Airway hyperresponsiveness, remodeling and inflammation in infants with wheeze.

BACKGROUND: The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. OBJECTIVE: To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. METHODS: Inclusion criteria were as follows: full-term, 3-23 months of age; doctor -diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body plethysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analysed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. RESULTS: Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function was correlated with AHR (P = .047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (P = .057 and 0.056, respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (P = .031). CONCLUSIONS AND CLINICAL RELEVANCE: These findings do not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.

Long-term outcomes of oesophageal atresia without or with proximal tracheooesophageal fistula - Gross types A and B.

PURPOSE: Because of an extended gap between esophageal pouches a variety of methods are employed to treat oesophageal atresia (OA) without (type A) or with (type B) proximal tracheooesophageal fistula. This retrospective observational study describes their single centre long-term outcomes from 1947 to 2014. METHODS: Of 693 patients treated for OA 68 (9.7%) had type A (n=58, 8.3%) or B (n=10, 1.4%). Hospital records were reviewed. Main outcome measures were survival and oral intake. RESULTS: Nine (13%) patients had early and 10 (15%) delayed primary anastomosis, 30 (44%) underwent reconstruction including colonic interposition (n=13), reversed gastric tube (n=11) and jejunum interposition (n=6), whereas19 (28%) had died without a definite repair. Median follow up was 35 (interquartile range, 7.4-40) years. Thirty-one (63%) of 49 patients with definitive repair survived long term. Survival was 22% for early and 80% for delayed primary anastomosis, 57% for colon interposition, 82% for gastric tube and 84% for jejunum interposition. Gastrooesophageal reflux was most common after gastric tube (80%), dysphagia after colon interposition (50%), and 3 (60%) of 5 survivors with jejunum interposition had permanent feeding ostomy because of neurological disorder. Endoscopic follow-up disclosed no oesophageal cancer or dysplasia. Repair in the most recent patients from 1985 to 2014 (n=14) included delayed primary anastomosis (n=7), jejunum interposition (n=6) and gastric tube (n=1) with 93% long-term survival. CONCLUSION: Morbidity among long-term survivors of type A or B OA is high. With modern management survival is, however, excellent and patients without neurological disorder achieve full oral intake either after primary anastomosis or reconstruction. LEVELS OF EVIDENCE: IV.

Endoscopic Surveillance After Repair of Oesophageal Atresia: Longitudinal Study in 209 Patients.

AIM: After repair of oesophageal atresia (OA), the need for endoscopic follow-up (EFU) remains unclear. To end this, we assessed the trends of oesophageal mucosal changes in successive follow-up biopsies. METHODS: EFU records of 264 patients including histological grades of oesophagitis (from 0 to III), gastric (GM) or intestinal (IM) metaplasia and dysplasia (mild to severe) at 1, 3, 5 10, 15, and >15 years after repair of OA were reviewed. RESULTS: Included were 209 patients with 616 biopsies. A total of 60 patients had undergone antireflux surgery and 24 had long-gap OA (LG). Median follow-up was 12 (range 1-17) years with 3 (1-6) endoscopies per patient. Highest grade of oesophagitis was Gr 0 (no oesophagitis) in 47%, Gr I in 37%, and Gr II or III in 16%. Metaplasia, GM (n = 31), IM (n = 4), occurred in 17% of patients and reached 15% prevalence by 15 years. Dysplasia and cancer were not found. From 1 to 15 years after repair grade of histological oesophagitis often fluctuated between Gr 0 and Gr I, but further progression was unlikely, hazard ratio = 0.2-3.4 (95% confidence interval 0.0-29), P = 0.06-0.87. LG and antireflux surgery predicted early detection of metaplasia (P < 0.001). Only 9% of patients with metaplasia and 32% with Gr II oesophagitis were symptomatic. A total of 6 (3%) patients had a symptomatic anastomotic stenosis at 1 year. CONCLUSIONS: EFU revealed frequent oesophagitis and metaplasia, but no dysplasia or cancer. Routine endoscopic surveillance had limited benefit and seems unnecessary during childhood after repair of OA.

A population-based, complete follow-up of 146 consecutive patients after transanal mucosectomy for Hirschsprung disease.

