury and repair. CONCLUSION: We conclude that the macrophage population is not directly involved in fibrotic liver repair. Rather, hepatic macrophages regulate the influx of neutrophils, which may play a direct role in matrix degradation.

Muratore CS, Ryder BA, Luks FI.
Image display in endoscopic surgery.
J Soc Image Display - Adv Display Col Sc July 2007 Vol. 23, No. 07.

Abstract - Advances in the technology of optical displays have changed the way surgeons are able to manage different illnesses. Minimally invasive surgery encompasses a wide range of endoscopic procedures, whereby the body cavity (abdomen, thorax, gastrointestinal tract, and joint spaces) is accessed through small incisions and the use of telescopes and fine, long instruments. These techniques have rapidly gained in popularity during the last decades, as patients are experiencing less discomfort after surgery. Visualization of the operative field requires optimal image capture, processing, and display. The introduction of charge-coupled devices has enabled surgeons to view the operative field on a video monitor, allowing ever-more-complex operations to be performed endoscopically. However, limitations include loss of 3-D perception and tactile sense, poor ergonomics, often suboptimal positioning of the image display, and image quality that is too dependent on outside influences. These limitations, and possible solutions, are addressed as is the "ideal" display system for endoscopic surgery.

Truitt AK, Sorrells DL, Halvorson E, Starring J, Kurkchubasche AG, Tracy TF Jr, Luks FI.
Pulmonary embolism: which pediatric trauma patients are at risk? J Pediatr Surg. 2005 Jan;40(1):124-7; discussion 127.

BACKGROUND/PURPOSE: Deep vein thrombosis and pulmonary embolism (DVT/PE) are rare in pediatric trauma patients, and guidelines for prophylaxis are scarce. The authors sought to identify subgroups of patients who may be at higher risk of developing DVT/PE. METHODS: Case-control study of pediatric trauma patients with DVT/PE. Odds ratios (ORs) and confidence intervals (CIs) were calculated for known risk factors of PE using matched trauma controls (chi2 analysis). RESULTS: A total of 3637 pediatric trauma patients was admitted over the last 7 years. Three patients developed DVT/PE (overall incidence, 0.08%). There were 2 girls and 1 boy, aged 15, 15, and 9 years, respectively. All 3 had an Injury Severity Score (ISS) > or =25 and an initial Glasgow Coma Score (GCS) < or =8. None of the known and potential risk factors significantly increased the OR for developing DVT/PE: age 9 years or older (OR, 3.6; CI, 0.4-26), presence of head injury (OR, 2.9; CI, 0.3-22), female sex (OR, 1.2; CI, 0.15-9.1), GCS < or =8 (OR, 9.2; CI, 0.9-230), except ISS > or =25 (OR, 82; CI, 7.6-2058). The OR for a combination of age and GCS was 106, and the OR for the 3 risk factors (age, ISS, GCS) common to all 3 patients was 114 (CI, 10-5000; P < .001). CONCLUSIONS: The overall incidence of DVT/PE in pediatric trauma patients is <0.1% and routine prophylaxis is not recommended. Children aged 9 years or older with an initial GCS < or =8 and patients with an estimated ISS > or =25 may constitute a high-risk group in which prophylaxis could be considered.

Young JY, Kim DS, Muratore CS, Kurkchubasche AG, Tracy TF Jr, Luks FI.
High incidence of postoperative bowel obstruction in newborns and infants.
J Pediatr Surg. 2007 Jun;42(6):962-5

BACKGROUND: Postoperative bowel obstruction (PBO) plagues patients of all ages after intraabdominal surgery. We examined the incidence, risk factors, and the need for operative intervention of PBO. METHODS: We reviewed all children who underwent a laparotomy or laparoscopy. Parameters included age, diagnosis, type and number of procedures, complications, time interval to PBO, treatment of PBO, morbidity, and mortality. RESULTS: From 2001 to 2005, 2187 abdominal operations were performed. Overall, 61 patients (2.8%) developed a PBO; 43 (70.5%) required reoperation. Postoperative bowel obstruction was more common in patients younger than 1 year (28/601, 4.7%) compared with older children (33/1586, 2.1%; P = .01, beta = .80). In infants, PBO was not influenced by initial diagnosis (P = .26) or whether the initial operation was clean/clean-contaminated or contaminated/dirty (P = .12). In children older than 1 year, nonoperative treatment was more likely to be successful if PBO occurred within 12 weeks of initial operation (12/16 vs 3/14; P = .01). In contrast, all but one infant (16/17) with early PBO required reoperation. CONCLUSION: The incidence of PBO is significantly higher in newborns and infants than in older children (who have rates comparable to those reported in adults). Infants are significantly more likely to require operative intervention, particularly if PBO occurs early after the initial operation.

Chang J, Tracy TF Jr, Carr SR, Sorrells DL Jr, Luks FI.
Port insertion and removal techniques to minimize premature rupture of the membranes in endoscopic fetal surgery.
J Pediatr Surg. 2006 May;41(5):905-9

BACKGROUND: Premature rupture of membranes (PROM) remains a significant complication of fetal surgery. Rates of 40% to 100% have been reported after both open and endoscopic fetal surgery. We describe a technique of endoscopic port insertion and removal that minimizes trauma to the membranes. METHODS: Twenty-seven consecutive patients undergoing endoscopic laser ablation for twin-to-twin transfusion syndrome were reviewed. In each case, a minilaparotomy was performed, and the amniotic cavity was entered under direct vision of the uterus using a Seldinger technique. The entry site was carefully dilated to accommodate a 4.0-mm-diameter cannula. A gelatin sponge plug was placed at port removal. Postoperative management and outcome were evaluated. RESULTS: Median gestational age at operation was 21.3 weeks. Median operating time was 60 minutes. One patient delivered intraoperatively because of fetal distress. Seventeen (65.4%) patients required postoperative tocolysis (median duration, 12 hours). Median postoperative gestation was 6.5 weeks (range, 1-20 weeks). Only 1 (4.2%) of 24 patients with successful gelatin sponge placement developed PROM. CONCLUSIONS: Meticulous technique and atraumatic insertion and removal of ports help minimize the risk of postoperative amniotic leak after endoscopic fetal surgery. Our PROM rate of 4.2% contrasts sharply with previously reported rates after similar operations.

Gehring S, Dickson EM, San Martin ME, van Rooijen N, Papa EF, Harty MW, Tracy TF Jr, Gregory SH.
Kupffer cells abrogate cholestatic liver injury in mice.
Gastroenterology. 2006 Mar;130(3):810-22 Abstract

BACKGROUND & AIMS: Biliary obstruction and cholestasis can cause hepatocellular apoptosis and necrosis. Ligation of the common bile duct in mice provides an excellent model in which to study the underlying mechanisms. Kupffer cells play a key role in modulating the inflammatory response observed in most animal models of liver injury. This study was performed to determine the role of Kupffer cells in the injury attending cholestasis. METHODS: Mice were not treated or were rendered Kupffer cell-depleted by intravenous inoculation of multilamellar liposome-encapsulated dichloromethylene diphosphonate, the common bile duct was ligated and divided; sham-operated animals served as controls. Similarly, interleukin-6 (IL-6)-deficient and tumor necrosis factor-receptor-deficient mice underwent bile duct ligation (BDL) or sham operations. RESULTS: Serum alanine transaminase levels were increased in all BDL mice at 3 days after surgery, but were significantly higher in IL-6-deficient mice or mice rendered Kupffer cell-depleted before ligation. Histologic examination of BDL livers showed portal inflammation, neutrophil infiltration, bile duct proliferation, and hepatocellular necrosis. Photoimage analyses confirmed more necrosis in the livers of Kupffer cell-depleted and IL-6-deficient animals. Purified Kupffer cells derived from BDL animals produced more IL-6 in culture. Similarly, Kupffer cells obtained by laser capture microdissection from the livers of BDL mice expressed increased levels of IL-6 messenger RNA. Recombinant mouse IL-6 administered 1 hour before BDL completely reversed the increased liver damage assessed otherwise in Kupffer cell-depleted mice. CONCLUSIONS: These findings indicate that Kupffer cells abrogate cholestatic liver injury by cytokine-dependent mechanisms that include the production of IL-6.

Harty MW, Huddleston HM, Papa EF, Puthawala T, Tracy AP, Ramm GA, Gehring S, Gregory SH, Tracy TF Jr.
Repair after cholestatic liver injury correlates with neutrophil infiltration and matrix metalloproteinase 8 activity.
Surgery. 2005 Aug;138(2):313-20 Abstract

BACKGROUND: Although timely surgical treatment of liver disease can interrupt inflammation and reduce fibrosis, the mechanisms of repair are unknown. We questioned whether these mechanisms of repair include changes in the inflammatory infiltrate and associated biological activity of matrix metalloproteinases (MMPs) 8 and 2. METHODS: Rats (n >or= 3) underwent biliary ductal suspension for 7 days followed by decompression. Livers were collected after 7 days of obstruction (d0) and after 2, 5, and 7 days of repair (d2, d5, d7, respectively), and assessed morphometrically for collagen, polymorphonuclear cells (PMNs), Kupffer cells (KCs), and inflammatory mononuclear phagocytes (MNPs). In situ zymography was performed by using fluorogenic substrates for MMP-8 and MMP-2 to spatially localize enzymatic activity. RESULTS: Cholestatic injury resulted in significantly elevated (P <or= .001) collagen deposition (3-fold), and elevated numbers of MNPs (10-fold), KCs (5-fold), and PMNs (4-fold), compared with shams. PMNs remained elevated through d7, while collagen deposition, KCs, and MNPs returned to sham levels by d2. In situ zymography showed no significant changes in MMP-2 activity after cholestatic injury and repair. MMP-8 activity was significantly (P <or= .05) elevated only during repair. Activity was localized to fibrotic portal triads containing PMNs. CONCLUSIONS: Cholestatic injury results in increased fibrosis, MNPs, KCs, and PMNs but no MMP-2 or MMP-8 activity. Biliary decompression results in increased MMP-8 activity co-localized to areas of portal fibrosis and PMN accumulation. We conclude that secretion of MMP-8 by neutrophils may play a critical role in resolving the fibrotic scar generated during cholestasis.

Lui F, Gormley P, Sorrells DL Jr, Biffl WL, Kurkchubasche AG, Tracy TF Jr, Luks FI.
Pediatric trauma patients with isolated airway compromise or Glasgow Coma Scale less than 8: does immediate attending surgeon's presence upon arrival make a difference? J Pediatr Surg. 2005 Jan;40(1):103-6.

BACKGROUND/PURPOSE: Optimal trauma care requires an attending pediatric surgeon to head a trauma team for the most severely injured patients. Recently, the American College of Surgeons-Committee on Trauma has added "Glasgow Coma Scale (GCS) <8" and "airway compromise" to the existing anatomical and physiological criteria for immediate attending presence. This report analyzes the outcome of children who met these isolated criteria and were treated before the change in guidelines was made. METHODS: The trauma registry of this level I trauma center was queried for all pediatric patients with GCS <8 or airway compromise. Age, sex, initial GCS, Revised Trauma Score, Injury Severity Score, outcome, and probability of survival (TRISS methodology) were recorded. The subgroup of patients for whom an attending surgeon was not immediately present was further analyzed. RESULTS: Over a 5-year period, 2895 trauma patients (aged 0-16 years) were admitted. One hundred fifteen patients had a GCS <8 and/or airway compromise. In 61 cases, an attending surgeon was not present upon patient arrival. Of these patients, 24 died (group D), 15 were discharged to a rehabilitation facility (group R), and 22 were discharged home (group H). Ten patients with a probability of survival of lower than 0.5 survived. Only 4 of the 24 patients who died had a probability of survival of >0.5 (mean, 0.697). All 4 had an Injury Severity Score >25 and a GCS < or =4. All deaths were reviewed through a quality improvement program and were deemed nonpreventable by objective reviewers. Patient outcome was not affected by the presence or absence of an attending surgeon upon patient arrival. CONCLUSIONS: Outcome of severely injured children with GCS <8 or airway compromise met and, in some cases, exceeded expectations of survival according to the TRISS methodology. The lack of immediate attending surgeon's presence does not appear to have negatively influenced the outcome in these children. Based on this series, there is no evidence to justify mandatory immediate presence of an attending surgeon for these 2 criteria alone.

Vrochides DV, Sorrells DL Jr, Kurkchubasche AG, Wesselhoeft CW Jr, Tracy TF Jr, Luks FI.
Is there a role for routine preoperative endoscopic retrograde cholangiopancreatography for suspected choledocholithiasis in children? Arch Surg. 2005 Apr;140(4):359-61.

HYPOTHESIS: Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used preoperatively in adult patients with suspected choledocholithiasis. Cholelithiasis occurs much less often in children, and the indications for ERCP are not established. We hypothesized that the natural history of choledocholithiasis in children is spontaneous passage of stones through the papilla and that these children can be managed without routine preoperative ERCP. DESIGN: Retrospective analysis of patients treated over a 10-year period. SETTING: Tertiary care children's hospital. PATIENTS: All patients with cholecystectomy for biliary disease. INTERVENTIONS: Cholecystectomy; intraoperative cholangiography for suspected choledocholithiasis: hyperbilirubinemia, gallstone pancreatitis, and ultrasonographic evidence of common bile duct dilation or common bile duct stones; and postoperative ERCP for symptomatic choledocholithiasis: pain and jaundice. MAIN OUTCOME MEASURES: Incidence and complications of choledocholithiasis and frequency of ERCP. RESULTS: One hundred patients (63 females) were studied. Indications included acute cholecystitis (10%), chronic cholecystitis (59%), gallstone pancreatitis (26%), and choledocholithiasis (5%). An intraoperative cholangiography was performed in 45 patients, and common bile duct stones were identified in 13. Expectant management of asymptomatic common bile duct stones was associated with sonographic resolution within 1 week. One patient with intraoperative cholangiography-proven choledocholithiasis required ERCP for symptoms 24 hours after operation. One additional patient, who did not undergo intraoperative cholangiography, developed symptomatic choledocholithiasis and required ERCP. There were no choledocholithiasis- or ERCP-related complications. CONCLUSIONS: This study suggests that choledocholithiasis occurs frequently in children and that spontaneous passage of common bile duct stones is common. This could explain the relatively high incidence of gallstone pancreatitis. Conservative management of choledocholithiasis is successful in the majority of patients. Routine preoperative or postoperative ERCP is usually not indicated.

