Silja Kosola

High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma

Kosola S, Lauronen J, Sairanen H, Heikinheimo M, Jalanko H, Pakarinen M. High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma.
Pediatr Transplantation 2010: 14:646–650.

Endoscopic surveillance and primary prophylaxis sclerotherapy of esophageal varices in biliary atresia.

Objectives: Evidence-based recommendations on endoscopic screening and prophylactic treatment of esophageal varices in patients with biliary atresia (BA) are scarce. We assessed the efficiency of endoscopic surveillance and risk factors of esophageal varices and associated upper gastrointestinal bleeding. Methods: A total of 47 consecutive children with BA and portoenterostomy underwent yearly endoscopies and prophylactic injection sclerotherapy of esophageal varices between 1987 and 2009. The median follow-up was 1.7 years (range 0.5–18.9) and overall 2-year survival 71%. Disease characteristics, clearance of jaundice, laboratory tests reflecting liver function and hypersplenism, as well as sonographic signs of portal hypertension were related to endoscopic findings and bleeding episodes. Results: Grade 2 to 3 varices developed with similar frequency after failed (18/28, 64%) and successful portoenterostomy (10/19, 53%) in 28 patients. Following failed portoenterostomy, esophageal varices were encountered significantly earlier (8 [4–23] vs 19 [4–165] months, P = 0.004), and they reappeared after eradication more often (16/16 vs 4/10, P = 0.001). Varices bled only after failed portoenterostomy (13/28 vs 0/19, P < 0.001). Increased serum bilirubin concentration >40 &mgr;mol/L at 3 months after portoenterostomy was a risk factor of upper gastrointestinal bleeding (odds ratio [OR] 17, 95% confidence interval [CI] 1.7–175, P = 0.017). Conclusions: In future studies as well as clinical surveillance of BA patients’ varices, successful and failed portoenterostomy patients should be approached as separate groups with divergent prognoses. After failed portoenterostomy, surveillance should start early, for example, at 6 months.

Low‐dose steroids associated with milder histological changes after pediatric liver transplantation

Controversy remains about the role of protocol liver biopsy for symptom‐free recipients and about the long‐term use of low‐dose steroids after pediatric liver transplantation (LT). We conducted a national cross‐sectional study of pediatric recipients who underwent LT between 1987 and 2007. Liver biopsy samples were taken from 54 patients (82% of survivors) after a median posttransplant follow‐up of 11 years, and they were reviewed by 2 pathologists blinded to the clinical data. Biopsy samples from 18 patients (33%) showed nearly normal histology with no inflammation, fibrosis, or steatosis. Portal inflammation was detected in 14 samples (26%), showed no correlation with anti‐nuclear antibodies, and was less frequent in the 35 patients whose immunosuppression included steroids (14% versus 47% of patients not using steroids, P = 0.009). Fibrosis was present in 21 biopsy samples (39%). According to the Metavir classification, 15 were stage 1, 4 were stage 2, and 2 were stage 3. The fibrosis stage correlated negatively with serum prealbumin levels (r = −0.364, P = 0.007) and positively with chronic cholestasis (cytokeratin 7 staining; r = 0.546, P < 0.001) and portal inflammation (r = 0.350, P = 0.01). Microvesicular steatosis was found in 23 biopsy samples (43% of patients in 5%‐80% of hepatocytes), and it correlated with the body mass index (r = 0.517, P < 0.001) but not with steroid use. The age of the allograft (donor age plus follow‐up time) correlated with higher serum gamma‐glutamyltransferase (r = 0.472, P < 0.001) and conjugated bilirubin levels (r = 0.420, P = 0.002) as well as chronic cholestasis (r = 0.305, P = 0.03). The biopsy findings led to treatment changes in 10 patients (19%), whereas only 1 complication (subcapsular hematoma) was encountered. In conclusion, continuing low‐dose steroids indefinitely after pediatric LT may have a positive effect on the long‐term histological state of the liver graft. Allograft aging may lead to chronic cholestasis and thus contribute to the development of liver fibrosis. Liver Transpl 19:145–154, 2013.