OBJECTIVE: The objective of the study is to define the population-based bowel functional outcomes and enterocolitis following transanal endorectal pull-through (TEPT) in patients with Hirschsprung disease (HD) treated at our institution between 1986 and 2011. METHODS: 146 consecutive patients who had undergone primary surgical treatment for HD were included. The median follow-up time was 15 (3-33) years. The clinical details and prevalence of enterocolitis were evaluated in all patients, and bowel function in patients >3 years of age with functional intestino-anal continuity. RESULTS: No patients were lost to follow-up. Overall survival was 98%. The level of disease was rectosigmoid in 83%, long segment in 7%, total colonic in 4%, and extending up to the small bowel in 6%. 29% had an associated syndrome. 22% had a preoperative stoma. Operations included TEPT (89%), proctocolectomy with ileoanal anastomosis in 9%, and 3% had a permanent endostomy owing to small intestinal aganglionosis. One patient underwent intestinal transplantation. At the latest follow-up, 42% had occasional soiling, 12% had frequent soiling and 46% had no soiling. Constipation occurred in 9%. An associated syndrome was the only predictor for soiling or constipation (OR 4.3, 95% CI 1.5-12). 44% developed recurrent postoperative enterocolitis, which was predicted by extended aganglionosis (OR 6.9, 95% CI 2.4-20) and syndromatic disease (OR 2.4, 95% CI 1.2-5.0). CONCLUSION: The major functional sequelae following TEPT were recurrent enterocolitis and fecal soiling, which was mostly occasional. An associated syndrome was a predictor of a reduced bowel functional outcome, and alongside extended aganglionosis were significant risk factors for recurrent postoperative enterocolitis.

Revisional surgery for recurrent tracheoesophageal fistula and anastomotic complications after repair of esophageal atresia in 258 infants.

AIM: We assessed the occurrence and outcome of major reoperations following repair of esophageal atresia with or without tracheoesophageal fistula (TOF). Major outcome measures were survival, preservation of native esophagus, and long-term esophageal function. METHODS: Hospital charts of 258 consecutive patients treated for esophageal atresia from 1980 to 2013 were reviewed. RESULTS: Forty-two (16%) patients required a total of 57 reoperations after primary repair (n=37) or esophageal reconstruction (n=5). The indications were anastomotic leakage (n=17), anastomotic rupture after endoscopic dilatation (n=5), recurrent tracheoesophageal fistula (TOF) (n=12), undiagnosed proximal TOF (n=3), recalcitrant anastomotic stricture (n=11, primary anastomosis 9, reconstruction 2), undetected proximal fistula (n=3), and inadvertently perforated jejunal graft (n=1). Anastomotic leakage and rupture after dilatation were treated with rethoracotomy and suture and recurrent or undetected TOF by open repair. Strictures not manageable with repeated dilatations were resected and esophageal ends reanastomosed (n=10) or bridged with jejunum graft (n=1). Five (12%) patients required further reoperations, two after recurrent TEF (reocclusion n=1, reconstruction with gastric tube n=1), two after stricture operations (re-resection n=1, resuture after leakage n=1), and one after recurrent dilatation-related rupture. Mortality was 4/42 (10%). Two patients died of recurred leakage or TOF and two of unrelated cause. Of 38 survivors, 35 retained their native or initially reconstructed esophagus, and 3 had secondary reconstruction. After a median follow-up of 23 (range 0.6-32) years, 35 (95%) patients have acceptable esophageal function. Three patients remained dependent on gastrostomy feedings. CONCLUSION: Anastomotic and TOF complications required a substantial number of reoperations, including esophageal reconstructions. Over 90% of the patients survived with a functioning native or reconstructed esophagus.

Lung function, airway remodeling, and inflammation in infants: outcome at 8 years.

BACKGROUND: Associations between early deficits of lung function, infant airway disease, and outcome at school age in symptomatic infants are still unclear. OBJECTIVE: To report follow-up data on a unique cohort of children investigated invasively in infancy to determine predictive value of airway disease for school-aged respiratory outcomes. METHODS: Fifty-three infants previously studied using bronchoscopy and airway conductance were approached at 8 years of age. Symptoms, lung volumes, and airway responsiveness were reassessed. Data on lifetime purchase of asthma medication were obtained. Lung function was compared with that of 63 healthy nonasthmatic children. RESULTS: Forty-seven children were reevaluated. Physician-diagnosed asthma was present in 39 children (83%). Twenty-five children (53%) had current and 14 children (30%) had past asthma. No pathologic feature in infancy correlated with any outcome parameter. As expected, study children had significantly reduced lung function and increased airway responsiveness compared with healthy controls, and very early symptoms were risk factors for reduced lung function. Current asthma was associated with reduced infant lung function and parental asthma. Reduced lung function in infancy was associated with purchase of inhaled corticosteroids when 6 to 8 and 0 to 8 years of age. CONCLUSION: The lack of predictive value of any pathologic measure in infancy, reported here for the first time to our knowledge, demonstrates that pathologic processes determining the inception of asthma, which are as yet undescribed, are different from the eosinophilic inflammation associated with ongoing disease.

