Orbital growth retardation in retinoblastoma survivors: work in progress.

BACKGROUND: Orbital growth retardation, after enucleation and/or external beam radiation for retinoblastoma (RB), is a serious late effect. We measured orbital volumes of RB survivors treated at Hadassah University Hospital, Jerusalem, between 1980-1998. PROCEDURE: Forty-five orbits of 28 children with RB (17 bilateral, 11 unilateral) were examined. Thirty-six orbits were irradiated, 19 enucleated, and 10 both enucleated and irradiated. The orbital volumes were calculated from a three-dimensional orbital CT reconstruction. The orbits of RB survivors were compared to age-matched controls. RESULTS: The mean age at diagnosis was 13 months, mean follow-up time was 56 months. The mean volume of RB orbits (14.4 cc) was statistically significantly smaller than control orbits (17.8 cc). There was no difference between the mean volume of orbits treated with enucleation, irradiation or both. The orbital volume of children treated before the age of 12 months was statistically significantly smaller than those treated later. There was no difference between mean volume of fellow orbits in unilateral RB and controls. The mean orbital asymmetry index in control children (2.6%) was statistically significantly smaller than in RB survivors (14%). CONCLUSIONS: There was a significant orbital growth retardation after enucleation and/or irradiation for RB. There was no difference between mean orbital volumes after enucleation, radiation or both. Orbital growth retardation was most prominent in children treated in the first year of life. Although small in number, our study suggests that deferring enucleation and/or irradiation until after the age of 12 months may reduce long-term complications.

Expression of EBV encoded nuclear small non-polyadenylated RNA (EBER) molecules in 32 cases of childhood Burkitt's lymphoma from Israel.

We have analyzed paraffin sections from 32 children with histologically confirmed Burkitt's Lymphoma (BL) for the presence of EBV using in situ hybridization to detect expression of the EBV-encoded early RNAs (EBERs). EBV was present in the tumors of 11 patients (34%). Sixty nine percent of the children presented with abdominal disease, 19% had bone marrow infiltration and only one child had jaw involvement. There was no statistically significant difference between EBV positive and EBV negative children with regard to age, gender, origin, primary site at presentation, or clinical stage of disease. However, there was a trend for younger age in the children with EBV positive BL with a median age of 4, compared to 7 years in children with EBV negative BL. None of the 7 children of Ashkenazi Jewish origin had EBER positive disease. There was no difference in the treatment outcome between the EBV positive patients (estimated survival at 24 months of 82%) and EBV negative children (estimated survival rate of 71% (p=0.58)). In conclusion, although this is only a small series it seems that childhood BL in Israel has the clinical characteristics of sporadic, non-African type with 34% EBV association and a low incidence of jaw tumors. Our data suggest that Ashkenazi Jewish children with BL are less likely to have EBV positive tumors than other ethnic groups. However, more patients will need to be studied in order to assess the validity of this observation.

The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases.

Graft-versus-host disease (GVHD), graft rejection, disease recurrence and long-term toxicity remain significant obstacles to successful allogeneic bone marrow transplantation (BMT) in children with genetic diseases. In an attempt to improve results, we used a preparative regimen consisting of three alkylating agents, busulfan (BU), thiotepa (TTP) and cyclophosphamide (CY), for T cell-depleted allogeneic bone marrow transplantation instead of the conventional BU-CY protocol. The effect of this intensified regimen was investigated in 26 consecutive children with genetic diseases who underwent T cell-depleted BMT from HLA-identical siblings. Sixteen patients were males and 10 females, of median age 5 (0.2-14) years. The diseases included beta-thalassemia major, osteopetrosis, severe combined immunodeficiency, Wiskott-Aldrich syndrome, familial agranulocytosis, congenital idiopathic hemolytic anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome, and adrenoleukodystrophy. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was as expected, with WBC >1.0 x 10(9)/l at day +19 (10-33), ANC >0.5 x 10(9)/l at day +22 (10-56) and platelets >25 x 10(9)/l at day +32 (18-131). Transplant-related mortality was 19%. Overall survival and disease-free survival (DFS) at 60 months follow-up were both 77%. Our results with the BU-TTP-CY regimen followed by T cell-depleted BMT in genetic diseases may provide a basis for prospective comparison with the standard conditioning regimen of BU-CY in the management of children suffering from these conditions.

End-stage renal interstitial fibrosis in an adult ten years after ifosfamide therapy.

