Diseases of renal function and bone metabolism after treatment for early onset cancer: A registry-based study.

Modern cancer therapy has led to a growing number of pediatric and young adult cancer survivors, who are prone to increased morbidities caused by the late effects of therapy. The aim of our study was to investigate pediatric and young adult cancer survivors' morbidity due to renal and bone metabolism diseases and especially to study bone metabolism in cancer survivors with renal disease. Patients were identified from the Finnish Cancer Registry, and the cohort consisted of 13,860, 5-year survivors of cancer diagnosed below the age of 35 years. Healthy siblings were used as the comparison cohort. Information on the main outcomes was linked from the national Care Register for Health Care. Hazard ratios (HRs) comparing cancer survivors to siblings were calculated for various outcomes. The patient cohort was separated into two age groups, pediatric (0-19 years) and young adults (20-34 years). Significantly elevated HRs (p < 0.0001) in survivors were observed in both age groups for scoliosis (HR 1.6, 95% confidence interval [CI] 1.3-2.0), osteoporosis (HR 5.2, 95% CI 2.4-11.4), osteonecrosis (HR 12.7, 95% CI 5.4-29.7), nephritis (HR 1.9, 95% CI 1.5-2.2) and kidney failure (HR 3.6, 95% CI 2.4-5.3) for all. For cancer survivors with a renal outcome, the risk for developing any outcome of bone metabolism was increased (HR 2.3, 95% CI 1.4-3.6). These results show that pediatric and young adult cancer survivors have an elevated risk for long-term, adverse outcomes related to renal function and bone metabolism. These results suggest follow-up care for young cancer patients.

18F-FDG-PET/CT based total metabolic tumor volume change during neoadjuvant chemotherapy predicts outcome in advanced epithelial ovarian cancer.

OBJECTIVE: To evaluate the predictive potential of total metabolic tumor volume (MTV) reduction during neoadjuvant chemotherapy (NACT) with 18F-FDG-PET/CT in an advanced FIGO stage III/IV epithelial ovarian cancer (EOC) patient cohort. METHODS: Twenty-nine primarily inoperable EOC patients underwent 18F-FDG-PET/CT before and after NACT. The pre- and post-NACT total MTV, in addition to the percentage MTV reduction during NACT, were compared with primary therapy outcome and progression-free survival (PFS). ROC-analysis determined an optimal threshold for MTV reduction identifying patients with progressive or stable disease (PD/SD) at the end of primary therapy. A multivariate analysis with residual tumor (0/>0), FIGO stage (III/IV) and MTV reduction compared to PFS was performed. The association between MTV reduction and overall survival (OS) was evaluated. RESULTS: The median pre- and post-NACT total MTV were 352 cm3 (range 150 to 1322 cm3) and 51 cm3 (range 0 to 417 cm3), respectively. The median MTV reduction during NACT was 89% (range 24% to 100%). Post-NACT MTV and MTV reduction associated with primary therapy outcome (MTV post-NACT p = 0.007, MTV reduction p = 0.001) and PFS (MTV post-NACT p = 0.005, MTV reduction p = 0.005). MTV reduction <85% identified the PD/SD patients (sensitivity 70%, specificity 78%, AUC 0.79). In a multivariate analysis, MTV reduction (p = 0.002) and FIGO stage (p = 0.003) were statistically significant variables associated with PFS. MTV reduction during NACT corresponded to OS (p = 0.05). CONCLUSION: 18F-FDG-PET/CT is helpful in NACT response evaluation. Patients with total MTV reduction <85% during NACT might be candidates for second-line chemotherapy and clinical trials, instead of interval debulking surgery.

Prediction of pre-eclampsia and its subtypes in high-risk cohort: hyperglycosylated human chorionic gonadotropin in multivariate models.

