Building the foundation for expert care and future contributions in pediatric surgery.

There is a significant amount of interest among general surgery residency training programs in North America to have a rotation in an underserved part of the world. Usually, these global surgery rotations for the general surgery residents have been extended in duration to allow for emersion and continuity. There is similar interest among a few of the pediatric surgery training programs to initiate short, one month rotations in the global surgery arena as part of the two year pediatric surgery residency training.

Understanding the Operative Experience of the Practicing Pediatric Surgeon: Implications for Training and Maintaining Competency.

IMPORTANCE: The number of practicing pediatric surgeons has increased rapidly in the past 4 decades, without a significant increase in the incidence of rare diseases specific to the field. Maintenance of competency in the index procedures for these rare diseases is essential to the future of the profession. OBJECTIVE: To describe the demographic characteristics and operative experiences of practicing pediatric surgeons using Pediatric Surgery Board recertification case log data. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of 5 years of pediatric surgery certification renewal applications submitted to the Pediatric Surgery Board between 2009 and 2013. A surgeon's location was defined by population as urban, large rural, small rural, or isolated. Case log data were examined to determine case volume by category and type of procedures. Surgeons were categorized according to recertification at 10, 20, or 30 years. MAIN OUTCOME AND MEASURE: Number of index cases during the preceding year. RESULTS: Of 308 recertifying pediatric surgeons, 249 (80.8%) were men, and 143 (46.4%) were 46 to 55 years of age. Most of the pediatric surgeons (304 of 308 [98.7%]) practiced in urban areas (ie, with a population >50 000 people). All recertifying applicants were clinically active. An appendectomy was the most commonly performed procedure (with a mean [SD] number of 49.3 [35.0] procedures per year), nonoperative trauma management came in second (with 20.0 [33.0] procedures per year), and inguinal hernia repair for children younger than 6 months of age came in third (with 14.7 [13.8] procedures per year). In 6 of 10 "rare" pediatric surgery cases, the mean number of procedures was less than 2. Of 308 surgeons, 193 (62.7%) had performed a neuroblastoma resection, 170 (55.2%) a kidney tumor resection, and 123 (39.9%) an operation to treat biliary atresia or choledochal cyst in the preceding year. Laparoscopy was more frequently performed in the 10-year recertification group for Nissen fundoplication, appendectomy, splenectomy, gastrostomy/jejunostomy, orchidopexy, and cholecystectomy (P < .05) but not lung resection (P = .70). It was more frequently used by surgeons recertifying in the 10-year group (used in 11 375 of 14 456 procedures [78.7%]) than by surgeons recertifying in the 20-year (used in 6214 of 8712 procedures [71.3%]) or 30-year group (used in 2022 of 3805 procedures [53.1%]). CONCLUSIONS AND RELEVANCE: Practicing pediatric surgeons receive limited exposure to index cases after training. With regard to maintaining competency in an era in which health care outcomes have become increasingly important, these results are concerning.

Nonoperative treatment of acute appendicitis in children: A feasibility study.

PURPOSE: Nonoperative treatment of acute appendicitis appears to be feasible in adults. It is unclear whether the same is true for children. METHODS: Children 5-18 years with <48 h 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 14 months, three of the 24 failed on therapy, and 2/21 returned with recurrent appendicitis at 43 and 52 days, 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.

The effort and outcomes of the Pediatric Surgery match process: Are we interviewing too many?

PURPOSE: Increasing numbers of programs participating in the pediatric surgery match has resulted in economic and logistical issues for candidates, General Surgery residencies, and Pediatric Surgery training programs (PSTP). We sought to determine the ideal number of interviews conducted by programs based on resultant rank order lists (ROL) of matched candidates. METHODS: PSTPs received 4 online surveys regarding interview practices (2011-2012, 2014), and matched candidate ROL (2008-2010, 2012, 2014). Program directors (PD) also provided estimates regarding minimum candidate interview numbers necessary for an effective match (2011-2012, 2014). Kruskal-Wallis equality-of-populations rank tests compared ROL and interview numbers conducted. Quartile regression predicted ROL based on the interview numbers. Wilcoxon signed rank-sum tests compared the interview numbers to the minimal interview number using a matched pair. p Values<0.05 were significant. RESULTS: Survey response rates ranged from 85-100%. Median ROL of matched candidates (2-3.5) did not differ between programs (p=0.09) and the lowest matched ROL for any year was 10-12. Interview numbers did not affect the final candidate ROL (p=0.22). While PDs thought the minimum median interview number should be 20, the number actually conducted was significantly higher (p<0.001). CONCLUSION: These data suggest that PSTPs interview excessive numbers of candidates. Programs and applicants should evaluate mechanisms to reduce interviews to limit costs and effort associated with the match.