De Paepe ME, Mao Q, Luks FI.
Expression of apoptosis-related genes after fetal tracheal occlusion in rabbits. J Pediatr Surg. 2004 Nov;39(11):1616-25.

BACKGROUND/PURPOSE: Late-gestation lung remodeling is associated with alveolar type II cell apoptosis early in the saccular stage (day 28 in fetal rabbits). Intrauterine tracheal occlusion (TO), a potent stimulus of fetal lung growth and maturation, significantly increases type II cell apoptosis. The aim of this study was to determine the effect of fetal TO on the spatiotemporal expression of key apoptosis-related signaling molecules. METHODS: Tracheal occlusion of fetal rabbits was performed at gestational day 25 (term, 31 days), and apoptotic gene expression was studied between days 26 and 28. RESULTS: At days 26 and 27, the protein levels of Fas and Fas-ligand (FasL) in lung lysates were similar in TO fetuses and sham-operated controls. At day 28, however, synchronous with the onset of TO-induced pulmonary distension and type II cell apoptosis, the FasL protein content was 8-fold higher in TO lungs compared with controls (P < .01), whereas Fas levels were comparable. In contrast, Bax and Bcl-2 protein levels were similar in TO and control fetuses at all time-points. TO significantly increased the cellular concentration of immunoreactive FasL in type II cells and bronchial epithelial Clara cells. Furthermore, bronchoalveolar lavage fluid (BAL) from TO fetuses at day 28 induced significantly more type II cell apoptosis in vitro compared with control BAL, an effect that was inhibited by neutralizing anti-FasL antibody. CONCLUSIONS: Our findings show that TO results in time-specific increase of both cellular and soluble FasL in fetal lungs and implicate the Fas/FasL pathway as a pivotal autocrine and/or paracrine regulator of TO- induced type II cell apoptosis.

Spencer AU, Yu S, Tracy TF, Aouthmany MM, Llanos A, Brown MB, Brown M, Shulman RJ, Hirschl RB, Derusso PA, Cox J, Dahlgren J, Strouse PJ, Groner JI, Teitelbaum DH, Stechmiller JK.
Parenteral nutrition-associated cholestasis in neonates: multivariate analysis of the potential protective effect of taurine. J PEN J Parenter Enteral Nutr. 2005 Sep-Oct;29(5):337-44.
BACKGROUND: Neonates receiving parenteral nutrition (PN) are at risk for PN-associated cholestasis (PNAC); however, no preventive factors for PNAC have been clearly identified. Despite reports suggesting that taurine may prevent PNAC in neonates, such an effect of taurine has not yet been definitively demonstrated. We determined whether taurine supplementation reduces the incidence of PNAC in premature or critically ill neonates. METHODS: This study was part of a prospective, randomized, multi-institutional trial designed to assess cholecystokinin vs placebo as a potential preventive therapy of PNAC. Taurine supplementation of PN varied between institutions. The presence or absence of taurine in PN was analyzed by multivariate analysis, with a primary outcome measure of serum conjugated bilirubin (CB) as a measure of PNAC. RESULTS: Taurine reduced PNAC in premature infants (estimated maximum CB [95% confidence interval] 0.50 mg/dL [-0.17 to 1.18] for those receiving taurine, vs 3.45 mg/dL [1.79-5.11] for neonates not receiving taurine, approaching significance, p = .07). Taurine significantly reduced PNAC in infants with necrotizing enterocolitis (NEC; estimated maximum CB 4.04 mg/dL [2.85-5.23], NEC infants receiving taurine, vs 8.29 mg/dL [5.61-10.96], NEC infants not receiving taurine, p < .01). There were too few neonates with surgical anomalies to evaluate the effect of taurine in this group. CONCLUSIONS: Within specific subgroups of neonatal patients, taurine supplementation does offer a very significant degree of protection against PNAC. Patients with NEC or severe prematurity are most likely to benefit substantially from taurine supplementation.

Cloutier DR, Baird TB, Gormley P, McCarten KM, Bussey JG, Luks FI. Pediatric splenic injuries with a contrast blush: successful nonoperative management without angiography and embolization. J Pediatr Surg. 2004 Jun;39(6):969-71.
BACKGROUND: The presence of a contrast blush on computed tomography (CT) in adult splenic trauma is a risk factor for failure of nonoperative management. Arterial embolization is believed to reduce this failure rate. The significance of a blush in pediatric trauma is unknown. The authors evaluated the outcome of children with blunt splenic trauma and contrast extravasation. METHODS: The trauma registry was queried for all pediatric patients with blunt splenic injuries. Admission CT was reviewed for injury grade and presence of an arterial blush by a radiologist blinded to patient outcome. Hospital and office charts were reviewed for success of nonoperative management, late splenic rupture, and other complications. RESULTS: One hundred seven children with blunt splenic trauma were identified over a 6-year period. Mean injury grade was 2.9. Six patients required emergency splenectomy. An additional 7 patients met hemodynamic criteria for surgical intervention (3 splenectomies, 4 splenorrhaphies). Admission CT was available in 63 patients. An arterial blush was identified in 5 (9.7%). Four remained stable and were treated conservatively. One underwent splenectomy for hemodynamic instability. There were no cases of delayed splenic rupture, failed nonoperative treatment, or long-term complications. CONCLUSIONS: Contrast blush in children with blunt splenic trauma is rare, and its presence alone does not appear to predict delayed rupture or failure of nonoperative treatment. Based on this limited series, splenic artery embolization does not have a place in the management of splenic injuries in children.

Luks FI, Carr SR, Plevyak M, Craigo SD, Athanassiou A, Ralston SJ, Tracy TF Jr. Limited prognostic value of a staging system for twin-to-twin transfusion syndrome. Fetal Diagn Ther. 2004 May-Jun;19(3):301-4.
OBJECTIVE: Severe twin-to-twin transfusion syndrome (TTTS) is usually classified according to a staging system (I-V) based on ultrasonographic findings of polyhydramnios in the recipient, oligohydramnios in the donor, the presence or absence of the donor's bladder, Doppler waveform changes and (impending) hydrops. Stage correlates with the severity of disease, and it is assumed that, without intervention, severe TTTS will evolve in succession from stage I to stage V (fetal demise). However, this progression has not been validated in longitudinal studies. Herein, we report on the natural progression of severe TTTS in a cohort of patients from a regional Fetal Treatment Program. METHODS: Eighteen patients with severe TTTS, diagnosed between 15 and 25 weeks of gestation, were managed over a 28-month period. Data were collected until delivery, endoscopic surgical intervention or dual fetal demise. Patients were evaluated at least once a week. Stage, estimated fetal weight, percent recipient/donor body weight discordance and survival were recorded. RESULTS: The present study represents a total follow-up of 108 patient-weeks. Of 90 week-to-week evaluations, 65 showed no change in stage; 11 showed downstaging (by more than 1 stage in 3, or 27%), and 13 showed upstaging (by more than 1 stage in 8, or 62%). Nine patients (all stage II or above) underwent endoscopic laser ablation. Overall survival was 67%, and survival of at least 1 twin occurred in 78% of pregnancies. Weight discordance between the donor and recipient did not predict outcome. CONCLUSION: The current staging system for severe TTTS may not be helpful in predicting the direction, degree or speed of progression of the condition. Indications for intervention should remain stage-related, and not based on projected progression.

De Paepe ME, Friedman RM, Poch M, Hansen K, Carr SR, Luks FI. Placental findings after laser ablation of communicating vessels in twin-to-twin transfusion syndrome. Pediatr Dev Pathol. 2004 Mar-Apr;7(2):159-65. Epub 2004 Mar 17.
As laser ablation of placental vascular communications gains acceptance as treatment option for severe twin-to-twin transfusion syndrome (TTTS), pathologists are increasingly confronted with the interpretation of laser-treated placentas. We present our preliminary institutional experience with the gross and microscopic analysis of these specimens. Patients underwent selective ablation for severe TTTS (Quintero stages II to V) between 16 and 25 wk gestation and the placentas were examined between < 24 h and 19 wk postoperatively. The placental vasculature was injected with gelatin-dye mixtures. The type and number of vascular anastomoses were recorded, followed by routine histopathological analysis of the placenta. Foci of laser impact were identified in all placentas examined within 1 month after laser coagulation. Located along the recipient side of the dividing membrane, the laser-treated vessels appeared hemorrhagic and showed a characteristic abrupt interruption of dye filling after vascular injection. In placentas examined more than 1 month after intervention, the most frequent gross finding was the absence or relative paucity of intertwin anastomoses, associated with subchorionic fibrin deposition. Microscopically, laser-treated vessels showed varying degrees of necrosis, associated with focal hemorrhage, avascular villi, and fibrin deposition in the underlying parenchyma. In some cases of intrauterine fetal demise or placental disruption, no definite laser scars were identified. As expected, the number of residual anastomoses (all types) was significantly smaller in laser-treated placentas than in control monochorionic placentas (2.4 +/- 2.2 [ n = 10] vs. 6.2 +/- 3.2 [ n = 70], P < 0.01). Velamentous cord insertion was noted in 50% of cases; markedly uneven placental sharing in 60%. Detailed analysis of laser-treated placentas and clinicopathological correlation may lead to a better understanding of the pathophysiology of TTTS and continued refinement of therapeutic approaches for this often lethal condition.

Oka T, Kurkchubasche AG, Bussey JG, Wesselhoeft CW Jr, Tracy TF Jr, Luks FI. Open and laparoscopic appendectomy are equally safe and acceptable in children. Surg Endosc. 2004 Feb;18(2):242-5. Epub 2003 Dec 29.
BACKGROUND: The aim of this study was to evaluate prospectively whether laparoscopic (LA) and open appendectomy (OA) are equally safe and feasible in the treatment of pediatric appendicitis. METHODS: A total of 517 children with acute appendicitis were randomly assigned to undergo LA or OA appendectomy, based on the schedule of the attending surgeon on call. Patient age, sex, postoperative diagnosis, operating time, level of training of surgical resident, length of postoperative hospitalization, and minor and major postoperative complications were recorded. Chi-square analysis and the Student t-test were used for statistical analysis. RESULTS: In all, 376 OA and 141 LA were performed. The two groups were comparable in terms of patient demographics and the incidence of perforated appendicitis. The operative time was also similar (47.3 +/- 19.7 vs 49.9 +/- 12.9 min). The overall incidence of minor or major complications was 11.2% in the OA group and 9.9% in the LA group. CONCLUSION: Pediatric patients with appendicitis can safely be offered laparoscopic appendectomy without incurring a greater risk for complications. Nevertheless, a higher (but not significantly higher) abscess rate was found in patients with perforated appendicitis who underwent laparoscopy.

Bussey JG, Luks F, Carr SR, Plevyak M, Tracy TF Jr. Minimal-access fetal surgery for twin-to-twin transfusion syndrome.Surg Endosc. 2004 Jan;18(1):83-86. Epub 2003 Nov 21.
Background: Laser ablation of placental vessels effectively halts severe twin-to-twin transfusion syndrome (TTTS), but fetal surgery remains a dangerous approach. The authors present the technical aspects of endoscopic fetal surgery in their initial clinical experience. Methods: Altogether, 11 women underwent endoscopic fetal surgery for severe TTTS. Access to the recipient's sac was obtained by the Seldinger technique via minilaparotomy. A 12-Fr peel-away introducer was used as a cannula to accommodate a custom-curved 9-Fr sheath containing a 1.9-mm semirigid fiber endoscope. Laser ablation was performed on all unpaired vessels crossing the intertwin membrane using a 400- micro m neodymium: yttrium-aluminum-garnet (Nd: YAG) fiber. The cannula was removed over a gelatin sponge plug. Results: The median operating time was 65 min (range, 45-105 min). No patient experienced amniotic leak postoperatively. The length of hospital stay was 2.8 +/- 1.6 days. Immediate improvement of the TTTS was noted in all but two patients. Pneumonia developed, in one mother leading to premature labor. There were no other major surgical complications. Fetal survival at 2 weeks was 73%. Conclusions: The safety and efficacy of endoscopic fetal surgery for severe TTTS can be optimized with the application of current minimal-access techniques. The superiority of this approach over less invasive means is still being evaluated through prospective studies.

Biffl WL, Schiffman JD, Harrington DT, Sullivan J, Tracy TF Jr, Cioffi WG. Legal prosecution of alcohol-impaired drivers admitted to a level I trauma center in Rhode Island. J Trauma. 2004 Jan;56(1):24-9.
BACKGROUND: Despite harsh legislation, driving under the influence of alcohol (DUI) is exceedingly common, and alcohol-related motor vehicle crashes (MVCs) account for significant morbidity, mortality, and economic loss. Legal sanctions can keep offenders off the road (protecting other drivers and pedestrians) and ensure compliance with treatment programs (reducing recidivism). However, even with clear evidence of a transgression, the law seems to be inconsistently enforced among trauma patients. The purpose of this study was to measure the rate of legal prosecution among impaired drivers admitted to a trauma center after MVCs, and to determine the recidivism rate among these individuals. METHODS: Our trauma registry was queried to identify intoxicated drivers admitted during an 18-month period. Court records identified patients who had been charged with traffic offenses, including prior (2 years) and subsequent (1 year) charges. RESULTS: Blood alcohol concentration (BAC) was measured in 387 (74%) of 525 drivers, of whom 137 (35%) had BAC > or =100 mg/dL. Of 113 state residents, 22 (19%) were charged with an offense related to the MVC. Of 12 charged with DUI, 10 were convicted, for an overall DUI conviction rate of just 9%. Seven (32%) of those who were charged had prior or subsequent charges. Of 91 patients not charged for the index event, 31 (34%) had prior or subsequent charges. CONCLUSION: Alcohol is involved in a large percentage of MVCs in our region. The infrequency of prosecution for DUI despite property damage and/or personal injury, and the high recidivism rate, are significant social concerns. These data suggest the need for processes to facilitate legal prosecution--possibly including revision of legislation involving reporting of BACs.

