The Influence of the Extracorporeal Membrane Oxygenation Circuit and Components on Anticoagulation Management: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

Objectives: To derive systematic-review informed, modified Delphi consensus regarding the influence of extracorporeal membrane oxygenation (ECMO) circuit components on anticoagulation practices for pediatric ECMO for the Pediatric ECMO Anticoagulation CollaborativE.

Data Sources: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

Study Selection: Management of ECMO anticoagulation in the setting of different ECMO circuit components.

Anticoagulation during extracorporeal membrane oxygenation: A narrative review.

Extracorporeal Membrane Oxygenation (ECMO) is a technology that offers organ support for critically ill patients with respiratory and/or cardiac failure. Despite improvements in recent years in technology and the biocompatibility of circuits, patients on ECMO remain at high risk of hematologic complications, such as bleeding or thrombosis. Anticoagulation is required in most cases to limit the risk of clotting, but questions persist regarding the optimal anticoagulation strategy.

Modified AngioVac System use With Extracorporeal Membrane Oxygenation in a Child With Fontan Thrombosis.

The AngioVac System (AVS) extracts venous and pulmonary artery (PA) thrombi. We report modified use of the second-generation AVS with concurrent venoarterial extracorporeal membrane oxygenation (VA-ECMO) in a 10-year-old, 23 kg patient with failing Fontan circulation due to acute-on-chronic Fontan and PA thrombosis. Emergent femoral VA-ECMO was initiated for profound hypoxemia during cardiac catheterization.

Molecular characterization of DICER1-mutated pituitary blastoma.

Pituitary blastoma (PitB) has recently been identified as a rare and potentially lethal pediatric intracranial tumor. All cases that have been studied molecularly possess at least one DICER1 pathogenic variant. Here, we characterized nine pituitary samples, including three fresh frozen PitBs, three normal fetal pituitary glands and three normal postnatal pituitary glands using small-RNA-Seq, RNA-Seq, methylation profiling, whole genome sequencing and Nanostring® miRNA analyses; an extended series of 21 pituitary samples was used for validation purposes.

Clinical Outcomes and Complications of Pituitary Blastoma.

Context: Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome.

Objective: This work aims to describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases.

Design And Setting: A multi-institutional case series is presented from tertiary pediatric oncology centers.

DICER1 screening in 15 paediatric paratesticular sarcomas unveils an unusual DICER1-associated sarcoma.

Individuals with DICER1 syndrome, a genetic disorder caused by pathogenic germline variants in DICER1, are at increased risk of developing a wide array of predominantly childhood onset conditions, including genitourinary sarcomas. However, data on DICER1 involvement in paratesticular sarcomas have not been published. Herein, we analyse a series of 15 paediatric paratesticular sarcomas and describe in detail the case of a male infant with a paratesticular myxoid tumour, considered to be a low-grade sarcoma, who also manifested a cystic nephroma, a classic DICER1 syndrome phenotype.

Imaging of DICER1 syndrome.

DICER1 syndrome is a highly pleiotropic tumor predisposition syndrome that has been increasingly recognized in the last 10 years. Diseases in the syndrome result from mutations in both copies of the gene DICER1, a highly conserved gene that is critically implicated in micro-ribonucleic acid (miRNA) biogenesis and hence modulation of messenger RNAs. In general, susceptible individuals carry an inherited germline mutation that disables one copy of DICER1; within tumors, a very characteristic second mutation alters function of the other gene copy.

Mesenchymal Hamartoma of the Liver and DICER1 Syndrome.

Mesenchymal hamartoma of the liver (MHL) is a benign tumor affecting children that is characterized by a primitive myxoid stroma with cystically dilated bile ducts. Alterations involving chromosome 19q13 are a recurrent underlying cause of MHL; these alterations activate the chromosome 19 microRNA cluster (C19MC). Other cases remain unexplained.

gene mutations in endocrine tumors.

In this review, the importance of the gene in the function of endocrine cells is discussed. There is conclusive evidence that mutations play a crucial role in the development, progression, cell proliferation, therapeutic responsiveness and behavior of several endocrine tumors. We review the literature of gene mutations in thyroid, parathyroid, pituitary, pineal gland, endocrine pancreas, paragangliomas, medullary, adrenocortical, ovarian and testicular tumors.

