Thoracoscopic decortication vs tube thoracostomy with fibrinolysis for empyema in children: a prospective, randomized trial.

PURPOSE: Management of empyema has been debated in the literature for decades. Although both primary video-assisted thoracoscopic surgery (VATS) and tube thoracostomy with pleural instillation of fibrinolytics have been shown to result in early resolution when compared to tube thoracostomy alone, there is a lack of comparative data between these modes of management. Therefore, we conducted a prospective, randomized trial comparing VATS to fibrinolytic therapy in children with empyema. METHODS: After Institutional Review Board approval, children defined as having empyema by either loculation on imaging or more than 10,000 white blood cells/microL were treated with VATS or fibrinolysis. Based on our retrospective data using length of postoperative hospitalization as the primary end point, a sample size of 36 patients was calculated for an alpha of .5 and a power of 0.8. Fibrinolysis consisted of inserting a 12F chest tube followed by infusion of 4 mg tissue plasminogen activator mixed with 40 mL of normal saline at the time of tube placement followed by 2 subsequent doses 24 hours apart. RESULTS: At diagnosis, there were no differences between groups in age, weight, degree of oxygen support, white blood cell count, or days of symptoms. The outcome data showed no difference in days of hospitalization after intervention, days of oxygen requirement, days until afebrile, or analgesic requirements. Video-assisted thoracoscopic surgery was associated with significantly higher charges. Three patients (16.6%) in the fibrinolysis group subsequently required VATS for definitive therapy. Two patients in the VATS group required ventilator support after therapy, one of whom required temporary dialysis. No patient in the fibrinolysis group clinically worsened after initiation of therapy. CONCLUSIONS: There are no therapeutic or recovery advantages between VATS and fibrinolysis for the treatment of empyema; however, VATS resulted in significantly greater charges. Fibrinolysis may pose less risk of acute clinical deterioration and should be the first-line therapy for children with empyema.

Single daily dosing ceftriaxone and metronidazole vs standard triple antibiotic regimen for perforated appendicitis in children: a prospective randomized trial.

INTRODUCTION: Appendicitis is the most common emergency condition in children. Historically, a 3-drug regimen consisting of ampicillin, gentamicin, and clindamycin (AGC) has been used postoperatively for perforated appendicitis. A retrospective review at our institution has found single day dosing of ceftriaxone and metronidazole (CM) to be a more simple and cost-effective antibiotic strategy. Therefore, we performed a prospective, randomized trial to compare efficacy and cost-effectiveness of these 2 regimens. METHODS: After internal review board approval (IRB no. 04 12-149), children found to have perforated appendicitis at appendectomy were randomized to either once daily dosing of CM (2 total doses per day) or standard dosing of AGC (11 total doses per day). Perforation was defined as an identifiable hole in the appendix. The operative approach (laparoscopic), length of antibiotic use, and criteria for discharge were standardized for the groups. Based on our retrospective analysis using length of postoperative hospitalization as a primary end point, a sample size of 100 patients was calculated for an alpha of .5 and a power of 0.82. RESULTS: One hundred patients underwent laparoscopic appendectomy for perforated appendicitis. On presentation, there were no differences in sex distribution, days of symptoms, temperature, or leukocyte count. There was no difference in abscess rate or wound infections between groups. The CM group resulted in significantly less antibiotic charges then the AGC group. CONCLUSIONS: Once daily dosing with the 2-drug regimen (CM) offers a more efficient, cost-effective antibiotic management in children with perforated appendicitis without compromising infection control when compared to a traditional 3-drug regimen.

Open vs laparoscopic repair of congenital duodenal obstructions: a concurrent series.