Ambruso DR. Knall C. Abell AN. Panepinto J. Kurkchubasche A. Thurman G. Gonzalez-Aller C. Hiester A. deBoer M. Harbeck RJ. Oyer R. Johnson GL. Roos D. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proceedings of the National Academy of Sciences of the United States of America. 97(9):4654-9, 2000 Apr 25.

A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O(2)(-)) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes >96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O(2)(-) production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O(2)(-) production in an in vitro assay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2(D57N)). Asp57 is invariant in all defined GTP-binding proteins. Rac2(D57N) binds GDP but not GTP and inhibits oxidase activation and O(2)(-) production in vitro. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.


Ramm GA. Carr SC. Bridle KR. Li L. Britton RS. Crawford DH. Vogler CA. Bacon BR. Tracy TF. Morphology of liver repair following cholestatic liver injury: resolution of ductal hyperplasia, matrix deposition and regression of myofibroblasts. Liver. 20(5):387-96, 2000 Oct.

BACKGROUND/AIMS: Myofibroblasts are the primary cells responsible for increased matrix deposition in hepatic fibrosis. Activation of hepatic stellate cells and portal fibroblasts to myofibroblasts during cholestatic liver injury is accompanied by increased expression of the activation marker, alpha-smooth muscle actin (SMA), and collagen genes. In contrast to our understanding of injury, the cellular mechanisms of liver repair are not well defined. This study was designed to examine the morphological relationship between bile duct hyperplasia, matrix deposition and myofibroblast phenotype in a model of chronic cholestatic liver injury and repair. METHODS: Reversible extrahepatic obstruction was accomplished in rats using a soft vessel loop suspended from the anterior abdominal wall: duct manipulation alone was performed in sham-operated controls. After 7 days, rats were either sacrificed or decompressed by release of the loop and subsequently sacrificed 2-10 days after reversal. Liver sections were obtained for in situ hybridization for procollagen alpha1(I) mRNA, immunohistochemical staining for SMA and cytokeratin 19, and histochemical staining for reticulin. RESULTS: Cholestatic livers demonstrated bile duct hyperplasia, which reversed to normal within 10 days after decompression. Fibrosis was also substantially reduced during this period. SMA-positive myofibroblasts were abundant and localized to regions adjacent to proliferating ducts and excess matrix in the obstructed animals. Decompressed livers showed a dramatic time-dependent reduction in the number of SMA-positive cells and in the expression of procollagen I mRNA. CONCLUSIONS: Our results show that the disappearance of bile duct hyperplasia after biliary decompression is accompanied by a similarly rapid loss of SMA-positive myofibroblasts. Both cellular events may abrogate enhanced matrix synthesis and allow repair to occur.

Phornphutkul C. Okubo T. Wu K. Harel Z. Tracy TF Jr. Pinar H. Chen S. Gruppuso PA. Goodwin G. Aromatase p450 expression in a feminizing adrenal adenoma presenting as isosexual precocious puberty. Journal of Clinical Endocrinology & Metabolism. 86(2):649-52, 2001 Feb.

A 7-yr-old girl presented with isosexual precocious puberty secondary to a feminizing adrenal adenoma. The adrenal tumor was found to express aromatase messenger ribonucleic acid. Enzyme kinetic studies revealed a high level of aromatase activity in the adrenal tumor, with a K(m) of 45 nmol/L and a maximum velocity of 25.6 pmol/mg.h. Aromatase activity was approximately 500-fold higher in the tumor than in adjacent normal adrenal tissue. Although histopathological examination of the tumor was most consistent with a benign adenoma, the aromatase transcripts present in the tumor corresponded to those previously associated with malignant as well as benign tumors. We consider the pattern of aromatase expression sufficient to warrant continued follow-up for tumor recurrence. Our case demonstrates that isosexual precocious puberty secondary to a feminizing adrenal tumor can be due to estrogen synthesis from the tumor itself rather than peripheral aromatization as had been previously theorized.


Luks FI. Roggin KK. Wild YK. Piasecki GJ. Rubin LP. Lesieur-Brooks AM. De Paepe ME. Effect of lung fluid composition on type II cellular activity after tracheal occlusion in the fetal lamb. Journal of Pediatric Surgery. 36(1):196-201, 2001 Jan.

BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) causes accelerated lung growth. However, prolonged TO is associated with a decline in the type II cell number. Type II cell function after TO is unclear. Herein, the authors examine type II cell function after TO and the role of tracheal fluid. METHODS: Fetal lambs (term, 145 days) underwent TO at 122 days. Tracheal pressure was recorded daily. In one group of animals (TF; n = 6), lung fluid was aspirated, measured, and reinfused daily. In their respective twins, NS group, lung fluid was replaced milliliter per milliliter with normal saline (NS; n = 6). At death near term, lung weight was obtained, and tissues were processed for stereologic volumetry. Type II cells were quantitated using antisurfactant protein B immunohistochemistry. Surfactant protein B-mRNA expression was studied by Northern analysis. Wilcoxon signed rank test and single factor analysis of variance (ANOVA) were used for statistical analysis (P<.05 was significant). RESULTS: In both experimental groups, intratracheal pressure rose from 1.9+/-1.0 torr to 3.7 to 4.8 torr by day 1, and remained constant thereafter. Lung fluid volume increased from 11.9+/-4.2 on day 0 to 36.8+/-8.0 mL/kg in TF, and to 28.4+/-9.3 mL/kg in NS by day 1 (P<.05). At death, lung weight/body weight ratio was higher in TF (5.45% +/- 0.91%) than in NS (4.40% +/- 0. 67%) or control (3.83%+/-0.58%; P<.05). Type II numerical density was substantially reduced after TO: 57.7+/-12.8 x 10(6)/mL (TF) and 45.0 +/-25.9 x 10(6)/mL (NS), versus 82.3+/-13.6 x 10(6)/mL in controls. Ultrastructurally, remaining type II cells in TF were enlarged and engorged with lamellar bodies; in NS, they were smaller and contained fewer lamellar bodies. Surfactant protein B mRNA expression was significantly decreased in NS, but not in TF, compared with controls. CONCLUSIONS: Type II cell function as well as overall lung growth are stimulated by TO. Lung growth after TO is therefore not unavoidably detrimental to type II cells. After isobaric saline exchange of lung fluid, type II cell function is severely inhibited, confirming the role of tracheal fluid composition in type II stimulating type II cell function.


Roggin KK. Chwals WJ. Tracy TF. Institutional Review Board approval for prospective experimental studies on infants and children. Journal of Pediatric Surgery. 36(1):205-8, 2001 Jan.

BACKGROUND/PURPOSE: The Declaration of Helsinki requires Institutional Review Board (IRB) approval for experimental studies on human subjects. The authors questioned whether published prospective surgical experimental studies document IRB approval for infants and children. METHODS: Prospective studies were identified in 5 surgical and 2 major pediatric journals from 1997 through 1999. Documentation of IRB approval was recorded. Results were analyzed using Pearson chi(2) tests and a multivariate regression model. Statistical significance was defined as P less than .05. RESULTS: A total of 149 prospective experimental studies on pediatric subjects were evaluated; the majority being interventional or therapeutic studies (105 of 149). More than 75% were from academic medical centers (125 of 149), grant-supported (110 of 149), and appeared in surgical journals (110 of 149). Slightly less than 25% of studies (40 of 149) documented IRB approval. Observational studies, grant support, and publication in nonsurgical journals all correlated positively with IRB approval and were statistically significant variables (P<.001, P<.001, P<.001, respectively). Interventional or therapeutic, institutionally or privately-funded studies found in surgical journals were most likely to avoid IRB documentation (P<.001). CONCLUSIONS: The majority of prospective pediatric studies in the surgical journals omit IRB documentation. Strict requirements for specific IRB approval and documentation in compliance with the Declaration of Helsinki would allow higher ethical standards for the clinical investigation of infants and children.


Roggin KK. Kim JC. Kurkchubasche AG. Papa EF. Vezeridis AM. Tracy TF. Macrophage phenotype during cholestatic injury and repair: the persistent inflammatory response. Journal of Pediatric Surgery. 36(1):220-8, 2001 Jan.

BACKGROUND/PURPOSE: Biliary decompression for congenital or acquired obstruction (eg, biliary atresia) does not uniformly lead to liver repair, restore function, or prevent cholangitis. The authors hypothesize that failed repair is caused by altered macrophage (Mo) phenotypes central to an ongoing inflammatory and fibrogenic response. METHODS: In adult rats, biliary obstruction was performed by suspension of the common bile duct for 5 or 7 days. Decompression followed release of the loop until death during the course of liver repair. To determine Mo phenotype in the presence or absence of resident macrophages, animals were either administered gadolinium chloride or saline before injury and repair. At death, hepatic Mo were isolated, stained with MAC-1 (CD11b/CD 18) and OX-3 (MHC class II), and quantified with flow cytometry. Liver sections were immunostained for ED-1 and ED2; positive Mo were counted per square millimeter of tissue. RESULTS: Obstruction led to bile duct proliferation, fibrosis, and inflammation. Decompression relieved jaundice and ductal hyperplasia. After injury, hepatic Mo showed an 80% phenotypic conversion to MAC-1 and OX-3-positive cells. Cells isolated from livers at 9 days of repair persisted with 60% MAC-1 and 77% OX-3 expression. Gadolinium reduced Kupffer cells at all stages of repair. Recruited Mo in treated animals increased 4-fold greater than controls. CONCLUSIONS: Kupffer cells appear to limit the recruitment and persistence of a systemic macrophage phenotype in liver injury and repair. Cell surface markers for systemic macrophages appear after injury and persist during repair, despite adequate biliary decompression. After biliary decompression, this macrophage phenotype accounts for inflammatory complications such as cholangitis and ongoing fibrosis.


Liao, S. L.; Luks, F. I.; Piasecki, G. J.; Wild, Y. K.; Papadakis, K., and De Paepe, M. E. Late-gestation tracheal occlusion in the fetal lamb causes rapid lung growth with type II cell preservation. J Surg Res. 2000 Jul; 92(1):64-70.

BACKGROUND: Fetal tracheal occlusion (TO) results in varying degrees of lung growth. This study examines whether gestational age influences lung growth response following TO. MATERIALS AND METHODS: Fetal lambs (term = 145 days) underwent TO early (108 days, n = 6) or late (122 days, n = 6) in gestation. Aspirated lung fluid volume (LFV) and intratracheal pressure (ITP) were recorded daily. Two weeks after TO, the fetuses were sacrificed. Lung growth was assessed by lung weight and stereologic volumetry. Type II cellular density was assessed by computer-assisted morphometry using antisurfactant protein B antibody. RESUTLS: After early TO, ITP remained below 2 mm Hg for all but one of the first 5 days. In late TO, ITP rose to 4.8 +/- 1.7 mm Hg by Day 1 and remained elevated. LFV remained lower after early than after late TO (P < 0.05) for 8 days. Thereafter, pressure and volume reached similar levels in both TO groups; both were significantly higher than their respective controls (P < 0.05). Parenchymal fraction (1 - air- space fraction) was significantly smaller after late TO (22.8 +/- 1.2%) than after early TO (31.3 +/- 0.5%). Type II density was 38.0 +/- 12.4 x 10(6)/mL after early TO and 84.0 +/- 24.3 x 10(6)/mL in control (P < 0.05); the difference between late TO and control was not significant. CONCLUSIONS: Late tracheal occlusion in fetal lambs caused more rapid lung growth than earlier TO, although ultimate lung size was similar in both groups. Late TO also resulted in greater air-space fraction and better preservation of the type II cell population than early TO. Late- gestation tracheal occlusion may therefore be preferable to prolonged occlusion initiated earlier. Copyright 2000 Academic Press.

Luks, F. I.; Wild, Y. K.; Piasecki, G. J., and De Paepe, M. E. Short-term tracheal occlusion corrects pulmonary vascular anomalies in the fetal lamb with diaphragmatic hernia. Surgery. 2000 Aug; 128(2):266-72.

BACKGROUND: Sustained fetal tracheal occlusion (TO) results in accelerated lung growth but causes severe type II cell depletion. Temporary TO fails to cause lung growth in a congenital diaphragmatic hernia (CDH) model but preserves type II cells and corrects pulmonary hypertension. Herein, we study the pulmonary vascular changes caused by temporary TO. METHODS: CDH was created in 12 fetal lambs (65-70 d; term, 145 days). In 6 lambs, the trachea was occluded for 2 weeks (CDH + TO; 108-122 d). Animals were killed at 136 days. The lungs were processed with elastin stains and anti-alpha-smooth muscle actin antibody. Partial or circumferential presence of inner and outer elastic lamina was used to determine muscularization of pulmonary arterioles. The percent of medial wall thickness was plotted against vessel diameter for each group. RESULTS: Lung weight/body weight was smaller in lambs with CDH (1. 35% +/- 0.56%) and CDH + TO (1.70% +/- 0.34%) than in control lambs (3.55% +/- 0.56%; P <.05, single-factor analysis of variance). The smallest muscularized vessel was 113 +/- 50 &mgr;m, and the largest nonmuscularized vessel was 138 +/- 49 &mgr;m in lambs with CDH, significantly different from control lambs (185 +/- 69 &mgr;m and 350 +/- 116 &mgr;m, respectively) and lambs with CDH + TO (185 +/- 97 &mgr;m and 245 +/- 100 &mgr;m, respectively; P <.05). In lambs with CDH, only 25% of vessels of less than 60 &mgr;m were nonmuscularized, compared with 81% in control lambs (P <.05) and 74% in lambs with CDH + TO.Conclusions. Temporary tracheal occlusion, from 108 to 122 days, corrects the abnormal muscularization of pulmonary arterioles seen in CDH. These morphometric findings parallel physiologic results at birth and further suggest that short-term occlusion, which preserves surfactant-producing type II pneumocytes without lung growth, may be sufficient to improve neonatal outcome of diaphragmatic hernia.