BACKGROUND: The proportion of hyperglycosylated human chorionic gonadotropin (hCG-h) to total human chorionic gonadotropin (%hCG-h) during the first trimester is a promising biomarker for prediction of early-onset pre-eclampsia. We wanted to evaluate the performance of clinical risk factors, mean arterial pressure (MAP), %hCG-h, hCGß, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF) and mean pulsatility index of the uterine artery (Uta-PI) in the first trimester in predicting pre-eclampsia (PE) and its subtypes early-onset, late-onset, severe and non-severe PE in a high-risk cohort. METHODS: We studied a subcohort of 257 high-risk women in the prospectively collected Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) cohort. Multivariate logistic regression was used to construct the prediction models. The first model included background variables and MAP. Additionally, biomarkers were included in the second model and mean Uta-PI was included in the third model. All variables that improved the model fit were included at each step. The area under the curve (AUC) was determined for all models. RESULTS: We found that lower levels of serum PlGF concentration were associated with early-onset PE, whereas lower %hCG-h was associated with the late-onset PE. Serum PlGF was lower and hCGß higher in severe PE, while %hCG-h and serum PAPP-A were lower in non-severe PE. By using multivariate regression analyses the best prediction for all PE was achieved with the third model: AUC was 0.66, and sensitivity 36% at 90% specificity. Third model also gave the highest prediction accuracy for late-onset, severe and non-severe PE: AUC 0.66 with 32% sensitivity, AUC 0.65, 24% sensitivity and AUC 0.60, 22% sensitivity at 90% specificity, respectively. The best prediction for early-onset PE was achieved using the second model: AUC 0.68 and 20% sensitivity at 90% specificity. CONCLUSIONS: Although the multivariate models did not meet the requirements to be clinically useful screening tools, our results indicate that the biomarker profile in women with risk factors for PE is different according to the subtype of PE. The heterogeneous nature of PE results in difficulty to find new, clinically useful biomarkers for prediction of PE in early pregnancy in high-risk cohorts. TRIAL REGISTRATION: International Standard Randomised Controlled Trial number ISRCTN14030412 , Date of registration 6/09/2007, retrospectively registered.

Postoperative human epididymis protein 4 predicts primary therapy outcome in advanced epithelial ovarian cancer.

Primary chemotherapy treatment response monitoring in advanced epithelial ovarian cancer (EOC) is currently based on CT-imaging and serum CA125 values. Serum HE4 profile during first line chemotherapy has not been previously studied. We evaluated the HE4 profile during first line chemotherapy after primary (PDS) and interval debulking surgery (IDS). In total, 49 FIGO stage III/IV EOC patients were included in the study. 22 patients underwent PDS and 27 patients neoadjuvant chemotherapy (NACT) followed by IDS. Serial HE4 and CA125 serum samples were taken during first line chemotherapy. The association of postoperative tumor markers to surgery outcome, primary therapy outcome and progression free survival (PFS) were determined. The lowest HE4 and CA125 values during chemotherapy were compared to primary therapy outcome and PFS. The postoperative HE4 was associated to residual tumor after surgery (p = 0.0001), primary therapy outcome (p = 0.004) and PFS (p = 0.03) in all patients (n = 40). The postoperative CA125 was associated to PFS after IDS (n = 26, p = 0.006), but not after PDS. In multivariate analysis with FIGO stage (III/IV), residual tumor (0/>0) and postoperative CA125, the postoperative HE4 was the only statistically significant prognostic variable predicting PFS. Both HE4 and CA125 nadir corresponded to primary therapy outcome (HE4 p < 0.0001, CA125 p < 0.0001) and PFS (HE4 p = 0.009, CA125 p < 0.0001). HE4 is a promising candidate for EOC response monitoring. In our study, the performance of HE4 in response monitoring of first line chemotherapy was comparable to that of CA125. Of the postoperative values, only HE4 was statistically significantly associated to primary therapy outcome.

Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial).

PURPOSE: To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). MATERIALS AND METHODS: Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. RESULTS: TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. CONCLUSION: Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095.

Compulsory military service as a measure of later physical and cognitive performance in male survivors of childhood cancer.