OBJECTIVE: The advantages of using laparoscopy for repair of congenital duodenal obstructions (CDO) are unclear because of scant data about complications and outcomes. Nitinol U-clips (Medtronic Surgical, Minneapolis, Minn) were developed to assist in the creation of vascular anastomoses in small vessels. Because of their ability to approximate tissue tightly with little tissue damage, we have begun to use these U-clips for laparoscopic repair of CDO. In this report, we investigate the impact of laparoscopic U-clip repair of CDO compared to the traditional open repair. METHODS: With institutional review board approval, a retrospective analysis of all patients undergoing repair of CDO from January 2003 to July 2007 was performed. During this study period, patients who underwent open repair of CDO (group 1) were compared with patients that underwent laparoscopic repair using the U-clip technique (group 2). RESULTS: Twenty-nine patients underwent repair of CDO. Fourteen patients (11 atresia, 3 stenosis) were in group 1 and 15 patients (11 atresia, 4 stenosis) in group 2. A female sex bias existed in group 1 (female-male [9:5]) compared to group 2 (female-male [7:8]). There was no difference in birth weight, age at operation, chromosomal anomalies, or congenital heart disease between the groups. There were no duodenal anastomotic leaks in either group. Operative times were similar between groups (96 vs 126 minutes; P = .06). The length of postoperative hospitalization (20.1 vs 12.9 days; P = .01), time to initial feeding (11.3 vs 5.4 days; P = .002), and time to full oral intake (16.9 vs 9 days; P = .007) were all statistically shorter in group 2. CONCLUSIONS: The laparoscopic approach to CDO repair using U-clips is safe and efficacious. In addition, patients undergoing laparoscopic repair of CDO had a shorter length of hospitalization and more rapid advancement to full feeding compared to babies undergoing the open approach. We feel that in the hands of experienced laparoscopic surgeons, the preferred technique for correction of CDO will become the laparoscopic U-clip repair.

Chest radiograph after central line placement under fluoroscopy: utility or futility?

BACKGROUND: Postoperative portable chest films are routinely performed after fluoroscopic placement of central venous catheters to evaluate positioning and to rule out significant complications (eg, pneumothorax). Emerging evidence in the literature has called this practice into question suggesting that routine postoperative chest x-ray is unnecessary. Therefore, we investigated our recent experience to examine the utility of these films, to examine the development of symptoms relative to therapeutic intervention, and to report a cost-benefit analysis. METHODS: After obtaining institutional review board approval, all charts of patients undergoing central venous catheter placement from January 2004 to December 2005 at our institution were reviewed. Outcome measures included whether or not there was a complication and whether or not that complication required an intervention. Peripherally inserted central catheters were not included. RESULTS: In the study population, 237 catheters were placed in the operating room. There were two complications, both pneumothoraces (0.085%). One patient required tube thoracostomy, whereas the other was asymptomatic and the pneumothorax resolved spontaneously. Fourteen patients had no postoperative chest film without adverse consequences. Total cost for portable chest films was $56,196. CONCLUSIONS: For catheters placed under fluoroscopic guidance, postoperative chest films in asymptomatic patients add unnecessary cost. For this reason, we feel discontinuation of postoperative chest films in asymptomatic patients undergoing catheter placement with fluoroscopy is justifiable.

Current significance of meconium plug syndrome.

BACKGROUND: The significance of meconium plug syndrome is dependent on the underlying diagnosis. The incidence of pathologic finding, particularly Hirschsprung's disease, contributing to the presence of these plugs, has been debated. However, there are little recent data in the literature. Therefore, we reviewed our experience with meconium plugs as a cause of abdominal distension to evaluate the associated conditions and incidence of Hirschsprung's disease. METHODS: We reviewed the records of newborns with meconium plugs found in the distal colon on contrast enema from 1994 to 2007. Demographics, radiologic findings, histologic findings, operative findings, and clinical courses were reviewed. RESULTS: During the study period, 77 patients were identified. Mean gestational age was 37.4 weeks and birth weight, 2977 g. Hirschsprung's disease was found in 10 patients (13%). One had ultrashort segment disease and another had total colonic aganglionosis. Maternal diabetes was identified in 6 patients. No patients were diagnosed with cystic fibrosis, meconium ileus, malrotation, or intestinal atresia. CONCLUSION: Meconium plugs found on contrast enema are associated with a 13% incidence of Hirschsprung's disease in our experience. Although all patients with plugs and persistent abnormal stooling patterns should prompt a rectal biopsy and genetic probe, the incidence of Hirschsprung's and cystic fibrosis may not be as high as previously reported.