Kurkchubasche, A. G.; Halvorson, E. G.; Forman, E. N.; Terek, R. M., and Ferguson, W. S. The role of preoperative chemotherapy in the treatment of infantile fibrosarcoma. J Pediatr Surg. 2000 Jun; 35(6):880-3.

Infantile fibrosarcoma (IFS) is a rare tumor most often affecting the extremities of infants and young children. Unlike its adult counterpart, IFS has a low potential for metastatic spread, and surgical extirpation alone has therefore resulted in an excellent prognosis. The amputation rate, however, exceeds 50%. The dramatic response in 2 recent cases to preoperative chemotherapy, given in an attempt to avoid amputation, prompted this report and a review of the literature.

Wild YK, Piasecki GJ, De Paepe ME, Luks FI. Short-term tracheal occlusion in fetal lambs with diaphragmatic hernia improves lung function, even in the absence of lung growth. Journal of Pediatric Surgery. 35(5):775-779, 2000 May.

Background: Prolonged tracheal occlusion (TO) accelerates lung growth, but impairs surfactant production. Short-term TO results in less lung growth, but preserves type II cell function. We studied the effects of short-term TO on lung physiology in diaphragmatic hernia.Methods: Diaphragmatic hernia was created in nine fetal lambs at 90-95 d. Five were left uncorrected (CDH), four underwent 2-week TO (108-122 d; CDH+TO). Five unoperated lambs served as controls. Near term (136 d), fetuses were ventilated for 90-150 min. Pulmonary arterial pressure, postductal blood gases, quasi-static compliance, total lung capacity (TLC) and lung weight/body weight (LW/BW) were measured. Results: There was an overall survival rate of 89% at term. Short-term occlusion did not induce lung growth (TLC and LW/BW 6.07 ± 2.92 mL/kg and 0.022 ± 0.008 in CDH, 4.86 mL/kg and 0.019 ± 0.005 in CDH+TO, 10.81 ± 3.55 mL/kg and 0.036 ± 0.006 in controls, respectively). However, pulmonary hypertension in CDH (47.4 ± 12.32/35.8 ± 12.19 torr) was corrected by short-term occlusion (20.2 ± 4.0/16.0 ± 4.8 torr in CDH+TO, P<0.05, single-factor ANOVA; similar to control). Best pO2 and pCO2 improved after occlusion (CDH: 48.6 ± 6.7 torr and 107.1 ± 34.3 torr, respectively; CDH+TO: 101.5 ± 16.3 torr and 81.9 ± 2.4 torr; control: 291.4 ± 4.7 torr and 37.7 ± 17.3), as did oxygenation index (P<0.05, CDH vs. CDH+TO) (CDH: 97.2 ± 23.0, CDH+TO: 28.7 ± 3.1, control: 5.6 ± 0.6). Conclusions: Short-term TO corrects pulmonary hypertension and improves gas exchange in fetal lambs with diaphragmatic hernia, despite failure to produce accelerated lung growth. Inducing lung maturation and correcting the physiologic derangement in diaphragmatic hernia may be more important than achieving lung growth alone.

Roggin K K, Breuer CK, Carr SR, Hansen K, Kurkchubasche AG, Wesselhoeft CW, Jr., Tracy TF, Jr., Luks FI. The unpredictable character of congenital cystic lung lesions. Journal of Pediatric Surgery. 35(5):801-805, 2000 May.

Background: The spectrum of congenital cystic disease of the lung ranges from hydrops and neonatal respiratory distress to asymptomatic lesions. Operative management is dictated by the presence of symptoms, recurrent infection, and the risk of malignant transformation.
Methods: Since 1995, all consecutive congenital cystic lung lesions were followed for symptoms, operative treatment, and correlation of presumptive with pathologic diagnosis. Results: Twelve cystic lung lesions were identified. Six were diagnosed with mediastinal shift before 25 weeks of gestation; in four of six, the shift subsequently resolved. Overall, six of seven lesions that were followed serially decreased in size. Two patients were symptomatic in utero; one underwent thoracoamniotic shunting, one pleurocentesis for impending hydrops. Postnatally, these two, and two others required urgent surgery. Four of eight asymptomatic patients had elective resection by 16 months and four await operation. In five of the eight operative cases (63%), there was a discrepancy between preoperative and pathologic diagnosis. There were four hybrid CAM/sequestrations. Conclusions: At least 80% of congenital cystic lung lesions decreased in size regardless of gestational age or presence of mediastinal shift. Antenatal intervention is therefore rarely indicated. Because of uncertain pathologic diagnosis, even stable asymptomatic lesions should be resected.

Roggin K K, Papa EF, Kurkchubasche A G, Tracy TF,Jr. Kupffer cell inactivation delays repair in a rat model of reversible biliary obstruction. Journal of Surgical Research. 90(2):166-73, 2000 May

Background. During cholestatic liver injury, Kupffer cells (KC) and activated macrophages modulate cell proliferation and subsequent matrix deposition. The role of KC in the restoration of cell architecture and matrix metabolism during repair following chronic cholestatic liver injury is unknown. Materials and methods. To determine the effect of KC inactivation, adult male Sprague-Dawley rats underwent bile duct suspension (BDS) for 5 days followed by reversal of the obstruction. Saline (control) and gadolinium chloride (10 mg/kg) were administered 1 day prior to BDS and 1 day prior to reversal, to inactivate KC during both injury and repair. Serum bilirubin and quantitative cell morphometry were compared to verify the reversibility of the model. Collagen content of the liver was measured in trichrome-stained paraffin sections using NIH imaging software. Results. Reversibility of the obstruction was verified by normalization of direct serum bilirubin, which peaked at 8.42 +/- 0.76 mg/dL following 5 days of BDS and returned to sham-operated levels 2 days after reversal, 0.36 +/- 0.15 mg/dL. Hematoxylin and eosin (H&E)-stained paraffin-embedded liver sections from gadolinium-treated animals at 4 and 7 days after reversal exhibited persistent bile duct proliferation, matrix deposition, and inflammation. Gadolinium-treated animals had altered collagen metabolism compared to saline controls. Whereas the collagen content in the saline group slowly returned to sham-operated levels over time, the treatment group demonstrated progressive accumulation of collagen during repair which was statistically significant at 7 days following reversal (8.79%/mm(2) +/- 2.17 in gadolinium group vs 2.33%/mm(2) +/- 0.34 in saline group, P = 0.0003). Conclusions. These results demonstrate that inactivation of resident hepatic macrophages during liver repair impairs collagen metabolism, inhibits the resolution of fibrosis, and allows the persistence of inflammatory cell infiltrates in the portal areas. This is the first evidence of profibrogenic responses in the absence of an intact KC compartment during repair after cholestatic injury.

Lessin MS. Wesselhoeft CW. Luks FI. DeLuca FG. Primary repair of long-gap esophageal atresia by mobilization of the distal esophagus. European Journal of Pediatric Surgery. 9(6):369-72, 1999 Dec.

Long-gap esophageal atresia remains a difficult problem for the pediatric surgeon. Several strategies for lengthening of the proximal esophageal segment have been used with relative success. Autogenous tissue conduits have resulted in less than optimal long-term results. Five patients since 1991 with long gap esophageal atresia (2 with distal tracheo-esophageal fistula [Type C], and 3 with isolated esophageal atresia [Type A]) underwent mobilization of the distal esophagus to the level of the diaphragm in order to perform a primary anastomosis. A retrospective analysis evaluated the timing of repair, when oral feeds were successfully begun, with particular attention to any ischemic sequelae related to the distal esophageal dissection. Two patients underwent immediate repair, three had delayed repair. There were no anastomotic leaks. Three patients healed without stricture. Of four patients who survived long-term, three patients are eating well and only one still requires jejunoenteric supplementation. Classic teaching dictates that dissection of the distal esophagus should not be done because of disruption of its segmental blood supply. In this series, distal esophageal mobilization was successful in facilitating a primary anastomosis. These results are encouraging as an alternative to the high morbidity and marginal long-term results of interposition grafting or gastric transposition.

Luks FI. Logan J. Breuer CK. Kurkchubasche AG. Wesselhoeft CW Jr. Tracy TF Jr. Cost-effectiveness of laparoscopy in children. Archives of Pediatrics & Adolescent Medicine. 153(9):965-8, 1999 Sep.

BACKGROUND: Laparoscopy may offer fast recovery and improved cosmesis, but its cost has been perceived as excessive. OBJECTIVE: To analyze the total hospital costs of laparoscopy vs open surgery. DESIGN: Retrospective cost-effectiveness analysis evaluating all cases performed in a 36-month period (September 1995 to August 1998). Cases were evaluated for operative time, itemized cost of supplies, and length of hospitalization. SETTING: Operations performed by pediatric surgeons in a tertiary care children's hospital. PATIENTS: Consecutive children undergoing laparoscopic or open appendectomies, cholecystectomies, fundoplications, and splenectomies. Patients were not randomized to laparoscopy, or open surgery. INTERVENTIONS: Laparoscopic procedures performed with a core set of reusable equipment and a limited number of disposable instruments. MAIN OUTCOME MEASURES: Cost surplus of laparoscopy was evaluated, and compared with savings associated with decreased hospital stay, to obtain cost-effectiveness of laparoscopy per procedure. RESULTS: There were 26 laparoscopic and 359 open appendectomies; 33 laparoscopic and 3 open cholecystectomies; 16 laparoscopic and 18 open fundoplications; and 16 laparoscopic and 7 open splenectomies. Excess operating costs per procedure were $442.00 for appendectomy, $634.60 for fundoplication, $847.50 for cholecystectomy, and $1551.30 for splenectomy. Hospital stay was decreased for all laparoscopies, resulting in an overall savings per laparoscopic procedure of $2369.90 for appendectomy, $5390.90 for fundoplication, $1161.00 for cholecystectomy, and $858.90 for splenectomy. CONCLUSIONS: Laparoscopy is cost-effective, particularly for fundoplication, appendectomy, and cholecystectomy. Detailing the costs of supplies, operating time, and length of stay allows interinstitutional comparison and critical cost-analysis of laparoscopy. With a more selective use of reusable instruments and further shortening of operative time, the global savings of laparoscopy may increase.

Lessin MS. Luks FI. Brem AS. Wesselhoeft CW Jr. Primary laparoscopic placement of peritoneal dialysis catheters in children and young adults. Surgical Endoscopy. 13(11):1165-7, 1999 Nov.

BACKGROUND: Primary placement of peritoneal dialysis catheters in children often requires suturing of the catheter into the pelvis. We describe our experience with a gasless laparoscopy technique in children and young adults. METHODS: During an 18-month period, 12 patients (mean age, 14 years) underwent primary laparoscopic placement of peritoneal dialysis catheters. A single umbilical port was used for abdominal wall elevation, telescope, and catheter. A needleholder was introduced via an accessory port at the future catheter exit site or through the umbilical port. Omentectomy was performed through the umbilical incision. The catheter was tunneled to the lateral abdominal wall. Follow-up data (>/= 15 months) included time to initiation of dialysis, hospitalization, and outcome. End points were cure, transplantation, or death. RESULTS: Diet was started on the day of surgery and dialysis on the following day. Four patients had seven complications, including leakage and entanglement of the catheter in tubal fimbriae. Long-term revision-free catheter survival was 67% at 24 months. CONCLUSIONS: This minimal access technique for primary placement of peritoneal dialysis catheters includes securing of the catheter tip in a dependent location and omentectomy. It allows nearly immediate use of the catheter, leads to a minimal hospital stay, and has acceptable long-term patency.

De Paepe ME. Sardesai MP. Johnson BD. Lesieur-Brooks AM. Papadakis K.  Luks FI. The role of apoptosis in normal and accelerated lung development in fetal   rabbits.   Journal of Pediatric Surgery. 34(5):863-70; discussion 870-1, 1999 May. 

  BACKGROUND/PURPOSE: During fetal development, the mammalian lung undergoes   progressive parenchymal involution. Intrauterine tracheal occlusion induces   accelerated architectural maturation of the fetal lungs associated with   depletion of the surfactant-producing type II cells. This study investigates   the spatiotemporal pattern of apoptosis during normal fetal lung development   and its modulation in tracheal occlusion-induced accelerated fetal lung   growth. METHODS: Fetal rabbit lungs were studied at 25 to 31 days'   gestational age (DGA; term, 31 DGA), corresponding to late pseudoglandular   through terminal air sac stages of fetal lung development. Intrauterine   tracheal ligation (TL) was performed at 24 DGA. TL fetuses were monitored   until 29 DGA, a time-point previously shown to coincide with significant type   II cell depletion. Apoptotic cells were identified by light and electron   microscopy, as well as terminal deoxynucleotidyl transferase-mediated   dUTP-FITC nick-end labeling (TUNEL). Epithelial (type I and II) cell   apoptosis was studied by TUNEL labeling in conjunction with antisurfactant   protein and anticytokeratin immunohistochemistry. DNA fragmentation was   analyzed by gel electrophoresis. Sham-operated littermates served as   controls. RESULTS: The number of apoptotic cells progressively increased with   advancing lung growth and architectural maturation (apoptotic index [Al] 1.2   +/- 0.7 x 10(-3) at 25 DGA v 4.2 +/- 1.4 x 10(-3) at 31 DGA; P< .05, analysis   of variance). In TL fetuses, the apoptotic rate was significantly higher than   in non-TL fetuses from the third postligation day on, coinciding with the   onset of significantly increased airspace distension (Al 4.9 +/- 1.3 x 10(-3)   in TL v2.6 +/- 0.4 x 10(-3) in controls at 29 DGA; P< .05, Student's ttest).   Apoptosis occurred in parenchymal cells and in isolated cells within the   airspaces. The apoptotic activity of type II cells was significantly higher   in TL fetuses than C fetuses at 29 DGA (type II Al 25.5 +/- 6.3 x 10(-3) in   TL v2.3 +/- 0.8 x 10(-3) in C; P< .001). Electron microscopic studies   confirmed the presence of apoptotic nuclei in interstitial macrophages and in   degenerating intraluminal type II cells. DNA analysis showed nucleosomal   bands. CONCLUSIONS: Normal fetal lung development is associated with a   progressive increase of epithelial and interstitial apoptotic activity, a   process enhanced by TL. Tracheal occlusion induces a significant increase of   type II cell apoptosis, which likely contributes to the observed type II cell   depletion after TL. We speculate that fetal type II cell apoptosis after TL   may be induced by mechanical distension (stretch) of the airspaces.