Increasing occurrence of choledochal malformations in children: a single-center 37-year experience from Finland.

OBJECTIVE: Few reports on choledochal malformations (CMs) in European populations exist. MATERIALS AND METHODS: The medical records of pediatric CM patients managed in our nationwide referral center for pediatric hepatobiliary surgery between 1976 and 2013 (n = 38; 71% females) were reviewed. RESULTS: Over follow-up time, the relative proportion of fusiform CMs increased significantly (p = 0.007) and the estimated total incidence rose from 1:128,000 to 1:38,000 (p = 0.017). Cystic CMs (42%) presented at younger age than fusiform CMs (47%) (0.8 vs. 4.6 years, p = 0.001). Two-thirds had abdominal pain and half were cholestatic at presentation. Pancreatitis had occurred in 16%. In addition to ultrasound, 71% underwent magnetic resonance cholangiopancreatography and 39% underwent endoscopic retrograde cholangiopancreatography. Median CM dilatation was 15 (10-28) mm and a 12 (9-13) mm long common pancreaticobiliary channel was confirmed in 61%, increasingly during recent years. Intrahepatic biliary tree was dilated in 19%, whereas main ducts were dilated in 50%. Apart from two operated in the 1970s and one with choledochocele, patients underwent resection of extrahepatic bile ducts with Roux-en-Y hepaticojejunostomy at age of 4.2 (0.8-9.2) years. Postoperative bile leakage and hemorrhage required reoperations in two. At last follow-up 4.8 (1.3-13.2) years postoperatively, none had dilated intrahepatic biliary ducts or elevated plasma bilirubin (5 [3-7] µmol/l). Single cholangitis episodes had occurred in two, whereas others were asymptomatic. CONCLUSION: CM incidence has increased significantly in Finland, being currently over threefold higher than previous estimates in the Western world would suggest. Removal of the extrahepatic biliary tree with hepaticojejunostomy for type I and IV CMs yielded excellent results.

Resection of the stenotic segment with individually tailored anastomosis for symptomatic congenital tracheal stenosis in infants.

OBJECTIVES: To analyse retrospectively population-based results of congenital tracheal stenosis (CTS) repair in infants in Finland. METHODS: Data on infants who were operated on for CTS in Helsinki Children's Hospital between August 1988 and May 2013 were analysed retrospectively. Fibreoptic bronchoscopy was performed perioperatively and in follow-up of all the surviving patients. The median follow-up time was 7 (range 1-20) years. RESULTS: Thirteen infants were operated on for CTS. Resection of the stenotic segment with individually tailored anastomosis was used in 12 patients and slide tracheoplasty in 1 patient. The median age at the operation was 2.9 (range 0.2-19) months. Eight (62%) patients had associated cardiovascular defects, which were corrected during the same operation. The median length of stenosis was 35% (range 25-60%) of the total length of the trachea. The median length of time of postoperative mechanical ventilation was 10 (range 5-19) days. The median length of time of intensive care treatment was 15 (range 7-40) days. One patient died from hypoplastic lung tissue and fibrosis, and multiorgan failure. One patient required reoperation, and 3 other patients received balloon bronchodilatations postoperatively. There was no late mortality. All of the 12 survivors had a good outcome. CONCLUSION: Resection with individually tailored anastomosis with up to 55% of the stenotic segment of the trachea presented a good long-term outcome.

Bronchoalveolar lavage in infants with recurrent lower respiratory symptoms.

BACKGROUND: Few data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies. METHODS: Thirty-nine infants (median age 0.9 years) underwent lung function testing by whole-body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies. RESULTS: The differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro-inflammatory cytokine proteins IL-1ß, IL-17A, IL-18, IL-23, and IL-33 were found, whereas levels of Th2-type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro-inflammatory cytokine profile. Lung function did not correlate with any cytokine. CONCLUSIONS: A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro-inflammatory cytokines associated positively with frequent wheeze.

Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision.

The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report's conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non-US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.

Outcomes of early infancy laryngeal reconstruction on health- and voice-related quality of life.

