Abstracts of Staff Publications
aWinter 2003
Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae
Tan TQ, Mason EO Jr, Wald ER, Barson WJ, Schutze GE, Bradley JS, Givner LB, Yogev R, Kim KS, Kaplan SL.
Pediatrics 2002 Jul;110(1 Pt 1):1-6
Objective: The frequency of children who are hospitalized with pneumococcal pneumonia complicated by necrosis, empyema/ complicated parapneumonic effusion, and lung abscess seems to be increasing. The factors that contribute to this increase are unclear; therefore, the objective of this study was to describe and compare the relative frequency, clinical characteristics, and outcome of hospitalized children with complicated pneumonia with those of children with uncomplicated pneumonia caused by Streptococcus pneumoniae in the era of antibiotic resistance.
Methods: A multicenter, retrospective study of 8 children’s hospitals in the United States was undertaken. A total of 368 children who were hospitalized with pneumococcal pneumonia identified from patients enrolled in the US Pediatric Multicenter Pneumococcal Surveillance Study over the period from September 1, 1993, to January 31, 2000 were studied. Demographic and clinical variables, antibiotic susceptibility, pneumococcal serotypes, antimicrobial therapy, and clinical outcome in hospitalized children with complicated versus uncomplicated pneumococcal pneumonia were measured.
Results: A total of 368 patients with pneumococcal pneumonia were identified. Of the 368 isolates, 47 (12.8%) were intermediate and 37 (10.1%) were resistant to penicillin; 18 (5%) were intermediate to ceftriaxone, and 9 (2.5%) were resistant to ceftriaxone. A total of 133 patients met the criteria for complicated pneumonia and had a chest tube placed; 56 of these patients subsequently underwent decortication. The proportion of hospitalized patients with complicated pneumococcal pneumonia increased progressively over the study period from 22.6% in 1994 to 53% in 1999. Patients with complicated disease were older (median age: 45 vs 27 months) and significantly more likely to be of white race and have chest pain on presentation compared with patients with uncomplicated disease. Patients who had complicated disease and underwent decortication were more likely to have pleural fluid lactate dehydrogenase levels of >7500 IU/L compared with those patients who had chest tube placement alone. Fifty-three percent of children who were > or =61 months of age and were hospitalized had complicated pneumonia. This group of children accounted overall for 42% of the patients with complicated pneumonia, 48.2% of the patients who subsequently underwent decortication, and 44% of the patients who had received a course of antibiotics before diagnosis. Pneumococcal serotypes 1, 6, 14, and 19 were the most prevalent serotypes causing disease, with serotype 1 causing 24.4% of the complicated cases versus 3.6% of the uncomplicated cases. Ninety-eight percent of the patients in both groups recovered from their pneumonia. Antibiotic resistance was not found to be more prevalent in those patients with complicated disease.
Conclusions: The relative frequency of complicated disease in hospitalized children with pneumococcal pneumonia is increasing. Patients with complicated pneumococcal disease were older and significantly more likely to be of white race compared with those patients with uncomplicated disease. Pneumococcal serotype 1 caused significantly more disease in patients with complicated versus uncomplicated pneumonia. Patients with complicated disease were not more likely to be infected with an antibiotic-resistant isolate.
Prevention of pneumococcal meningitis
Tan TQ.
Curr Infect Dis Rep 2002 Aug;4(4):317-323
With the success of the conjugated Haemophilus influenzae type b vaccines, Streptococcus pneumoniae has become one of the most important causes of bacterial meningitis worldwide, causing significant morbidity and mortality. Additionally, the increasing amount of resistance that this organism is developing to multiple classes of antimicrobial agents has made the treatment of pneumococcal infections, especially meningitis, much more difficult. Immunization has been shown to be one of most effective methods for preventing pneumococcal meningitis, resulting not only in a decrease in disease burden, but also a decrease in antimicrobial resistance. Currently, a 23-valent pneumococcal polysaccharide vaccine and a heptavalent protein conjugate vaccine are licensed for use. However, the 23-valent polysaccharide vaccine is poorly immunogenic in infants and young children. The continued development, licensing, and use of pneumococcal conjugate vaccines have the best potential to both prevent disease and decrease the prevalence of pneumococcal meningitis.
The role of protease inhibitor therapy in children with HIV Infection
Gavin PJ, Yogev R.