The influence of trisomy 21 on the incidence and severity of congenital heart defects in patients with duodenal atresia.

Duodenal atresia is associated with a wide variety of congenital malformations. Trisomy 21 occurs in approximately one-thirds of infants with duodenal atresia. Congenital heart disease in patients with trisomy 21 and duodenal atresia is well known. However, the frequency and spectrum of congenital heart defects in infants with duodenal atresia and a normal karyotype has not been outlined in the literature. Therefore, we conducted a retrospective chart review to clarify our knowledge about this population. Retrospective review of the medical record was performed on patients with duodenal atresia/stenosis from January 1995 to September 2007. Demographic data included birth weight and gestational age. Variables of interest included cardiac defects and karyotype. Surgical repair for duodenal and cardiac malformations were reviewed. Ninety-four patients with duodenal atresia/stenosis were identified. Average gestational age was 36 weeks and birth weight was 2,536 g. Trisomy 21 was identified in 39 (41%) patients. Overall, 37 patients (39.3%) had a congenital heart defect. Defects were identified in 24 (61.5%) patients with trisomy 21, when compared to 13 (23.6%) patients with a normal karyotype. Of the patients with congenital heart defects and trisomy 21, 11 (28.2%) required operative repair compared to the 6 (10.9%) patients with a defect and normal karyotype. Therefore, in patients with duodenal atresia, the presence of trisomy 21 carries a relative risk of 2.61 for congenital heart defects, and relative risk of 2.59 for open heart surgery. In patients with duodenal atresia, the presence of trisomy 21 carries a 2.5-fold increased risk of cardiac defect and the same increased risk for repairing a cardiac defect.

Management of pediatric acute appendicitis in the computed tomographic era.

BACKGROUND/PURPOSE: The treatment options for complicated appendicitis in children continue to evolve. Optimal management of complicated appendicitis relies on an accurate preoperative diagnosis. We examined the accuracy of our preoperative diagnosis including computed tomography (CT) and the influence on the management of children with perforated and nonperforated appendicitis. METHODS: Following IRB approval, a 6-year review of all patients that underwent an appendectomy for suspected appendicitis was performed. Treatments included immediate operations and initial nonoperative management (antibiotic therapy +/- percutaneous drainage of abscess). Appendicitis was confirmed by histological examination. RESULTS: One thousand seventy-eight patients underwent appendectomy for suspected appendicitis. Preoperative CT scans were performed in 697 (64.7%) patients: 615 (88.2%) positive for appendicitis; 42 (6.0%) negative; and 40 (5.7%) equivocal. One hundred seventy-three (28.1%) positive CT scans further suggested perforation. Initial nonoperative management was initiated in 39 (22.5%) cases of suspected perforated appendicitis with abscess. The positive-predictive value (PPV) for suspected acute appendicitis based on history and physical examination alone was 90.8%. The PPV for positive CT scan for acute appendicitis was 96.4% with a PPV of 91.9% for positive CT scan for perforated appendicitis. CONCLUSIONS: The correct preoperative diagnosis of appendicitis appears statistically more accurate with CT scan compared to history and physical examination alone (PPV 96.4% versus 90.8%, P = 0.045). For those with clinically suspicious complicated appendicitis, CT evaluation may direct therapy toward initial nonoperative management. The efficacy of this regimen warrants further investigation.

Justification for an abbreviated protocol in the management of blunt spleen and liver injury in children.

