Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study.

Treatment for Hodgkin's disease (HD) is associated with a variety of thyroid abnormalities, including hypothyroidism, hyperthyroidism, and thyroid neoplasms. Due to the small sample size and short follow-up time of most published studies, it has been difficult to appreciate the full extent of the problem and to characterize the interaction between various patient and treatment variables. To overcome these limitations we have assessed thyroid status in 1,791 (959 males) HD survivors from among 13,674 participants in the Childhood Cancer Survivor Study, a cohort of 5-yr survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. Thyroid abnormalities were ascertained as part of a 22-page questionnaire sent to participants. Survivors were a median of 14 yr (range, 2-20 yr) at diagnosis of HD and a median of 30 yr (range, 12-47 yr) at follow-up. Seventy-nine percent of subjects were treated with radiation (median dose of radiation to the thyroid, 3,500 cGy; range, 0.37-5,500 cGy). Control data were available from 2,808 (1,346 males) sibling controls. Thirty-four percent of the entire cohort has been diagnosed with at least one thyroid abnormality. Hypothyroidism was the most common disturbance, with a relative risk of 17.1 (P < 0.0001) compared to sibling controls. Increasing dose of radiation, older age at diagnosis of HD, and female sex were all independently associated with an increased risk of hypothyroidism. Actuarial risk of hypothyroidism for subjects treated with 4,500 cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism was reported by 5% of survivors, which was 8-fold greater (P < 0.0001) than the incidence reported by the controls. Thyroid dose of 3,500 cGy or more was the only risk factor identified for hyperthyroidism. The risk of thyroid nodules was 27 times (P < 0.0001) that in sibling controls. Female sex and radiation dose to the thyroid of 2,500 cGy or more were independent risk factors for thyroid nodules. The actuarial risk of a female survivor developing a thyroid nodule is 20% at 20 yr from diagnosis. Thyroid cancer was diagnosed in 20 survivors, which is 18 times the expected rate for the general population. After taking into account the possibility that some of the relative risk estimates may be exaggerated due to ascertainment bias, abnormalities of the thyroid are still extremely common in young adult survivors of childhood HD, particularly among females treated with high doses of radiation to the neck.

Health status in 52 long-term survivors of pediatric brain tumors.

The percentage of children who survive childhood brain tumors is increasing. A number have neurological and other sequelae which impact on the quality of their survival. We reviewed long-term survivors using a standardized health status instrument. The mothers of 52 survivors of brain tumors were surveyed. Eight different aspects (attributes) of health status were scored. The first 6 of these attributes were scored in a health status index (HSI) developed at McMaster University. Subgroup analysis was performed. Limitation in the quality of life was found in one of the 8 attributes in all but 2 of the subjects. The health status index (HSI) score using the first 6 attributes of this survey had a median of 0.73 (range 0.16-1.00). This score is lower than that found in previously surveyed survivors of leukemia or other childhood cancers. Examination of age at diagnosis, extent of surgery, sex and therapeutic modalities used showed no correlation with HSI score. Those with supratentorial astrocytomas had a lower HSI score (0.65) than those with infratentorial astrocytomas (0.85) (p = 0.05). Children with craniopharyngiomas had a poor score (0.64). This survey shows that the survivors of brain tumors have an appreciable burden of morbidity. Most have deficits in health status that affect many areas of their lives. Apart from site of the primary tumor, there was little correlation between subgroups studied and health status. The health status of children who survive brain tumors is lower than that of survivors of other childhood malignancies.

Unusual dural and skull-based mesenchymal neoplasms: a report of four cases.

Dural and skull-base mesenchymal neoplasms other than meningiomas are rare. We report four such tumors, some of which are uncommon even in nonintracranial sites, in three adults and one child. The adult tumors consisted of a synovial sarcoma of the third ventricle region in a 19-year-old woman, a leiomyoma of the suprasellar region in a 57-year-old woman, and an Epstein-Barr virus (EBV)-associated smooth muscle tumor of the cavernous sinus in a 35-year-old woman with acquired immunodeficiency syndrome (AIDS). The pediatric tumor was an EBV-associated leiomyosarcoma of the left dural transverse sinus in a 14-year-old girl with common variable immunodeficiency syndrome. All tumors were thought to be primary in their dural or skull-base locations. The two EBV-associated smooth muscle tumors in immunocompromised patients expand the locations for EBV-associated smooth muscle tumors to dural and skull-base sites, the synovial sarcoma is unique to the intracranial space, and the sellar leiomyoma represents the third reported sellar smooth muscle tumor.