Paediatr Drugs 2002;4(9):581-607
In comparison with HIV infection in adults, higher HIV RNA levels in children with perinatal HIV infection, differences in the natural history of HIV disease progression, and the presence of a relatively immature immune system contribute to the more complex and problematic nature of pediatric antiretroviral therapy. Current US treatment guidelines for pediatric HIV infection advocate aggressive therapy with potent combination antiretroviral regimens, to achieve profound and durable suppression of viral replication and preservation of immune function. The combination of a protease inhibitor (PI) and dual nucleoside reverse transcriptase inhibitors (NRTIs) is the most commonly recommended form of highly active antiretroviral treatment (HAART). However, use of PI therapy in pediatrics has been constrained by the lack of suitable drug formulations, a paucity of pharmacokinetic and safety data, and drug intolerance. Pharmacokinetic studies of PIs demonstrate frequent differences between children and adults, and greater variability among children, which has led to subtherapeutic dosage regimens and the development of viral resistance. The optimal dosage of many PIs in younger children is not yet known. A therapeutically important drug interaction associated with PIs is that occurring between the various PIs themselves, which allows lower doses of PI at less frequent intervals. Dual PI regimens will probably become more common, as they permit a simpler antiretroviral regimen, lower pill/medication burden, fewer adverse effects and improved adherence. Poor adherence to antiretroviral therapy remains the greatest barrier to overall success in the treatment of HIV-infected children. The key to improving adherence in HIV-infected children is to find treatment regimens that are better suited to their normal life. With improvements in existing PIs and the development of newer ones, simplification of current antiretroviral therapy to once-daily regimens without loss of potency should be achievable. PI-containing HAART has transformed HIV infection into a chronic illness, and HIV-infected children now live longer.
Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children
Gavin PJ, Katz BZ.
Pediatrics 2002 Jul;110(1 Pt 1):e9
Background: Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. Ribavirin, a guanosine analogue, has broad antiviral activity against both RNA and DNA viruses, including documented activity against adenovirus in vitro. Ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis C. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity.
Objective: We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature.
Design/Methods: We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial DiGeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol.
Results: Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failure and neutropenia.
Discussion: Our series of patients is representative of the spectrum of immunocompromised children at greatest risk for severe adenovirus disease, namely solid-organ and bone marrow transplant recipients, neonates, and children with immunodeficiency. Although intravenous ribavirin was not effective for all children with severe adenovirus disease in this series or in the literature, therapy is unlikely to be of benefit if begun late in the course of the infection. Early identification, eg by polymerase chain reaction of those patients at risk of disseminated adenovirus disease may permit earlier antiviral treatment and better evaluation of therapeutic response.
Conclusions: Two of 5 children with severe adenovirus disease treated with intravenous ribavirin recovered. The availability of newer rapid diagnostic techniques, such as polymerase chain reaction, may make earlier, more effective treatment of adenovirus infection possible. Given the seriousness and increasing prevalence of adenovirus disease in certain hosts, especially children, a large, multicenter clinical trial of potentially useful anti-adenoviral therapies, such as intravenous ribavirin, is clearly required to demonstrate the most effective and least toxic therapy.
Lead poisoning and asthma: an examination of comorbidity
Myers SN, Rowell B, Binns HJ.
Arch Pediatr Adolesc Med 2002 Sep;156(9):863-6
Objectives: To determine the comorbidity of lead poisoning and asthma in urban children, and to examine associated clinical factors.
Methods: One-hundred-one patients at an inner-city clinic with blood lead levels (BLLs) of 25 micro g/dL or higher (>/=1.2 micro mol/L) (BLL25 group) were randomly selected from a tracking lead database and matched on age, sex, and primary language to 101 randomly selected patients with a first BLL recorded in the database of lower than 5 micro g/dL (<0.2 micro mol/L) (BLL5 group) and no subsequent BLLs of 10 micro g/dL or higher (>/=0.5 micro mol/L). Medical records were reviewed to determine diagnosis or symptoms of asthma or wheezing at any visit, immunization status, and number of visits. Analyses for matched pairs were conducted.
Results: The BLL25 and BLL5 groups did not differ on age at diagnostic BLL (26.6 months vs 24.2 months), sex (54% male), or language (12% Spanish). The BLL25 and BLL5 groups had a similar number of subjects with a diagnosis of asthma (6% vs 11%; odds ratio, 0.5; 95% confidence interval, 0.2-1.6); 26% of BLL25 and 34% of BLL5 subjects had either a diagnosis or symptoms of asthma or wheezing (odds ratio, 0.7; 95% confidence interval, 0.4-1.3). Subjects with BLL25 were more likely to have delayed immunization and a first clinic visit when older than subjects with BLL5.