OBJECTIVE(S): The current management of blunt spleen/liver injury in children requires a number of days of bed rest equal to the grade of injury plus 1. This protocol is used even when there is no clinical indication of ongoing bleeding. To establish a prospective protocol with an abbreviated period of bed rest, we conducted a retrospective review of our blunt spleen and liver trauma experience to examine the safety of such an attenuated protocol. METHODS: A retrospective analysis of our most recent 10-year experience (January 1996 to December 2005) with blunt spleen or liver injury was performed. Patient demographics, vital signs, hemoglobin levels, need for transfusion, operations, and outcomes were measured. An abbreviated protocol using 1 night of bed rest for grades 1 and 2 injuries and 2 nights of bed rest for higher grades was designed. This protocol was then applied to our patient population to assess its safety. Data are expressed as mean +/- SD. RESULTS: During the study period, 243 patients were admitted with blunt spleen and/or liver injury. The mean patient age was 9.0 +/- 4.6 years, and the mean weight was 35.3 +/- 19.3 kg. Sixty-three percent were male. The spleen was injured in 148 (61.2%) patients and the liver in 121 (50.0%), and 26 (10.6%) had both. The mean grade was 2.0 +/- 1.1, for which the mean bed rest was 3.5 +/- 1.1 days. This resulted in 5.6 +/- 6.5 days of hospitalization. There were 9 patients who died, 7 with severe brain injury and 2 with massive liver hemorrhage on presentation. No patient required an operation or transfusion after 2 nights of observation who did not have clinically obvious signs of ongoing blood loss. Implementation of the abbreviated protocol would have affected 65.8% of our patients and would have saved a mean of 2.0 +/- 1.5 hospital days per patient. CONCLUSIONS: According to our data, an abbreviated trauma protocol with overnight bed rest for grades 1 and 2 injuries and 2 nights for higher grades could be safely used. This protocol would immensely improve current resource use. Based on these retrospectively collected data, we have initiated a prospective consecutive controlled series to assess the safety of such an attenuated protocol.

Treatment of bronchopleural fistula with small intestinal mucosa and fibrin glue sealant.

Bronchopleural fistula can be a devastating complication of pulmonary resections. Treatment options are often limited and carry significant morbidity or mortality, or both. We present a case of bronchopleural fistula occurring after pulmonary lobectomy for aspergilloma in a patient with recurrent acute lymphoblastic leukemia. The bronchopleural fistula was treated using bronchoscopic obliteration with Tisseel VH Fibrin Sealant (Baxter Healthcare Corp, Westlake Village, CA) and small intestinal submucosa with complete resolution and no morbidity. The relevant literature is reviewed.

Anorectal hamartoma in a neonate: a unique anorectal mass.

Neonates presenting with perineal masses are uncommon. When encountered, most perineal masses are anorectal malformations, sacrococcygeal teratomas, rectal prolapse, or duplication cysts. We present an otherwise healthy newborn with a patent anal canal and a pedunculated anal mass. The mass was initially believed to be a prolapsed rectal duplication cyst. Further evaluation for concomitant congenital abnormalities was negative. The patient underwent mass excision at the bedside under local anesthesia. Histopathologic evaluation revealed benign hamartoma. This case is presented because of its rarity, unique presentation, and simplicity of management.

Laparoscopic duodenal atresia repair using surgical U-clips: a novel technique.

Laparoscopic repair of duodenal atresia has been reported. Reports to date have indicated use of standard laparoscopic suturing and knot tying. Unfortunately, there has been a high leak rate associated with the technique. We report our technique of using U-clips for the duodenoduodenostomy, thus limiting trauma to the duodenum during the anastomosis and less risk for postoperative leakage.

The use of fundoplication for prevention of apparent life-threatening events.