A 33-year-old male presented with end-stage renal failure. Renal biopsy showed severe interstitial fibrosis without glomerulopathy or vasculopathy. More than 10 years previously the patient had been successfully treated for recurrent rhabdomyosarcoma. The treatment included ifosfamide, a drug known to cause acute tubular dysfunction. Though a possible synergistic effect of previous radiation which was well within accepted tolerance limits cannot be excluded, it would appear that ifosfamide was almost certainly the major cause of the late onset chronic renal disease.

Parathyroid adenoma after radiation in an 8-year-old boy.

We describe an 8-year-old boy who had asymptomatic hypercalcemia 4 years after radiotherapy involving the left orbit and lungs. A right parathyroid adenoma was diagnosed, and normocalcemia was achieved after its removal. Routine monitoring of serum calcium and phosphate levels is recommended for children after head and neck irradiation.

CT appearances of involvement of the peritoneum, mesentery and omentum in Wilms' tumor.

BACKGROUND: Peritoneal involvement by Wilms' tumor indicates stage III disease. CT is the single preferred modality in determining the extent and staging of Wilms' tumor; however, the CT appearances of Wilms' tumor involvement of the peritoneum have not been specifically addressed in the literature. OBJECTIVE: The objective of this study was to demonstrate the CT manifestations when there is involvement of the peritoneum, mesentery and/or omentum in Wilms' tumor. MATERIALS AND METHODS: Four cases of Wilms' tumor form the basis of this report. They were examined on Elscint CT scanners. RESULTS: Masses ("dropped metastases") in the pelvis were present in all four patients. Three patients had masses in the mesentery of the small bowel and sigmoid colon. Infiltration of the greater omentum was identified in two patients as a mantle of tumor separating bowel from the anterior abdominal wall. Ascites was present in two patients. In one patient broad-based solid masses of varying sizes were noted on the parietal and on the visceral surfaces of the peritoneum, and in a different patient a discrete mass was noted in the lesser omentum. CONCLUSION: The peritoneal spaces, recesses, ligaments and folds are invisible unless invaded by disease which is well demonstrated on CT.

Retrospective epidemiological study of Burkitt's lymphoma in Israel and diagnosis by a conservative incisional biopsy.

The clinical features of 74 patients with Burkitt's lymphoma diagnosed at the Hadassah Medical Center in Jerusalem, Israel, are described. The prompt diagnosis of a child with high grade malignant jaw involvement of non-Hodgkin's Burkitt's lymphoma is reported. The use of the open biopsy with special emphasis on the incisional biopsy is discussed in light of the incidental exfoliation of the two primary molar teeth and one permanent successor in this case.

Primary Burkitt's lymphoma of the appendix.

Appendicitis is a very rare presenting symptom of abdominal Burkitt's lymphoma. Only four cases have previously been identified in the literature, all of them males. This is the first reported case of a female as well as the youngest and is representative of the therapeutic considerations in this unusual manifestation of the disease.

High frequency of benign mediastinal uptake of gallium-67 after completion of chemotherapy in children with high-grade non-Hodgkin's lymphoma.

We observed increased gallium-67 uptake in the mediastinum after completion of chemotherapy in 10 of 62 patients with non-Hodgkin's lymphoma. All 10 were under 15 years of age, yielding a frequency of 43% in this age group. The interval between cessation of chemotherapy and the development of increased gallium-67 uptake ranged from 1 to 8 months, and the abnormality persisted for 2 to 59 months. Serial chest x-rays were performed in all patients, and four of the 10 had transient widening of the mediastinum that remained within normal limits for the children's ages. Three patients had chest computed tomographic (CT) scans at the time of increased gallium-67 uptake, and one of the three had serial scans that showed a mediastinal mass consistent with thymic enlargement. All of the patients were asymptomatic and none were biopsied. All 10 remained well, with a mean follow-up of 52.5 months. The phenomenon we describe is probably due to "rebound" thymic hyperplasia, which is a benign and transient condition. We conclude that abnormal mediastinal gallium-67 uptake after completion of chemotherapy is likely to be benign and transient if the patients are young, have small non-cleaved-cell histology, are without other evidence of lymphoma recurrence, and do not have initial mediastinal involvement. Progressive widening of the mediastinum on chest x-ray is cause for suspicion and requires further evaluation. Serum lactate dehydrogenase (LDH) levels may not be helpful in differentiating a benign from a malignant process.

Osteogenesis in in vivo diffusion chamber cultures of human marrow cells.