BACKGROUND: Compromised physical fitness and cognitive difficulties have been reported as late effects of cancer treatment during childhood. To assess this issue, the military rankings of cancer survivors in medical checkups at call-up, and conscripts' physical and cognitive performance during the first weeks of compulsory military education were compared to those of matched population controls without a history of cancer. MATERIAL AND METHODS: A total of 1680 male patients born between 1960 and 1992 with a malignancy diagnosed before the age of 16 who were alive at the call-up age (18 years) were identified using the Finnish Cancer Registry, and five age, sex and place of residence matched controls for each patient using the Population Register Centre. Data on military service were gathered from Finnish Defense Forces. A conditional logistic regression analysis, the GEE-method with the cumulative logit link function, the chi-square test, the chi-square test for trend and a one-way analysis of variance were used in different analyses. RESULTS: Cancer survivors were exempted from military service more often than the controls (p < .001). The fit-for-service frequency was highest for survivors of kidney tumors (68%) and lowest after irradiated brain tumors (19%). In service, the results of the 12-min running test were poorer than those of controls for leukemia/non-Hodgkin lymphoma (p = .03) and brain tumor (p = .01) survivors. Interestingly, the standing long-jump test was the only muscle test for which survivor groups performed worse than controls. Performance on cognitive tests only differed from controls in brain tumor survivors. CONCLUSIONS: Exemption from service is still common under the current guidelines, but fit-for-service survivors do well in military education. These results can be used for reassuring survivors that completion of military service is possible for those fulfilling the national general guidelines for military fitness.

Performance of MALDI-TOF MS for identification of oral Prevotella species.

During the past decade, the clinically relevant genus Prevotella has expanded considerably. Prevotella species can be isolated from nearly all types of oral infections but also from various non-oral infections. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been introduced in clinical microbiology laboratories as a convenient method for identifying bacterial isolates from clinical specimens. Here we tested the diagnostic accuracy of a total of 123 oral Prevotella isolates, selected based on their biochemical profile, by Bruker MALDI-TOF MS. Partial 16S rRNA sequencing was used as a reference method. The performance of MALDI-TOF MS to identify the isolates to the genus level was excellent with 100.0% accuracy, while a good identification rate of 88.6% was achieved to the species level with a log score of ≥2.0. The isolates representing P. aurantiaca and P. jejuni, which are currently missing from the MALDI BioTyper database, were identified correctly to the genus level. Of the 123 isolates, one P. pallens isolate (0.8%) was identified with a score variation of 1.7-1.999. Overall, biochemical testing produced a high proportion (70.7%) of incorrect identifications within different species. MALDI-TOF MS offers a reliable and rapid method for the identification of Prevotella species included in the database.

Child and family-related predictors of psychological outcomes in children adopted from abroad; what is the role of caregiver time?

International adoptees need to cope with stressful transitions and to develop secure attachment with their caregivers at the same time. Although most children adopted from abroad adjust fine, they are at increased risk of psychological problems. We investigated whether both child and family-related factors are associated with later psychological problems and whether the length of time spent at home after adoption before daycare moderates these associations among internationally adopted children in Finland (FinAdo, Finnish Adoption Study). The sample consisted of 1,265 children (708 girls, 557 boys) who arrived in Finland before they started school (mean age 2 years at arrival). Later behavioral problems were measured using the Child Behavior Check List (CBCL). According to our results, male gender, older age, child's early clinical symptoms (problems of sensory processing) and single parenthood were associated with later behavioral problems measured by CBCL scores. Longer stay at home before the start of daycare or school modified these results. Longer stay at home was associated with less later behavioral externalizing problems in girls but not in boys compared to those who spent a shorter time at home.

18F-FDG-PET/CT can identify histopathological non-responders to platinum-based neoadjuvant chemotherapy in advanced epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to examine the relationship between the reduction of maximum standardized uptake values (SUVmax) in 18F-FDG-PET/CT to histopathological changes obtained with neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC). We wanted to evaluate whether 18F-FDG-PET/CT is useful for identifying patients who will not respond to NACT and would therefore benefit from second-line chemotherapy instead of interval debulking surgery (IDS). METHODS: Twenty-six primarily inoperable EOC patients treated with NACT were enrolled in this study. 18F-FDG-PET/CT imaging was performed before diagnostic laparoscopy and after three to four NACT cycles. The relationship between the decrease in omental SUVmax from before to after NACT with omental histopathological response was examined in samples taken from the corresponding anatomical sites during IDS. Patients were divided into three groups according to chemotherapy-induced histopathological changes. Serum CA125 and HE4 halftimes during NACT as well as Ki-67 antigen expression in IDS samples were determined. RESULTS: The median omental SUVmax change during NACT was -64% (range-16% to -84%), and it was associated with histopathological response (p=0.004, OR 0.9, CI 0.84-0.97). A SUVmax decrease of less than 57% identified histopathological non-responders. Progression-free survival (PFS) differed between the poor, moderate and good histopathological response groups (0.9 year vs. 1.2 years vs. 1.4 years, respectively, p=0.05). The SUVmax change was not associated with PFS. CONCLUSION: 18F-FDG-PET/CT was able to identify patients who would not respond to NACT. To obtain a histopathological response in EOC, a substantial metabolic response in 18F-FDG-PET/CT is necessary.