Use of white blood cell count and negative appendectomy rate.

BACKGROUND: Despite increased utilization of laboratory, radiologic imaging, and scoring systems, negative appendectomy (NA) rates in children remain above 3% nationwide. We reviewed the clinical data of patients undergoing appendectomy to further reduce our NA rate. METHODS: A retrospective review was conducted of all appendectomies performed for suspected appendicitis at a tertiary children's hospital during a 42-month period. Preoperative clinical, laboratory, and radiographic data were collected. Variables absent or normal in more than half of NAs were further analyzed. Receiver operating characteristic curves were constructed for continuous variables by using appropriate cutoff points to determine sensitivity and false-positive rates. The results were validated by analyzing the 12 months immediately after the establishment of these rules. RESULTS: Of 847 appendectomies performed, 22 (2.6%) had a pathologically normal appendix. The only variables found to be normal in more than half of NAs were white blood cell (WBC) count (89%) and neutrophil count (79%). A receiver operating characteristic curve indicates that using WBC cutoffs of 9000 and 8000 per µL yielded sensitivities of 92% and 95%, respectively, and reduction in NA rates by 77% and 36%, respectively. Results observed in the subsequent 12 months confirmed these expected sensitivities and specificities. CONCLUSIONS: Absence of an elevated WBC count is a risk factor for NA. Withholding appendectomy for WBC counts <9000 and 8000 per µL reduces the NA rate to 0.6% and 1.2%, respectively. Missed true appendicitis in patients with normal WBC counts can be mitigated by a trial of observation in those presenting with early symptom onset.

Surgical residents' perceptions of 2011 Accreditation Council for Graduate Medical Education duty hour regulations.

IMPORTANCE: In 2010, the Accreditation Council for Graduate Medical Education (ACGME) proposed increased regulation of work hours and supervision for residents. New Common Program requirements that took effect in July 2011 dramatically changed the customary 24-hour in-house call schedule. Surgical residents are more likely to be affected by these duty hour restrictions. OBJECTIVE: To examine surgical residents' views of the 2011 ACGME Common Program requirements after implementation in July 2011. DESIGN: A 20-question electronic survey was administered 6 months after implementation of 2011 ACGME regulations to 123 participating institutions. SETTING: ACGME-accredited teaching hospitals in the United States and US territories. PARTICIPANTS: The total sample was 1013 voluntarily participating residents in general surgery and surgical specialties at ACGME-accredited institutions. MAIN OUTCOMES AND MEASURES: Residents' perceptions of changes in education, patient care, and quality of life after institution of 2011 ACGME duty hour regulations and their compliance with these rules. RESULTS: A subset of 1013 residents training in general surgery or a surgical subspecialty was identified from a demographically representative sample of 6202 survey respondents. Most surgical residents indicated that education (55.1%), preparation for senior roles (68.4%), and work schedules (50.7%) are worse after implementation of the 2011 regulations. They reported no change in supervision (80.8%), safety of patient care (53.4%), or amount of rest (57.8%). Although quality of life is perceived as better for interns (61.9%), most residents believe that it is worse for senior residents (54.4%). A majority report increased handoffs (78.2%) and a shift of junior-level responsibilities to senior residents (68.7%). Finally, many residents report noncompliance (67.6%) and duty hour falsification (62.1%). CONCLUSIONS AND RELEVANCE: A majority of surgical residents disapprove of 2011 ACGME Common Program requirements (65.9%). The proposed benefits of the increased duty hour restrictions-improved education, patient care, and quality of life-have ostensibly not borne out in surgical training. It may be difficult for residents, particularly in surgical fields, to learn and care for patients under the 2011 ACGME regulations.

Neutrophil depletion blocks early collagen degradation in repairing cholestatic rat livers.