The osteogenic diffusion chamber culture of rodent marrow cells is a well established system. In the present study, marrow cells from children and adult human donors were incubated in diffusion chambers implanted intraperitoneally in athymic mice. After 4 or 8 weeks, the chamber content was examined by light and electron microscopy. Child-cell cultures showed osteogenic tissue consisting of a mineralizing fibrous component and cartilage. Ultrastructurally, the fibrous tissue was similar to osteoid and exhibited osteoblast-like cells and mineralizing nodules. Mineral aggregates were also found in the cartilage. These features in child-cell chambers were similar to those found in control chambers of rabbit marrow cells. Adult-cell chambers showed only unmineralized fibrous tissue. These results render previous findings in animal-cell diffusion chamber systems relevant to the understanding of bone formation in man. It is suggested that the difference between child- and adult-cell chambers reflects an age-related decline in the number of marrow osteoprogenitor cells or their potential to undergo terminal osteogenic differentiation.

Adverse prognostic influence of hepatitis B virus infection in acute lymphoblastic leukemia.

Liver function test abnormalities were examined in a retrospective survey in a population of 90 children with acute lymphoblastic leukemia (ALL) treated in a similar fashion with therapy, using primarily methotrexate, mercaptopurine, vincristine, and prednisone. A twofold or greater elevation of serum glutamyl pyruvic transaminase (SGPT) was found in 80% of the patients during induction therapy, in 63% of the patients during maintenance therapy, and 31% of the patients who completed therapy. Circulating hepatitis B virus surface antigen (HBsAg) was noted in 26% of patients with liver function test abnormalities during maintenance therapy, and 45% of patients with liver function test abnormalities after the completion of therapy. Hepatitis B virus infection was therefore, the most important single cause of abnormal liver function during remission in our patient population. Though others have asserted that hepatitis B virus infection is relatively benign in immunosuppressed individuals, in our population, this agent often caused severe pathological and clinical sequelae. This may be related to the high frequency (50%) of co-infection with the delta agent in our HBsAg-positive patients. Furthermore, hepatitis B virus surface antigenemia conferred an adverse prognostic influence for these children in terms of their leukemia-free survival.

Renal sonography in American Burkitt lymphoma.

Renal involvement is a common finding at necropsy in patients with American Burkitt lymphoma, but its in vivo sonographic features have received little attention in the literature. Of 29 patients with American Burkitt lymphoma who underwent sonography, 10 were found to have renal involvement. The 10 patients demonstrated a range of abnormalities, notably renomegaly (nine patients), diffuse increase in cortical echogenicity (six), and focal renal masses (three). The focal infiltrations were, unexplicably, hypoechoic in two patients and hyperechoic in one. Hydronephrosis was seen in five patients. One patient had evidence of calcium phosphate renal stones. Response to therapy can be assessed by changes in renal size and cortical echogenicity, as well as disappearance of focal lesions.

Abnormal CT scans of the brain in asymptomatic children with acute lymphocytic leukemia after prophylactic treatment of the central nervous system with radiation and intrathecal chemotherapy.

Thirty-two asymptomatic patients with acute lymphocytic leukemia, who had received prophylactic cranial radiation (2400 rads) and either intrathecal methotrexate or cytosine arabinoside were studied by computed tomography of the brain 19 to 67 months after initiation of prophylaxis. Seventeen of 32 (53 per cent) had one or more abnormal findings. Dilatation of the ventricles (eight patients) and widening of the subarachnoid spaces (nine patients) were equally distributed among patients in both intrathecal-chemotherapy groups. Areas of decreased attenuation coefficient (hypodense, abnormally radiolucent regions) (four patients) and intracerebral calcification (one patient)--lesions previously described in methotrexate leukoencephalopathy--were found only in those who had received intrathecal methotrexate. Mild central-nervous-system dysfunction was detected in seven patients but did not correlate with the presence of tomographic abnormalities. Nevertheless, these tomographic findings may represent preclinical lesions. The unexpectedly high prevalence of such abnormalities contrasts with the essentially normal tomographic findings in a control group with acute lymphocytic leukemia who received no central-nervous-system prophylaxis. These results suggest that alternative approaches to such prophylaxis be considered.

Computer assisted tomography in methotrexate encephalopathy.

Five children with acute lymphocytic leukemia (ALL) developed encephalopathy following treatment with intrathecal or intraventricular methotrexate (MTX). In these patients computer assisted tomography was informative by revealing areas of decreased attenuation coefficient located periventricularly and in each centrum semiovale (three cases) and calcifications, mostly in the deep and cortical gray matter (two cases), as well as ventricular dilatation (four cases). Contrast injection used in one of these five patients, as well as in another child (not affected by ALL) with MTX encephalopathy, failed to reveal enhancement.