Genomic complexity and dynamics of clonal evolution in childhood acute myeloid leukemia studied with whole-exome sequencing.

Despite significant improvement in treatment of childhood acute myeloid leukemia (AML), 30% of patients experience disease recurrence, which is still the major cause of treatment failure and death in these patients. To investigate molecular mechanisms underlying relapse, we performed whole-exome sequencing of diagnosis-relapse pairs and matched remission samples from 4 pediatric AML patients without recurrent cytogenetic alterations. Candidate driver mutations were selected for targeted deep sequencing at high coverage, suitable to detect small subclones (0.

MicroRNA fingerprints in juvenile myelomonocytic leukemia (JMML) identified miR-150-5p as a tumor suppressor and potential target for treatment.

Juvenile myelomonocytic leukemia (JMML) is an aggressive leukemia of early childhood characterized by aberrant proliferation of myelomonocytic cells and hypersensitivity to GM-CSF stimulation. Mutually exclusive mutations in the RAS/ERK pathway genes such as PTPN11, NRAS, KRAS, CBL, or NF1 are found in ~90% of the cases. These mutations give rise to disease at least in part by activating STAT5 through phosphorylation and by promoting cell growth.

Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group.

Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.

Gut microbiota and hematopoietic stem cell transplantation: where do we stand?

Advances in biological techniques have potentiated great progresses in understanding the interaction between human beings and the ∼10 to 100 trillion microbes living in their gastrointestinal tract: gut microbiota (GM). In this review, we describe recent emerging data on the role of GM in hematopoietic stem cell transplantation, with a focus on immunomodulatory properties in the immune system recovery and the impact in the development of the main complications, as GvHD and infections.

The Venous Lymph Node Flap: Concepts, Experimental Evidence, and Potential Clinical Implications.

Background Traditionally, lymph node flaps (LNF) have been designed as arteriovenous flaps, with little attention given to the functional anatomy of lymphatic system included in the flap. Based on the anatomical and physiological features of lymphatic system, we believe that a new concept of LNF, the venous LNF, should be investigated. In this article, we report the concepts and findings of venous LNF, and help gauge its potential clinical application in the treatment of lymphedema.

Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study.

Genetic abnormalities and early treatment response are the main prognostic factors in acute myeloid leukemia (AML). Acute megakaryoblastic leukemia (AMKL) is a rare subtype of AML. Deep sequencing has identified CBFA2T3/GLIS2 and NUP98/KDM5A as recurrent aberrations, occurring in similar frequencies as RBM15/MKL1 and KMT2A-rearrangements.

Penile cancer metastasizing to the breast: a case report.

Background: Penile cancer is a relatively uncommon cancer in developed nations. Metastatic disease is rare, but lymphatic or vascular spreading has been previously reported to the liver, lungs, bones, brain, heart and skin.

Case Presentation: We report a case of a 49-year-old white man with a penile squamous cell carcinoma previously treated with partial penectomy and bilateral inguinal lymph node dissection, followed by adjuvant therapy.

GSK3 Deficiencies in Hematopoietic Stem Cells Initiate Pre-neoplastic State that Is Predictive of Clinical Outcomes of Human Acute Leukemia.

Initial pathway alternations required for pathogenesis of human acute myeloid leukemia (AML) are poorly understood. Here we reveal that removal of glycogen synthase kinase-3α (GSK-3α) and GSK-3β dependency leads to aggressive AML. Although GSK-3α deletion alone has no effect, GSK-3β deletion in hematopoietic stem cells (HSCs) resulted in a pre-neoplastic state consistent with human myelodysplastic syndromes (MDSs).

LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive stem cell disease of early childhood. RAS activation constitutes the core component of oncogenic signaling. In addition, leukemic blasts in one-fourth of JMML patients present with monosomy 7, and more than half of patients show elevated age-adjusted fetal hemoglobin (HbF) levels.

New trends in breast cancer surgery: a therapeutic approach increasingly efficacy and respectful of the patient.

The surgical management of breast cancer has undergone continuous and profound changes over the last 40 years. The evolution from aggressive and mutilating treatment to conservative approach has been long, but constant, despite the controversies that appeared every time a new procedure came to light. Today, the aesthetic satisfaction of breast cancer patients coupled with the oncological safety is the goal of the modern breast surgeon.

Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents.

Germline GATA2 mutations cause cellular deficiencies with high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia.

X chromosome gain in male breast cancer.

Male breast cancer (MBC) is an uncommon disease whose molecular profile is not well known. X chromosome gain has been described as a marker of aggressive behavior in female breast cancer. The aim of this study is to investigate the role of the X chromosome in male breast cancer.