The motor profile of preterm infants at 11 y of age.

BACKGROUND: Preterm infants are at a higher risk for poor motor outcome than term infants. This study aimed to describe the long-term motor profile in very preterm born children. METHODS: A total of 98 very preterm infants were included. Volumetric brain magnetic resonance imaging (MRI) was performed at term age, and the Movement Assessment Battery for Children-Second Edition (The Movement ABC-2) was employed at 11 y of age. The diagnosis of Developmental Coordination Disorder (DCD) was determined at 11 y of age according to the International Classification of Diseases. RESULTS: Eighty-two of 98 (84%) very preterm infants had normal motor development at 11 y of age. In these children, the mean percentile for the total test score in the Movement ABC-2 examinations was 42 (SD 20). Eight (8%) children had DCD. The mean percentile in these children was 4 (SD 2). Eight (8%) children had CP. Their mean percentile was 6 (SD 14). Decreased volumes in all brain regions associated with lower Movement ABC-2 total scores. CONCLUSION: The majority of the very preterm infants had normal motor development at 11 y of age. Volumetric brain MRI at term age provides a potential tool to identify risk groups for later neuromotor impairment.

Use of endocrinological and neurological medication among 5-year survivors of young onset brain tumors.

The burden of late-effects for young onset brain tumor (BT) survivors needs more careful evaluation. Our aim was to assess the need for endocrinological and neurological medication among this specific group. We identified 5-year survivors diagnosed at the age of 0-24 years between 1988 and 2004 from the Finnish Cancer Registry (N = 602). Data on endocrinological and neurological drug purchases were collected from the Social Insurance Institution of Finland. Five years after diagnosis the most commonly purchased drugs had been: antiepileptics (44.8 %), systemic hydrocortisone (18.3 %), female sex hormones (17.6 %), thyroid hormones (11.2 %), and growth hormone (10.0 %). The survivors showed an increased hazard ratio (HR) for a need for new types of drugs still 5 years after diagnosis. Thyroid hormones (HR 10.6, 95 % CI 5.1-21.4), estrogens (HR 8.0, 95 % CI 2.1-25.7), and antiepileptics (HR 6.3, 95 % CI 3.4-11.2) were bought with high frequencies. Irradiation increased the hazard for drug-purchases other than antiepileptics. Cumulative incidence of purchases of estrogens or androgens increased still 15 years after diagnosis. The cumulative incidence of purchasing thyroid hormones and antiepileptics showed continuous increase for the youngest group, whereas survivors diagnosed at 15-24 years of age reached stable level before 15 years from diagnosis. The need for new medication continued more than a decade after BT diagnosis. Especially the need for new thyroid or sex hormone medication among childhood BT survivors may emerge long after diagnosis.

Immunological Reconstitution in Children After Completing Conventional Chemotherapy of Acute Lymphoblastic Leukemia is Marked by Impaired B-cell Compartment.

Humoral and cellular immunity were studied in 28 children completing conventional treatment of standard-risk (SR) or intermediate-risk (IR) acute lymphoblastic leukemia (ALL). Both naïve and memory B cells were most severely affected and showed slow recovery during the 2-year follow-up, while the T-cell compartment showed only minor changes. Immunoglobulins and IgG subclasses, components, and antibodies against vaccine-preventable diseases were not significantly affected. In conclusion, immune recovery after conventional chemotherapy for SR and IR ALL is marked by B-cell depletion, but otherwise did not show any severe deficiencies in lymphocyte function.

Induced abortion - impact on a subsequent pregnancy in first-time mothers: a registry-based study.

