Very long-term molecular follow-up of minimal residual disease in patients with neuroblastoma.

In high-risk neuroblastoma (HR-NB), the clinical significance of long-term minimal residual disease (MRD) monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for neuroblastoma mRNAs has not been investigated. We report long-term MRD follow-ups of four patients with HR-NB throughout the disease (diagnosis, remission, and relapse) and treatment course (chemotherapy, autologous and allogeneic stem cell transplantation, and donor lymphocyte and natural killer cell infusions). The results showed the stability of mRNA marker expression after different treatments and demonstrated their validity to predict relapse and assess therapeutic response. This opens up the possibility of investigating the utility of long-term molecular monitoring of MRD in prospective multicenter studies.

A rare case of pediatric primary central nervous system differentiating neuroblastoma: an unusual and rare intracranial primitive neuroectodermal tumor (a case report).

Neuroblastoma represents the most common solid extracranial tumor in children under 5, accounting for 8% to 10% of all childhood cancers. Primary central nervous system (CNS) neuroblastomas are a very rare location and only few cases are available in the literature. It was first described in 1973 by Hart and Earl as supratentorial primitive neuroectodermal tumors. Clinical presentation is highly variable and depends on the initial location of the tumor. Regarding imaging, primary brain neuroblastoma shows no pathognomonic appearance on brain computed tomography (CT) whether or not enhanced or magnetic resonance imaging (MRI). There were no standard guidelines available for the adjuvant treatment in case of primary CNS neuroblastoma. Surgery remains the main and the first tool toward these lesions. Radiotherapy associated or not to chemotherapy is offered based on patient´s age. Here, the authors report a new pediatric case of primitive central nervous system neuroblastoma revealed by an intracranial hypertension syndrome and confirmed by both histopathological and immunohistochemistry study after a gross total surgical excision. The postoperative course was uneventful and the child had good recovery.

[Retroperitoneal mass in children : clinical cases of Wilms tumor and neuroblastoma]. / Le cas clinique du mois. Les masses rétropéritonéales chez l'enfant : a propos d'une tumeur de Wilms et d'un neuroblastome.

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. We present the case-reports of 2 children under the age of 5 years admitted to the University Hospital of Liège, one with a Wilms tumor and one with a neuroblastoma.

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt.

AIM: The study aims to evaluate survival outcome in newly diagnosed pediatric intermediate risk neuroblastoma patients treated at the Children Cancer Hospital - Egypt and their relation to various clinical and pathological factors. METHODS: The study included stage 3 patients <1.5 years, children 1.5 years or older with stage 3 disease and favorable histopathological features, infants (<1 year) with International Neuroblastoma Staging System (INSS) stage 4 disease, stage 4 children 1-1.5 years with favorable biology, and infants stage 4 s (with unfavorable biologic features). Patients received systemic chemotherapy, in the form of etoposide and carboplatin alternating with cyclophosphamide, doxorubicin and vincristine, administered at 3-week intervals, with a total of 6 or 8 cycles guided by reaching objective overall response (complete/very good partial/partial response). RESULTS: The study included 136 patients, 67 males and 69 females. 101 patients had abdominal primary tumors, 28 had mediastinal masss and 7 with masses in the neck; 68% were stage 3 and the remaining (n = 44) had metastatic disease. The three-year overall survival (OS) and event-free survival (EFS) estimates were 94% ±â€¯2% and 90.9% ±â€¯2.5%, respectively. OS and EFS by gender, age, pathology and INPC were all statistically not significantly different. Moreover, OS for patients having surgery versus no surgery (inoperable residual only) was statistically significant (98.4% ±â€¯1.6% & 88.7% ±â€¯5.3%, respectively, p = .034). CONCLUSION: A very high rate of survival is currently achievable in patients with intermediate risk neuroblastoma by chemotherapy or chemotherapy and surgery. In addition to response, our plan is to adopt biologically-based treatment to reduce treatment-induced complications among survivors.

[Difficulty in diagnosing pediatric tuberculosis]. / Tubercolosi pediatrica una diagnosi difficile.

