Surgical management of rare tumors (Part 1).

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g.

Imaging adjuvants in pediatric surgical oncology.

Surgery is a crucial component of pediatric cancer treatment, but conventional methods may lack precision. Image-guided surgery, including fluorescent and radioguided techniques, offers promise for enhancing tumor localization and facilitating precise resection. Intraoperative molecular imaging utilizes agents like indocyanine green to direct surgeons to occult deposits of tumor and to delineate tumor margins.

Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.

ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.

Intraoperative Radiation Therapy for Relapsed or Refractory High-Risk Neuroblastoma: A 27-Year Experience.

Purpose: To evaluate outcomes after intraoperative radiation therapy (IORT) in high-risk neuroblastoma (NB), including local control, overall survival, and toxicity.

Methods And Materials: This was a single institution retrospective study of 92 pediatric patients with NB treated with IORT from 1995 to 2022. Each IORT application was considered a separate event for a total of 110 sites treated.

Novel combination of imipridones and histone deacetylase inhibitors demonstrate cytotoxic effect through integrated stress response in pediatric solid tumors.

There is a demonstrated need for new chemotherapy options in pediatric oncology, as pediatric solid tumors continue to plateau at 60% with event-free survival. Imipridones, a novel class of small molecules, represent a potential new therapeutic option, with promising pre-clinical data and emerging clinical trial data in adult malignancies. ONC201, ONC206, and ONC212 are imipridones showing pro-apoptotic anti-cancer response.

Critical elements of pediatric neuroblastoma surgery.

Neuroblastoma (NB) is the most common solid extracranial malignancy of childhood with an incidence of 1 per 100,000 in the United States compromising approximately 10 % of childhood cancer. Unfortunately, patients with high-risk NG continue to have long-term survival less than 50 %. Both Children's Oncology Group and the International Society of Paediatric Oncology have demonstrated the important role of surgery in the treatment of high-risk NB.

Molecular Targets for Novel Therapeutics in Pediatric Fusion-Positive Non-CNS Solid Tumors.

Chromosomal fusions encoding novel molecular drivers have been identified in several solid tumors, and in recent years the identification of such pathogenetic events in tumor specimens has become clinically actionable. Pediatric sarcomas and other rare tumors that occur in children as well as adults are a group of heterogeneous tumors often with driver gene fusions for which some therapeutics have already been developed and approved, and others where there is opportunity for progress and innovation to impact on patient outcomes. We review the chromosomal rearrangements that represent oncogenic events in pediatric solid tumors outside of the central nervous system (CNS), such as Ewing Sarcoma, Rhabdomyosarcoma, Fibrolamellar Hepatocellular Carcinoma, and Renal Cell Carcinoma, among others.

ONC201 and imipridones: Anti-cancer compounds with clinical efficacy.

ONC201 was originally discovered as TNF-Related Apoptosis Inducing Ligand (TRAIL)-inducing compound TIC10. ONC201 appears to act as a selective antagonist of the G protein coupled receptor (GPCR) dopamine receptor D2 (DRD2), and as an allosteric agonist of mitochondrial protease caseinolytic protease P (ClpP). Downstream of target engagement, ONC201 activates the ATF4/CHOP-mediated integrated stress response leading to TRAIL/Death Receptor 5 (DR5) activation, inhibits oxidative phosphorylation via c-myc, and inactivates Akt/ERK signaling in tumor cells.

Injuries among Amish children: opportunities for prevention.

Objectives: The purpose of this study was to examine the injury risk patterns among Amish children, many of whom may be exposed to uncommon injuries and limited access to care due to their agrarian lifestyle and remote communities.

Design: Retrospective Chart Review.

Methods: With IRB approval, we performed a retrospective review of Amish patients age ≤ 12 years presenting to a level I pediatric trauma center between January 1, 2005, and December 31, 2015.