OBJECTIVE: Gastroesophageal reflux disease (GERD) is cited by many to be a common cause of apparent life-threatening events (ALTEs). However, there are few reports in the literature regarding the surgical treatment of GERD to prevent a recurrent ALTE. METHODS: A retrospective review of infants undergoing fundoplication between 2000 and 2005 for the prevention of another ALTE was undertaken. Preoperative, operative, and postoperative data as well as follow-up information were collected. RESULTS: During the study period, 81 patients underwent fundoplication after presenting with an ALTE. All but 3 patients (96.3%) had been treated with antireflux medication. Moreover, 71 infants (87.7%) were taking antireflux medication at the time of their ALTE. A significant number of infants (77.8%) were hospitalized with a second ALTE before referral for fundoplication. After fundoplication, only 3 patients (3.7%) experienced a recurrent ALTE during the follow-up period; 2 required a second fundoplication and 1 underwent pyloromyotomy. None of these 3 patients have experienced a recurrent ALTE after the second operation. The median follow-up has been 1738 days. CONCLUSION: Our data suggest that among patients who had an ALTE and are found to have GERD, fundoplication appears to be an effective method for preventing recurrent ALTE.

Laparoscopic evaluation for contralateral patent processus vaginalis in children with unilateral inguinal hernia.

BACKGROUND: Management of the contralateral inguinal region in children with a unilateral inguinal hernia remains controversial. The role of laparoscopy in evaluation for contralateral patent processus vaginalis remains unclear. We report the results of an investigation of 1676 consecutive children younger than 10 years of age who underwent unilateral inguinal hernia repair between May 1992 and January 2003. MATERIALS AND METHODS: Bilateral inguinal hernias were noted preoperatively in 194 of the total of 1870 patients, leaving 1676 patients in the study group. In all patients, the contralateral inguinal region was examined under general anesthesia and the operating surgeon noted whether or not a contralateral patent processus vaginalis was suspected. All patients then underwent attempted laparoscopic evaluation of the contralateral inguinal region at the time of unilateral inguinal hernia repair. RESULTS: Laparoscopy was successful in 1603 cases (95.6%) but 73 patients (4.4%) had hernia sacs that were too thin to allow insertion of a 3-mm cannula and 2.7-mm 70-degree telescope. A contralateral patent processus vaginalis was identified in 643 of the laparoscopically examined children (40.1%). At the examination, it was predicted that 446 of the 1603 patients would have a contralateral patent processus vaginalis. Laparoscopy confirmed the presence of a contralateral patent processus vaginalis in 192 (43.0%) of the children predicted to have a contralateral patent processus vaginalis. A contralateral patent processus vaginalis was not suspected from the examination under anesthesia in 1157 of the examined children, and the absence of a contralateral patent processus vaginalis was confirmed by laparoscopy in 706 of these children (61.0%); however, a contralateral patent processus vaginalis was found in 451 (39.0%) of this group. CONCLUSION: We conclude that examination under anesthesia is a poor predictor for the presence or absence of a contralateral patent processus vaginalis. Laparoscopy can reliably evaluate the contralateral inguinal region and is the best method to evaluate for the presence of a contralateral patent processus vaginalis.

Aberrant fibroblast growth factor receptor 2 signalling in esophageal atresia with tracheoesophageal fistula.

BACKGROUND: Although the pathogenesis of esophageal atresia with tracheoesophageal fistula (EA/TEF) remains unknown, it has been shown that despite its esophageal appearance, the fistula tract originates from respiratory epithelium. The authors now hypothesize that defects in fibroblast growth factor (FGF) signaling contribute to the esophaguslike phenotype of the fistula tract. FGF2R is critical to normal lung morphogenesis and occurs in 2 isoforms (FGF2RIIIb and FGF2RIIIc), each with different ligand-binding specificity. To characterize FGF signaling in the developing EA/TEF, the authors analyzed levels of FGF2R splice variants in experimental EA/TEF. METHODS: The standard Adriamycin-induced EA/TEF model in rats was used. Individual foregut components from Adriamycin-treated and control embryos were processed for real-time, fluorescence-activated semiquantitative reverse transcriptase polymerase chain reaction on gestational days 12.5 and 13.5. RESULTS: Both fistula tract and Adriamycin-treated or normal esophagus showed significantly lower levels of FGF2RIIIb than either Adriamycin-treated lung buds (E12.5, P =.02; E13.5, P <.005) or normal lung buds (E12.5, P <.005; E13.5, P <.01). At E13.5, the fistula tract had lower levels of FGF2RIIIc than either treated (P <.01) or normal lung (P <.05). CONCLUSIONS: Levels of FGF2R in the developing fistula tract resemble that of distal esophagus rather than developing lung. This defect in FGF2RIIIb signaling may account for the nonbranching, esophaguslike phenotype of the fistula, despite its respiratory origin.