Tuberculosis (TB) in children is an important warning sign in a community, as it could signal recent infection of a cavitary form in an adult. Thus, while early diagnosis is crucial for effective treatment in children, it is also imperative for the control of tuberculosis at the public health level since it allows rapid identification of contagious adult cases. Here we report four cases of difficult and delayed diagnosis of TB in children. From this experience we highlight the need for an extensive medical history of the patient during diagnostic work-up. This includes: the positive history for contact with infected adults, especially for immigrant children; exclusion of TB diagnosis for persistent respiratory symptoms (2-3 weeks) after antibiotic therapy; and the need for high-definition CT scan when the radiological picture is not specific, especially for children under 5 years of age.

[Ethical and practical problems of secondary prevention. Two paediatrics examples]. / Problemas prácticos y éticos de la prevención secundaria. A propósito de dos ejemplos en pediatría.

The concept of prevention is surrounded by a halo of optimism that can sometimes confuse, since it is not always borne out by the facts. The saying, "An ounce of prevention is worth a pound of cure", is not always true. Moreover, preventive activities should be based on a much more solid scientific basis than curative activities, since we offer the former as an option, whereas we are required to provide the latter. This article reviews two examples of paediatric screening instruments-one for neuroblastoma, and the other for hip dysplasia-which provide an opportunity to evaluate the practical problems of secondary prevention. These two instruments are used to examine a few general but important issues in screening, such as the need to know the natural history of the disease, and the "point of no return" (the moment past which early diagnosis and early intervention are no longer so effective in improving the course of the disease). In conclusion, only sometimes "an ounce of cure is worth a pound of prevention", and regardless of the value of a given screening instrument, clinicians should use the same level of scientific rigor to judge preventive activities as they use for curative activities.

[Anesthetic management in two infants undergoing hemilaminectomy for giant mediastinal neuroblastoma].

We report the anesthetic management in two infants who were a three-month-old boy (case 1) and a two- month-old girl (case 2), undergoing hemilaminectomy for giant mediastinal neuroblastoma. Neuroblastoma invades into the intrathecal space in a rare occasion, resulting in paraplegia, which requires emergent operation to save the spinal cord. Mediastinal neuroblastoma also possesses significant respiratory and cardiovascular risks due to the close anatomic relationship with vital organs. In the present report, we show that preoperative computed tomography (CT) scan and/or echocardiography revealed tracheal deviation in case 1 and mass compression of the left atrium in case 2. Therefore, the patients with mediastinal masses should be carefully evaluated before subjecting them to anesthesia. Especially, there is a possibility that the masses which do not appear to compress the airway and cardiovascular systems develop the airway obstruction and cardiovascular collapse after induction of general anesthesia. In fact, before induction of general anesthesia in the case 2, trial of the prone positioning which was scheduled for the hemilaminectomy, resulted in bradycardia and hypotension, presumably due to the compression of the left atrium. In summary, the authors here discussed the preoperative evaluation and anesthetic management for giant mediastinal neuroblastoma in infants.

Unremitting watery diarrhoea in early childhood period.

Chronic watery diarrhoea can be a presentation of gastrointestinal disease itself or a less-evident systemic disease. A 17-month-old boy presented with intractable diarrhoea, failure to gain weight, refractory tachycardia and severe hypertension. The ability to recognise and make a quick diagnosis of secretory type of diarrhoea dictated the outcome of patients with this ailment. Catecholamine hypersecretion was considered with the additional clues of refractory tachycardia and hypertension, a well-recognised phenomenon of neuroblastic tumours. A neuroblastic tumour can lead to vasoactive intestinal peptide (VIP) overexpression, which may result in secretory diarrhoea. In this situation, measurements of plasma VIP enabled crucial diagnosis. Imaging studies were used to identify and localise a neuroblastic tumour. Subsequent removal of the tumour was curative and led to the resolution of the symptoms.

Treatment of neuroblastoma using the fused imaging guided radiotherapy (FIGURA) system.