BACKGROUND: To date, several studies concerning the effects of induced abortion (IA) on women's later psychosocial well-being and future delivery complications have been published. However, the lack of reports on woman's physical well-being during their first full-term pregnancy occurring after IA is what inspired the current study. Here, we evaluate the physical well-being and use of maternity services of first-time mothers with a history of IA. METHODS: Finnish National Birth Registry data from 2008 to 2010 were linked with the Induced Abortion Registry data from 1983 to 2007. After excluding first-time mothers with a history of miscarriage, ectopic pregnancy or delivery, 57,406 mothers were eligible for the study, with 5,167 (9.0 %) having experienced prior IA. Data from the pregnancy follow-up visits were evaluated and compared between IA mothers and primiparous mothers. RESULTS: Women with IA had higher rates of smoking after the first trimester and were more likely to be overweight (body mass index >25 kg/m2) than the control group mothers. A higher use of maternity health clinic (MHC) services, thrombosis prophylaxis and participation in a second trimester ultrasound and amniotic fluid sample testing were evident in IA mothers, whereas the likelihood of assisted fertilisation procedure(s) was elevated in the control group. A shorter interpregnancy interval (IPI) seemed to contribute to a late first MHC visit and first trimester serum screening test participation, a higher incidence of placenta samples and an increased presence of preeclampsia and maternal care for poor foetal growth. CONCLUSIONS: IA is associated with being overweight before the subsequent pregnancy and with smoking after the first trimester. More frequent pregnancy follow-up visits in the IA group may be due to greater participation in the placenta sample testing and use of thrombosis prophylaxis. No association between IA and preeclampsia, hypertension, gestational diabetes or preterm premature rupture of membranes was evident in the pregnancy parameters. According to our findings, experiencing IA decreased the need for fertilisation procedures before the next pregnancy when compared to primiparous mothers. Among the IA mothers, the short IPI seemed to contribute to the higher risk for preeclampsia and maternal care for poor foetal growth. However, more research is needed around the IPI before establishing its effect on later pregnancy.

Late psychiatric morbidity in survivors of cancer at a young age: a nationwide registry-based study.

Childhood cancer survivors have been shown to be prone to psychosocial adverse outcomes. Data on young adults and their psychiatric late effects are still scarce. In a nationwide, registry-based study, we explored the risk (HR) of new psychiatric diagnoses in 5-year survivors of childhood and young adulthood (YA) cancer (n = 13,860) compared with a sibling cohort (n = 43,392). Hazard ratios (HRs) were calculated using Cox regression models. Patients and siblings were identified from the Finnish Cancer Registry and Central Population Registry, respectively. Outcome diagnoses were retrieved from the national hospital discharge register. The risk of organic memory/brain disorders was significantly increased in both childhood (HR 4.9; 95%CI 2.7-8.9) and YA (HR 2.1; 95%CI 1.4-3.1) cancer survivors compared with siblings. Mood disorders were also more common in childhood (HR 1.3; 95%CI 1.1-1.7) and YA survivors (1.3; 95%CI 1.1-1.5) than in siblings. Radiotherapy did not explain the differences. Female childhood cancer survivors had significantly increased HRs for mood disorders, psychotic disorders, neurotic/anxiety disorders, somatization/eating disorders and personality disorders. In survivors of YA cancers, females had significantly increased HR for neurotic/anxiety disorders, and the difference between female survivors and siblings was significantly (p < 0.05) higher than that between male survivors and male siblings. The effect of treatment era was also analyzed, and the risk of organic memory and brain disorders in childhood cancer survivors did not diminish over time. Despite the trend of decreased use of cranial irradiation in children, the risk of organic memory/brain disorders was elevated, even during the most recent era. Thus, additional research on chemotherapy-only protocols and their impact on mental health, is warranted.

Late mortality among 5-year survivors of early onset cancer: a population-based register study.

To date, only few studies have been published documenting late mortality among early onset cancer survivors, especially regarding young adulthood (YA) malignancies. Our nation-wide population-based registry study provides information concerning cause-specific long-term mortality among 16,769 5-year survivors of early onset cancer (aged 0-34 years at diagnosis), with follow-up for death extending from 1971 through 2012. A sibling cohort and population data were used as reference. The overall standardized mortality ratio (SMR) of cancer patients was 4.6-fold, (95% CI 4.4-4.8). Highest SMRs were found for malignancies (12.8, 95% CI 12.3-13.3), infectious (4.8, 95%CI 2.9-6.7) and cardiovascular diseases (1.9, 95% CI 1.7-2.1). Malignancies and cardiovascular diseases accounted for the largest number of deaths. Childhood and YA cancer survivors with the same primary cancer site had a similarly elevated overall SMR with the exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest cumulative non-malignancy-related mortality was due to cardiovascular disease with a steady rise throughout the follow-up, but strongly dependent on the primary cancer site and age at diagnosis. In childhood cancer survivors, the cumulative cardiovascular mortality did not reduce over time. However, overall and malignancy-related mortality showed a declining tendency towards the most recent periods after both, childhood and YA cancer. Our findings on non-malignancy-related mortality stress the need to set up long-term individual follow-up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lacking those.