Transcriptomic characterization of fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a deletion of ∼ 400 kb in chromosome 19, resulting in a fusion of the genes for the heat shock protein, DNAJ (Hsp40) homolog, subfamily B, member 1, DNAJB1, and the catalytic subunit of protein kinase A, PRKACA. The resulting chimeric transcript produces a fusion protein that retains kinase activity. No other recurrent genomic alterations have been identified.

The genomic landscape of fibrolamellar hepatocellular carcinoma: whole genome sequencing of ten patients.

Fibrolamellar hepatocellular carcinoma is a rare, malignant liver tumor that often arises in the otherwise normal liver of adolescents and young adults. Previous studies have focused on biomarkers and comparisons to traditional hepatocellular carcinoma, and have yielded little data on the underlying pathophysiology. We performed whole genome sequencing on paired tumor and normal samples from 10 patients to identify recurrent mutations and structural variations that could predispose to oncogenesis.

Experience with retroperitoneal partial nephrectomy in bilateral Wilms tumor.

Introduction: Retroperitoneal partial nephrectomy has not been studied as a surgical approach for children with bilateral Wilms tumor. There are advantages to this technique, including isolation of urine leaks to the retroperitoneum, decreased risk of bowel injury, and decreased time to resuming a diet. Presently, all bilateral Wilms tumors are treated with neoadjuvant chemotherapy and attempted nephron-sparing surgery.

Endogenous antibodies for tumor detection.

The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice.

Risk factors and predictors of severity score and complications of pediatric hemorrhagic cystitis.

Purpose: We retrospectively analyzed our institutional incidence of hemorrhagic cystitis, identified risk factors, and examined associations of risk factors with disease severity and genitourinary complication rates.

Materials And Methods: We reviewed charts of all consecutive pediatric patients treated from 1986 to 2010. We analyzed demographics, underlying diagnosis and treatment data to assess risk factors for hemorrhagic cystitis.

Desmoid fibromatosis in children and adolescents: a conservative approach to management.

Purpose: Desmoid fibromatosis is associated with frequent recurrence and significant morbidity, but no metastases. To examine the impact of initial non-operative management on event-free survival (EFS) in children, we reviewed our institutional experience with this tumor.

Methods: We retrospectively reviewed our institutional database for pediatric cases of desmoid fibromatosis treated between 1970 and 2010.

Malignant liver tumors.

Malignant tumors of the liver comprise a relatively small fraction of the total number of pediatric malignancies. However, these tumors can be a significant cause of morbidity and mortality, and there have been significant therapeutic gains during the past few decades through advances in systemic therapy and surgical treatment. Even in patients with advanced local disease, complete resection is now a possibility because of improvements in liver transplantation techniques.

Factors associated with relapse and survival in Wilms tumor: a multivariate analysis.

Purpose: Lymph node metastasis and anaplasia predict relapse-free survival in Wilms tumor. We performed a multivariate analysis of our institutional database to identify factors independently associated with relapse-free and overall survival.

Methods: We retrospectively reviewed cases of confirmed Wilms tumor diagnosed between 1990 and 2010 and treated at our institution.

Desmoid tumors in the pediatric population.

Desmoid tumors are benign soft tissue tumors associated with locally aggressive growth and high rates of morbidity, but they do not metastasize via lymphatic or hematogenous routes. While most of the data on desmoid tumors originates in the adult literature, many of the findings have been applied to the management of pediatric patients. This article discusses the epidemiology, etiology, clinical presentation, pathology, and treatment of this rare tumor in the pediatric population and includes a literature review of the most recent large series of pediatric patients with desmoid tumors.

Hodgkin lymphoma presenting with chest wall involvement: a case series.

Chest wall tumors in the pediatric population can have a variety of etiologies, malignancy being the most worrisome. Hodgkin lymphoma (HL) rarely presents as a chest wall mass in the pediatric population. In this report, we describe 3 male pediatric patients, all of whom had chest wall masses present at the initial diagnosis of HL.