PURPOSE: The purpose of this study was to describe our department's experience with the fused imaging-guided radiotherapy (FIGURA) system for planning radiation treatment of high-risk neuroblastoma. PATIENTS AND METHODS: Between 1999 and 2002, 11 patients received radiation therapy as consolidation after chemotherapy in 9 and for palliation in 2. Diagnostic metaiodobenzylguanidine (MIBG) imaging was used, which is specific for neuroblastoma, to identify the residual tumor, followed by computed tomography scanning in the radiation treatment position. The FIGURA software fused the images obtained by the 2 modalities and transferred the result to a 3-dimensional radiation treatment planning system. Radiation was delivered at a total dose of 25.2 Gy according to the FIGURA. RESULTS: Five patients achieved complete remission and 2 partial remission; 3 were stabilized. One child with a highly rapid progressive course died of the disease. CONCLUSION: FIGURA is a new, feasible technique for defining target volumes. By using standard hospital equipment, it is possible to treat residual disease identified by sensitive metaiodobenzylguanidine imaging and localized with the anatomic computed tomography scan. Treating a more accurate target volume spares normal tissue and organs and minimizes side effects.

¹³¹I-Metaiodobenzylguanidine Theranostics in Neuroblastoma: Historical Perspectives; Practical Applications.

Much efficacy is gained in clinical practice if a single agent can be used for both diagnosis and therapy, a practice termed theranostics. Metaiodobenzylguanidine (mIBG), a norepinephrine analogue with high sensitivity and specificity for neuroblastoma, is an exemplar of theranostics. The physiologic biodistribution of mIBG, with absence of uptake in bone and bone marrow, allows ready detection not only of primary soft tissue tumors but also of disease in bone and marrow, the two most common sites of metastases in those with neuroblastoma. Owing to its increased sensitivity and specificity in disease detection compared to the Technetium-99m methylene diphosphonate bone scan, (123)I-mIBG has become the cornerstone of staging and therapeutic response monitoring in patients with neuroblastoma. More recently, semiquantitative scoring systems have been developed to evaluate disease burden and response to treatment based on (123)I-mIBG scans. Initial data suggest that the use of these semiquantitative scoring methods has prognostic value in assessing outcomes for patients with high-risk neuroblastoma. When labeled with (131)I, mIBG can be used as a systemic therapeutic agent to treat high-risk disease, and to date, over 1000 patients with neuroblastoma have been treated worldwide with this agent. This article reviews the evolution of (131)I-mIBG therapy from its initial use as a single therapeutic agent to modern applications involving high-dose chemotherapy and autologous stem-cell transplant as well as its use as a front-line agent in high-risk neuroblastoma.

Superficial temporal artery interposition graft after resection of bilateral anterior cerebral arteries. Case report.

A patient with an olfactory neuroblastoma in the frontal skull base was treated with primary tumor excision and partial resection of the A2 segment of both anterior cerebral arteries (ACA's). Revascularization was carried out using a superficial temporal artery (STA) interposition graft between the proximal and distal stumps with A3 segment-to-A3 segment end-to-side anastomosis. This technique established flow to the peripheral territories of the ACA's through the interposed STA graft. The technical aspects and possible role of this procedure are presented.

Detection and management of gangliogliomas in children.

Forty-two children treated for gangliogliomas were reviewed to identify the best methods of detection and management. Thirty-two of the tumors were supratentorial, four infratentorial, and six were in the spinal cord. Twenty-five patients presented with seizures; the mean duration of symptoms was 5 years in contrast to 1 year in non-seizure patients. Of 31 children studied by computed tomography (CT), calcification in the tumor lesion was found in 19. Magnetic resonance imaging (MRI) showed abnormal high-signal intensity on T2 imaging in six of eight patients. All patients underwent surgical resection and were diagnosed pathologically. Twenty-four patients had total resection, and 14 underwent temporal lobectomies including hippocampectomy. The management of this tumor remains surgical resection without the need for any adjuvant therapy.

Diagnosis of childhood cancer.