Primary leiomyosarcoma of brain in an adolescent with common variable immunodeficiency syndrome.

A 14-year-old girl with common variable immunodeficiency syndrome was found to have a low-grade malignant neoplasm arising in the left temporal lobe of the brain. Ultrastructural and immunohistochemical studies established a diagnosis of leiomyosarcoma, despite the rarity of this tumor in children. In situ hybridization with the EBER probe revealed essentially all of the neoplastic cells to be infected with Epstein-Barr virus (EBV). Children with the acquired immunodeficiency syndrome (AIDS) are known to exhibit an increased incidence of smooth muscle tumors associated with EBV. Similar tumors have been reported in EBV-infected patients undergoing therapeutic immunosuppression. This appears to be the first reported case of childhood leiomyosarcoma where the cause of the underlying immunodeficiency was a genetic rather than acquired disorder. The authors conclude that electron microscopy, immunohistochemistry, and other ancillary techniques are essential in the evaluation of unusual tumors in immunocompromised children, whether the cause is hereditary or acquired.

Polymyositis as a manifestation of chronic graft-versus-host disease.

A syndrome indistinguishable from idiopathic polymyositis occurred in 11 patients as a manifestation of chronic GVHD. All patients had elevation of creatine phosphokinase (CPK). Immunohistology demonstrated the effector cells in the muscle infiltrates as cytotoxic T cells, a finding similar to idiopathic polymyositis. Polymyositis is a rarely reported complication of chronic graft-versus-host disease (GVHD) with only 8 cases described in the literature. We encountered this syndrome in a small but significant percentage of our patients with chronic GVHD. Polymyositis associated with chronic GVHD does not affect the overall prognosis for the patient. Moreover, polymyositis can be the only manifestation of chronic GVHD. Awareness of this complication is important because it can be confused with other causes of muscle weakness after bone marrow transplantation. Finally, prompt initiation of corticosteroid therapy results in a rapid improvement of the associated symptoms.

Cessation of antibiotics regardless of ANC is safe in children with febrile neutropenia. A preliminary prospective trial.

PURPOSE: This study was designed to evaluate the safety and efficacy of stopping antibiotic treatment regardless of absolute neutrophil count (ANC) or signs of impending neutrophil recovery in children with febrile neutropenia (FN) and no identifiable infectious source. PATIENTS AND METHODS: Thirty-two consecutive cases of FN without identifiable source were prospectively evaluated. Patients were examined, cultured, and initially treated with ceftazidime +/- vancomycin. Antibiotics were discontinued and patients discharged regardless of ANC (WBC/microliter x [% segs + bands]) once all the following criteria were met: afebrile > or = 24 h; cultures negative at 48 h; thermometer and telephone available at home. Prompt notification of fever (T > 38.3 degrees C) and readmission were required. RESULTS: Median ANC was 60/microliters on admission and 160/microliters at discharge. Median length of treatment was 3 days. Four patients were readmitted for FN, and two patients were readmitted afebrile for cultures which became positive after discharge. None of the 32 cases suffered apparent complications from early discharge. CONCLUSION: Results of this preliminary trial suggest that cessation of antibiotics regardless of ANC is safe in cases of FN without identifiable source, provided that marrow is not infiltrated and that recurrent fever receives prompt antibiotic retreatment.

Intracranial malignant germ cell tumor and the Klinefelter syndrome. Case report and review of the literature.

A case of intracranial mixed malignant germ cell tumor (GCT) in a patient with the Klinefelter syndrome (KS) is reported. Extragonadal GCTs, including those of intracranial origin, have previously been noted in KS patients. A review of the English literature suggests that although this phenomenon is rare, there appears to be more than a coincidental relationship between GCTs and a 47,XXY karyotype. This case represents the sixth reported case of intracranial GCT in KS but the first to be histologically confirmed to have mixed malignant germ cell elements. This occurrence of malignant cell types in a KS patient emphasizes the need for a histologic diagnosis prior to initiation of therapy.

Indications for surgical intervention for gastrointestinal emergencies in children receiving chemotherapy.

