Vascular endothelial growth factor isoform and receptor expression during compensatory lung growth.

BACKGROUND: Vascular endothelial growth factor (VEGF) is required for blood vessel formation during lung growth and repair. Alteration of VEGF isoform expression has been demonstrated in response to fetal tracheal occlusion and in models of lung injury. The purpose of this study was to investigate VEGF expression during compensatory lung growth in the mouse. METHODS: Under general anesthesia, adult mice underwent left thoracotomy with (n = 5) or without (sham, n = 5) pneumonectomy. The right lungs were harvested at 1, 3, and 7 d after the operation. Lung-to-body weight ratio as well as total DNA and protein content were measured. VEGF protein expression was analyzed by Western blot and ELISA. VEGF isoform expression was evaluated using semi-quantitative PCR followed by Imagequant optical densitometry. Values were compared by Student's t-test and ANOVA using Fisher's protected least significant difference post-hoc test where appropriate. RESULTS: Compensatory lung growth was observed as measured by increases in right lung-to-body weight ratio and in DNA and protein content. Total VEGF RNA and protein expression did not change after pneumonectomy. However, on post-operative day 1, there was a decrease in the relative percentage of VEGF188 mRNA (P < 0.01), and an increase in the relative percentage of VEGF164 mRNA (P = 0.05). At 3 d postpneumonectomy, low relative VEGF188 expression persisted (P < 0.05), VEGF164 expression normalized, and relative VEGF120 expression increased (P < 0.01). Isoform expression in the pneumonectomy animals was identical to sham animals by the seventh d. There were no differences observed in VEGF receptor expression. CONCLUSION: During compensatory lung growth, we have observed an early postoperative reversion of VEGF isoform expression to the pattern seen during fetal lung development and in lung injury models.

Prognostic role of tumor-head volume ratio in fetal sacrococcygeal teratoma.

OBJECTIVE: To evaluate the ability of a tumor-head volume ratio to predict outcome and incidence of hydrops in fetuses with sacrococcygeal teratoma. METHODS: Seventy-one sonograms were reviewed retrospectively from 28 fetuses with sacrococcygeal teratoma managed in our institution. Head volume (HV) and total tumor volume were calculated from sonograms. Amount of cystic tumor was estimated to determine solid tumor volume (STV) for the STV/HV ratio. RESULTS: Twenty percent of sonograms with STV/HV <1 and 97.3% with STV/HV >1 were associated with 1 or more abnormal sonographic signs (p = 0.000). Overall mortality was 11/27 (41%). There was no mortality in fetuses with a ratio of <1, while 11/18 (61%) of fetuses with ratio >1 died (p = 0.003). CONCLUSION: The STV/HV ratio may be used to identify fetuses with a high risk of a poor outcome due to high-output cardiac failure and hydrops, and may help guide management.

Does congenital diaphragmatic hernia associated with bronchopulmonary sequestration portend a better prognosis?

INTRODUCTION: Congenital diaphragmatic hernia (CDH) continues to be a devastating disease in the newborn population, with well-documented morbidity and mortality. Bronchopulmonary sequestration is a separate congenital defect that has been associated with CDH. While the association of sequestration with CDH has been reported to be as high as 30-40%, the prognosis associated with the two simultaneous defects is unknown. We reviewed our experience to evaluate if prognosis was better in the CDH infants with associated bronchopulmonary sequestration. METHODS: Institutional approval was obtained. Our institutional database was examined from August 1995 to August 2005, identifying all mothers carrying fetuses with pulmonary masses and/or CDH and all neonates treated with bronchopulmonary sequestration and/or CDH. Patients who had both CDH and sequestration were identified by prenatal ultrasound reports, postnatal radiographs, and operative and pathology reports. RESULTS: 16 patients were identified in the fetal or neonatal period with concomitant diagnoses of CDH and bronchopulmonary sequestration. Of those proceeding to delivery, 6 expired and 6 survived. The presence of liver herniation and low lung-to-head ratio on antenatal ultrasound correlated with mortality. However, 2 patients survived with very low lung-to-head ratio that would usually be associated with 100% mortality at our institution. Two diagnoses of bronchopulmonary sequestration were reversed after final pathology revealed liver tissue. CONCLUSION: Given the limited series, we cannot conclude that bronchopulmonary sequestration confers an anatomic advantage to patients that have CDH. We did observe survivors in this group that, given their antenatal predictors of CDH severity, would ordinarily have dismal prognosis. The presence of a sequestration may be protective in a subset of patients with severe CDH, or may confound our antenatal predictors of disease severity in these patients.

Congenital diaphragmatic hernia associated with spinal anomalies.