Association between levels of persistent organic pollutants in adipose tissue and cryptorchidism in early childhood: a case-control study.

BACKGROUND: Congenital cryptorchidism, i.e. failure of the testicular descent to the bottom of the scrotum, is a common birth defect. The evidence from epidemiological, wildlife, and animal studies suggests that exposure to mixtures of endocrine disrupting chemicals during fetal development may play a role in its pathogenesis. We aimed to assess the association between cryptorchidism and prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polybrominated diphenyl ethers (PBDEs). METHODS: We conducted a case-control study consisting of 44 cryptorchid cases, and 38 controls operated for inguinal hernia, umbilical hernia, or hydrocele at the Turku University Hospital or Rigshospitalet, Copenhagen in 2002-2006. During the operation a subcutaneous adipose tissue biopsy was taken. Samples were analysed for 37 PCBs, 17 PCDD/Fs and 14 PBDEs by gas chromatography-high-resolution mass spectrometry. Chemical concentrations were adjusted for postnatal variation introduced by differences in duration of breastfeeding, age at the operation, and country of origin with a multiple linear regression. Association between adjusted and unadjusted chemical concentrations and the risk of cryptorchidism were analysed with logistic regression to get an estimate for odds ratio (OR) of cryptorchidism per multiplication of chemical concentrations with ca. 2.71 (Napier's constant). RESULTS: Total-TEq i.e. the WHO-recommended 2,3,7,8-TCDD equivalent quantity of 17 dioxins and 12 dioxin-like PCBs and sum of PCDD/Fs were positively associated with cryptorchidism [OR 3.21 (95% CI 1.29-9.09), OR 3.69 (95% CI 1.45-10.9), respectively], when adjusting for country of origin, the duration the child was breastfed, and age at operation. The association between the sum of PCBs and cryptorchidism was close to significant [OR 1.92 (95% CI 0.98-4.01)], whereas the association between the sum of PBDEs and cryptorchidism was not [OR 0.86 (95% CI 0.47-1.54)]. There were no associations between unadjusted chemical concentrations and the risk of cryptorchidism. CONCLUSIONS: Prenatal exposure to PCDD/Fs and PCDD/F-like PCBs may be associated with increased risk for cryptorchidism. Our finding does not exclude the possibility of an association between the exposure to PBDEs and cryptorchidism.

Serum HE4 and CA125 as predictors of response and outcome during neoadjuvant chemotherapy of advanced high-grade serous ovarian cancer.

Human epididymis protein 4 (HE4) is a novel tumour marker in epithelial ovarian cancer (EOC). Data on its profile and predictive potential for subsequent outcome after neoadjuvant chemotherapy (NACT) are still under investigation. The aim of this study was to compare CA125 and HE4 profiles with radiologic response after NACT and to evaluate their potential as predictors of clinical outcome in a primarily inoperable EOC patient cohort. Twenty-five EOC patients of high-grade subtype (HGSC) treated with NACT were enrolled in the study. Serum HE4 and CA125 samples were taken at the time of diagnosis and before interval debulking surgery (IDS). Pre-NACT and pre-IDS HE4 and CA125 and their percentage changes were compared with NACT response seen on CT and surgical outcome in IDS. We also evaluated the biomarkers' abilities to predict platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). All 25 patients were considered inoperable in laparoscopy at the time of diagnosis. HE4 and CA125 changes during NACT did not correlate with the changes seen on CT. Surgical outcome in IDS was associated with pre-IDS biomarker values but not with those taken before diagnosis. In IDS, 87 % had <1-cm residual tumour. In patients with HE4 change >80 and <80 % during NACT, the median OS was 3.38 and 1.60 years (p = 0.01), respectively. Serum HE4 is a promising additional tool when evaluating advanced HGSC patient's response to NACT. It may be helpful when deciding whether to proceed to IDS or to second-line chemotherapy.