BACKGROUND: Abdominal pain in children receiving chemotherapy for cancer presents the clinician with unique problems due to the altered immunity of these patients or to the oncologic setting. The major clinical decisions regarding these patients are to determine if and when operative intervention is indicated. METHODS: A retrospective study was done to examine the clinical, radiographic, and laboratory findings that indicate the need for surgical intervention. Sixty-eight of 1090 children who underwent treatment for cancer from October 1982 to December 1990 developed abdominal complaints requiring them to be hospitalized. Nineteen of these patients underwent exploratory laparotomy (operative), and the other 49 were observed (nonoperative). RESULTS: No significant differences were observed in the phase of chemotherapy, treatment with vincristine or corticosteroids, or the hematologic indices between the operative and nonoperative groups. Eighteen of nineteen patients survived their surgeries. Seventeen (89%) of these laparotomies were positive based on the surgical pathology and the operative report. Peritoneal signs on physical examination (P < 0.001) or pneumatosis intestinalis on abdominal radiographs correlated with positive laparotomies (P = 0.001). CONCLUSIONS: Peritoneal signs on physical examination or pneumatosis intestinalis on abdominal X-rays were associated with and specific for the presence of acute surgical disease of the abdomen in immunocompromised pediatric oncology patients.

Molecular forms of human protein C: comparison and distribution in human adult plasma.

Protein C (PC) is a vitamin K-dependent protein which functions as both an anticoagulant and profibrinolytic. It is synthesized as a single chain protein (SC-PC) and post-translationally modified into a two chain form (2C-PC). Two chain PC consists of a light chain (LC) and a heavy chain (HC). The present study was undertaken to determine the composition of the molecular forms of PC in plasma. PC was immunoprecipitated, subjected to SDS-PAGE and Western blotting. The blots were scanned by densitometry to determine the distribution of the various forms. The percentage of SC-PC and 2C-PC was found to be 10% and 90% respectively. This is in agreement with previous work. SC-PC and the heavy chain of 2C-PC consisted of three molecular forms ("alpha", "beta", and "gamma"). The "alpha" form of HC is the standard 2C form with a MW of 40 Kd. The "beta" form of HC has also been described and has MW which is 4 Kd less than the "alpha" form. The "gamma" species of the SC and 2C-PC has not been previously described. However, its 3 Kd difference from the "beta" form could be due to modification of the "beta" species or to a separate modification of the alpha-HC. The LC of PC was shown to exist in two forms (termed form 1 and form 2). The difference between these two forms is unknown. The molecular forms of PC are most likely due to a post-translational modification (either loss of a carbohydrate or a peptide) rather than from plasma derived degradation.

Neonatal protein C: molecular composition and distribution in normal term infants.

Protein C (PC) is a vitamin K-dependent serine protease which functions as the central regulatory protein with both anticoagulant and profibrinolytic properties. The PC levels in healthy term newborns are approximately one third of adult levels. Severely decreased levels of PC are seen in sick term and preterm infants. These neonates appear to have an increased incidence of thrombosis. Undetectable levels of PC are found in homozygous PC deficient infants with DIC and purpura fulminans symptoms. In this present study we report the composition and distribution of PC in term newborn and compare the results with adult values. Plasma was obtained from placental cord blood of 20 healthy term (38-42 weeks gestation) infants. PC was immunopurified, run on SDS-PAGE, and immuno-blotted. The composition of the PC molecule in neonatal plasma is identical to that seen in adults. Using densitometry to determine the distribution of the PC components, we observed a 2-fold increase in single chain PC in the neonate as compared to the adult. In the neonate, there was an inverse correlation between the level of total PC antigen and the amount of single chain. These findings suggest the possibility that the processing of PC may be developmentally influenced.

[Practical approaches for surgical procedures in congenital factor VII deficiency]. / Attitude pratique en cas d'intervention chirurgicale chez un sujet atteint d'un déficit congénital en facteur VII.

A 33 year old female with a congenital deficit in factor VII underwent four operations, all without any haemorrhage. One of then was carried out using substitutive therapy. She had a non-A non-B hepatitis one month after this treatment. Substitutive therapy depends on the assessment of the risk of haemorrhage, which can be estimated by the concentration of factor VII, the severity of spontaneous haemorrhage, the surgical history, and the planned operation. Since the risk of transmitting viruses with freeze-dried blood products would appear to be virtually nil, since 1985, fresh frozen plasma should be avoided for this type of indication. The doses of concentrated factor VII to be used lie between 20 IU.kg-1 every 4 h and 40 IU.kg-1 every 8 h. Such a dose should be administered in either one or several injections, according to whether the risk of haemorrhage is important or not. Substitutive therapy should be continued as long as the risk persists. Using a test dose of factor VII and, afterwards, measuring its biological activity can help to determine the best time for starting the treatment in order to obtain a level of factor VII greater than the minimum required for surgical haemostasis (10%).