OBJECTIVE: We aimed to study the voice, voice-related quality of life (VRQoL) and health-related quality of life (HRQoL) of children who in early infancy underwent a laryngeal split (cotton plasty operation) at the Helsinki University Central Hospital between January 1990 and December 2005. METHODS: A retrospective review identified 17 children, of whom 10 fulfilled the inclusion criteria and participated in the study. Age- and gender-matched volunteers formed a control group. We used generic 16D and 17D questionnaires to assess HRQoL; the Pediatric Voice Outcomes Survey (PVOS) and the pediatric voice-related quality of life (PVRQoL) instrument served to assess VRQoL. The children underwent indirect laryngoscopy and perceptual voice assessment. RESULTS: HRQoL and PVRQoL scores did not differ between subjects and controls. The subjects had lower PVOS scores than did the controls (P<0.01). Perceptual assessment revealed that the subjects' voices were worse off according to the following dimensions: voice is strained, voice is hoarse or husky, and voice is weak/does not resonate (P<0.05). CONCLUSIONS: This study adds to the knowledge on the long-term effects of laryngeal split on children through assessment of their HRQoL and PVRQoL. The study subjects' lower PVOS scores and findings of perceptual assessment point to the effect of cotton plasty on VRQoL and voice.

Lung function, airway remodelling and inflammation in symptomatic infants: outcome at 3 years.

BACKGROUND: Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3 years. METHODS: 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist children's hospital for recurrent lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12 months preceding the follow-up visit. RESULTS: 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p<0.001) and with the purchase of ICS (p=0.009) and ß agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3 years (p=0.003 and p=0.018, respectively). CONCLUSIONS: Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3 years in this highly selected group of children.

Esophageal morbidity and function in adults with repaired esophageal atresia with tracheoesophageal fistula: a population-based long-term follow-up.

OBJECTIVE: We assessed esophageal morbidity and relationships between surgical complications, symptoms, endoscopic findings, immunohistochemistry, and esophageal motility in adults with repaired esophageal atresia (EA). SUMMARY OF BACKGROUND DATA: There exist no previous population-based long-term follow-up studies on EA. METHODS: Participants were interviewed, and they underwent esophageal endoscopy and manometry. Matched control subjects (n = 287) served as controls. RESULTS: A total of 101 (42%) individuals representative of the entire study population participated at a mean age of 36 years (range, 21-57). Symptomatic gastroesophageal reflux had occurred in 34% and dysphagia in 85% of the patients and in 8% and 2% of the controls (P < 0.001 for both). Endoscopic findings included hiatal hernia (28%), Barrett's esophagus (11%), esophagitis (8%), and anastomotic stricture (8%). Immunohistochemistry revealed esophagitis in 25%, and CDX2-positive columnar epithelial metaplasia in 21%, with additional goblet cells and MUC2 positivity in 6%. Gastroesophageal reflux and dysphagia were equally common in individuals with normal histology, esophagitis, or epithelial metaplasia. Manometry demonstrated nonpropagating peristalsis in 80% of the patients, and low distal wave amplitudes of the esophagus in all the changes being significantly worse in those with epithelial metaplasia (P < or = 0.022 metaplasia vs. esophagitis/normal). Anastomotic complications (odds ratio [OR]: 8.6-24, 95% confidence interval [CI]: 1.7-260, P = 0.011-0.008), age (OR: 20, 95% CI: 1.3-310, P = 0.034), low distal esophageal body pressure (OR: 2.6, 95% CI: 0.7-10, P = 0.002), and defective esophageal peristalsis (OR: 2.2, 95% CI: 0.4-11, P = 0.014) predicted development of epithelial metaplasia. CONCLUSIONS: Significant esophageal morbidity associated with EA extends into adulthood. Surgical complications, increasing age, and impaired esophageal motility predict development of epithelial metaplasia after repair of EA.

Tumor markers AFP, CA 125, and CA 19-9 in the long-term follow-up of sacrococcygeal teratomas in infancy and childhood.

Given the tendency of a proportion of sacrococcygeal teratomas (SCT) to recur, we evaluated whether serial tumor marker measurements are helpful in the management of these children. Between 1985 and 2006, 32 children with SCT were followed up for 1-15 years, and a total of 344, 197, and 193 serial samples for serum alpha-fetoprotein (AFP), CA 125, and CA 19-9 were analyzed, respectively. Six children with neonatal SCT developed eight recurrences. Serum AFP was elevated in two of two children prior to diagnosis of malignant recurrences (yolk sac tumor and adenocarcinoma), and CA 125 was elevated in one third of mature and one third of immature recurrences. CA 19-9 remained within reference values in relation to recurrences of neonatal SCT. Taken together, serum CA 125 measurements may complement the use of serum AFP in the follow-up of SCT.

