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.
JT, Glick S, Silverman
K, Silverman HF, Luks FI.
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.
FI, Carr SR, Muratore
CS, O'Brien BM, Tracy TF.
The pediatric surgeons'
contribution to in utero treatment of twin-to-twin transfusion
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.
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
Harty MW, Papa EF, Huddleston
HM, Young E, Nazareth S, Riley CA, Ramm GA, Gregory SH, Tracy
Hepatic macrophages promote the neutrophil-dependent
resolution of fibrosis in repairing cholestatic rat livers.
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.
CS, Ryder BA, Luks
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.
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;
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.
JY, Kim DS, Muratore CS, Kurkchubasche AG, Tracy TF Jr, Luks
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.
J, Tracy TF Jr, Carr SR, Sorrells DL Jr, Luks FI.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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
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
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.
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
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.
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.
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.
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
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,
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.
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
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.
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
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.
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.
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.
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.
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.
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.
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.
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,
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,
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
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.
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.
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.
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,
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.
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,
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
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
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
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.
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.
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,
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
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.
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.
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,
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.
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
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
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
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.
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
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
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.
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.
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,
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
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:
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.
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.
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
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.
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.
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.
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.
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,
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
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
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