Defective sonic hedgehog signaling in esophageal atresia with tracheoesophageal fistula.

BACKGROUND: The pathogenesis of esophageal atresia and tracheoesophageal fistula (EA/TEF) remains unknown. We have found previously that an initial esophageal atresia, followed by an abnormal (absent) branching pattern of the middle branch of a trifurcation of the lung/tracheal bud, leads to the neonatal finding of TEF. Mice null mutant for hedgehog signaling can experience the development of EA/TEF, but the mechanism for this development is also unknown. Given that EA/TEF in humans appears not to be due to genetic defects, a hedgehog mutation cause seems very unlikely. However, defective hedgehog signaling that is caused by environmental effects in the human embryo likely could be implicated. We studied a teratogen-induced model of EA/TEF to determine the mechanism by which defective hedgehog signaling may lead to EA/TEF. METHODS: We injected Adriamycin into pregnant rats to induce EA/TEF in rat embryos. We first quantified sonic hedgehog (Shh) signaling pathway molecule expression using real-time, semiquantitative reverse-transcriptase polymerase chain reaction for Shh, Shh receptors (patched and smoothened), and downstream intracellular targets of those receptors (Gli family members). On the basis of these findings, we then developed an in vitro culture system for the day-12 embryonic TEF and manipulated Shh signaling using either exogenous Shh or Shh inhibitors. RESULTS: By reverse transcriptase-polymerase chain reaction, a unique difference between the fistula tract and control tissues was that Gli-2 (downstream signaling molecule of Shh) messenger RNA levels were much lower in the fistula tract than in the adjacent esophagus (P =.002). Surprisingly, in the culture experiments, the fistula tract was induced to branch by exogenous Shh. Such branching of the fistula was unexpected and further supports the presumed respiratory origin of the fistula tract because the normal lung, but not normal esophagus, branched in response to Shh. The Shh inhibitor had no effect, which indicated that defective signaling, rather than hyperfunctioning Shh, is critical to the nonbranching phenotype of the fistula tract in TEF. CONCLUSIONS: The recapitulation of respiratory developmental morphogenesis by the fistula tract of TEF in the presence of exogenous Shh, together with the quantitative reduction in normal, endogenous levels of Gli-2, strongly suggests that 1 mechanism for the formation of the fistula tract is the lack of proper Shh signaling because of Gli-2 deficiency, with subsequent straight, nonbranching caudal growth of the fistula tract. This deficiency can be rescued by excess exogenous Shh, thus reestablishing respiratory morphogenesis.

Necrotizing enterocolitis in full-term infants.

