Objective
To investigate the incidence, age of onset and tumor marker levels in benign and malignant pediatric ovarian neoplastic tumors.
Design
Retrospective database study.
Setting
Single‐center ...study.
Population
Forty‐five 0–15‐year‐old girls operated on for ovarian neoplastic tumors from the beginning of 1999 to the end of 2013.
Methods
Serum alpha‐fetoprotein, human chorionic gonadotropin and CA 125 levels as well as follow‐up data were recorded from patient charts and tumor histology was re‐evaluated.
Main outcome measures
Incidence of ovarian neoplastic tumors in the pediatric population. Differences in patient characteristics and tumor marker levels between those with benign and malignant tumors.
Results
The annual incidence of ovarian tumors was 2.2/100 000 females. Median age at presentation was 13.0 years (range 0.9–15.7), similar in both the 33 (73%) girls with a benign tumor and the 12 (27%) girls with a malignant tumor. The tumors with the highest propensity to metastasize (yolk sac tumors, mixed germ cell tumors, small cell carcinoma) were only found in girls > 9 years. Elevated serum alpha‐fetoprotein and CA 125 values associated more often with malignant tumors (p < 0.001 and p < 0.031, respectively). There were no deaths or local recurrences. Four girls with a mature teratoma developed a contralateral benign ovarian tumor during follow up.
Conclusions
Both benign and malignant ovarian tumors are rare in the pediatric population, but the incidence increases with age. High alpha‐fetoprotein and CA 125 levels were associated with malignant tumors. The prognosis of the pediatric ovarian tumors seems to be favorable.
Abstract Purpose To evaluate the risk for metachronous ovarian tumor in pediatric patients with mature ovarian teratoma. Methods During 1981–2011, 22 children underwent oophorectomy for mature ...teratoma at the median age of 11.4 (range 1.5–15.3) years. The patients were followed-up in median 4.4 (range 0.5–25.5) years. Results None of the patients had synchronous bilateral tumor at the time of primary operation, but during follow-up five patients (23%) got metachronous contralateral ovarian tumor. The contralateral tumor was observed in median 3.6 (range 1–8.8) years after the primary operation. According to Kaplan–Meier analysis the risk for contralateral tumor was 14% ± 8% (SE) within five years and 66% ± 26% (SE) within 10 years. In this series, the contralateral tumor was operated by ovary preserving surgery. Three of the metachronous tumors were mature teratomas and two were seromucinous infantile cystadenomas. One patient had a second teratoma recurrence 14 years after the first recurrence. Conclusions More than one fifth of the children with ovarian mature teratoma get metachronous benign tumor to the contralateral ovary. Therefore a yearly ultrasound follow-up is needed for these patients up to potential pregnancy to enable early diagnosis, ovary preserving surgery and maintenance of fertility in the case of metachronous tumor.
To evaluate the association between Wilms tumor histology at diagnosis and the change in Wilms' tumor volume during preoperative chemotherapy.
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.
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.
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.
Retrospective review.
Level III.
Membrane type-1 matrix metalloproteinase (MT1-MMP) degrades extracellular matrix components directly and indirectly by activation of other matrix metalloproteinases (MMPs). In the present study, we ...have isolated and characterized the human
MT1-MMP gene and its promoter. The gene consists of 10 exons and nine introns spanning more than 10 kilobases (kb). The locations of two exon–intron splicing sites are distinct from the preserved positions among other known
MMP genes. Primer extension and RNAse and S1 nuclease protection analyses indicated that there are four major and several minor transcription start sites. The 5′-flanking sequence of the gene contains putative regulatory elements, including one Sp-1 site and four CCAAT-boxes, whereas there is no TATA-box. The Sp-1 binding site was functional, as shown by gel shift and supershift analyses. Transfection studies with promoter constructs containing 0.1 to 7.2
kb of 5′-flanking sequence coupled to a luciferase reporter gene indicated that the promoter contains additional positive and negative regulatory sequences. Deletion of the Sp-1 binding site by site-directed mutagenesis reduced luciferase activity by about 90%, demonstrating the crucial role of this element in maintaining
MT1-MMP transcription. Our findings indicate that the human
MT1-MMP promoter has distinctive structural and functional features compared with other
MMP genes, which may lead to a unique expression pattern and regulation during physiological and pathological processes.
The implications of inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) in solid organ transplantation remain uncertain. Although this trait has been linked to unfavorable clinical ...outcomes, an association between viral reactivation and complications has only been conclusively established in a few cases. In contrast to these studies, which followed donor-derived transmission, our investigation is the first to examine the pathogenicity of a recipient´s iciHHV-6B and its impact on the graft.
We used hybrid capture sequencing for in-depth analysis of the viral sequences reconstructed from sequential liver biopsies. Moreover, we investigated viral replication through in situ hybridization (U38-U94 genes), real-time PCR (U89/U90 genes), immunohistochemistry, and immunofluorescence (against viral lysate). We also performed whole transcriptome sequencing of the liver biopsies to profile the host immune response.
We report a case of reactivation of a recipient´s iciHHV-6B and subsequent infection of the graft. Using a novel approach integrating the analysis of viral and mitochondrial DNAs, we located the iciHHV-6B intra-graft. We demonstrated active replication via the emergence of viral minor variants across time points, in addition to positive viral mRNAs and antigen stainings in tissue sections. Furthermore, we detected significant upregulation of cell surface molecules, transcription factors, and cytokines associated with antiviral immune responses, arguing against immunotolerance.
Our analysis underscores the potential pathological impact of iciHHV-6B, emphasizing the need for close monitoring of reactivation in transplant recipients. Most crucially, it highlights the critical role that the host's virome can play in shaping the outcome of transplantation, urging further investigations.
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.
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.
The CNB was diagnostic in all 59 Wilms tumors but only in two out of five 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).
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.
Retrospective review.
Level III.
Chronic lung problems are a rare but serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). We studied clinical phenotypes and polysomnography appearance of breathing ...abnormality in late onset non-infectious pulmonary complications (NIPS).
We reviewed Finnish national reference database between the years 1999 and 2016. We identified 12 children with most severely decreased pulmonary function and performed polysomnography and 24 aged-matched controls out of 325 performed pediatric allogeneic HSCTs.
All patients with NIPS had severely decreased pulmonary function already at 6 months post HSCT with median FEV
value 42% (interquartile range (IQR) 30-52%) of predicted normal values. Seven children had obstructive and five children more restrictive lung function. Children with obstructive lung function showed laborious breathing (7/7), decreased oxygenation and ventilation-to-perfusion mismatch (6/7), or REM-sleep-related hypoventilation (4/7) on polysomnography. Children with restrictive lung function (5/12) did not show sleep-related breathing disorder.
Children going through allogeneic HSCT who develop severe chronic obstructive lung function are more likely to present with sleep-related hypoxia and hypoventilation than children with restrictive lung function.
Children with severe obstructive lung function and chronic lung graft-versus-host disease following hematopoietic stem cell transplantation are more likely to present with sleep-related mild hypoxia and hypoventilation than children with restrictive lung disease. To our knowledge there are no reports on sleep-related breathing disorders and ventilatory function measured by polysomnography in children with pulmonary complications after allogeneic HSCT. Polysomnography may add to the differential diagnostics between patients with BOS and other non-infectious pulmonary complications.
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