Kokoska ER. Silen ML. Tracy TF Jr. Dillon PA. Kennedy  DJ. Cradock TV. Weber TR.   The impact of intraoperative culture on treatment and outcome in children   with perforated appendicitis.   Journal of Pediatric Surgery. 34(5):749-53, 1999 May. 

  BACKGROUND: Most protocols for the operative treatment of perforated   appendicitis use a routine culture. Although isolated studies suggest that   routine culture may not be necessary, these recommendations generally are not   based on objective outcome data. METHODS: The authors reviewed the records of   308 children who underwent operative treatment for perforated appendicitis   between 1988 and 1998 to determine if information gained from routine culture   changes the management or improves outcome. Inclusion criteria included   either gross or microscopic evidence of appendiceal perforation. RESULTS:   Mean patient age was 7.5 years, 51% were boys, and there was no mortality.   The majority of children (96%) underwent culture that was positive for either   aerobes (21%), anaerobes (19%), or both (57%). Antibiotics were changed in   only 16% of the patients in response to culture results. The use of empiric   antibiotics, as compared with modified antibiotics, was associated with a   lower incidence of infectious complication, shorter fever duration, and   decreased length of hospitalization. We also investigated the relationship   between culture isolates and antibiotic regimens with regard to outcome. The   utilization of antibiotics suitable for the respective culture isolate or   organism sensitivity was associated with an increased incidence of infectious   complication and longer duration of both fever and length of hospitalization.   Finally, the initial culture correlated poorly with subsequent intraabdominal   culture (positive predictive value, 11%). CONCLUSION: These outcome data   strongly suggest that the practice of obtaining routine cultures can be   abandoned, and empiric broad spectrum antibiotic coverage directed at likely   organisms is completely adequate for treatment of perforated appendicitis in   children. 

Tackett LD. Breuer CK. Luks FI. Caldamone AA. Breuer JG.  DeLuca FG. Caesar RE. Efthemiou E. Wesselhoeft CW Jr.  Incidence of contralateral inguinal hernia: a prospective analysis.   Journal of Pediatric Surgery. 34(5):684-7; discussion 687-8, 1999 May. 

  BACKGROUND/PURPOSE: Contralateral groin exploration in children with   unilateral inguinal hernia is still controversial, particularly in infants.   The authors have attempted to determine the age- and gender-stratified   incidence of contralateral hernia and the necessity of routine bilateral   procedures. METHODS: This is a prospective study of 656 patients during a   34-month period at a single institution. Patients with unilateral hernia   underwent an ipsilateral procedure only, regardless of age, gestational age,   or gender. Follow-up was 6 to 40 months (mean, 25.5 months). Chi-square   analysis was used for intergroup comparison (P < .05 significant). RESULTS:   Of 656 children, 108 (16.5%) presented with synchronous bilateral hernias.   Bilateral inguinal hernia was significantly more common in premature infants   (28.0%) and young children (33.8% if <6 months, 27.4% if <2 years). Of the   remaining 548, a metachronous contralateral hernia developed in 48 (8.8%) at   a median interval of 6 months (range, 4 days to 7 years). This incidence was   13 of 105 (12.4%) in infants less than 6 months of age, 20 of 189 (10.6%) in   children less than 2 years of age, 8 of 54 (14.8%) in premature infants, 6 of   81 (7.4%) in girls, and 8 of 29 (27.6%) in children with an incarcerated   hernia. In the latter group, P < .05, chi2 analysis. CONCLUSION: Routine   contralateral inguinal exploration, without clinical evidence of a hernia,   may be advisable in children with incarceration and possibly in premature   infants. The low incidence of contralateral hernias in all other patients,   regardless of gender or age, does not justify routine contralateral   exploration. 

Silen ML. Kokoska ER. Fendya DG. Kurkchubasche AG. Weber  TR. Tracy TF.   Rollover injuries in residential driveways: age-related patterns of injury.   Pediatrics. 104(1):e7, 1999 Jul. 

  BACKGROUND: The major objective of the present study was to determine the   severity of nonfatal injuries sustained by children (<16 years old) when a   motor vehicle rolls over them. We also sought to determine whether younger   children (<24 months old) demonstrated different patterns of injury and/or a   worse outcome, compared with older children (>24 months old). METHODS: We   reviewed the medical records of 3971 consecutive admissions to a single   trauma service at an urban children's hospital between March 1990 and October   1994. During this time period, 26 (0.7%) children presented with rollover   injuries incurred by motor vehicles in residential driveways. Outcome was   measured by length of both intensive care unit admission and hospitalization.   RESULTS: Two children died shortly after admission and were excluded from the   remainder of the study. Younger children (<24 months old) had significantly   higher injury severity scores and lower pediatric trauma scale scores. Both   the duration in the intensive care unit and the length of hospitalization   were significantly longer in younger children, compared with children >24   months old. One explanation for these observations was that younger children   had a significantly higher incidence of both head and neck and extremity   injury but a similar incidence and severity of chest and abdominal trauma,   compared with older children. Injuries requiring operative intervention were   rare. CONCLUSION: Younger patients sustaining rollover injuries in the   residential driveway have a worse outcome, in part, because of the head and   neck or extremity injures that they incur. The majority of rollover injuries   can be managed conservatively. pediatric trauma, driveway, pedestrian events,   rollover injuries, injury severity score, pediatric trauma scale.

Lessin MS. Chan M. Catallozzi M. Gilchrist MF. Richards C. Manera L.    Wallach MT. Luks FI.    Selective use of ultrasonography for acute appendicitis in children.   American Journal of Surgery. 177(3):193-6, 1999 Mar. 

  BACKGROUND: To evaluate the role of ultrasonography in children with   equivocal signs of acute appendicitis, and correlate with initial clinical   impression and pathological findings. METHODS: This is a prospective   evaluation of all children presenting with a possible diagnosis of   appendicitis during a 14-month study period. Patients with unequivocal   clinical signs of appendicitis underwent appendectomy without   ultrasonography. Patients with equivocal signs had documentation of the   clinical impression and subsequent abdominal ultrasound. Statistical analysis   of results was performed using the chi-square test (P <0.05 significant).   RESULTS: Two hundred fifteen consecutive children were enrolled. Signs were   unequivocal in 116 and equivocal in 99. Seven patients in the first group had   a normal appendix at operation. Of the 99 patients with equivocal signs,   there were 28 true positives, 3 false positives, 64 true negatives, and 4   false negatives. In equivocal cases, sensitivity of the initial clinical   impression versus ultrasound was 50% and 88%, respectively (P <0.05).   Specificity was 85% and 96%, respectively. The positive and negative   predictive values improved from 63% to 90% and 78% to 94%, respectively, with   the use of ultrasonography. CONCLUSIONS: The low false positive rate (6%) in   clinically obvious cases of appendicitis does not, in our opinion, warrant   ultrasonography. In clinically equivocal cases, ultrasonography is a fast,   sensitive, and specific diagnostic modality to diagnose or rule out   appendicitis, avoiding the need for prolonged observation and/or   hospitalization. 

Sadiq HF. Das UG. Tracy TF. Devaskar SU.    Intra-uterine growth restriction differentially regulates perinatal brain and  skeletal muscle glucose transporters.   Brain Research. 823(1-2):96-103, 1999 Mar 27. 

  Employing Western blot analysis, we investigated the effect of maternal   uterine artery ligation causing uteroplacental insufficiency with   asymmetrical intrauterine growth restriction (IUGR) upon fetal (22d) and   postnatal (1d, 7d, 14d and 21d) brain (Glut 1 and Glut 3) and skeletal muscle   (Glut 1 and Glut 4) glucose transporter protein concentrations. IUGR was   associated with a approximately 42% decline in fetal plasma glucose (p<0.05)   and a approximately 25% decrease in fetal body weights (p<0.05) with no   change in brain weights when compared to the sham operated controls (SHAM).   In addition, IUGR caused a approximately 45% increase in fetal brain Glut 1   (55 kDa) with no change in Glut 3 (50 kDa) protein concentrations. This fetal   brain Glut 1 change persisted, though marginal, through postnatal suckling   stages of development (1d-21d), with no concomitant change in brain Glut 3   levels at day 1. In contrast, in the absence of a change in fetal skeletal   muscle Glut 1 levels (48 kDa), a 70% increase was observed in the 1d IUGR   with no concomitant change in either fetal or postnatal Glut 4 levels (45   kDa). The change in skeletal muscle Glut 1 levels normalized by d7 of age. We   conclude that IUGR with hypoglycemia led to a compensatory increase in brain   and skeletal muscle Glut 1 concentrations with a change in the brain   preceding that of the skeletal muscle. Since Glut 1 is the isoform of   proliferating cells, fetal brain weight changes were not as pronounced as the   decline in somatic weight. The increase in Glut 1 may be protective against   glucose deprivation in proliferating fetal brain cells and postnatal skeletal   myocytes which exhibit 'catch-up growth', thereby preserving the specialized   function mediated by Glut 3 and Glut 4 towards maintaining the intracellular   glucose milieu.

Papadakis K. Chen EA. Luks FI. Lessin MS.   Wesselhoeft CW Jr. DeLuca FG.   The changing presentation of pyloric stenosis.   American Journal of Emergency Medicine. 17(1):67-9, 1999 Jan. 

  Metabolic abnormalities described in pyloric stenosis are now rare, probably   because of prompter recognition of the disease. This report reviews the trend   in presentation over three decades. All infants treated for pyloric stenosis   during three mid-decade target periods were reviewed. Comparison between the   1975 group and the 1985 group and between the 1995 group and previous decades   were designed to identify the impact of ultrasonography, since this modality   has only been available in the last decade. Parameters included age at   diagnosis and incidence of water and electrolyte imbalance as measures of   delay in presentation. Two hundred eighty-three patients were reviewed. Mean   age (weeks) at presentation was 5.4+/-3.0 in 1975, 4.6+/-2.0 in 1985, and   3.4+/-1.3 in 1995 (P < .05, ANOVA). Overall, 88% had no electrolyte anomalies   on admission. There was no statistical difference in frequency of abnormal   results between the three decades. Total and postoperative hospitalization   was significantly shorter in the recent period: in 1985, 5.34 and 4.36 days;   in 1985, 4.48 and 3.4 days; and in 1995, 3.8 and 2.8 days. These data show   that pyloric stenosis is now recognized earlier than in previous decades. The   availability of ultrasonography cannot solely be credited for earlier   diagnosis, since this trend was already apparent before its introduction. The   "classic" metabolic derangements associated with pyloric stenosis have been  highly uncommon for the past three decades.

Kokoska ER. Silen ML. Tracy TF Jr. Dillon PA. Cradock  TV. Weber TR.     Perforated appendicitis in children: risk factors for the development of   complications.   Surgery. 124(4):619-25; discussion 625-6, 1998 Oct. 

  BACKGROUND: Many aspects of the management of perforated appendicitis in   children remain controversial. The objective of this study was to define risk   factors associated with the development of postoperative complications in   children undergoing treatment for perforated appendicitis. METHODS: We   reviewed all children (age < 16 years) who were treated for perforated   appendicitis at Cardinal Glennon Children's Hospital between 1988 and 1997.   Inclusion criteria included either gross or microscopic evidence of   appendiceal perforation. RESULTS: Of 285 children with perforated   appendicitis, 279 underwent immediate operative treatment. Mean patient age   was 7.7 years and there were no deaths. Major postoperative complications   included intra-abdominal abscess (n = 17), ileus (n = 7), mechanical   intestinal obstruction (n = 6), and wound infection (n = 4). All children who   had a postoperative abscess had more than 5 days of symptoms before   operation. Within this subgroup, drain placement was associated with not only   decreased postoperative abscess formation and but also shorter duration of   fever and length of hospitalization. The incidence of mechanical obstruction   or ileus was not increased and the rate of wound infection was actually lower   after drainage. CONCLUSIONS: Drain placement appears to be helpful in   children with late diagnosis but is of little benefit when the duration of   symptoms is less than 5 days. Thus it is likely that drains are most useful   in patients with well-established and localized abscess cavities

Papadakis K. De Paepe ME. Tackett LD. Piasecki GJ. Luks  FI.    Temporary tracheal occlusion causes catch-up lung maturation in a fetal model   of diaphragmatic hernia.   Journal of Pediatric Surgery. 33(7):1030-7, 1998 Jul. 