Biliary obstruction results in a well-characterized cholestatic inflammatory and fibrogenic process; however, the mechanisms and potential for liver repair remain unclear. We previously demonstrated that Kupffer cell depletion reduces polymorphonuclear cell (neutrophil) (PMN) and matrix metalloproteinase (MMP)8 levels in repairing liver. We therefore hypothesized that PMN-dependent MMP activity is essential for successful repair. Male Sprague-Dawley rats received reversible biliary obstruction for 7 days, and the rat PMN-specific antibody RP3 was administered 2 days before biliary decompression (repair) and continued daily until necropsy, when liver underwent morphometric analysis, immunohistochemistry, quantitative RT-PCR, and in situ zymography. We found that RP3 treatment did not reduce Kupffer cell or monocyte number but significantly reduced PMN number at the time of decompression and 2 days after repair. RP3 treatment also blocked resorption of type I collagen. In addition, biliary obstruction resulted in increased expression of MMP3, MMP8, and tissue inhibitor of metalloproteinase 1. Two days after biliary decompression, both MMP3 and tissue inhibitor of metalloproteinase 1 expression declined toward sham levels, whereas MMP8 expression remained elevated and was identified in bile duct epithelial cells by immunohistochemistry. PMN depletion did not alter the hepatic expression of these genes. Conversely, collagen-based in situ zymography demonstrated markedly diminished collagenase activity following PMN depletion. We conclude that PMNs are essential for collagenase activity and collagen resorption during liver repair, and speculate that PMN-derived MMP8 or PMN-mediated activation of intrinsic hepatic MMPs are responsible for successful liver repair.

The pediatric surgeons' contribution to in utero treatment of twin-to-twin transfusion syndrome.

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.

Dexamethasone alters the hepatic inflammatory cellular profile without changes in matrix degradation during liver repair following biliary decompression.

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

Endotoxin alters early fetal lung morphogenesis.

BACKGROUND: The effects of immaturity and hypoplasia of the premature lung can be affected by proinflammatory stimuli in late gestation or the postnatal period from acute lung injury secondary to intensive ventilatory management or the metabolic consequences of surgery. These stimuli alter alveolarization and contribute to bronchopulmonary dysplasia. While prior research has focused primarily on late gestational effects of inflammation on alveolar development, we sought to study whether early gestational exposure to endotoxin affects branching morphogenesis, during the critical pseudoglandular stage of lung development. METHOD: Gestational day 15 (E15) fetal rat lung explants (term = 22 d) were treated with either 200 ng/mL or 2 microg/mL lipopolysaccharides (LPS) with controls and examined daily by phase microscopy. After 5 d, explants were fixed in 4% formaldehyde, paraffin embedded, and sectioned at 5 mum in the coronal plane. Immunohistochemical analysis was performed with platelet endothelial cell adhesion molecule (PECAM) to define endothelial cells, vascular endothelial growth factor (VEGF) to examine endothelial mitogenesis, and COX-2 antibodies as a marker for prostaglandin synthesis. Real-time PCR examined inducible nitric oxide synthase (iNOS), FGF9, FGF10, and FGFr2 gene expression. Air space fraction and airway epithelium were analyzed with Image J software. RESULTS: Phase contrast microscopy and hematoxylin-eosin histology revealed progressive, dose-related changes in air sac contraction and interstitial thickening. Compared with control E15 explants, day 5 explants incubated with high dose LPS demonstrated thickened and shrunken airway sacs with stunted branching and increased matrix deposition in interstitial areas. By immunohistochemical staining, COX-2 was quantitatively increased after high dose LPS exposure, while PECAM was reduced. VEGF expression was unaltered. LPS increased iNOS, but decreased FGF9, FGF10, and FGFr2 gene expression. CONCLUSIONS: These data support evidence for an inflammatory effect of LPS on the early phase of lung development in the fetal rat, affecting branching morphogenesis during the pseudoglandular phase. Fetal endothelial cells are clearly affected, while COX-2 elevation suggests activation of an as yet undefined fetal pulmonary inflammatory cascade. We speculate that proinflammatory stimuli may ultimately lead to abnormal pulmonary development via fibroblastic growth factor (FGF)-directed mechanisms that affect epithelial-mesenchymal interaction and differentiation at a much earlier gestational age than was previously recognized.

Hepatic macrophages promote the neutrophil-dependent resolution of fibrosis in repairing cholestatic rat livers.

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

High incidence of postoperative bowel obstruction in newborns and infants.

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.

Management of common head and neck masses.