OBJECTIVE: Increased mortality is seen in patients with congenital diaphragmatic hernia who have associated anomalies, such as cardiac defects. We reviewed our series of patients with congenital diaphragmatic hernia and spinal anomalies to evaluate if their prognosis was altered. METHODS: We examined our institutional database from August 1995 to August 2005, examining 679 cases of congenital diaphragmatic hernia, identifying all fetuses and newborns with congenital diaphragmatic hernia and spinal anomalies. Patients who had both congenital diaphragmatic hernia and spinal anomalies were identified by prenatal ultrasound reports, postnatal radiographs, operative notes, and pathology reports. RESULTS: Seven patients were identified in the fetal or neonatal period with concomitant diagnoses of congenital diaphragmatic hernia and spinal anomalies. All patients had normal karyotype analysis. Six of these patients had both defects diagnosed using prenatal ultrasonography. All patients died before hospital discharge. CONCLUSION: Although the numbers are limited in our series, patients with congenital diaphragmatic hernia and spinal anomalies have a dismal prognosis. This finding has significant implications for prenatal counseling. LEVEL OF EVIDENCE: III.

Prenatal and postnatal management of a patient with pentalogy of Cantrell and left ventricular aneurysm. A case report and literature review.

INTRODUCTION: Omphalocele is often associated with cardiac diverticulum in the pentalogy of Cantrell, however a prenatal diagnosis of omphalocele has not been described with a broad-based, thin-walled aneurysm of the ventricular wall in a surviving patient. CASE REPORT: A case of omphalocele with Morgagni hernia and left ventricular aneurysm diagnosed at 21 weeks, 6 days' gestational age is reported. Initial ultrasound examination demonstrated the cardiac defect and subsequent ultrasounds revealed the abdominal wall defect. Prenatal monitoring included serial ultrasound and echocardiography. A viable fetus was delivered via cesarean section at 37 weeks' gestational age. The omphalocele and Morgagni hernia were repaired on the infant's 4th day of life. The cardiac defect continues to be monitored with echocardiography at 15 months of age. DISCUSSION: The case is discussed along with a short review of the literature of midline thoracoabdominal defects and left ventricular apical aneurysms.

Surgical treatment of childhood recurrent pancreatitis.

BACKGROUND/PURPOSE: Surgical intervention that improves pancreatic ductal drainage is a reasonable treatment strategy for recurrent pancreatitis in children. METHODS: This study was approved by the Committee on Human Research (San Francisco, CA). A retrospective chart review was performed on children aged 0 to 17 years given the International Classification of Diseases, Ninth Revision coding diagnosis of chronic pancreatitis who underwent surgical intervention from 1981 to 2005. RESULTS: From 1981 to 2005, 32 children were treated for the diagnosis of chronic pancreatitis. The etiologies were obstructive (n = 13), idiopathic (n = 10), hereditary (n = 6), medications (n = 2), and infection (n = 1). Fifteen patients underwent 17 operations for chronic pancreatitis, including Puestow (n = 9), cystenterostomy (n = 2), Whipple (n = 1), distal pancreatectomy (n = 1), Frey (n = 1), DuVal (n = 1), excision of enteric duplication cyst (n = 1), and pancreatic ductal dilation (n = 1). The mean age at presentation of patients undergoing surgery was 6.0 +/- 4.1 years (mean +/- SD). The mean time from presentation to operation was 3.3 +/- 3.3 years. There were no deaths after surgical intervention. Of 15 patients, 2 (13%) required rehospitalization within 90 days of surgery, one for bowel obstruction, the other for splenic infarction. The median length of stay postoperatively was 8 days (range, 5-66 days). CONCLUSIONS: Chronic pancreatitis in children differs markedly in etiology when compared with adults. In most cases seen in our institution, chronic pancreatitis resulted from ineffective ductal drainage. These disorders are amenable to surgical decompression, which, ultimately, can prevent disease recurrence.

Fetal intervention for mass lesions and hydrops improves outcome: a 15-year experience.

PURPOSE: The natural history of certain prenatally diagnosed masses is well known. Large thoracic mass lesions can evolve one of 2 ways, either to regress and cause minimal morbidity, or to progress and enlarge, often resulting in hydropic changes in the fetus. This nonimmune hydrops carries a dismal prognosis, with nearly all fetuses expiring before or shortly after birth. However, hydrops associated with fetal mass lesions can be halted and even reversed with fetal intervention and treatment of the underlying defect. We examined our patients with fetal mass lesions to evaluate survival after intervention. METHODS: Institutional approval was obtained by the Committee on Human Research. A retrospective review was performed of 294 fetuses evaluated over 15 years with large mass lesions. All patients were evaluated for evidence of fetal hydrops using ultrasound criteria. Patients were divided according to type of intervention. Primary outcome measure was 30-day survival after birth. RESULTS: (1) Patients without fetal hydrops did not undergo fetal intervention and survived to 30 days after birth (167/172, 97%). (2) Patients with fetal mass lesions that developed hydrops fared poorly with no intervention (1/33 survival, 3%), whereas fetuses undergoing prenatal intervention fared much better (15/30 open, 50%; 3/10 percutaneous, 30%). (3) Four patients with hydropic congenital cystic adenomatoid malformation (n = 3) or pulmonary sequestration (n = 1) received steroids in preparation for surgery but underwent no intervention, and the patients survived the neonatal period. CONCLUSION: Fetuses with prenatal diagnoses of masses not associated with hydrops have excellent prognosis with survival higher than 95%. Nonimmune hydrops associated with prenatal diagnosis of a fetal mass is a devastating complication with less than 5% survival. Open resection of a mass causing hydrops resulted in 50% survival, with reversal of hydrops in a group with near-uniform fatality. Further investigation is warranted regarding the use of minimally invasive prenatal therapies including steroid administration for hydropic fetuses.