  BACKGROUND: The lungs of infants born with diaphragmatic hernia are   hypoplastic, immature, and surfactant-deficient. Tracheal occlusion in utero,   which is being proposed as antenatal treatment of diaphragmatic hernia by   promoting compensatory lung growth, decreases surfactant production as well,   through loss of type II pneumocytes. The authors studied whether temporary   tracheal occlusion might cause 'catch-up' lung growth and maturation, without   negative effects of prolonged tracheal occlusion on the surfactant system.   METHODS: Diaphragmatic hernia was created in time-dated fetal lambs (65 to 75   days). At 108 days, the trachea was occluded with an embolectomy catheter (DH   + TO, n = 6). After day 14, the balloon was deflated. Six congenital   diaphragmatic hernia (CDH) fetuses were left unobstructed (DH). For   comparison, a group of fetuses without diaphragmatic hernia were subjected to   prolonged tracheal ligation (TL; 4-week tracheal ligation, n = 3). Unoperated   littermates (n = 8) were used as controls (CTR). All were killed near term.   Lung tissue was processed for light and electron microscopy (computerized   stereologic morphometry). Type II pneumocytes were identified with   antisurfactant protein B antibody. RESULTS: Four animals in DH + TO and four   in DH survived to term. Lung fluid volume (LFV) at 108 days was 5.2 +/- 4.4   mL in DH and 24.6 +/- 6.8 mL in controls (P < .05, Student t test). In DH +   TO, LFV increased ninefold (to 48.3 +/- 13.3 mL) by 1 week postocclusion,   suggesting accelerated lung growth. At term, lung weight to body weight ratio   (LW/BW) was higher in TL (9.85% +/- 1.81%) than in CTR (3.55% +/- 0.56%; P <   .05, analysis of variance); LW/BW and parenchymal volume tended to be greater   in DH + TO than in DH, and air-exchanging parenchymal volume in DH + TO was   similar to CTR (v a 50% reduction in DH), indicating some degree of   hyperplasia after temporary occlusion. Pneumocyte II numerical density was   decreased more than 10-fold in TL (60 +/- 22 v 826 +/- 324 in CTR, P < .001;   it was slightly lower in DH + TO than in CTR, but individual type II   pneumocyte cell volume was greater in the latter, and they appeared more   mature than in DH (increased granulation by light microscopy, fewer glycogen   granules, and abundant lamellar bodies by electron microscopy). Surfactant   was also seen in the air spaces in DH + TO and CTR; it was absent in   unobstructed CDH and in TL. CONCLUSIONS: Temporary tracheal occlusion in   utero does not cause the dramatic decrease in type II pneumocytes seen after   prolonged occlusion. Although only minimal increase in lung volume is seen in   CDH, catch-up parenchymal growth and maturation occur, most notably in the   surfactant-producing system.

Papadakis K. Luks FI. Deprest JA. Evrard VE. Flageole H.  Miserez M. Lerut TE.   Single-port tracheoscopic surgery in the fetal lamb.   Journal of Pediatric Surgery. 33(6):918-20, 1998 Jun. 

  BACKGROUND/PURPOSE: Endoscopic fetal surgery could help avoid many of the   problems associated with open fetal surgery, but the use of multiple ports   may be too traumatic to the membranes. The authors describe a single-port   technique of tracheoscopic surgery in the fetus. METHODS: Time-dated pregnant   ewes (95 to 105 days; term, 145 days) underwent midline laparotomy under   general halothane anesthesia. A 5-mm-diameter balloon-tipped cannula was   introduced in the uterus by Seldinger technique. A 1.2-mm semirigid   mini-endoscope, fitted inside a 9F, 20 degrees curved sheath, was introduced   under continuous, low-pressure irrigation, inside the fetus' mouth, and   advanced into the trachea. RESULTS: Endotracheal procedures, including   temporary (n = 11) and permanent balloon tracheal occlusion (n = 30) and   placement of a barbed guide wire for endotracheal occlusion device insertion   (n = 12), were performed by introducing a 1-mm diameter instrument alongside   the telescope. These were successfully performed in 52 of the 53 fetuses. The   rigidity of the telescope allowed controlled access to the pharynx; its curve   allowed full tracheobronchial endoscopy with the fetus in utero. CONCLUSIONS:   The present technique marries the control and optical quality of a rigid   endoscope with the physiological curve only a flexible instrument could offer   until now. The types of procedures performed with this technique illustrate   its potential as a research tool; the size (1.2-mm diameter), shape, and   optical qualities of the telescope should make clinical applications   possible.

Lessin MS. Luks FI.   Laparoscopic appendectomy and duodenocolonic dissociation (LADD) procedure  for malrotation. Sorce  Pediatric Surgery International. 13(2-3):184-5, 1998 Mar. 

  The treatment of "asymptomatic" intestinal malrotation remains controversial,  particularly beyond the neonatal period. Two cases illustrate the application  of laparoscopy for correction of malrotation: one in an older child and   another in an asymptomatic infant. Both patients recovered well and were   discharged 2 days after surgery. Laparoscopic appendectomy and duodenocolonic   dissociation allows excellent visualization of the duodenocolic and Ladd's   bands and easily accommodates appendectomy. The availability of this   minimal-access technique should encourage correction of malrotation in the   asymptomatic patient.

Lechner AJ. Velasquez A. Knudsen KR. Johanns CA. Tracy  TF Jr. Matuschak GM.  Cholestatic liver injury increases circulating TNF-alpha and IL-6 and   mortality after Escherichia coli endotoxemia.   American Journal of Respiratory & Critical Care Medicine. 157(5 Pt  1):1550-8, 1998 May. 

  We employed a bile duct ligation (BDL) model of cholestatic liver injury to   test the hypothesis that this form of preexisting hepatic dysfunction alters   the kinetics of circulating TNF-alpha and IL-6 after Escherichia coli   endotoxemia, thereby augmenting mortality and lung injury by a   TNF-alpha:leukotriene (LT) axis of inflammation. Male rats were catheterized   13 d after BDL or sham surgery and studied while awake 18 to 24 h later.   Cholestasis after BDL was confirmed by baseline serum bilirubin (BDL = 7.34   +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p <   0.005) and histopathology. Sham and BDL animals received E. coli   lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9% NaCl (NS)   ending at t = 0 and were monitored over 24 h for vital signs and   hemodynamics. In parallel studies, lipoxygenase inhibition was performed   using diethylcarbamazine or the 5-lipoxygenase activating-protein inhibitor   MK-886. Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for   formed elements and for serum endotoxin, TNF-alpha, IL-6, bilirubin, and   alanine aminotransferase (ALT). Organs were evaluated at 24 h for   histopathology, including neutrophil (PMN) densities and wet/dry weight (W/D)   ratios. Cholestasis reduced survival after otherwise nonlethal endotoxemia,   with seven of 11 BDL + LPS rats dying within 24 h versus no deaths in BDL +   NS (n = 6), Sham + LPS (n = 14), or Sham + NS (n = 6) animals (p < 0.01).   Despite equivalent serum endotoxin between groups, circulating TNF-alpha was   8-fold higher in BDL + LPS than in Sham + LPS rats at 1.5 and 3.5 h (p <   0.001), whereas serum TNF-alpha did not differ between BDL + NS and Sham + NS   rats. IL-6 likewise was increased differentially by 1.5 h in BDL + LPS   animals (11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58 ng/ml, p   < 0.05). Hypothermia, bradycardic hypotension, and leukopenia were most   severe and prolonged in BDL + LPS rats, which also had significantly higher   ALT values, W/D ratios, and organ PMN counts. LT inhibition failed to reduce   BDL-related differences in serum cytokines or survival after endotoxemia.   Thus, cholestasis augments inflammatory responses to gram-negative   endotoxemia, sensitizing the host to enhanced fluid flux in multiple organs   and to mortality by a LT-independent mechanism.

Kurkchubasche AG. Cardona M. Watkins SC. Smith SD.   Albanese CT. Simmons RL. Rowe MI. Ford HR.    Transmucosal passage of bacteria across rat intestinal epithelium in the  Ussing chamber: effect of nutritional factors and bacterial virulence.   Shock. 9(2):121-7, 1998 Feb. 

  Transmucosal passage of bacteria across the intestine, the essential and   prerequisite step for bacterial translocation, cannot be effectively studied   using in vivo models of translocation. We have adapted the Ussing chamber   into a fresh, sterile organ culture system that can facilitate the study of   bacterial-epithelial interactions. Intestinal membranes were mounted in the   Ussing chamber and perfused with a solution rich in putative mucosal   micronutrients. The transmembrane potential difference was constantly   monitored as a marker of intestinal integrity. Transmucosal passage of   various bacteria across the normal intestinal epithelium was quantitated, and   the mucosal membrane was examined by light and transmission electron   microscopy. The addition of potassium cyanide to the mucosal perfusate   resulted in an irreversible loss of potential difference. Oxygen deprivation   also led to a precipitous drop in potential difference, but it was reversible   with prompt reoxygenation. In contrast, intestinal membranes perfused with a   solution consisting of Dulbecco's modified Eagle's medium + 20 mM glutamine   maintained their potential difference for a sustained period (>180 min). Both   the viability and structural integrity of the ileal intestinal membrane were   maintained in culture ex vivo using this perfusate. Qualitative differences   were observed in the mechanism of transmucosal passage of mild to moderately   virulent bacteria such as Escherichia coli C-25 and Proteus mirabilis M-13,   which pass through the intestinal epithelium without causing overt damage to   the mucosa, and more virulent organisms such as Salmonella typhimurium, which   cause extensive mucosal damage by light and transmission electron microscopy.   The Ussing system should provide a useful model of intact organ culture for   the study of the mechanisms of bacterial translocation and the pathogenesis   of enteric infections

Lessin MS. Luks FI. Wesselhoeft CW Jr.   Gilchrist BF. Iannitti D. DeLuca FG.  Peritoneal drainage as definitive treatment for intestinal perforation in   infants with extremely low birth weight (<750 g).   Journal of Pediatric Surgery. 33(2):370-2, 1998 Feb. 

  BACKGROUND: Advances in neonatal intensive care have improved the survival of   the extremely premature infant. However, survival at less than 25 weeks'   gestational age remains tenuous, with intestinal perforation presenting a   significant mortality. METHODS: During an 18-month period from 1995 to 1996,   nine patients weighing less than 750 g (range, 485 to 740 g; mean, 615 g)   presented with intestinal perforation. All patients were treated with   peritoneal drainage. Drains were removed after clinical improvement and the   cessation of peritoneal drainage. RESULTS: Seven patients survived the   initial drainage procedure (78%). At a mean follow-up of 12 months, the six   long-term survivors are all tolerating full enteral feeds, and none developed   intestinal strictures or intraabdominal abscess. No patient required   subsequent celiotomy. Peritoneal drainage has previously been considered in   some centers as temporary therapy in extremely ill neonates deemed unlikely   to survive operation. The authors have adopted drainage as the sole treatment   in selected patients. CONCLUSION: Peritoneal drainage alone may be considered   definitive therapy for intestinal perforation in the majority of   micropremature infants.

Weber TR. Kurkchubasche AG.    Operative management of asphyxiating thoracic dystrophy after pectus repair.   Journal of Pediatric Surgery. 33(2):262-5, 1998 Feb. 

  Pectus excavatum repair usually results in unchanged or improved pulmonary   function. However, a small subset of patients will experience severely   impaired pulmonary function after pectus repair caused by restrictive lung   disease, and no adequate surgical approach has been described for this   condition. A procedure is described that is a variation of an operation for   Jeune's thoracic dystrophy, that resulted in marked respiratory improvement   in this setting. A 14-year-old boy had undergone standard pectus excavatum   repair at age 4, from which he recovered uneventfully. Beginning at age 10 to   12 years progressive restrictive pulmonary disease, recurrent pneumonia, and   cor pulmonale developed, which resulted in almost constant shortness of   breath and the need for continuous nasal positive pressure support. Pulmonary   function test results were markedly abnormal and worsening. He underwent an   operative procedure consisting of sternal split that was wedged open   permanently with rib struts, opening of pleura bilaterally, and six rib   resections bilaterally. His postoperative recovery was satisfactory, and his   pulmonary functions have shown steady improvement. He is now completely off   oxygen and pressure support, has improved exercise tolerance, and has   returned to school. Severe restrictive lung disease after pectus repair can   be successfully managed with aggressive operative procedures. Patients should   have close follow-up after pectus repair for the development of this   potentially debilitating disorder to allow earlier repair. 

Olynyk JK. Yeoh GC. Ramm GA. Clarke SL. Hall PM. Britton RS. Bacon BR.    Tracy TF. Gadolinium chloride suppresses hepatic oval cell proliferation in rats with  biliary obstruction.   American Journal of Pathology. 152(2):347-52, 1998 Feb. 

  Liver injury due to bile duct ligation (BDL) is histologically characterized   by cholestasis, bile ductular proliferation, hepatocellular damage, portal   fibrosis, and ultimately biliary cirrhosis. Stem cells within the liver may   act as progenitor cells for small epithelial cells termed oval cells that can   differentiate into bile duct cells or hepatocytes, whereas myofibroblasts are   the principal source of collagen production in fibrosis. The aims of this   study were to determine 1) whether BDL induces oval cell proliferation and 2)   whether blockade of Kupffer cells affects oval cell proliferation, bile duct   proliferation, and myofibroblast transformation in experimental biliary   obstruction. Male Sprague-Dawley rats were divided into two groups to receive   either a single dose of gadolinium chloride (a selective Kupffer cell   blocking agent) or vehicle. One day later, the gadolinium- and   vehicle-treated groups were further subdivided to receive either BDL or sham   operation. The rats were sacrificed on day 7 postoperatively. Serum was   collected for measurement of aspartate aminotransferase, gamma-glutamyl   transpeptidase, and bilirubin levels. Liver tissue was taken for evaluation   of fibrosis, bile ductular cells, oval cells, and myofibroblasts. BDL   resulted in elevated aspartate aminotransferase, gamma-glutamyl   transpeptidase, and bilirubin in serum, and gadolinium pretreatment did not   modify these effects. BDL induced marked oval cell proliferation, which was   completely prevented by gadolinium pretreatment. Gadolinium did not affect   the induction of bile duct expansion or myofibroblasts after BDL. We conclude   that experimental biliary obstruction induces oval cell proliferation, which   can be prevented by gadolinium pretreatment. This suggests that bile ductular   proliferation and myofibroblast transformation are not mediated by Kupffer   cells and that ductular proliferation can proceed in the absence of oval   cells. Alternatively, gadolinium may directly affect oval cell proliferation   after BDL.

De Paepe ME. Johnson BD. Papadakis K. Sueishi K. Luks  FI.  Temporal pattern of accelerated lung growth after tracheal occlusion in the  fetal rabbit.   American Journal of Pathology. 152(1):179-90, 1998 Jan. 