Head and neck masses are a common clinical concern in infants, children, and adolescents. The differential diagnosis for a head or neck mass includes congenital, inflammatory, and neoplastic lesions. An orderly and thorough examination of the head and neck with an appropriate directed workup will facilitate the diagnosis. The most common entities occur repeatedly within the various age groups and can be differentiated with a clear understanding of embryology and anatomy of the region, and an understanding of the natural history of a specific lesion. Congenital lesions most commonly found in the pediatric population include the thyroglossal duct cyst and the branchial cleft and arch anomalies. The inflammatory masses are secondary to local or systemic infections. The most common etiology for cervical adenopathy in children is reactive lymphadenopathy following a viral or bacterial illness. Persistent adenopathy raises more concerns, especially enlarged lymph nodes within the posterior triangle or supraclavicular space, nodes that are painless, firm, and not mobile, or a single dominant node that persists for more than 6 weeks should all heighten concern for malignancy. In this review, we discuss the current principles of surgical management of the most common head and neck masses that present to pediatricians and pediatric surgeons.

Perinatal management of congenital cystic lung lesions in the age of minimally invasive surgery.

BACKGROUND: Most congenital cystic lung lesions (CCLLs) do not require in utero or perinatal intervention. The management of asymptomatic lesions is controversial: the theoretical risk of infection and malignancy is offset by whether thoracotomy in asymptomatic children is justified. We examined our recent experience and the role of minimally invasive surgery. METHODS: We analyzed the pre-, peri-, and postnatal findings of all consecutive CCLLs diagnosed between 1997 and 2005. We reviewed records for pre-, and postnatal imaging, management, and outcome. RESULTS: Thirty-five CCLL were diagnosed prenatally. Since 2000, all asymptomatic lesions were removed endoscopically at 6 to 18 months (thoracoscopy for 6 extralobar sequestrations, 3 intralobar sequestrations/congenital cystic adenomatoid malformations, 5 bronchogenic cysts, and retroperitoneal laparoscopy for 2 intraabdominal sequestrations). Congenital cystic adenomatoid malformation elements were present in more than 70%. Two abdominal lesions have regressed, and 2 patients are awaiting intervention. One symptomatic infant underwent thoracotomy for congenital lobar emphysema. CONCLUSIONS: It has been argued that the risks associated with congenital lung lesions (infection and malignancy) justify intervention in the asymptomatic patient. In our experience, all these lesions could be safely removed using endosurgical techniques. Counseling of (future) parents should be updated to include minimally invasive surgery in the management algorithm.

Port insertion and removal techniques to minimize premature rupture of the membranes in endoscopic fetal surgery.

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.

Kupffer cells abrogate cholestatic liver injury in mice.

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.

Isolated computed tomography diagnosis of pulmonary contusion does not correlate with increased morbidity.

BACKGROUND: Increased utilization of computed tomography (CT) has led to a rise in the diagnosis of pulmonary contusion. Its clinical significance, in the absence of findings on chest radiograph (CXR), has not been defined. This study examines the clinical course of patients with CT-only diagnosis of pulmonary contusion and compares it with that of patients with CXR-proven pulmonary contusion. METHODS: The trauma database identified all children undergoing chest CT for blunt thoracic trauma during a 3-year period. Records were reviewed for age, mechanism of injury, Injury Severity Score (ISS), length of hospital stay (LOS), need for intensive care unit admission, and need for endotracheal intubation. A pediatric radiologist reviewed all films in a blinded fashion. Statistical analysis was performed using analysis of variance and Fisher's Exact test for 2 x 3 tables. RESULTS: Eighty-two patients were identified. There were no CXR-positive, CT-negative cases. A CT diagnosis of pulmonary contusion was made in 46 patients. Of these, 31 had a contusion on CXR as well (CXR+ group) and 15 had a normal CXR (CT+ only group). Mean ISS score did not differ significantly between the two groups (27 +/- 12.3 and 22 +/- 10.3, respectively). Thirty-six patients had a normal CT (control). Mean LOS was significantly longer in the CXR+ group (13 +/- 12.0 days) than in the CT+ only and control groups (5 +/- 3.6 and 9 +/- 9.5 days, respectively; P < .01). The percentages of children requiring intensive care unit admission and intubation were also significantly higher in the CXR+ group. CONCLUSION: The finding of pulmonary contusion by CT alone does not increase patient morbidity and appears to be of limited clinical significance.