Physicians' Knowledge, Attitudes, and Perception Toward Pediatric Palliative Care in Saudi Arabia: A National Exploratory Survey.

Background: Pediatric palliative care (PPC) helps maintain the quality of life for both children and their families. It has been identified as an important goal within the global health agenda. In Saudi Arabia, the discipline remains in its infancy, as illustrated by the absence of PPC programs in academic and health care institutions. Aim: The aim was to conduct a pilot study assessing physicians' knowledge, attitudes, and perceptions toward PPC. Method: Data were gathered through a self-administered questionnaire sent to physicians working in Saudi Arabia. Results: One hundred twelve completed the survey (male 54.2%, n = 50). A total of 40.8% (n = 42) had 20 years or more of experience, 42.9% (n = 48) were from the hematology-oncology specialty, and 68.5% (n = 74) received no training in PPC. Half suggested that children should be informed of their condition but mostly when reaching 12 or 15 years of age. Various physicians reported that the most appropriate time to discuss a transition to palliative care goals is when diagnosing an incurable condition or when despite all efforts, a condition continues to progress and death is expected. Conclusion: Multiple gaps were identified. PPC basic concepts should be included in the formal medical curriculum (e.g., pain management, communication, and ethical considerations at the end of life). There is also a significant need to develop further both primary and specialized palliative care.

Eye-sparing Treatment of Localized Orbital Medulloepithelioma With Neoadjuvant Chemoradiation.

A 9-year-old girl presented with a 3-day history of progressive proptosis accompanied by transient discomfort and blurry vision in the OD. MRI revealed a heterogeneously enhancing intraconal lesion that partially encased and displaced the optic nerve. There was no intraocular or intracranial involvement, nor were there signs of distant metastasis. Histopathologic evaluation and immunohistochemistry were consistent with orbital medulloepithelioma. The patient received 4 cycles of chemoradiation per a retinoblastoma protocol. Repeat MRI scans showed significant tumor regression, and further surgical debulking was performed. There has been no evidence of recurrence for over 14 months. Herein, the authors describe an eye-sparing, multimodal treatment of a rare case of localized orbital medulloepithelioma.

Disparities in the use of antineoplastic immunotherapy in pediatric malignant adrenal tumors.

Dinutuximab is a costly life-prolonging immunotherapy for high-risk neuroblastoma. We used a large pediatric inpatient database to analyze the use of antineoplastic immunotherapy in patients with malignant adrenal tumors 1 year after Food and Drug Administration approval of dinutuximab for high-risk neuroblastoma. On multivariate modeling, children of Black race (odds ratio [OR] 0.62, P = .04; referent non-Black) and the lowest ZIP code income quartile (OR 0.74, P = .03; referent wealthier 3 quartiles) were significantly less like to receive antineoplastic immunotherapy. These results suggest substantial disparities in the distribution of a vital therapy in children with advanced cancer.

Novel Therapy for Pediatric Angiosarcoma With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

The management of pediatric abdominopelvic angiosarcoma remains unclear due to limited clinical experience. Herein, we presented the first 2 pediatric patients with abdominal angiosarcoma who were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant therapy. The first patient is alive with recurrent disease at 1-year follow-up and the second patient remains disease free after 1 year. CRS and HIPEC should be considered as a therapeutic option in the management of pediatric abdominal angiosarcomas. A multi-institutional international shared registry is needed to further evaluate the role of CRS and HIPEC in inducing remission of abdominopelvic angiosarcomas in the pediatric population.

Angiosarcoma of the Pelvis in a 13-Year-Old Girl.

Angiosarcomas are highly aggressive malignancies of vascular origin and are very rarely found in children. We report a case of a 13-year-old girl with a history of abdominal pain and increased abdominal girth. Radiologic imaging showed significant ascites and large pelvic masses involving bilateral adnexa with abdominal spread. Microscopic examination of a biopsy revealed pleomorphic epithelioid and spindle cells with brisk mitotic activity, intracytoplasmic vacuoles, vascular channels, and large areas of hemorrhage and necrosis. Immunohistochemistry analysis showed strong and diffuse positivity for CD31, D2-40, ERG, FLI-1, and focally for CD34, vWF, and EMA. The diagnosis of metastatic angiosarcoma was rendered. The patient was treated aggressively with systemic chemotherapy, immunotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy, with a favorable response after 1-year follow-up. Angiosarcoma should be considered when encountering a vascular tumor with pleomorphism, brisk mitotic activity, and necrosis. Immunohistochemistry studies are necessary for proper diagnosis.

Increased prevalence of false positive hemoglobinopathy newborn screening in premature infants.