  Tracheal occlusion in utero is a potent stimulus of fetal lung growth. We   describe the early growth mechanics of fetal lungs and type II pneumocytes   after tracheal ligation (TL). Fetal rabbits underwent TL at 24 days   gestational age (DGA; late pseudoglandular stage; term = 31 to 33 days) and   were sacrificed at time intervals ranging from 1 to 5 days after TL. Lung   growth was measured by stereological volumetry and bromodeoxyuridine (BrdU)   pulse labeling. Pneumocyte II population kinetics were analyzed using a   combination of anti-surfactant protein A and BrdU immunohistochemistry and   computer-assisted morphometry. Nonoperated littermates served as controls. TL   resulted in dramatically enhanced lung growth (lung weight/body weight was   5.00 +/- 0.81% in TL versus 2.52 +/- 0.13% in controls at 29 DGA; P < 0.001,   unpaired Student's t-test). Post-TL lung growth was characterized by a 3-day   lag-phase typified by relative stagnation of growth, followed by distension   of airspaces, increased cell proliferation, and accelerated architectural and   cellular maturation by postligation days 4 and 5. During the proliferation   phase, the replicative activity of type II cells was markedly increased (type   II cell BrdU labeling index was 10.0 +/- 4.1% in TL versus 1.1 +/- 0.3% for   controls at 29 DGA; P < 0.02), but their numerical density decreased (3.0 +/-   0.5 x 10(-3)/microm2 in TL versus 4.5 +/- 0.3 x 10(-3)/microm2 in controls at   29 DGA; P < 0.02), suggesting accelerated terminal differentiation to type I   cells. In conclusion, post-TL lung development is characterized by a well   defined temporal pattern of lung growth and maturation. The rabbit model   lends itself well to study the regulatory mechanisms underlying accelerated   fetal lung growth after TL. 

Fox ES. Kim JC. Tracy TF.   NF-kappaB activation and modulation in hepatic macrophages during cholestatic  injury.   Journal of Surgical Research. 72(2):129-34, 1997 Oct. 

  Cholestatic liver injury induces an inflammatory response that follows the   activation of hepatic macrophages. Constitutive activation of the   transcription factor, NF-kappaB, was found in these macrophages over the   course of hepatic injury. Since NF-kappaB activation has been shown to have a   key role in the inflammatory process, the modulatory effects of the   antioxidant, alpha-tocopherol succinate, and the glucocorticoid,   dexamethasone, on NF-kappaB activation were examined in this study. Male   Sprague Dawley rats underwent 2-7 days of common bile duct division and   ligation (CBDL) or sham laparotomy. Hepatic macrophages were isolated by   collagenase Pronase perfusion and purified by centrifugal elutriation.   Activation was determined by electrophoretic mobility shift assay and ELISA.   We determined that NF-kappaB activation in injured hepatic macrophages could   only be inhibited by dexamethasone. Dexamethasone-mediated inhibition of   NF-kappaB activation required the synthesis of a regulatory protein since   cycloheximide-treated cells were resistant to its effects. Furthermore,   dexamethasone-treated hepatic macrophages showed elevated steady-state levels   of IkappaB-alpha mRNA, suggesting the role of IkappaB-alpha as a potential   regulatory mediator. Consistent with constitutive transcriptional activation   we showed constitutive secretion of TNF-alpha from injured hepatic   macrophages which could be inhibited by dexamethasone. These data show for   the first time, in a biologically significant model of hepatic injury,   constitutive activation of the key inflammatory transcription factor   NF-kappaB and cytokine TNF-alpha. These results support an approach focused   on the NF-kappaB/IkappaB-alpha pathway as a critical target for therapeutic   intervention during hepatic injury, and the consideration of possible   steroid-based therapies.

Luks FI. Deprest JA. Gilchrist BF. Peers KH. van der  Wildt B. Steegers EA. Vandenberghe K.    Access techniques in endoscopic fetal surgery.    European Journal of Pediatric Surgery. 7(3):131-4, 1997 Jun. 

  Endoscopic surgery may in the future become an attractive alternative to open   fetal surgery. Herein, we present our evolving experience with minimal access   techniques in sheep and nonhuman primate models. Fifty-two pregnant sheep   (term = 145 d) were used. All underwent laparotomy. Cannulas were 5 mm   diameter with balloon fixation device. In group I (95-105 d, n = 22, and   70-74 d, n = 19), a total of 119 cannulas were placed by open hysterotomy and   pursestring suture through myometrium and membranes. In group II (n = 11),   access was obtained by Seldinger guidewire technique. Eight cannulas were   introduced over a dilator and 7 were radially expanding endoscopic cannulas.   Fifteen cannulas were also placed in 5 pregnant Rhesus monkeys using   Seldinger and radially expanding techniques. Cannula removal was followed by   insertion of a collagen sponge plug and oversewing of the myometrium.   Mini-hysterotomies with purse-stringing provided excellent access to the   amniotic cavity, without dissection of the membranes. Classic Seldinger   technique with forward dilatation was equally effective, but caused   stretching of membranes. In sheep and in primates, Seldinger technique with   radial dilatation allowed safe access without membrane separation. Leak-proof   removal of the cannulas was achieved in all primates. Open hysterotomy with   purse-string and balloon-tipped cannula provides efficient and safe access to   the gravid sheep uterus. Seldinger technique allows equally secure access,   and alleviates the need for hysterotomies. Radial dilatation of the porthole   eliminates forward dissection of the membranes, both in sheep and primate   models. This method, and collagen plug insertion upon completion of the   endoscopic procedure, may provide a truly minimally invasive approach to   in-utero surgery.  

Kurkchubasche AG. Fendya DG. Tracy TF Jr.  Silen ML. Weber TR.  Blunt intestinal injury in children. Diagnostic and therapeutic  considerations.    Archives of Surgery. 132(6):652-7; discussion 657-8, 1997 Jun. 

  OBJECTIVES: To identify computed tomographic (CT) findings in children who   have experienced blunt trauma and who have known intestinal injuries and to   correlate these findings with the findings of the initial physical   examination. DESIGN: A retrospective review of children (aged < 18 years)   known to have an intestinal injury as a consequence of blunt trauma. SETTING:   A university-affiliated children's hospital with a level 1 pediatric trauma   center. PATIENTS: Children younger than 18 years who were admitted for   examination of injuries or for management of complications related to   intestinal injuries. INTERVENTIONS: Clinical and radiographic evaluation and   laparotomy for intestinal injuries other than duodenal hematoma. MAIN OUTCOME   MEASURES: The identification and correlation of relevant findings during the   physical examination, on the CT scan, and during surgery. The assessment of   intervals from injury to diagnosis and intervention and the description of   associated injuries. RESULTS: Twenty-two patients sustained intestinal   injuries as a result of blunt trauma. Most (15) of the patients were   passengers injured in motor vehicle crashes; 14 of these patients were   wearing seat belts. Focal blows to the abdomen from bicycle handlebars,   hockey sticks, or falls onto blunt objects were implicated in the remaining   patients. For 19 of the 22 patients, the initial physical examination was   conducted at Cardinal Glennon Children's Hospital, St Louis, Mo, and 18 of   the 19 patients underwent a concurrent CT evaluation. Peritonitis was found   in 5 of these 18 patients. Tenderness on physical examination was noted in 9   of the 18 patients (tenderness was not noted in 3 patients, and 1 patient had   unreliable examination findings due to a cervical spinal cord injury).   Computed tomographic findings of pneumoperitoneum and extravasation of   enteral contrast material were uncommon but diagnostic (in 5 patients). Free   fluid in the pelvis in the absence of a solid organ injury, bowel wall   thickening, and fluid-filled loops of bowel were more frequently useful signs   of possible intestinal injury (in 9 of the 18 patients) and led to earlier   exploration when used in conjunction with physical examination as an   indication for surgery. Most injuries were treated with segmental resection   or suture repair, but enterostomies were required in 2 patients.   Complications (i.e., the need for enterostomy and fascial dehiscence) were   seen as a result of late or missed diagnosis, which could occur as late as 4   to 6 weeks after injury as intestinal obstruction due to stricture.   CONCLUSIONS: The initial physical examination findings and CT evaluation can   independently identify the presence of intestinal injury in approximately 25%   of cases. In the remainder of cases, the awareness of the more subtle   findings of bowel injury on a CT scan can complement the physical examination   findings and potentially lead to a more timely intervention for bowel injury.  

Papadakis K. Luks FI. De Paepe ME. Piasecki GJ.    Wesselhoeft CW Jr.   Fetal lung growth after tracheal ligation is not solely a pressure  phenomenon.   Journal of Pediatric Surgery. 32(2):347-51, 1997 Feb. 

  Fetal tracheal ligation increases lung growth in utero, making it potentially   applicable for antenatal treatment of diaphragmatic hernia. This phenomenon   has been ascribed to increased intratracheal pressure, which activates as yet   unidentified pulmonary stretch receptors. The purpose of this study was to   determine whether the composition of lung fluid has any effect on fetal lung   development after tracheal obstruction. Six sets of fetal lamb twins   underwent tracheal ligation with placement of intratracheal catheters at 122   days' gestation (term, 145 days). In group 1 (n = 6), tracheal fluid was   aspirated daily, measured, and replaced with equal volumes of saline. Their   respective twins (group 2, n = 6) had daily reinfusion of their own tracheal   aspirates. Intratracheal pressure was recorded daily in both groups.   Unobstructed fetal lambs (n = 7) were used as negative controls. Animals were   killed on postoperative day 14 (136 days). Lungs were weighed, perfusion   fixed at 25 cm H2O, and processed for standard morphometric analysis.   Intratracheal pressure remained between 3 and 5 torr in both experimental   groups throughout the entire postoperative period. In all 12 experimental   fetuses, tracheal ligation resulted in an almost threefold increase in lung   fluid volume by day 1; a slight decrease at a mean of 2.4 days; and a second   surge from day 4 on. Lung fluid volume was significantly higher in group 2   than in group 1 at all measured time points (P < .05, Wilcoxon rank sum test)   except on days 3, 4, and 8 (P = .06). Lung weight per body weight (LW/BW) at   delivery was 0.045 +/- 0.008 in group 1, not significantly different from   unobstructed controls (0.038 +/- 0.006). LW/BW in group 2 was 0.055 +/-   0.010, significantly larger than either group 1 or control (P < .05, single   factor analysis of variance). Air space fraction was comparable between the   three groups. Alveolar numerical density was significantly lower in groups 1   and 2 than in unobstructed controls (P < 0.05). Replacement of tracheal fluid   with saline inhibits the lung hypertrophy seen after tracheal ligation. This   phenomenon therefore appears more dependent on tracheal fluid growth factors   than on increased intratracheal pressure after obstruction. The immediate   decrease in net lung fluid production after saline exchange suggests that   these humoral factors play an important role in the initiation of lung cell   proliferation.  

Fox ES. Wang L. Tracy TF Jr.    Lipopolysaccharide and tumor necrosis factor-alpha synergy potentiate  serum-dependent responses of rat macrophages.   Shock. 5(6):429-33, 1996 Jun. 

  Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta)   are major mediators of sepsis and multiple organ failure. Serum-mediated   macrophage activation requires lipopolysaccharide (LPS) and its serum binding   protein, lipopolysaccharide binding protein as a ligand for the receptor   CD14. This study was designed to determine whether cytokines participate in   regulation of serum-mediated LPS activation. Rat macrophages were stimulated   with LPS with and-without TNF-alpha or IL-1 beta and activation was   determined by detection of TNF-alpha by specific enzyme-linked immunosorbent   assay or TNF-alpha mRNA by Northern blot analysis. The addition of TNF-alpha   but not IL-1 beta, in the presence of serum, leads to potentiation of   macrophage activation after LPS stimulation. This effect could be   specifically inhibited by neutralization of LPS with polymyxin B or an   antibody against TNF-alpha. This study shows that LPS and TNF-alpha synergize   to potentiate serum-mediated macrophage activation. These results demonstrate   another element of the control mechanism of cytokine secretion following   macrophage activation in sepsis. 

Tracy TF Jr. Fox ES.   Molecular and cellular control points in pediatric liver injury and repair.  [Review]  Seminars in Pediatric Surgery. 5(3):175-81, 1996 Aug. 

  Several exciting areas of cellular and molecular biology of the liver have   led to a better understanding of the mechanisms of pediatric liver injury and   repair. Soon these advances will lead to treatment options for specialized   areas of pediatric hepatology. Most of the current goals of surgical therapy   lead to either successful hepatic resection for tumors or biliary   decompression for atresia. We have come to accept the unfortunate fact that   ongoing chronic liver disease ultimately leads to replacement by   transplantation. The purpose of this article is to demonstrate areas of   recent basic science advancement, directly related to pediatric liver   disease, that may provide opportunities and new strategies to obviate the   progression from early injury to end-stage liver disease or to augment repair   of the injured liver. [References: 24]   

Luks FI. Peers KH. Deprest JA. Lerut TE. Vandenberghe K.   The effect of open and endoscopic fetal surgery on uteroplacental oxygen  delivery in the sheep.   Journal of Pediatric Surgery. 31(2):310-4, 1996 Feb. 

  Open fetal surgery predictably results in postoperative uterine contractions   and often in premature labor, but its intraoperative effects on the uterus   are not known. In 10 pregnant ewes (108 to 115 days' gestation), uterine   artery flow, uterine venous oxygen saturation, arterial saturation, and   uterine electromyography were recorded simultaneously (control). Six ewes   underwent a stapled hysterotomy, and four underwent placement of three   endoscopic surgery cannulas and amnioinfusion. Uterine contractions were   present 52% of the time (range, 34% to 72%), and there was no significant   difference between control, hysterotomy, and endoscopic access. Uterine   artery blood flow and uteroplacental oxygen delivery at rest decreased (to   73% of control) after hysterotomy (P < .05), but not after endoscopy. Fetal +   uteroplacental oxygen consumption did not differ significantly between the   groups. In conclusion, (1) uteroplacental oxygen delivery after hysterotomy   alone decreased to levels critical for adequate fetal oxygenation; (2)   endoscopy did not alter uteroplacental oxygen delivery; and (3) during open   fetal surgery, further oxygen demand/delivery mismatch is likely, by traction   on uterine and umbilical vessels and fetal stress. 