Longitudinal follow-up of bronchial inflammation, respiratory symptoms, and pulmonary function in adolescents after repair of esophageal atresia with tracheoesophageal fistula.

OBJECTIVE: To characterize symptoms, pulmonary function tests (PFT) and bronchial responsiveness (BR) in adolescents after repaired esophageal atresia with tracheoesophageal fistula and correlate these with endobronchial biopsy findings. STUDY DESIGN: After a primary operation, 31 patients underwent endoscopies and bronchoscopies at the age of <3, 3 to 7, and >7 years. A questionnaire on respiratory and esophageal symptoms was sent to patients at a mean age of 13.7 years (range, 9.7-19.4). The questionnaire was completed by 27 of 31 patients (87%), and 25 of the 31 patients (81%) underwent clinical examination and pulmonary functioning tests. Endobronchial biopsies were analyzed for reticular basement membrane (RBM) thickness and inflammatory cells. RESULTS: The prevalence of current respiratory and esophageal symptoms was 41% and 44%, respectively. "Doctor-diagnosed asthma" was present in 22% of patients. A restrictive and obstructive spirometric defect was observed in 32% and 30% of patients, respectively. Increased bronchial responsiveness, detected in 24% of patients, was weakly associated with current respiratory symptoms and low forced vital capacity. Mean exhaled nitric oxide was within predicted range. RBM thickness increased slightly with age, whereas inflammatory cell counts varied from normal to moderate, with intraindividual variation. CONCLUSION: Inflammation of the airways in adolescents with a history of tracheoesophageal fistula, even in the presence of atopy, does not lead, in most cases, to the type of chronic inflammation and RBM changes seen in asthma.

Cancer after repair of esophageal atresia: population-based long-term follow-up.

OBJECTIVE: Esophageal atresia (EA) predisposes to gastroesophageal reflux that is associated with intestinal metaplasia and may result in development of adenocarcinoma of the esophagus. To date, the literature has reported 5 cases of esophageal cancer in adult patients treated for EA. The aim of this study was to find out the incidence of esophageal cancer in adult patients with repaired EA. PATIENTS AND METHODS: Five hundred two consecutive patients treated for EA from 1949 to 1978 were followed-up for cancer through the files of the population-based countrywide cancer registry from 1967 to 2004. The number of cancer cases observed and person-years at risk were counted, and the expected number of cancer cases estimated from the national cancer incidence rates. The standardized incidence ratios (SIRs) were calculated by dividing the number of cancer cases observed by the expected numbers. RESULTS: None of the 502 patients were lost to follow-up; 230 patients who died before 1967 younger than the median age of 8 days were excluded from further analysis. The 272 remaining patients (142 males) were eligible for follow-up (median age, 35 years; range, 2 days to 56 years). Three cases of cancer were found (SIR, 1.0; 95% confidence interval, 0.20-2.8). One was lymphoma in small intestine, 1 was leukemia, and 1 carcinoma of the uterus but no cases of esophageal cancer. CONCLUSIONS: Our study is able to exclude long-term risk for esophageal cancer after repair of EA 500-fold higher than that of the normal population. Considering the relatively young age of the survivors, further studies and continued follow-up are warranted to elucidate risk for esophageal cancer and need for endoscopic surveillance after repair of EA.

The cumulative incidence of significant gastroesophageal reflux in patients with congenital diaphragmatic hernia-a systematic clinical, pH-metric, and endoscopic follow-up study.