BACKGROUND: The objective was to investigate the specificity of the hemoglobinopathy newborn screening in premature neonates as compared to term neonates. PROCEDURE: The screening results from infants suspected to have hemoglobinopathy disease identified by the Florida Newborn Screening Program for years 2002-2007 were compared to the corresponding confirmatory testing. The risks for false positives for preterm and full term newborns were calculated by Chi-square or the Cochran-Armitage test for trend. Isoelectric focusing and HPLC were the methods of hemoglobin screening. RESULTS: Over 2,300 neonates (1/576 neonates born in Florida) were suspected to have hemoglobinopathy. The most common abnormal pattern in term and preterm infants (gestational age 22-36 weeks) suggesting disease at screening was FS. Overall, 93% of the children who screened positive for FCA and 64% of infants identified with FSA were later confirmed with trait. FSC was confirmed in 96% of the cases in both preterm and term infants. Compared to term newborns, preterm newborns were more likely to have a false positive result for FS or FC at screening. Twenty-three percent of preterms with FS and 59% of preterms with FC were diagnosed as traits by confirmatory testing, compared to only 2% and 6% for term infants (P < 0.001). CONCLUSIONS: As compared to term newborns, more preterm newborns with trait were misidentified as having sickle cell anemia or hemoglobin C at screening. We speculate that abnormal hemoglobins may precede the development of hemoglobin A during fetal life.

Placental site trophoblastic tumor in the ovary of a young child with isosexual precocious puberty.

The authors report a unique case of a primary ovarian placental site trophoblastic tumor (PSTT) in a 30-month-old girl who presented with isosexual precocious puberty of 1 month duration. Laboratory studies revealed mildly elevated beta human chorionic gonadotropin (37.5 mIU/ml; reference range <3.0 mIU/ml) and estradiol (74 pg/ml; reference range 0 to 56 pg/ml) serum levels. A 3.5-cm right ovarian mass was detected radiographically. The tumor was confined to the ovary as proven by the preoperative staging workup and the exploratory laparotomy. Microscopically, it was composed of intermediate trophoblastic cells with angioinvasive growth and deposition of fibrinoid material. The tumor cells were diffusely positive for human leukocyte antigen G, melanoma cell adhesion molecule (CD146), and cytokeratins (AE1/AE3, CK18, and CAM 5.2). Stains for human chorionic gonadotropin, alpha-inhibin, and human placental lactogen showed focal immunoreactivity. Serum markers returned to normal postoperatively. The patient remains disease-free at 24-months follow-up. We propose that tumors morphologically identical to uterine PSTT may rarely occur as gonadal germ cell tumors in children.

Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement.

Langerhans' cell histiocytosis (LCH) is manifested in a variety of ways, the most common being the eosinophilic granuloma, a localized, often solitary bone lesion that occurs predominantly in the pediatric age group. The hallmark of LCH is the proliferation and accumulation of a specific histiocyte: the Langerhans' cell. In bone this may cause pain and adjacent soft-tissue swelling, but some lesions are asymptomatic. LCH can involve any bone, but most lesions occur in the skull (especially the calvarium and temporal bones), the pelvis, spine, mandible, ribs, and tubular bones. Imaging diagnosis of the disease in bone is first based on the plain radiographic appearance, which is usually a central destructive, aggressive-looking lesion. In the skull, the lesions develop in the diploic space, are lytic, and their edges may be beveled, scalloped or confluent (geographic), or show a "button sequestrum." Vertebral body involvement usually causes collapse, resulting in vertebra plana. With significant recent improvements in the quality of gamma cameras, imaging techniques, and in studying children, bone scintigraphy at diagnosis and on follow-up usually reveals the sites of active disease, especially when the involvement is polyostotic. CT and MR imaging are very useful in providing detailed cross-sectional anatomic detail of the involved bone, including the bone marrow and the adjacent soft tissues. CT is better suited for demonstrating bone detail and MR imaging for bone marrow and soft-tissue involvement.

In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation.

Skp1 is involved in a variety of crucial cellular functions, among which the best understood is the formation together with Cul1 of Skp1-cullin-F-box protein ubiquitin ligases. To investigate the role of Skp1, we generated transgenic (Tg) mice expressing a Cul1 deletion mutant (Cul1-N252) able to sequestrate and inactivate Skp1. In vivo interference with Skp1 function through expression of the Cul1-N252 mutant into the T-cell lineage results in lymphoid organ hypoplasia and reduced proliferation. Nonetheless, after a period of latency, Cul1-N252 Tg mice succumb to T-cell lymphomas with high penetrance (>80%). Both T-cell depletion and the neoplastic phenotype of Cul1-N252 Tg mice are largely rescued in Cul1-N252, Skp1 double-Tg mice, indicating that the effects of Cul1-N252 are due to a sequestration of the endogenous Skp1. Analysis of Cul1-N252 lymphomas demonstrates striking karyotype heterogeneity associated with c-myc amplification and c-Myc overexpression. We show that the in vitro expression of the Cul1-N252 mutant causes a pleiotrophic phenotype, which includes the formation of multinucleated cells, centrosome and mitotic spindle abnormalities, and impaired chromosome segregation. Our findings support a crucial role for Skp1 in proper chromosomal segregation, which is required for the maintenance of euploidy and suppression of transformation.