Conclusions: There was no increased likelihood of asthma diagnosis or symptoms among young children with lead poisoning. Children with lead poisoning also had delayed medical care. These data may help guide interventions aimed at preventing or reducing the impact of lead poisoning and asthma.
Firearm-related death and injury among children and adolescents
Fingerhut LA, Christoffel KK.
Future Child 2002 Summer-Fall;12(2):24-37
This article analyzes trends and current status in firearm death and injury, based on nationwide data collected by the federal government. Several key findings emerge from the data: Firearm death rates among children and youth in the United States have declined dramatically since 1993, but remain high compared with historical rates in this country and rates in other developed nations. A majority of these deaths are homicides. Certain groups of children and youth, especially adolescents, boys, minority youth, and those residing outside the Northeast, are particularly at risk for firearm death. The problem is most acute among black teenage males. Firearm injuries are much more likely to result in death than are other injuries for which children and youth visit emergency departments—a reflection of the extreme lethality of firearms. Given these findings, the authors call for a concerted effort to reduce youth firearm deaths to levels comparable to those of other industrialized nations, using a wide variety of approaches that span the public health, criminal justice, and educational spheres. They also recommend improved data systems to track firearm injury and death, so that researchers can better analyze these incidents and evaluate intervention strategies.
Incidence and description of high chair-related injuries to children
Powell EC, Jovtis E, Tanz RR.
Ambul Pediatr 2002 Jul-Aug;2(4):276-8
Study Objective: To describe the incidence, circumstances, and types of high chair-related injuries among US children.
Design: Retrospective review of data for children 3 years old and younger from the National Electronic Injury Surveillance System of the US Consumer Product Safety Commission for 1994-98.
Results: There were an estimated 40 650 high chair-related injuries (95% confidence interval [CI], 32 657-48 643) to children 3 years old and younger treated in hospital emergency departments in the US during the 5-year study period. An estimated 5231 injuries (13%) were related to use of an attachable high chair (including booster seats), and an estimated 4067 (10%) were related to the use of a youth chair. The annual rate of injury among children < or =3 years old was 5.3 per 10 000. The mean age was 10 months (median, 1 year); 56% were boys. Ninety-four percent of injuries resulted from a fall from the chair. Most injuries involved the head (44%) or face (39%). Injury diagnoses included contusions or abrasions (36%), lacerations (25%), closed head injury (21%), and fractures (8%). Two percent of injured children, an estimated 941 (95% CI, 399-1487), were admitted to the hospital during the study period, an annual admission rate of 0.1 per 10 000. There were no significant differences between attachable high chairs, youth chairs, and high chairs in anatomic sites of injury, injury diagnosis, or frequency of hospital admission.
Conclusions: Injuries related to high chairs are common, particularly among children in the first year of life. They often result from falls from the chair. The data suggest that restraint use would prevent most of these injuries.
Differing postneonatal mortality rates of African-American and white infants in Chicago: an ecologic study
Papacek EM, Collins JW Jr, Schulte NF, Goergen C, Drolet A.
Matern Child Health J 2002 Jun;6(2):99-105
Objectives: This study sought to determine whether neighborhood impoverishment explains the racial disparity in urban postneonatal mortality rates.
Methods: Stratified and multivariate logistic regression analyses were performed on the vital records of all African-Americans and whites born in Chicago by means of a linked 1992-1995 computerized birth-death file with appended 1990 U.S. census income and 1995 Chicago Department of Public Health data. Four community-level variables (low median family income, high rates of unemployment, homicide, and lead poisoning) were analyzed. Communities with one or more ecologic risk factors were classified as impoverished.
Results: The postneonatal mortality rate of African-Americans (N=104,656) was 7.5/1000 compared to 2.7/1000 for whites (N=52,954); relative risk (95% confidence interval) equaled 2.8 (2.3-3.3). Seventy-nine percent of African-American infants compared to 9% of white infants resided in impoverished neighborhoods; p < 0.01. In impoverished neighborhoods, the adjusted odds ratio (controlling for infant and maternal individual-level risk factors) of postneonatal mortality for African-American infants equaled 1.5 (0.5-4.2). In nonimpoverished neighborhoods, the adjusted odds ratio of postneonatal mortality for African-American infants equaled 1.8 (1.1-2.9).