Quadrantectomy with oxidized regenerated cellulose ("QUORC"): an innovative oncoplastic technique in breast conserving surgery.

Unlabelled: Oncoplastic surgery of the breast has generated great excitement over the past years and has become an integrated component of the surgical treatment of breast cancer. Oncoplastic procedures (OPP) associate the best surgical oncologic principles to achieve wide tumor-free margins with the best principles of plastic surgery to optimize cosmetic outcomes. Thanks to oncoplastic techniques, the role of breast conserving surgery (BCS) has been extended to include a group of patients who would otherwise require mastectomy to achieve adeguate tumor clearance.

Integrated breast cancer surgical treatment: novel aspects of minimally-invasive treatments.

The surgical management of breast cancer has been undergoing continuous and profound changes over the last 40 years. The evolution from aggressive and mutilating treatment to conservative approach has been long but constant, despite the controversies arising every time a new procedure came to light. Today, the esthetic satisfaction of breast cancer patients coupled with oncological safety is the goal of the modern breast surgeon.

Impact of aromatase inhibitor treatment on vertebral morphology and bone mineral density in postmenopausal women with breast cancer.

Objective: The aim of this study was to evaluate the impact of aromatase inhibitor (AI) treatment on vertebral morphology by vertebral fracture assessment in postmenopausal women with early-stage breast cancer.

Methods: A clinical cross-sectional study was conducted. A group of 156 postmenopausal women with breast cancer (mean [SD] age, 60.

Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial.

Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients.

Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study.

Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age ≤18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.

Identification of the NUP98-PHF23 fusion gene in pediatric cytogenetically normal acute myeloid leukemia by whole-transcriptome sequencing.

The genomic landscape of children with acute myeloid leukemia (AML) who do not carry any cytogenetic abnormality (CN-AML) is particularly heterogeneous and challenging, being characterized by different clinical outcomes. To provide new genetic insights into this AML subset, we analyzed through RNA-seq 13 pediatric CN-AML cases, corroborating our findings in an independent cohort of 168 AML patients enrolled in the AIEOP AML 2002/01 study. We identified a chimeric transcript involving NUP98 and PHF23, resulting from a cryptic t(11;17)(p15;p13) translocation, demonstrating, for the first time, that NUP98-PHF23 is a novel recurrent (2.

Oxidized regenerated cellulose in breast surgery: experimental model.

Background: Breast-conserving surgery (BCS) combined with postoperative radiotherapy has become the gold standard of locoregional treatment in patients with early-stage breast cancer. When large tumor resections are needed in small medium size breasts, oncoplastic procedures (OPP) have been introduced to improve the cosmetic result; but in several cases, OPP may be not sufficient to accomplish this purpose. Oxidized regenerated cellulose (ORC, Tabotamp fibrillar; Johnson & Johnson; Ethicon) has been reported to be useful in OPP to optimize the cosmetic results after OPP.

Contralateral breast symmetrisation in immediate prosthetic breast reconstruction after unilateral nipple-sparing mastectomy: the tailored reduction/augmentation mammaplasty.

Background: In the literature on nipple-sparing mastectomy (NSM) with one-stage immediate implant reconstruction, contralateral symmetrisation has drawn little attention, with many surgeons still performing standard cosmetic mammaplasty procedures. However, standard implant-based mammaplasty usually does not result in proper symmetry with the mastectomy side, especially regarding breast projection, overall shape, and volume distribution.

Methods: We retrospectively reviewed 19 consecutive patients undergoing unilateral NSM with immediate prosthetic reconstruction and contralateral simultaneous symmetrisation by using the tailored reduction/augmentation mammaplasty technique between June 2012 and August 2013.

Impact of inflammatory cytokine gene polymorphisms on developing acute graft-versus-host disease in children undergoing allogeneic hematopoietic stem cell transplantation.

Single nucleotide polymorphisms (SNPs) in gene encoding pro- and anti-inflammatory factors have been associated with the occurrence of aGvHD. We retrospectively tested a wide panel of 38 polymorphisms in 19 immunoregulatory genes, aiming to first establish, in a pediatric HSCT setting, which SNPs were significantly associated with the development of aGvHD. A significant association was found between aGvHD grades II-IV and SNPs of donor IL10-1082GG, and Fas-670CC + CT and recipient IL18-607 TT + TG genotype.

Acute myeloid leukemia in infants: biology and treatment.

Children aged 0-2 years (i.e., infants) with acute myeloid leukemia (AML) are a peculiar subgroup of patients in the childhood AML scenario.