OBJECTIVES: Although necrotizing enterocolitis (NEC) is primarily a disease of prematurity, full-term infants account for approximately 10% of cases. Previous studies have reported conflicting results regarding NEC in full-term (FT) versus preterm (PT) infants. A review of all infants diagnosed with NEC at our institution over the past 3 decades was performed to identify factors associated with this disease in full-term neonates. METHODS: The charts of all infants with definitive NEC from January 1, 1972 through January 1, 2001 were reviewed. Two hundred seventy-seven patients made up the study group: 251 PT and 26 FT infants. Data regarding demographics, clinical presentation, management, outcome, and other variables were collected. FT and PT infants were compared. RESULTS: Mean gestational age and birth weight in the FT group were 39.3 weeks and 3,132 g versus 30.2 weeks and 1,396 g for PT infants. Apgar scores were similar. Mean age at diagnosis was 5 days in FT versus 13 days in PT neonates (P <.001). Enteral nutrition was initiated earlier in FT infants (1.6 days v 3.1 days; P <.001), and FT infants were discharged an average of 14 days earlier than PT infants (P value not significant). Factors predisposing to NEC were found in 62% (16 of 26) of patients-heart disease in 6 infants and other conditions in 10 patients. Cardiac disease was found significantly more often (23% v 10%; P =.027) in FT infants. Survival rate was 65% (17 of 26) in the FT group versus 69% (173 of 251) in the PT infants (P value not significant). CONCLUSIONS: FT infants with NEC differ from their PT counterparts in several distinct ways. FT neonates had NEC at a significantly earlier age, perhaps owing to earlier initiation of feeding. There was a correlation between age at which feeding was begun and age of onset of NEC. Additionally, an association between cardiac disease and development of NEC in term infants was shown. Predisposing factors were present in a majority of FT infants. In contrast to other reports, the outcome of NEC in full-term infants was no better than for PT infants.

Evaluation of pectus bar position and osseous bone formation.

PURPOSE: Minimally invasive repair has become a popular approach for pectus excavatum (PE). The bar is secured to the thoracic wall and left for approximately 2 years. The authors have noticed an intense bone formation (BF) around some of these bars at removal. A review of children undergoing bar removal was performed to better understand this BF in relation to bar placement. METHODS: A retrospective review of children undergoing bar removal after PE repair since January 1998 was performed. Chart review included age at bar insertion and removal, bar insertion position (subcutaneous [SC] v submuscular [SM]), BF on Chest x-ray and at bar removal, operating time, and estimated blood loss (EBL). RESULTS: Thirty-six patients underwent bar removal during the study period (16 SC and 20 SM). Chest x-ray evaluation was possible in 27 patients (16 SM, 11 SC). No difference existed for length of time the bar was in place or age at insertion/removal between groups. EBL was higher in the SM (18.3 v 8.8 mL, not significant). BF was seen radiographically in 15 SM and 3 SC patients (P <.001). BF was encountered at removal in 19 SM patients and a single SC patient (P <.001). Operating time was statistically longer (P <.01) for the SM group (30.2 v 15.6 min). CONCLUSIONS: Bar position during repair of PE is important. SM positioning virtually always results in BF with increased EBL and statistically longer operating time at removal. Careful placement of the bar in the SC position without violating the fascia should be used to avoid these undesirable effects.

Fibroblast growth factor signaling in the developing tracheoesophageal fistula.

BACKGROUND/PURPOSE: The Adriamycin-induced rat model of esophageal atresia and tracheoesophageal fistula (EA/TEF) provides a reliable system for the study of EA/TEF pathogenesis. The authors previously hypothesized that faulty branching lung morphogenesis pathways were a critical component of its pathogenesis. The authors have found evidence for faulty fibroblast growth factor (FGF) signaling related to epithelial-mesenchymal interactions in the fistula tract. To better define FGF signaling, the differential expression of FGF ligands and their receptors between lung, fistula tract, and esophagus are described. METHODS: Time-dated pregnant, Sprague-Dawley rats were injected with Adriamycin (2 mg/kg intraperitoneally) on days 6 through 9 of gestation. Tissues were processed for histology and reverse transcriptase polymerase chain reaction. FGF-1, -7 and -10 were measured from whole lung, fistula tract, and esophagus of TEF or normal embryos. Expression of FGF2RIIIb and FGF2RIIIc receptors was measured in isolated epithelium and mesenchyme of lung and fistula tract of TEF embryos as well as lung and esophagus from normal controls. RESULTS: FGF-1 mRNA was present in the fistula tract and normal and Adriamycin-exposed lung but absent from whole esophagus. Interestingly, FGF-7 mRNA was present only in normal lung. FGF-10 was present in all tissues examined. FGF2RIIIb mRNA was absent in fistula mesenchyme but present in all other tissues examined. However, the splice variant FGF2RIIIc mRNA was present in all tissues examined. CONCLUSIONS: These findings support defective FGF signaling in the rat model of EA/TEF. Absence of FGF-7 mRNA in Adriamycin-exposed tissues suggests the primary effect of Adriamycin may be to inhibit FGF-7 expression. Moreover, absence of FGF2RIIIb in fistula mesenchyme may be caused by loss of positive feedback from FGF-7, its normal obligate ligand. Understanding these specific defects in FGF signaling may provide insight into faulty mechanisms of EA/TEF.