Conclusions: We conclude that urban African-American infants who reside in nonimpoverished neighborhoods are at high risk for postneonatal mortality.
Utility of WT1 as a reliable tool for the detection of minimal residual disease in children with leukemia
Kletzel M, Olzewski M, Huang W, Chou PM.
Pediatr Dev Pathol 2002 May-Jun;5(3):269-75
WT1 encodes a transcription factor involved in the pathogenesis of Wilms’ tumor. A high level of expression has been reported in blasts from patients with various hematological malignancies. The study was performed to evaluate the utility of monitoring WT1 expression in children with leukemia at diagnosis, during therapy, and following bone marrow transplant. We tested a total of 204 samples prospectively. These included samples from patients with the following diagnoses: acute lymphoblastic leukemia (ALL) at diagnosis (n=45), at relapse (n=14), and in remission (n=45); acute non-lymphoblastic leukemia (ANLL) at diagnosis (n=14), at relapse (n=5), and in remission (n=12); and chronic myelogenous leukemia (CML) in blast crisis (n=1) and in chronic phase (n=1). A total of 33 of these patients were transplanted: 19 ALL, 12 ANLL, and 2 CML. In addition, samples from 5 patients with aplastic anemia and 28 controls were obtained from peripheral blood (n=17), cord blood (n=3), and bone marrow (n=8). Primer pairs were designed to locate specific nucleotide sequences for mRNA of WT1. RT-PCR was performed in all samples and compared with K562 cells from ATCC (defined as 1.0) as positive control. A positive test was arbitrarily defined as WT1/K562 > 0.5. Samples at diagnosis and relapse, including 56 out of 59 ALL (95%), 26 ANLL (100%), and 1 CML in blast crisis, demonstrated high levels of WT1 expression. In contrast, only 5 of 90 samples obtained in remission or post-transplant showed high levels of WT1 expression (P<0.0001; 95% CI=0.66-0.94). The five patients with high WT1 expression during follow-up relapsed within 2 to 6 months. In conclusion, we have found that WT1 is consistently elevated in children with leukemia. Significant differences in the level of WT1 expression were noted between these patients during diagnosis and at relapse, and those during remission. More importantly, following bone marrow transplant, a significant high level of WT1 expression preceded clinical relapse by 2 to 6 months. Therefore, WT1 is a reliable marker for monitoring minimal residual disease during therapy as well as in the post-transplant period.
Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and stem-cell rescue: results of the Chicago Pilot II Study.
Kletzel M, Katzenstein HM, Haut PR, Yu AL, Morgan E, Reynolds M, Geissler G, Marymount MH, Liu D, Kalapurakal JA, Shore RM, Bardo DM, Schmoldt J, Rademaker AW, Cohn SL.
J Clin Oncol 2002 May 1;20(9):2284-92
Purpose: To investigate whether intensive induction therapy followed by triple-tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue and local irradiation will improve event-free survival for patients with high-risk neuroblastoma.
Patients and Methods: From August 1995 to January 2000, 25 consecutive newly diagnosed high-risk neuroblastoma patients and one child with recurrent MYCN-amplified disease were enrolled onto the Chicago Pilot II Protocol. After induction therapy and surgery, peripheral-blood stem cells were mobilized with three cycles of high-dose cyclophosphamide and granulocyte colony-stimulating factor. Patients then underwent triple-tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue followed by radiation to the primary site.
Results: Twenty-two of the 26 patients successfully completed induction therapy and were eligible for the triple-tandem consolidation high-dose therapy. Sufficient numbers of peripheral-blood stem cells were collected in all but one patient. Seventeen patients were able to complete all three cycles of high-dose therapy and peripheral-blood stem-cell rescue, two patients completed two cycles, and three patients completed one cycle. There was one toxic death, and one patient died from complications of treatment for graft failure. With a median follow-up of 38 months, the 3-year event-free survival and survival rates are 57% +/– 11% and 79% +/– 10%, respectively.
Conclusion: The results of this pilot study demonstrate that it is feasible to intensify consolidation with triple-tandem high-dose chemotherapy and peripheral-blood stem-cell rescue and local irradiation, and suggest that this treatment strategy may lead to improved survival for patients with high-risk neuroblastoma.