The prevalence and predictive value of weak language skills in children with very low birth weight--a longitudinal study.

AIM: Previous findings regarding the prevalence and predictive value of weak language skills in preterm children with very low birth weight (VLBW) are unclear. This study analysed the prevalence of weak language skills, the predictive value of early weak language skills on later weak language skills, and the sensitivity and specificity of cognitive scores for identifying concurrent weak language skills in a longitudinal sample of VLBW children (n = 141) and their full-term controls (n = 146). METHODS: Data on language skills and cognitive development were gathered at two and five years of age. Weak language skills were defined by the 10th percentile value of the controls. RESULTS: In VLBW children, the prevalence of weak language skills varied between 16% and 18% at 2 years of age (controls: 8 to 10%) and between 20% and 27% at 5 years of age (controls: 10%). Early weak language skills predicted later weak language skills in VLBW children. Cognitive scores were specific, but their sensitivity for identifying concurrent weak language skills was low. CONCLUSION: The prevalence of weak language skills in VLBW children increased during the follow-up period and was higher than the controls. Language-sensitive methods should be used in the clinical follow-up of VLBW children.

A prospective comparison of integrated FDG-PET/contrast-enhanced CT and contrast-enhanced CT for pretreatment imaging of advanced epithelial ovarian cancer.

OBJECTIVE: The use of tumor debulking surgery in the management of epithelial ovarian cancer (EOC), which is often disseminated in the peritoneal cavity at the time of diagnosis, has a significant impact on prognosis. We compared (18)F-fluorodeoxyglucose (FDG) positron emission tomography/contrast-enhanced computed tomography (PET/CT) to contrast-enhanced CT for the detection of dissemination into the abdominal cavity preventing successful primary debulking surgery. METHODS: Forty-one women with EOC underwent preoperative whole-body low-dose FDG-PET/CT followed by diagnostic high dose contrast-enhanced CT scan, and the results were compared with systematically recorded surgical findings as a reference standard. Both site-based and patient-based analyses were conducted. RESULTS: FDG-PET/CT was superior to conventional CT for the detection of carcinomatosis in subdiaphragmatic peritoneal surfaces (p=0.020) and in the bowel mesentery (p=0.001). Patient-based analysis of upper abdominal areas requiring extensive surgical procedures showed no significant differences between the two imaging methods. The sensitivity of PET/CT and CT was poor in certain areas of the peritoneal cavity (64% vs. 27% in the small bowel mesentery and 65% vs. 55% in the right upper abdomen). Extra-abdominal disease spread was detected by PET/CT in 32 patients and by CT in 25 patients. CONCLUSIONS: PET/CT was not superior to CT for the detection of intra-abdominal disease spread. Patients with suspected EOC should be referred for upfront radical surgery regardless of the results of preoperative imaging studies. PET/CT is more effective for the detection of extra-abdominal disease than CT, but the clinical significance of this finding is unclear.

Effect of antenatal growth on brain white matter maturation in preterm infants at term using tract-based spatial statistics.

BACKGROUND: White matter maturation of infants can be studied using diffusion tensor imaging (DTI). DTI of the white matter of the infant brain provides the best available clinical measures of brain tissue organisation and integrity. OBJECTIVE: The purpose of this study was to compare white matter maturation between preterm infants born small for gestational age (SGA) and preterms with weight appropriate for gestational age (AGA) at birth. MATERIALS AND METHODS: A total of 36 preterm infants were enrolled in the study (SGA, n = 9). A rater-independent method called tract-based spatial statistics (TBSS) was used to assess white matter maturation. RESULTS: When measured by TBSS, the AGA infants showed higher fractional anisotrophy values in several white matter tracts than the SGA infants. Areas with significant differences included anterior thalamic radiation, corticospinal tract, forceps major and minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus, and superior longitudinal fasciculus (temporal part). No significant difference was found for mean diffusivity. CONCLUSION: As an objective and user-independent method, TBSS confirmed that preterm infants with impaired antenatal growth have impaired white matter maturation compared to preterm infants with normal antenatal growth. The differences were mainly detected in radiations that are myelinated first.