Evaluation of effect of preoperative chemotherapy on Wilms' tumor histopathology

Purpose: To evaluate usefulness of cutting needle biopsy (CNB) to recognize pediatric renal tumors and to predict the evolution of histology during preoperative chemotherapy of Wilms tumors. Methods: Ninety pediatric patients were operated for renal tumors at our institution in 1988-2015. We included all 64 patients who had undergone CNB at diagnosis and whose CNB and nephrectomy samples were available for re-evaluation. Results: The CNB was diagnostic in all 59 Wilms tumors but only in two out of live non-Wilms tumors. Anaplasia was missed by CNB in one of three with diffuse anaplasia in nephrectomy specimens. In Wilms tumors the proportions of the blastemal, stromal and epithelial components were 55% (IQR 25-85), 28% (IQR 10-58) and 2% (IQR 0-10) in CNB samples and 5% (IQR 0-64), 15% (IQR 0-50) and 15% (IQR 0-44) in the nephrectomy specimens (p-values 0.002,0.599 and 0.005 respectively). The degree of tumor necrosis was in median 80% (IQR 21-97), after preoperative chemotherapy. The degree of tumor necrosis after chemotherapy had a positive correlation with the proportion of blastemal component (p = 0.008) and a negative correlation with proportion of epithelial component in pre-chemotherapy CNB samples (p <0.001). Conclusions: Wilms tumors are usually recognizable unlike non-Wilms tumors in CNB at diagnosis. In Wilms tumors, high blastemal cell content is associated with significant tumor necrosis during pre-operative chemotherapy. Our results do not support routine use of CNB in diagnosis of renal tumors. Type of study: Retrospective review. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Adrenal function after induction therapy for acute lymphoblastic leukemia in children short : adrenal function in ALL

Prednisolone used in the induction phase of the treatment of acute lymphoblastic leukemia (ALL) may suppress hypothalamic-pituitary-adrenal axis and require hydrocortisone substitution. In this retrospective analysis, we reviewed altogether 371 ACTH stimulation tests of 352 children after a uniform NOPHO (Nordic Society of Pediatric Hematology and Oncology) ALL induction. Both low- and standard-dose ACTH tests were used. Full recovery of adrenal function was defined by both normal basal and stimulated cortisol levels. Sixty-two percent of patients were detected with normal adrenal function in median of 15 days after tapering of prednisolone. Both low basal and stimulated cortisol levels were detected in 13% of patients. The median time to normal adrenal function was 31 days (95% CI 28-34), 24 days (95% CI 18-30), and 12 days (95% CI 10-14) for those with basal cortisol 183 nmol/L at first ACTH testing, respectively. Patients with fluconazole prophylaxis had higher median baseline cortisol levels compared to patients without prophylaxis (207 nmol/L, range 21-839 nmol/L vs. 153 nmol/L, range 22-832 nmol/L, P = 0.003). Conclusion: These data can be used to reduce unnecessary substitution or testing, but also to guarantee hydrocortisone substitution for those at risk.What is Known:center dot These data can be used to reduce unnecessary hydrocortisone substitution or ACTH testing.center dot Our data helps to guarantee hydrocortisone substitution for those at risk of adrenal insufficiency.What is New:center dot Full recovery of adrenal function after ALL induction is detected in 62% of patients already at 15 days after tapering of prednisolone.center dot Both basal and stimulated cortisol testing are required for detection of full adrenal recovery.center dot Recovery time of adrenal function is extended over 3-4 weeks after tapering of prednisolone in patients with low basal cortisol levels (Peer reviewe

Effect of Wilms tumor histology on response to neoadjuvant chemotherapy

Purpose: To evaluate the association between Wilms tumor histology at diagnosis and the change in Wilms' tumor volume during preoperative chemotherapy. Methods: We included all the 52 patients operated for Wilms tumor at 1988-2015, who had both pathology samples and either CT or MRI-images before and after preoperative chemotherapy, available for reevaluation. Results: The median tumor volume was 586 ml (IQR 323-903) at diagnosis. The median change in tumor volume was -68% (IQR -85 to -40, p <0.001) and the proportion of tumor necrosis 85% (IQR 24-97), after preoperative chemotherapy. There was a correlation between blastemal cell content in prechemotherapy cutting needle biopsy (CNB) sample and the reduction in tumor volume (Rho = -0.452, p = 0.002). High stromal and epithelial cell contents in CNB samples were associated with the lesser change in tumor volume (Rho = 0.279, p = 0.053 and Rho = 0.300, p = 0.038 respectively). Reduction of tumor volume and the proportion of tumor necrosis after chemotherapy were associated (Rho = -0.502, p <0.001). The actual viable tumor volume decreased in median by 97% (IQR 65-100), and the decrease could be seen in all cellular components. In three patients, the tumor volume increased more than 10% during the preoperative chemotherapy. Two of them had anaplastic tumor in the nephrectomy specimen. Conclusion: Wilms tumor total and viable tumor volumes were reduced by 68% and 97% with preoperative chemotherapy, respectively. High proportion of blastemal cells in CNB was associated with greatest decrease in Wilms tumor volume. Increase in tumor volume during preoperative chemotherapy may indicate anaplastic tumor and prolonging of preoperative therapy should be avoided. Type of study: Retrospective review. (C) 2018 Elsevier Inc. All rights reserved.Peer reviewe

Immunodeficiency in cartilage-hair hypoplasia : Pathogenesis, clinical course and management