Fetal surgery for congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) continues to account for significant mortality in neonates. Advances in postnatal therapies have reduced mortality rates in the less severely affected infants, though surviving infants continue to display significant comorbid conditions. The history of fetal treatment for CDH is a microcosm for the development of fetal therapy in general. This paper traces this history from early clinical observations and imaging advances to experimental animal studies and finally to safe human application and development of clinical trails. Encouraging recent results and improved outcomes lend credence to the idea than prenatal interventions may give clinicians and families more hope.

Prosthetic patches for congenital diaphragmatic hernia repair: Surgisis vs Gore-Tex.

PURPOSE: The sequelae of congenital diaphragmatic hernia (CDH) continue well beyond the perinatal period. Up to 50% of these patients have subsequent recurrent herniation or small bowel obstruction (SBO). A recent trend has been toward the use of bioactive prosthetic materials. We reviewed different patch closure techniques used for CDH repair at our institution and their association with these sequelae. METHODS: A retrospective review was performed of 152 records for patients with CDH. Newborns that underwent patch repair for CDH and survived for at least 30 days were included in the analysis. Primary outcomes evaluated were recurrent herniation and SBO. Two types of prostheses were examined, Gore-Tex, an artificial material, and Surgisis, a bioactive material. RESULTS: Twelve (44%) of 27 patients who had Surgisis repair had recurrent herniation. Seventeen (38%) of 45 patients who had a Gore-Tex repair had recurrent herniation. Two additional patients in each group presented with SBO. No significant difference in recurrent herniation rates was observed (P > .5). The time to recurrence was similar in both groups (log-rank, P = .75), with most recurrences (92% Surgisis, 76% Gore-Tex) occurring in the first year. CONCLUSION: The rates of recurrent herniation and SBO after neonatal prosthetic patch repair of CDH were similar regardless of the prosthetic material used (Surgisis or Gore-Tex).

Long-term follow-up after thymectomy for myasthenia gravis: thoracoscopic vs open.

PURPOSE: The aim of this study was to determine if patients are in remission or weaning off medication after thymectomy for myasthenia gravis (MG) and to examine the thoracoscopic versus open approaches. METHODS: A retrospective review of all patients who underwent thymectomy for MG at a tertiary referral center between 1992 and 2004 (N = 14). Six patients (42.9%) underwent thoracoscopic resection. Eight patients underwent open resection; 5 (35.7%) had median sternotomy and 3 (21.4%) by transcervical approaches. Follow-up was obtained in 12 (85.7%) of 14 patients by both chart review and telephone. The mean follow-up was 43.0 months (range, 4-111 months). Statistical significance was determined by Student's t test or Fisher's Exact Test. RESULTS: The thoracoscopic group had a mean operating time of 138.8 minutes compared with 139.8 minutes in the open group (P = .9). The thoracoscopic group had a mean estimated blood loss of 7.5 mL compared with 52.5 mL in the open group (P = .02). The mean length of stay for the thoracoscopic group was 1.5 days (range, 1-2 days) and was 10.6 days (range, 3-41 days) in the open group (P = .13). Three (60%) of 5 patients were entirely off medication in the thoracoscopic group at the time of follow-up compared with 3 (50%) of 6 patients in the open group (P = 1.0). In the thoracoscopic group, 5 (83.3%) of 6 were in class 1 to 3 of the DeFilippi classification (complete remission or improved with decreased medication requirements). One patient had no change in symptoms (class 4). In the open group, 5 (83.3%) of 6 were classified as DeFilippi 1 to 3 at the time of follow-up, and one patient had worsening symptoms (class 5). CONCLUSIONS: Both thoracoscopic and open approaches to thymectomy in patients with MG are effective, with more than 80% of patients in both groups in remission or with improvement at the time of follow-up. The thoracoscopic group has the added benefits of decreased estimated blood loss, decreased length of hospital stay, and improved cosmesis. We advocate the thoracoscopic approach for thymectomy in the treatment of juvenile MG.