Multiple DICER1-related tumors in a child with a large interstitial 14q32 deletion.

Germ-line interstitial deletions involving the 14q32 chromosomal region, resulting in 14q32 deletion syndrome, are rare. DICER1 is a recently described cancer-predisposition gene located at 14q32.13.

Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma.

Background: Sarcomas are rare and heterogeneous cancers. We assessed the contribution of DICER1 mutations to sarcoma development.

Methods: The coding region of DICER1 was sequenced in 67 sarcomas using a custom Fluidigm Access Array.

Deep Sequencing Reveals Spatially Distributed Distinct Hot Spot Mutations in DICER1-Related Multinodular Goiter.

Context: Nontoxic multinodular goiter (MNG) occurs frequently, but its genetic etiology is not well established. Familial MNG and MNG occurring with ovarian Sertoli-Leydig cell tumor are associated with germline DICER1 mutations. We recently identified second somatic DICER1 ribonuclease (RNase) IIIb mutations in two MNGs.

Germline and Somatic DICER1 Mutations in a Well-Differentiated Fetal Adenocarcinoma of the Lung.

Germ-line DICER1 mutations predispose to a distinctive tumour predisposition syndrome, the DICER1 syndrome, which is associated with a spectrum of rare mainly childhood-onset tumours. In 2014, a case of well-differentiated fetal adenocarcinoma of the lung (WDFA) was reported in a 16-year-old germ-line DICER1 mutation carrier. Here we report our finding of a characteristic somatic DICER1 RNase IIIb c.

High-sensitivity sequencing reveals multi-organ somatic mosaicism causing DICER1 syndrome.

Background: Somatic mosaicism is being increasingly recognised as an important cause of non-Mendelian presentations of hereditary syndromes. A previous whole-exome sequencing study using DNA derived from peripheral blood identified mosaic mutations in DICER1 in two children with overgrowth and developmental delay as well as more typical phenotypes of germline DICER1 mutation. However, very-low-frequency mosaicism is difficult to detect, and thus, causal mutations can go unnoticed.

Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome.

Embryonal rhabdomyosarcoma (ERMS), a soft tissue sarcoma, is one of the most common pediatric cancers. Certain ERMSs are associated with the DICER1 syndrome, a tumor predisposition syndrome caused by germ-line DICER1 mutations. Characteristic somatic mutations have also been identified in DICER1-associated tumor types.

Radiographic screening of infants and young children with genetic predisposition for rare malignancies: DICER1 mutations and pleuropulmonary blastoma.

Objective: The purpose of this study was to compare the risks of radiation in screening strategies using chest radiographs and CT to detect a rare cancer in a genetically predisposed population against the risks of undetected disease.

Materials And Methods: A decision analytic model of diagnostic imaging screening strategies was built to predict outcomes and cumulative radiation doses for children with DICER1 mutations screened for pleuropulmonary blastoma. Screening strategies compared were chest radiographs followed by chest CT for a positive radiographic result and CT alone.

Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry.

Background: Pleuropulmonary blastoma (PPB) has 3 subtypes on a tumor progression pathway ranging from type I (cystic) to type II (cystic/solid) and type III (completely solid). A germline mutation in DICER1 is the genetic cause in the majority of PPB cases.

Methods: Patients confirmed to have PPB by central pathology review were included, and their clinical characteristics and outcomes were reported.

DICER1: mutations, microRNAs and mechanisms.

Dicer is central to microRNA-mediated silencing and several other RNA interference phenomena that are profoundly embedded in cancer gene networks. Most recently, both germline and somatic mutations in DICER1 have been identified in diverse types of cancer. Although some of the mutations clearly reduce the dosage of this key enzyme, others dictate surprisingly specific changes in select classes of small RNAs.

Germ-line and somatic DICER1 mutations in pineoblastoma.

Germ-line RB-1 mutations predispose to pineoblastoma (PinB), but other predisposing genetic factors are not well established. We recently identified a germ-line DICER1 mutation in a child with a PinB. This was accompanied by loss of heterozygosity (LOH) of the wild-type allele within the tumour.