Hepatocellular carcinoma in children and adolescents:
results from the Pediatric Oncology Group and the Children’s Cancer Group intergroup study
Katzenstein HM, Krailo MD, Malogolowkin MH, Ortega JA, Liu-Mares W, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Newman K, Finegold MJ, Haas JE, Sensel MG, Castleberry RP, Bowman LC.
J Clin Oncol 2002 Jun 15;20(12):2789-97
Purpose: To determine surgical resectability, event-free survival (EFS), and toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP and continuous-infusion doxorubicin (regimen B).
Patients and Methods: Forty-six patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098 (Pediatric Oncology Group (POG) 8945/Children’s Cancer Group (CCG) 8881). After initial surgery or biopsy, children with stage I (n=8), stage III (n=25), and stage IV (n=13) HCC were randomly assigned to receive regimen A (n=20) or regimen B (n=26).
Results: For the entire cohort, the 5-year EFS estimate was 19% (SD=6%). Patients with stage I, III, and IV had 5-year EFS estimates of 88% (SD=12%), 8% (SD=5%), and 0%, respectively. Five-year EFS estimates were 20% (SD=9%) and 19% (SD=8%) for patients on regimens A and B, respectively (P=.78), with a relative risk of 1.2 (95% confidence interval, 0.60 to 2.3) for regimen B when compared with regimen A. Outcome was similar for either regimen within disease stages. Events occurred before postinduction surgery I in 18 (47%) of 38 patients with stage III or IV disease, and tumor resection was possible in two (10%) of the remaining 20 children with advanced-stage disease after chemotherapy.
Conclusion: Children with initially resectable HCC have a good prognosis and may benefit from the use of adjuvant chemotherapy. Outcome was uniformly poor for children with advanced-stage disease treated with either regimen. New therapeutic strategies are needed for the treatment of advanced-stage pediatric HCC.
Treatment of unresectable and metastatic hepatoblastoma:
a Pediatric Oncology Group phase II study
Katzenstein HM, London WB, Douglass EC, Reynolds M, Plaschkes J, Finegold MJ, Bowman LC.
J Clin Oncol 2002 Aug 15;20(16):3438-44
Purpose: To estimate the disease-response rate, proportion of patients whose tumors can be made resectable, event-free survival (EFS), and toxicity in children with unresectable or metastatic hepatoblastoma (HB) after sequential treatment with the following: (1) carboplatin (CARBO); (2) CARBO, vincristine, and fluorouracil (CARBO-VCR-5-FU); and (3) high-dose cisplatin and etoposide (HDDP-ETOP).
Patients and Methods: Thirty-three assessable patients with stage III (n=22) and stage IV (n=11) HB were treated sequentially with one course of CARBO (700 mg/m(2)), followed by three courses of CARBO (700 mg/m(2)), day 0; 5-FU (1,000 mg/m(2)/d), by continuous infusion days 0 to 2; and VCR (1.5 mg/m(2)), days 0, 7, and 14. After that therapy, patients whose tumors were resectable underwent surgery and then received two additional courses of CARBO-VCR-5-FU. Children whose tumors remained unresectable after CARBO-VCR-5-FU or who demonstrated no response or progressive disease during this therapy received two courses of HDDP (40 mg/m(2)/d), days 1 to 5; and ETOP (100 mg/m(2)/d), days 2 to 4.
Results: Five-year EFS estimates were 59% +/– 11% for stage III disease (n=22) and 27% +/– 16% for stage IV disease (n=11), respectively (P=.037). Twenty-seven (82%) of 33 patients had at least a partial response to chemotherapy; 18 (55%) of 33 responded to CARBO; 24 (80%) of 30 responded to CARBO and CARBO-VCR-5-FU; and nine (75%) of 12 responded to HDDP-ETOP. Surgical resection was achieved in 19 (58%) of 33 patients, including 15 (68%) of 22 stage III patients and four (36%) of 11 stage IV patients. Five-year EFS for patients whose tumors were completely resected was 79% +/– 10%.
Conclusion: Patients treated sequentially with CARBO, CARBO-VCR-5-FU, and HDDP-ETOP had response rates and EFS comparable to other therapeutic regimens. This regimen is effective in treating localized, unresectable HB and potentially has less toxicity than other regimens. Novel approaches are needed for patients with metastatic disease.
Astrocytomas of the cerebral peduncle in children:
surgical experience in seven patients
Tomita T, Cortes RF.