Childhood cancer is uncommon but remains the leading cause of disease-related death in children. Symptoms are often vague or insidious; they may suggest a more common alternative diagnosis, and they are quite different from those associated with adult malignancy. The skilled office practitioner must consider cancer as a diagnosis when symptoms/signs persist or when multiple symptoms point toward a possible diagnosis of malignancy. Early diagnosis is critical, as survival rates have increased dramatically over the past decades. Prolonged delay in diagnosis is common, especially for brain tumors and certain lymphomas (Hodgkin disease). When one encounters symptoms suspicious for a childhood malignancy, it is imperative that the child be referred to a pediatric cancer center. These centers possess not only the ability to further evaluate and manage children with malignancy, but also are able to provide support for patients and their families. This evaluation may include further imaging, but often involves obtaining tissue for histologic review. This will require appropriate tumor or bone marrow biopsy, preferably before the start of treatment. Depending upon the type of suspected malignancy, direct tumor biopsy can be facilitated by imaging-guided biopsy (ultrasound, CT, or MRI), which spares the patient additional surgery. This optimally is performed by a skilled team: hematologist/oncologist, surgeon, radiologist, and pathologist. Best results depend upon early referral by the thoughtful practitioner.

Pelvic teratoma with extensive spinal involvement in a neonate: an important differential diagnosis.

A 6-week-old girl presented with an abdominal mass and spinal cord compression. Clinical and radiological features indicated a diagnosis of congenital neuroblastoma. Histology revealed a diagnosis of germ cell tumour after therapy for neuroblastoma had been commenced. This is, to the authors' knowledge, the first reported case of paediatric dumbbell retroperitoneal teratoma.

Late presentation of opsoclonus-myoclonus-ataxia syndrome in a child with stage 4S neuroblastoma.

Opsoclonus-myoclonus-ataxia syndrome (OMA) in children is most commonly associated with occult neuroblastoma (NB). Although children with OMA and NB have decreased mortality, they suffer from increased neurologic morbidity. The pathogenesis of OMA in NB is not well understood, but current research and treatments support an immune-mediated process. The authors describe an unusual presentation of OMA occurring following 6 months of chemotherapy in a child with stage 4S NB who presented with partial Horner syndrome. Histopathologic examination of his primary cervical tumor showed NB maturation, which may have played a role in precipitating OMA syndrome. Further study of unusual cases of OMA in NB may provide better understanding of the syndrome and additional treatment options for these children.

Recognition of common childhood malignancies.

Although cancer has an annual incidence of only about 150 new cases per 1 million U.S. children, it is the second leading cause of childhood deaths. Early detection and prompt therapy have the potential to reduce mortality. Leukemias, lymphomas and central nervous system tumors account for more than one half of new cancer cases in children. Early in the disease, leukemia may cause nonspecific symptoms similar to those of a viral infection. Leukemia should be suspected if persistent vague symptoms are accompanied by evidence of abnormal bleeding, bone pain, lymphadenopathy or hepatosplenomegaly. The presenting symptoms of a brain tumor may include elevated intracranial pressure, nerve abnormalities and seizures. A spinal tumor often presents with signs and symptoms of spinal cord compression. In children, lymphoma may present as one or more painless masses, often in the neck, accompanied by signs and symptoms resulting from local compression, as well as signs and symptoms of systemic disturbances, such as fever and weight loss. A neuroblastoma may arise from sympathetic nervous tissue anywhere in the body, but this tumor most often develops in the abdomen. The presentation depends on the local effects of the solid tumor and any metastases. An abdominal mass in a child may also be due to Wilms' tumor. This neoplasm may present with renal signs and symptoms, such as hypertension, hematuria and abdominal pain. A tumor of the musculoskeletal system is often first detected when trauma appears to cause pain and dysfunction out of proportion to the injury. Primary care physicians should be alert for possible presenting signs and symptoms of childhood malignancy, particularly in patients with Down syndrome or other congenital and familial conditions associated with an increased risk of cancer.

A case of opsoclonus-myoclonus-ataxia with neuroblastoma.

A 2 year old boy presented with features of opsoclonus, myoclonus and ataxia. Routine investigations of blood, urine, x-ray chest, bone scan, EEG and MRI of brain, were normal. Urine for VMA was negative. A right suprarenal mass was detected at MRI of abdomen. The mass was resected completely and was found histologically to be of differentiating type of neuroblastoma. The child was treated initially with prednisolone for 6 weeks along with sodium valproate. He is still on sodium valproate for his neurological symptoms. His symptoms still persist though they have decreased in intensity.