Neuschwander-Tetri BA. Nicholson C. Wells LD. Tracy TF  Jr.    Cholestatic liver injury down-regulates hepatic glutathione synthesis.    Journal of Surgical Research. 63(2):447-51, 1996 Jul 1. 

  Hepatocellular injury caused by cholestasis may be caused in part by oxidant   stress. The purpose of this study was to establish how acute cholestasis   might alter hepatic glutathione homeostasis and to determine whether injured   hepatocytes are capable of reverting to normal glutathione homeostatic   mechanisms. Acute cholestasis was achieved by surgical ligation of the common   bile duct in rats. Bile duct ligation induced a 3.7-fold increase in hepatic   glutathione content over 4 days. This increase was not due to increased   hepatic activity of gamma-glutamylcysteine synthetase (GCS); on the contrary,   whole-liver GCS activity was substantially diminished in the bile   duct-ligated liver to 34 and 11% of normal after 4 and 7 days, respectively.   To determine if hepatocytes removed from the cholestatic environment   maintained these changes in glutathione homeostasis, hepatocytes were   isolated from bile ductligated livers and established in primary culture. In   cells isolated after 4 days of bile duct ligation, the elevated hepatocyte   glutathione content decreased and the low GCS activity increased over 2 days   in culture. More importantly, the ability of postcholestatic hepatocytes to   substantially increase their glutathione synthetic capacity by increasing GCS   activity in response to stress was preserved. This compensatory increase was   due primarily to new protein synthesis. Together, these observations suggest   that acute cholestasis impairs the ability of the liver to synthesize   glutathione by down-regulating the key regulatory enzyme for its synthesis in   response to acutely elevated glutathione levels and that the impaired   glutathione synthetic capacity is corrected after cells are removed from the   cholestatic environment.  

Luks FI. Gilchrist BF. Jackson BT. Piasecki GJ.  Endoscopic tracheal obstruction with an expanding device in a fetal lamb  model: preliminary considerations.   Fetal Diagnosis & Therapy. 11(1):67-71, 1996 Jan-Feb. 

  Tracheal obstruction to promote lung growth may be a less aggressive   alternative to open fetal surgery in the antenatal treatment of congenital   diaphragmatic hernia. Herein, we explore the feasibility of placing an   occluding device through fetal tracheoscopy. A self-expanding umbrella   allowed adequate sealing of the tracheal lumen even as the tracheal diameter   more than doubled between 110 and 138 days of gestation (term = 145 days) in   a sheep model. Distal intratracheal pressures after umbrella placement, and   lung weight at delivery, were comparable to those after formal tracheal   ligation. 

DeLuca FG. Gilchrist BF. Paquette E. Wesselhoeft CW.   Luks FI.     External compression as initial management of giant omphaloceles.    Journal of Pediatric Surgery. 31(7):965-7, 1996 Jul. 

  The authors describe a noninvasive technique for the management of giant   omphaloceles. Two patients with giant omphaloceles were managed with external   compression. Dry sterile dressings were used, buttressed by an Ace bandage in   the first case and by a handcrafted Velcro abdominal binder in the second.   The binder was tightened every 2 or 3 days. Renal, cardiovascular,   respiratory, and gastrointestinal parameters were measured regularly to   determine whether the binder was too tight. The first patient had only   occasional emesis, and the defect was repaired after 40 days of compression.   The second patient experienced intermittent hypertension, occasional emesis,   and mild oxygen desaturation, which resolved when the binder was loosened   slightly. The fascia muscle and skin were closed after 30 days of external   compression. Both patients are currently living at home and doing well. This   form of external compression is an effective, inexpensive, and low-risk   method for the gradual reduction of giant omphaloceles, and should be   considered for patients born with this problem.

Chen EA. Luks FI. Gilchrist BF.   Wesselhoeft CW Jr. DeLuca FG.    Pyloric stenosis in the age of ultrasonography: fading skills, better   patients? [see comments]. Comments  Comment in: J Pediatr Surg 1997 Feb;32(2):382   Journal of Pediatric Surgery. 31(6):829-30, 1996 Jun. 

  Hypertrophic pyloric stenosis can be diagnosed accurately by physical   examination alone. However, ultrasonographic confirmation is obtained in the   majority of cases, often before clinical evaluation by the surgeon. The   present study examines whether the easy access to ultrasonography by the   primary physician has affected the care of infants with pyloric stenosis.   During a 24-month period, 100 infants were treated for pyloric stenosis at   the authors' institution. There were 78 boys and 22 girls; the age range was   9 to 90 days (median, 30.0 days). The children were referred for surgical   evaluation, but abdominal ultrasonography was ordered concomitantly (or   within 1 hour of surgical consultation) in all cases. The median age at the   onset of the first symptoms was 24.0 days. The time between onset and   hospital admission was less than 7 days for 72 patients, and more than 2   weeks for seven. Metabolic alkalosis or acidosis, hypokalemia, hypochloremia,   and dehydration were noted in 10%, 5%, 3% and 9%, respectively. Six infants   had prolonged pre- and postoperative courses, because of prematurity (4) or   associated conditions (2). For the remaining patients, total hospitalization   period and postoperative stay were 3.8 +/- 0.9 days and 2.8 +/- 0.6 days,   respectively. Although the diminished importance of clinical skills in the   diagnosis of pyloric stenosis may be regrettable, the availability to the   primary care physician of this easy, safe, inexpensive, and reliable imaging   modality may contribute to prompter treatment. The patients were   hospitalized, with a correct diagnosis, within days of the appearance of the   initial symptoms. Because so little time had elapsed, water and electrolyte   imbalances were not present, and the patients could be operated on within   hours of admission. 

Pricolo VE. Potenti FM. Luks FI.   Selective preservation of the anal transition zone in ileoanal pouch  procedures.   Diseases of the Colon & Rectum. 39(8):871-7, 1996 Aug. 

  PURPOSE: A prospective trial was conducted to evaluate use of certain   preoperative criteria in the choice of operative technique for ileal   pouch-anal anastomosis (IPAA). Handsewn vs. stapled anastomotic techniques   were compared as was preservation vs. excision of the anal transition zone   (ATZ). METHODS: Over an 18-month period, 40 consecutive patients underwent   restorative proctocolectomy with IPAA for ulcerative colitis (31 cases) or   familial adenomatous polyposis (9 cases). In 28 patients, ATZ was completely   excised, by either a transanal mucosectomy with handsewn anastomosis (Group   I, 13 cases) or by double-stapled technique (Group II, 15 cases). The ATZ was   preserved and the anastomosis was double-stapled in colitis patients with   suboptimum sphincter function and/or greater than 50 years of age in the   absence of dysplasia or severe distal proctitis (Group III, 12 cases).   RESULTS: Groups I and II patients were homogeneous in their preoperative   variables and had equivalent functional outcome. Group III patients were   older (P = 0.0001), with weaker preoperative anal sphincter resting tone (P =   0.024). Compared with Groups I and II, patients in Group III had   significantly greater 24-hour stool frequency (P = 0.0056), daytime stool   frequency (P = 0.0125), and incidence of daytime fecal seepage (P = 0.007).   There was no significant difference in other outcome variables in Group III   patients. There was no difference in morbidity in the three groups.   CONCLUSIONS: Transanal mucosectomy with handsewn anastomosis provided early   functional results equivalent to low anal transection with double-stapled   IPAA in younger patients with excellent preoperative sphincter function. A   double-stapled technique with preservation of the ATZ may be reserved for   older patients, with poorer anal sphincter function, at minimum   dysplasia/cancer risk, to optimize continence figures. 

Fox ES. Tracy TF Jr.  Alterations in tumor necrosis factor-alpha expression by hepatic macrophages  following acute cholestatic liver injury.   Shock. 5(2):112-5, 1996 Feb. 

  The liver is unique for its large resident macrophage (HM phi) population as   a potential source of immunoregulatory cytokines. The present study was   designed to determine HM phi function in a rat model of cholestasis (CBDL).   Northern blot analysis of TNF-alpha mRNA showed a profound difference in the   dose response to bacterial lipopolysaccharide (LPS) between sham and CBDL HM   phi. Sham HM phi demonstrated an 8-fold difference in induction of TNF-alpha   mRNA versus CBDL HM phi. TNF-alpha secretion, determined by enzyme-linked   immunosorbent assay, was significantly higher from LPS-activated sham HM phi   versus the same cells activated with Gram-positive bacterial peptidoglycan   while CBDL HM phi were more responsive to peptidoglycan than to LPS. These   results demonstrate stimulus- and response-specific functional alterations in   the HM phi population during acute cholestatic injury. We speculate that   these functional alterations are phenotypically induced in acute liver injury   resulting in responses that are not characteristic of normal HM phi.   <31> 

Tracy TF Jr. Dillon P. Fox ES. Minnick K. Vogler C.   The inflammatory response in pediatric biliary disease: macrophage phenotype  and distribution.    Journal of Pediatric Surgery. 31(1):121-5; discussion 125-6, 1996 Jan. 

  PURPOSE: Extrahepatic biliary obstruction in infants and children leads to   ductal hyperplasia and portal fibrosis. Inflammatory mediators responsible   for increased cellular proliferation and matrix deposition are hypothesized   to result from the intrahepatic recruitment and activation of lymphocytes and   macrophages (M phi). The authors previously showed components of this   mechanism in studies that demonstrated increased adhesion molecule expression   in biliary atresia, as well as evidence of altered hepatic M phi function   during the course of experimental cholestatic liver injury. Therefore they   sought determine the expression of macrophage receptor markers CD68 and CD14   in pediatric biliary disease. METHODS: Sixteen liver specimens were   snap-frozen and cryosectioned onto polylysine-coated slides. Sections were   stained with murine monoclonal antibodies to CD68 (resident M phi) and CD14   (monocyte-M phi lipopolysaccharide [LPS] receptor) glycoproteins. The   sections were analyzed using a semiquantitative scale of proliferation and   were position-graded from 0 to 3 (maximal). RESULTS: Blinded analysis showed   that marked proliferation of CD68-positive cells occurred in five of the six   patients with biliary atresia (BA) and in one patient who had severe   cholestasis. Normal perisinusoidal liver M phi were found in specimens from   patients with hepatitis (2), choledochal cyst (1), and congenital hepatic   fibrosis (1). Similarly, expression of CD14 periportal M phi was found only   in patients with BA or cholestasis (1.9 +/- 0.3 [mean +/- SEM]) and was   absent in other diseases. Strong sinusoidal expression of CD14 was evident in   all patients who had extrahepatic biliary obstruction. An early biopsy   specimen from a premature infant with BA did not show cholestasis, fibrosis,   CD68 Mo proliferation, or CD14 expression; however, another biopsy specimen,   obtained further in the course of jaundice showed the progressive development   of all features. CONCLUSION: These findings suggest proliferation of resident   M phi in association with cholestasis. The presence of the LPS receptor on   periportal cells during cholestatic liver injury points to a potential source   of cytokines responsible for the inflammatory reaction of biliary atresia. 

Fortuna RS. Weber TR. Tracy TF Jr. Silen ML. Cradock TV.   Critical analysis of the operative treatment of Hirschsprung's disease.   Archives of Surgery. 131(5):520-4; discussion 524-5, 1996 May. 

  OBJECTIVE: To critically analyze complications and long-term results of the   operative treatment of Hirschsprung's disease. DESIGN: Medical records of   patients with Hirschsprung's disease were reviewed retrospectively. Follow-up   was obtained using a standardized telephone questionnaire. SETTING: Major   pediatric referral center. PATIENTS: Eighty-two infants and children (68   boys, 14 girls) were treated for Hirschsprung's disease during a 20-year   period (1975 to 1994). The age at diagnosis was younger than 30 days in 47   neonates (57%), 30 days to 1 year in 22 infants (27%), and older than 1 year   in 13 children (16%). Aganglionosis was limited to the rectosigmoid region in   66 patients (81%). Fifty-five Soave (endorectal) and 27 Duhamel (retrorectal)   primary pull-through operations were performed. MAIN OUTCOME MEASURES:   Postoperative complications, reoperations, hospitalization, and current bowel   habits. RESULTS: Eighteen children (67%) undergoing the Duhamel operation   recovered uneventfully compared with 33 children (60%) undergoing the Soave   operation. The complications following the Duhamel operation included   enterocolitis in five cases (19%), rectal achalasia in four cases (15%), and   persistent rectal septum in two cases (7%). Additional operations, which   included myomectomy, rectal septum division, diverting enterostomy, and   sphincterotomy, were required in seven patients (26%). Only one patient   required more than one reoperation. In contrast, complications following the   Soave operation included enterocolitis in 15 cases (27%), rectal stenosis in   12 (22%), anastomotic leak in four (7%), late perirectal fistula in three   (5%), rectal prolapse in one (2%), and recurrent severe constipation in one   (2%). Sixteen patients (29%) required additional operations, including   diverting enterostomy, myomectomy, redo pull-through, sphincterotomy,   fistulectomy, and revision of rectal prolapse. In this group nearly two   reoperative procedures per patient were required. Telephone follow-up (mean,   89.3 months) after pull-through operations in 61 patients (74%) showed a mean   of 2.8 stools per day, with 13 patients (21%) requiring daily medications.   CONCLUSIONS: The most common operations (Soave and Duhamel) for   Hirschsprung's disease result in an uneventful recovery in only 60% to 67% of   patients. Although both Soave and Duhamel pull-through operations have nearly   identical reoperation rates (26% vs 29%), complications after Soave   pull-through operations often require multiple, more extensive procedures.   Short-term total continence rates for both procedures are less than 50%,   however, 100% became continent by 15 years after the pull-through procedure.   Further refinement in operative technique and close follow-up are warranted.  




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