Retinoid signaling controls mouse pancreatic exocrine lineage selection through epithelial-mesenchymal interactions.

BACKGROUND & AIMS: The early embryonic pancreas gives rise to exocrine (ducts and acini) and endocrine lineages. Control of exocrine differentiation is poorly understood, but may be a critical avenue through which to manipulate pancreatic ductal carcinoma. Retinoids have been shown to change the character of pancreatic ductal cancer cells to a less malignant phenotype. We have shown that 9-cis retinoic acid (9cRA) inhibits acinar differentiation in the developing pancreas, in favor of ducts, and we wanted to determine the role of retinoids in duct versus acinar differentiation. METHODS: We used multiple culture systems for the 11-day embryonic mouse pancreas. RESULTS: Retinoic acid receptor (RAR)-selective agonists mimicked the acinar suppressive effect of 9cRA, suggesting that RAR-RXR heterodimers were critical to ductal differentiation. RARalpha was only expressed in mesenchyme, whereas RXRalpha was expressed in epithelium and mesenchyme. Retinaldehyde dehydrogenase 2, a critical enzyme in retinoid synthesis, was expressed only in pancreatic epithelium. 9cRA did not induce ductal differentiation in the absence of mesenchyme, implicating a requirement for mesenchyme in 9cRA effects. Mesenchymal laminin is necessary for duct differentiation, and retinoids are known to enhance laminin expression. In 9cRA-treated pancreas, immunohistochemistry for laminin showed a strong band of staining around ducts, and blockage of laminin signaling blocked all 9cRA effects. Western blot and RT-PCR of pancreatic mesenchyme showed laminin-beta1 protein and mRNA induction by 9cRA. CONCLUSIONS: Retinoids regulate exocrine lineage selection through epithelial-mesenchymal interactions, mediated through up-regulation of mesenchymal laminin-1.

Complete discontinuity of the distal fistula tract from the developing gut: direct histologic evidence for the mechanism of tracheoesophageal fistula formation.

The embryogenesis of tracheoesophageal anomalies remains controversial. The purpose of this study was to better define the embryogenesis of developing esophageal atresia with tracheoesophageal fistula (EA/TEF), with specific attention to the controversial issue of whether a discontinuity exists in the foregut during its development of EA/TEF. Pregnant outbred rats were injected with adriamycin (2 mg/kg i.p.) on days 6-9 of gestation (E6-E9). At E12.5 and 13.5, microdissection of the entire foregut was performed. Foreguts were examined by phase microscopy, and serial, precisely transverse sections were created for hematoxylin and eosin (H&E) staining. Gross microdissection of the developing foregut at E12.5 (n = 9) revealed a blind-ending, bulbous fistula tract arising from the middle branch of the tracheal trifurcation (as seen by direct and phase microscopy). No connection with the gut could be appreciated at E12.5, but by E13.5 (n = 10) there was an obvious connection between the fistula and the stomach. Serial H&E transverse sections also demonstrated a blind-ending fistula tract arising from the trachea at E12.5. This fistula tract was clearly discontinuous from the developing stomach, which appeared much further caudal to the end of the fistula tract. These results strongly support a model of experimental TEF wherein the fistula tract arises from a trifurcation of the trachea, and (only during a specific gestational window between days 12.5 and 13.5) there is discontinuity between the fistula tract and the stomach. By day 13.5, the fistula joins with the stomach anlage. These observations in the developing EA/TEF should help to resolve the controversy about the mechanism of EA/TEF formation.