Charles G. Howell

Interferon-alpha-2a for the treatment of complex hemangiomas of infancy and childhood.

ObjectiveThe authors describe the use of interferon–alpha-2a (IFN–α-2a) in the treatment of complex hemangiomas and review the role of interferon (IFN) in this example of an angiogenic disease. Summary Background DataHemangiomas are the most frequent tumors of infants and children. They grow rapidly for 6 to 8 months and then resolve over a period of years. Approximately 5% produce life-, sight-, or limbthreatening complications, with mortality rates between 20% and 50%. Aggressive therapy with steroids, arterial ligation or embolization, or surgery has been used in these situations with variable results and high morbidity. Recently, IFN–α was found to be effective treatment in these complex hemangiomas. MethodsFour infants and one child were treated with IFN–α-2a at an initial subcutaneous dose of 1 million units/m2/day and a sustained dose of 3 million units/m2/day for 5 to 11 months. Appropriate laboratory values were monitored and adverse reactions and ultimate response to therapy were recorded. ResultsTwo patients experienced minor complications that were managed easily. Three patients had total or near-total regression of the hemangioma, one had partial (50%) regression, and one had stabilization but no regression after an average of 7.1 months of IFN therapy. ConclusionInterferon–α inhibits angiogenesis and endothelial cell migration and proliferation in vitro. The patients in this study add to the growing number who have benefited from IFN therapy. As such, IFN–α should be considered as a first-line agent in treating complex hemangiomas of infants and children.

Antenatal diagnosis and early surgery for choledochal cyst

The pathogenesis and optimal treatment of choledochal cyst have long remained questions of considerable speculation and dispute. Because the pregnancy of a 37-year-old woman was felt to be at risk, five antenatal ultrasound examinations were made. The fourth examination at 31.5 weeks of gestation demonstrated a choledochal cyst. Following birth, the child was studied with repeat ultrasound examinations and scintigraphy. The results of these studies plus the findings at surgery contributed new evidence regarding the possible pathogenesis and optimal treatment of choledochal cysts. Although the time at which the cyst originated is compatible with the concept of reflux of pancreatic juice into the common duct, no abnormal junction of the pancreatic and common duct was identified. No evidence of obstruction as part of the pathogenesis could be demonstrated. Progressive changes in the choledochal cyst in the first ten days of life suggested that delay in diagnosis and treatment of a choledochal cyst may contribute to early complications such as cholangitis. Early excision of the cyst in the newborn is considered to be the optimal treatment and may pose less risk to the patient than delayed surgical exploration.

Right common carotid artery ligation in extracorporeal membrane oxygenation

The effect of right common carotid artery ligation required for arteriovenous extracorporeal membrane oxygenation (ECMO) was investigated in 35 infants. Their neonatal course was reviewed for evidence of right-sided ischemia of the brain, as suggested by the presence of focal seizures, hemiparesis, focal abnormalities on electroencephalography, or infarct or hemorrhage demonstrable on neuroimaging studies. A significant incidence of left focal seizures (9/35) versus right focal seizures (2/35) was noted, suggesting an effect of the carotid ligation on right hemisphere function. Computed tomographic scans (20/35 infants), electroencephalograms (18/35), ultrasound scans (31/35), and neurologic examinations did not reveal an increased incidence of right hemisphere abnormalities. These data suggest that systematic evaluation of the effects of right common carotid ligation should proceed as discussion continues on expanding the use of ECMO.

Successful management of an infant with a giant hemangioma of the retroperitoneum and Kasabach-Merritt Syndrome with α-interferon

Giant vascular neoplasms in neonates generally require aggressive medical or surgical therapy for treatment of complications. Steroids, chemotherapy, embolization, radiation, and surgery have all been used with short-term beneficial and sometimes unknown long-term side effects. A new modality of treatment, alpha-interferon, has recently been described. The majority of hemangiomas in children involute by 8 years of age. Occasionally, hemangiomas can endanger vital structures and are associated with a consumption coagulopathy and thrombocytopenia (Kasabach-Merritt Syndrome). These hemangiomas occasionally do not respond to steroids, radiation therapy, cytotoxic drugs, or embolization. The mortality rates approach 50% in nonresponders. Alpha-interferon has been used in these children with life-threatening complications of hemangiomas with relief of symptoms. This case illustrates the potential use of alpha-interferon in the management of giant hemangiomas in children. This emerging form of biological therapy avoids the risks of radiation therapy, embolization, and surgery with only minimal side effects.