Native liver histology after successful portoenterostomy in biliary atresia.

Background: Biliary atresia is the most common indication for childhood liver transplantation. The effects of successful portoenterostomy (PE) on native liver histology remain unclear. Aims: We assessed changes in native liver histology after a successful PE in relation to liver function and clinical outcomes. Methods: In total, 70 native liver biopsies of 44 biliary atresia patients were obtained at PE (n=30), 4.2 years after successful PE (n=23) and 1.1 years after failed PE (n=17), and reviewed for cholestasis, fibrosis, inflammation, and cytokeratin 7 (CK7) immunopositivity (chronic cholestasis). Ten transplant donor livers served as controls. Results: After a successful PE [serum bilirubin 11 (2 to 35) &mgr;mol/L at biopsy], histologic native liver cholestasis completely resolved in 83% of the patients and portal inflammation significantly decreased. Nevertheless, enhanced fibrosis [Metavir stage 2 (1-4) vs. 4 (1-4)], bile duct proliferation [grade 2 (1-2) vs. 1 (0-2)], and periportal CK7 immunostaining [grade 1 (0-2) vs. 1 (0-4)] persisted in 100%, 87%, and 61% of subjects, respectively. Metavir fibrosis stage corresponded cirrhosis (stage 4) in 52% of the patients, associated with the presence of portal hypertension, and correlated with serum-conjugated bilirubin (r=0.601, P=0.002), bile duct proliferation (r=0.657, P=0.001), and CK7 positivity (r=0.657, P=0.001). Aspartate transferase to platelet ratio index predicted native liver fibrosis and development of esophageal varices. The degree of fibrosis and portal inflammation at PE were unrelated to native liver survival. Conclusions: Despite resolution of cholestasis and decreasing inflammation, bile duct proliferation, periportal CK7 immunostaining, and fibrosis persist after successful PE. Fibrosis is associated with biochemical cholestasis, bile duct proliferation, CK7 immunopositivity (chronic cholestasis), and development of portal hypertension.

Pain and learning in primary school: a population-based study

Abstract Despite the frequency of pain among children, little is known about its effects on learning and school outcomes. The objective of this study was to quantify the association of pain and academic achievement while taking into account the presence of co-occurring emotional symptoms. A population-based stratified random sample of 1239 students aged 8 to 9 years from primary schools in Melbourne, Australia, was recruited for the Childhood to Adolescence Transition Study. Children indicated sites of pain that had lasted for a day or longer in the past month using a pain manikin. Depressive- and anxiety-related symptoms were assessed using child-reported items. National assessment results for reading and numeracy were used to measure academic achievement. Sixty-five percent of children reported pain in at least 1 body site and 16% reported chronic pain. Increasing number of pain sites was associated with poorer reading scores in a dose–response fashion (&bgr; = −3.1; 95% confidence interval −4.9 to −1.3; P < 0.001). The association was only partly attenuated when adjusting for emotional symptoms (&bgr; = −2.6; 95% confidence interval −4.5 to −0.8; P < 0.001) and was not moderated by emotional symptoms. Children with chronic pain were a year behind their peers in both reading and numeracy. Among primary school students, pain was associated with lower reading scores even after adjusting for the presence of emotional symptoms. Although population-based longitudinal studies will be required to ascertain consistency and possible causality, grounds exist for considering pain and emotional symptoms in the assessment of children with reading difficulties.