Cartilage-hair hypoplasia (CHH) is an autosomal recessive syndromic immunodeficiency with skeletal dysplasia, short stature, hypotrichosis, variable degree of immune dysfunction and increased incidence of anaemia, Hirschsprung disease and malignancy. CHH is caused by variants in theRMRPgene, encoding the untranslated RNA molecule of the mitochondrial RNA-processing endoribonuclease, which participates in for example cell cycle regulation and telomere maintenance. Recent studies have expanded our understanding of the complex pathogenesis of CHH. Immune dysfunction has a major impact on clinical course and prognosis. Clinical features of immune dysfunction are highly variable, progressive and include infections, lung disease, immune dysregulation and malignancy. Mortality is increased compared with the general population, due to infections, malignancy and pulmonary disease. Several risk factors for early mortality have been reported in the Finnish CHH cohort and can be used to guide management. Newborn screening for severe combined immunodeficiency can possibly be of prognostic value in CHH. Regular follow-up by a multidisciplinary team should be implemented to address immune dysfunction in all patients with CHH, also in asymptomatic cases. Haematopoietic stem cell transplantation can cure immune dysfunction, but its benefits in mildly symptomatic patients with CHH remain debatable. Further research is needed to understand the mechanisms behind the variability of clinical features, to search for potential molecular treatment targets, to examine and validate risk factors for early mortality outside the Finnish CHH cohort and to develop management guidelines. This review focuses on the pathogenesis, clinical course and management of CHH.Peer reviewe

Rusto-hiushypoplasiaa sairastavat tarvitsevat tarkkaa seurantaa : immuunivaje keskeinen sairastavuutta ja kuolleisuutta lisäävä tekijä

Vertaisarvioitu.Rusto-hiushypoplasia (RHH) on peittyvästi periytyvä syndroominen immuunivaje, johon kuuluvat luuston kasvuhäiriö, lyhytkasvuisuus, hennot hiukset, vaihteleva immuunihäiriö, syöpäalttius sekä suurentunut anemian ja Hirschsprungin taudin ilmaantuvuus. RHH aiheutuu RMRP-geenin mutaatioista. Geenin koodaama RNA-molekyyli on osa endoribonukleaasikompleksia ja osallistuu mitokondriaalisen RNA:n prosessointiin, solunjakautumisen säätelyyn ja telomeerien ylläpitoon. Immuunivajeen kliiniset ominaisuudet ovat vaihtelevia ja eteneviä. Immuunivaje lisää kuolleisuutta erityisesti infektioiden, keuhkosairauden ja syöpäalttiuden myötä. Suomalaisessa RHH-kohortissa tunnistettiin useita varhaisen kuoleman riskitekijöitä, ja näitä havaintoja voidaan hyödyntää hoidosta päätettäessä. Hematopoieettisten kantasolujen siirto saattaa parantaa immuunivajeen, mutta on vielä epävarmaa, onko siitä hyötyä vähäoireisille RHH-potilaille. Moniammatillinen säännöllinen immuunivajeen seuranta pitäisi kohdistaa kaikkiin, myös vähäoireisiin, RHH-potilaisiin.Peer reviewe

Käänteishyljintä kantasolusiirroissa

English summar

Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations

Peer reviewe

Completeness of Pediatric Cancer Registration in the Finnish Cancer Registry

Johdanto Suomen Syöpärekisteri ylläpitää rekisteriä kaikista Suomessa todetuista syöpätapauksista. Väestöpohjainen syöpätapausten rekisteröinti tarjoaa kattavan ja luotettavan tietokannan syöpätutkimuksessa käytettäväksi. Rekisteröinnin kattavuuden ja rekisteröidyn tiedon oikeellisuuden puutteilla voi kuitenkin olla suuri vaikutus erityisesti harvinaisten sairauksien insidenssi- prevalenssi- ja elossaoloarvioihin. Tutkimuksessamme pyrimme tarkentamaan aiempaa arviota lapsuussyövän rekisteröinnin kattavuudesta Suomen Syöpärekisterissä (Leinonen ym. 2017). Materiaalit ja menetelmät Poimimme Syöpärekisteristä sekä Hoitoilmoitusrekisteristä kaikki 0–14-vuotiaiden syöpätapaukset vuosina 2009–2013. Tarkastimme jokaisen Syöpärekisteristä puuttuneen tapauksen syöpädiagnoosin oikeellisuuden joko lähettämällä potilasta hoitaneeseen sairaalaan täytettävä lomake tai tarkastamalla potilastiedot potilastietoarkistoista. Laskimme Syöpärekisterin rekisteröinnin kattavuusarviot 95 %:n luottamusvälein tauti- sekä ikäryhmittäin. Tulokset Vuosina 2009–2013 Syöpärekisteriin oli rekisteröity 741 uutta lapsisyöpätapausta. Hoitoilmoitusrekisteriin syöpätapauksia oli rekisteröity 1072. Virheellisten syöpädiagnoosien karsimisen jälkeen vahvistimme 49:n syöpätapauksen puuttuvan Syöpärekisteristä. Syöpärekisterin kattavuudeksi arvioimme 94% (95% luottamusväli 91.9¬–95.4); 92% (95% luottamusväli 89.1–94.2) kiinteiden ja 97% (95% luottamusväli 94.1–98.4) ei-kiinteiden kasvainten osalta. Retinoblastooman rekisteröinnin kattavuus oli huomattavan matala, 54% (95% luottamusväli 36.4–71.9). Myös luusto- ja keskushermostosyöpien kattavuusarviot olivat matalat. Lymfoomien ja munuaissyöpien rekisteröinnin kattavuusarvio sen sijaan oli 100%. Diskussio Suomen Syöpärekisteri tuottaa korkealaatuista tietoa lapsuusajan syövistä. Ei-kiinteiden syöpien rekisteröinti on kattavampaa kuin kiinteiden syöpien. Syöpäilmoituksia Syöpärekisterille on puuttunut erityisesti potilaista, joiden tautia ei aina varmenneta histologisesti, kuten silmä- ja keskushermostosyöpäpotilaista