Bypass circuits as the source of thromboemboli during extracorporeal membrane oxygenation

To determine the presence and extent of thrombus formation in the apparatus used for extracorporeal membrane oxygenation we studied various portions of the polyvinylchloride circuit from five infants who received extracorporeal membrane oxygenation for 70 to 330 hours. All infants had right-sided cannulation. Sections were cut from the circuit at the time of decannulation and subjected to light and scanning electron microscopy. The site that contained the most thrombus formation was the membrane oxygenator bypass circuit, which is subjected to repeated periods of unclamping and clamping to direct blood flow through the membrane oxygenator. Autopsy results from nonsurvivors showed evidence of pulmonary and renal infarcts, a left frontal lobe infarct, a thromboembolus of the left external and internal carotid arteries, and thrombi in the lungs, kidney, brain, and coronary arteries. One survivor had computed tomographic evidence of infarction of the left middle cerebral artery distribution. We suggest that the areas of the extracorporeal membrane oxygenation circuit subjected to repeated changes in flow dynamics may be the source of microemboli.

Incidence of hypertension in infants on extracorporeal membrane oxygenation

Systemic hypertension has been associated with extracorporeal membrane oxygenation (ECMO) applied in neonatal respiratory failure. To determine the incidence of ECMO-related hypertension, we reviewed blood pressure measurements from indwelling aortic catheters in 31 infants consecutively placed on ECMO. Systemic hypertension (systolic blood pressures greater than 100 mm Hg for 4 or more consecutive hours) developed in 18 of the 31. Causes investigated included the roles of renin secretion, sodium, and colloid loads. There was no evidence of increased plasma renin activities in hypertensive infants (H), when compared with their own pre-ECMO controls or with the nonhypertensive infants (NH). Sodium and colloid loads and their rates of delivery were not different between H and NH. No consistent duration of ECMO was clearly associated with development of hypertension (mean time on ECMO at onset of hypertension, 43.8 +/- 38.5 hours; range, 1 to 142 hours). Demographic information was not statistically significant. Contrary to previous reports, H did not seem predisposed to an increased incidence of intracranial hemorrhage. Development of hypertension during ECMO is not related to increased plasma renin activity, sodium or colloid loads, or their rates of infusion.

A mouse model for the study of necrotizing enterocolitis

A mouse model for the study of necrotizing enterocolitis is presented. It is a model of temporary intestinal ischemia and consists of occluding both superior mesenteric vessels with a bulldog clamp for varying periods of time. The resultant lesions resemble the intestinal lesions seen in necrotizing enterocolitis in respect to the gradual development of the necrotizing lesions and their patchy distribution. We also studied the effect of intravenous saline and low molecular weight dextran in preventing the development of these ischemic lesions. In moderate ischemia, saline and dextran show a similar protective effect, and in severe ischemia, both show a protective effect, with dextran being more effective than saline.

Bilateral ovarian fibromas in children

The case of bilateral ovarian fibromas occurring in an 8-year-old black girl is reported. These lesions occur rarely in premenarchal females and may be a manifestation of Nevoid Basal Cell Syndrome. Calcifications are reported to occur rarely in ovarian fibromas but seem to occur frequently in fibromas in children. Management is guided by the benignity of the lesion and consists of surgical excision of the fibroma. Preservation of normal ovarian tissue is recommended with the acknowledged risk of recurrence of the fibroma.

Rectosigmoid perforation and intestinal evisceration from transanal suction.

Transanal suction injuries were sustained in 1981 by five children when they sat upon uncovered swimming area drain sites. Tears of the rectosigmoid areas occurred in each with associated evisceration and loss of substantial amounts of small intestine because of mesenteric separation. These cases are reviewed.

The significance of ductal shunting during extracorporeal membrane oxygenation

The purpose of this study was to evaluate the significance and direction of shunts at the level of the foramen ovale or ductus arteriosus in full-term newborns with neonatal respiratory failure who were placed on extracorporeal membrane oxygenation (ECMO). A decrease in left ventricular dimension was expected when infants were placed on ECMO but did not occur. A left-to-right shunt was demonstrated at the ductal level in nine of 12 infants early in the course of ECMO before pulmonary resistance decreased. Presumably, the lack of change in the left ventricular dimension when infants were placed on bypass was due to a left-to-right shunt at the ductal level with ductal flow replacing the right heart output, being drawn into the bypass circuit.