BACKGROUND: Gastroesophageal reflux (GER) is common in patients with congenital diaphragmatic hernia (CDH). Gastroesophageal reflux may occur early after the primary repair of CDH and require antireflux surgery (ARS). It is unknown how many patients will be severely affected later on. We conducted an objective long-term follow-up for the cumulative incidence of CDH-associated GER based on symptoms, pH-metry, and histology. MATERIALS AND METHODS: From March 1990 to July 2006, we admitted 33 newborn patients with CDH. Twenty-six patients (79%) (male 13, left-sided 21) survived. Extracorporeal membrane oxygenation was required in one patient and patch closure in 10 patients. The follow-up consisted of assessment of GER symptoms at 6 months, 1 year, 3 years, 5 years, and 10 years; endoscopy; and pH-metry for all patients at 1 year and to selected patients (with symptoms or complications of GER) from 3 to 10 years after the primary closure of CDH. Gastroesophageal reflux was considered significant (sGER) when a symptomatic patient required ARS, had endoscopic biopsies showing at least moderate esophagitis, or total and preprandial reflux index of more than 10% and 5%, respectively. MAIN RESULTS: The incidence of sGER (patients with sGER/total amount assessed) at 6 months, 1 year, 3 years, 5 years, and 10 years was 27% (7/26), 42% (11/26), 53% (8/15), 53% (8/15), and 55% (5/9), respectively. During a median follow-up of 60 months (range, 12-195 months), 12 (46%) of 26 patients had sGER and 4 (15%) required ARS. After the assessment at 1 year, only one new case of sGER appeared. Endoscopic and/or pH-metric assessment covered 100% of the patients at 1 year follow-up, but later on only 70%. CONCLUSION: One year after the primary closure of CDH, the incidence of sGER was 42%. After 1 year follow-up, only one new case of sGER was found, and ARS was not required. In patients who required ARS manifested before 6 months.

Prospective controlled long-term follow-up for functional outcome after anoplasty in boys with perineal fistula.

BACKGROUND: Functional outcomes after treatment of low anorectal anomalies remain controversial. To address this, we conducted a controlled, prospective single-center long-term follow-up study of functional outcome in boys treated for perineal fistula with anoplasty. PATIENTS AND METHODS: Twenty-four consecutive boys treated exclusively for perineal fistula from 1992 to 2001 underwent prospective follow-up after completion of toilet training. All of the patients had identical surgical treatment. Functional outcome was assessed according to a previously validated bowel function score (7 questions, maximum score of 20). Daytime and nighttime wetting, as well as the age at toilet training, were also recorded. Thirty-seven age-matched boys served as healthy controls. An independent nurse specialist interviewed caregivers. RESULTS: Age of the patients (9.1 +/- 2.6 years) and controls (9.0 +/- 2.9 years) were similar. Seven patients (32%) had bowel function scores below the 10th percentile (17.2) of the controls, which was chosen as a lower limit of normality. The overall mean bowel function score was significantly lower (P < 0.01) among the patients (17.9 +/- 1.9) compared with the controls (19.1 +/- 1.2). The difference was attributed mainly to significantly lower scores (0-3) among patients in questions assessing constipation (2.4 +/- 0.8 vs 2.9 +/- 0.3; P < 0.05) and soiling (2.5 +/- 0.5 vs 2.8 +/- 0.4; P = 0.05). Constipation and soiling were significantly more common (P < 0.05) among patients (41% and 55%, respectively) compared with controls (8% and 24%, respectively). CONCLUSIONS: Overall long-term bowel function is impaired in one third of boys with perineal fistula. The main reasons for impaired functional outcome are constipation and soiling, which affect as many as half the patients.

Human rhinovirus in bronchial epithelium of infants with recurrent respiratory symptoms.

BACKGROUND: Human rhinoviruses (HRVs) are a common cause of upper respiratory tract infections. There is growing evidence that HRVs are also important in lower respiratory tract infections and often induce asthma exacerbations. OBJECTIVE: We evaluated the presence of HRV in the lower respiratory tract by obtaining bronchial biopsies from infants with recurrent asthmalike respiratory symptoms. METHODS: A total of 201 steroid-naive infants age 3 to 26 months with recurrent respiratory symptoms for at least 4 weeks within the preceding 2 months were studied for lung function using body plethysmography. Bronchoscopy was performed in 68 children, and bronchial biopsies were available from 59 infants for HRV detection with in situ hybridization. RESULTS: Human rhinovirus was detected in 21 of 47 (45%) specimens. Abnormal lung function (decreased airways conductance) was found in 18 of 21 (86%) HRV(+) infants and in 15 of 26 (58%) HRV(-) infants (P = .037). Occurrence of a respiratory infection in the 6 weeks preceding bronchoscopy correlated with HRV positivity (P = .036). CONCLUSION: Human rhinovirus is frequently found in the lower airways in infants with recurrent respiratory symptoms, and the majority of these HRV(+) infants also showed increased airway resistance. CLINICAL IMPLICATIONS: Human rhinovirus is a common pathogen causing upper and lower respiratory symptoms. Follow-up of these infants will reveal whether the presence of HRV in the bronchial biopsy and abnormal lung function with recurrent respiratory symptoms predicts subsequent asthma.