Childs Nerv Syst 2002 May;18(5):225-30
Objects: Cerebral peduncle tumors are rare in childhood but often consist of benign astrocytomas. Surgical resection, however, is considered to be detrimental because of the highly sensitive neural structures. These tumors are often treated by radiation therapy (RT). We resected such tumors in seven patients, whom we then followed up without adjuvant therapy. The surgical approach and postoperative course are analyzed.
Methods: Seven children, ranging in age from 4 to 16 years, were treated from 1993 to 2000. Tumors showed extension in various directions to the thalamus, pons and neighboring cisterns. All were treated by surgical resection through a subtemporal approach: total resection was achieved in three and subtotal resection in four. Operative complications were minimal. Two patients were worse after surgery, albeit temporarily, in motor, oculomotor or memory functions. All the tumors were benign astrocytomas. None of the patients received postoperative RT. Only one patient had a recurrence during the follow-up period, which ranged from 1 year to 8.5 years in duration.
Conclusions: Benign astrocytomas of the cerebral peduncle are amenable to radical tumor resection by an appropriate surgical approach and with microsurgical techniques. Even following subtotal resection, these tumors frequently remain stable or involute. These children can be spared RT.
Surgical management of aortopulmonary window:
a 40-year experience
Backer CL, Mavroudis C.
Eur J Cardiothorac Surg 2002 May;21(5):773-9
Objectives: An aortopulmonary window (APW) is a communication between the pulmonary artery (PA) and the ascending aorta in the presence of two separate semilunar valves. The purpose of this review is to describe the evolution of surgical techniques and results of surgical correction of APW at a single center over a 40-year time period.
Methods: Between 1961 and 2001, 22 patients underwent repair of APW. Age ranged from 11 days to 13 years (median 0.3 years). Associated cardiac lesions included interrupted aortic arch (IAA) (four), right PA origin from the aorta (four), ventricular septal defect (three), atrial septal defect (one), tetralogy of Fallot (one), and transposition of the great arteries (one). Mean preoperative pulmonary vascular resistance was 5.4 U/m2 (n=17). Two patients had attempted ligation without cardiopulmonary bypass (CPB), one patient had division and oversewing of the APW between clamps on CPB. Ten patients had the APW divided on CPB with primary aortic closure. Three patients had circulatory arrest for APW division, IAA repair, and anastomosis right PA to main PA. Most recently, six patients have had open transaortic patch closure (one of these had simultaneous arterial switch, one had simultaneous IAA repair). Follow-up in operative survivors ranges from 1 month to 26 years (median 8 years).
Results: There were five early deaths and one late death (pulmonary hypertension) in the first 16 patients where the primary strategy was APW division (37% mortality). There have been no deaths in the most recent six patients having transaortic patch closure. The patients with transaortic patch closure at a maximum of 8 years follow-up are demonstrating normal PA and aortic growth.
Conclusions: Early correction of APW with a transaortic patch and repair of all other associated cardiac anomalies at the time of diagnosis is advised.
Partial external biliary diversion for intractable pruritus and xanthomas in Alagille syndrome
Emerick KM, Whitington PF.
Hepatology 2002 Jun;35(6):1501-6
Alagille syndrome (AGS) causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol. This study was performed to determine whether partial external biliary diversion (PEBD) is effective for relief of pruritus and xanthomas in AGS patients who fail conventional medical therapy. Between the years 1985 and 2001, 9 AGS patients underwent PEBD. Complete follow-up data were available for all patients. The average age at PEBD was 4.8 (range 1.4-10) years. The average duration of follow-up was 7.5 (range 0.5-16.0) years. All 9 patients had severe, mutilating pruritus (grade 4) prior to diversion. At 1 year post-PEBD, the average pruritus score was 1.1; 8 patients had only mild scratching when undistracted. Three patients with extensive xanthomas prior to PEBD had complete resolution within 1 year. Mean serum bile salt levels (n=5) decreased from 136.5 to 37.1 micromol/L and mean cholesterol (n=7) from 724 to 367 mg/dL 1 year after PEBD. A single 21-year-old patient with PEBD for 14 years experienced an increase in pruritus from grade 1 to grade 4 within 2 months of elective reversal of PEBD. In conclusion, PEBD is effective for treating severe pruritus and hypercholesterolemia in AGS patients without cirrhosis who did not respond to medical therapy. PEBD should be considered as a therapeutic option for these patients before referral for liver transplantation because of morbid complications.