Outcome of transition phase patients with juvenile idiopathic arthritis

Abstract Objectives: Across diagnosis groups, successful transition of adolescent and young adults from children’s hospitals to adult care is often associated with decreased treatment adherence and treatment results. The aim of this study was to characterize disease activity and anti-rheumatic medications following transfer of care of juvenile idiopathic arthritis (JIA) patients to the adult clinic. Method: All consecutive JIA patients aged 16–20 years who visited the specific transition clinic in the rheumatology outpatient clinic of Helsinki University Hospital between November 2012 and May 2013 and between April 2015 and April 2016 were evaluated. Results: A total of 214 patients were identified, and 23 appeared in both cohorts. Females had higher disease activity scores (DAS) than males (DAS28-CRP 1.9 ± 0.7 versus 1.6 ± 0.3, p = .019; and DAS44-CRP 1.0 ± 0.7 versus 0.7 ± 0.5, p = .005; respectively) in the latter cohort. Disease-modifying antirheumatic drugs (DMARDs) were prescribed to 86% of patients, and 48% were on biological DMARDs (bDMARDs), whereas 14% had no specific treatments. Conclusion: Disease activity and clinic attendance remained stable during the transition period. The proportion of transition phase JIA patients on bDMARDs was high and disease activity was low. Reasons for lower disease activity in males in the latter cohort require further investigation.

Who benefit from school doctors’ health checks: a prospective study of a screening method

BackgroundSchool health services provide an excellent opportunity for the detection and treatment of children at risk of later health problems. However, the optimal use of school doctors’ skills and expertise remains unknown. Furthermore, no validated method for screening children for school doctors’ assessments exists. The aims of the study are 1) to evaluate the benefits or harm of school doctors’ routine health checks in primary school grades 1 and 5 (at ages 7 and 11) and 2) to explore whether some of the school doctors’ routine health checks can be omitted using study questionnaires.MethodsThis is a prospective, multicenter observational study conducted in four urban municipalities in Southern Finland by comparing the need for a school doctor’s assessment to the benefit gained from it. We will recruit a random sample of 1050 children from 21 schools from primary school grades 1 and 5. Before the school doctor’s health check, parents, nurses and teachers fill a study questionnaire to identify any potential concerns about each child. Doctors, blinded to the questionnaire responses, complete an electronic report after the appointment, including given instructions and follow-up plans. The child, parent, doctor and researchers assess the benefit of the health check. The researchers compare the need for a doctor’s appointment to the benefit gained from it. At one year after the health check, we will analyze the implementation of the doctors’ interventions and follow-up plans.DiscussionThe study will increase our knowledge of the benefits of school doctors’ routine health checks and assess the developed screening method. We hypothesize that targeting the health checks to the children in greatest need would increase the quality of school health services.Trial registrationClinicalTrials.gov Identifier: NCT03178331, date of registration June 6 th 2017.

Quality of Life and Parental Worrying in A National Cohort of Biliary Atresia Children Living with Their Native Livers.

Objectives: The aim of the study was to evaluate health-related quality of life (HRQoL) and parental distress in a national cohort of children with biliary atresia (BA) with their native livers in relation to BA complications and HRQoL of normal population controls. Methods: We invited all Finnish children with BA surviving with their native livers at age 2 to 18 years to participate in 2009 and in 2014. Parents filled the Pediatric Quality of Life Inventory (PedsQL) proxy questionnaire, a survey of their childs health and evaluated parental distress on a visual-analog scale from 0 to 7. Overall participation rates were 80% (12/15) for the longitudinal and 83% (20/24) for the cross-sectional assessment. A control population of 324 children matched for age and sex was randomly picked, and 108 (33%) participated. Results: Overall, patients and controls had comparable HRQoL. Patients reported significantly lower scores for school functioning (P = 0.004) as depicted by missing school or day care due to hospital visits. Eighty-five percent of parents reported extreme worry (7.0) when hearing their childs BA diagnosis. At 6 years after diagnosis, parents reported significantly less worry: median score 3.8 (interquartile range 3.0–5.4, P < 0.001 for difference). Parents of patients with optimal health were less worried than parents whose childrens health was suboptimal: median worry score 3.3 (3.0–4.8) versus 5.3 (3.8–5.9), P = 0.05. Conclusions: BA patients’ HRQoL was comparable to matched peers in general but reduced by missing school days due to frequent hospital visits. At diagnosis, parents experienced considerable worry that diminished over the years after successful portoenterostomy, especially if the childs health was optimal.