Malignant pancreatic tumors in children and young adults: evaluation of 228 patients identified through the Surveillance, Epidemiology, and End Result (SEER) database.

BACKGROUND: Malignant pancreatic tumors are rare in young patients, few epidemiologic data are available. We reviewed prognostic factors and outcome of 228 patients <30 years with malignant pancreatic tumors identified through the U.S. National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) Public-use Database from 1973 to 2004. METHODS: Cases were grouped using the ICD-O-3. 5-year overall survival (OAS) was assessed by gender, ethnicity, SEER stage, and 5-year age intervals using univariate and Cox regression analysis. RESULTS: 228 patients with malignant pancreatic tumors were identified, resulting in an incidence of 0.46/million (100 carcinomas, 85 endocrine tumors, 8 solid pseudopapillary neoplasms (SPN), 11 pancreatoblastomas) in the USA. OAS was worse in males than females (37% vs. 55%, p=0.005). OAS according to stage was 87%, 68%, 21% for local (n=54), regional (n=42), distant metastatic disease (n=108), respectively. OAS of patients with carcinoma was 33%, endocrine tumors 58%, SPNs 88%, pancreatoblastomas 66%. Cox regression revealed stage (p=< 0.001), histology (p=< 0.001), age group (p=0.05) to be independent prognostic factors. CONCLUSION: Malignant pancreatic tumors are extremely rare in children and young adults. Entities change over the age groups towards more carcinomas with worse outcome in older patients. Tumor stage, histology and age group are important predictors for outcome. International collaboration is needed to learn more about pediatric pancreatic tumors.

Early deaths in childhood cancer.

BACKGROUND: Deaths prior to or shortly after the diagnosis of childhood cancer may reflect inadequacies in detection and appropriate referral for care. This study was performed to determine the extent of and factors associated with early death in childhood cancer. PROCEDURE: Patients with of primary cancer, aged <20 years at diagnosis, were identified from the SEER data (n = 23,470) from 1973 to 1995. Early deaths were defined as cases identified by 1) death certificate, 2) autopsy report, or 3) death within 1 month of initial diagnoses (n = 481). Cause of death was determined by ICD-8 and -9 codes. Age at diagnosis, year of diagnosis, morphology, site of disease, race, and gender were evaluated for association with early death. RESULTS: Age <1 year at diagnosis (6.2% early deaths), being diagnosed earlier in the observation period, and a diagnosis of a brain tumor, neuroblastoma, leukemia, or liver tumor were associated with increased early death. Gender and race were not associated with early death. Among the cases for whom the malignant diagnosis was made at the time of death (n = 119), the cause of death was nonmalignant for 36. For 22 of these cases the malignancy was an incidental finding and appeared not to contribute directly to the cause of death. Among these patients, 11 had neuroblastoma, 9 being <1 year of age. CONCLUSIONS: A decrease in the proportion of early deaths associated with childhood cancer has occurred during the past 2 decades. This decrease may reflect earlier diagnosis or improved imaging capabilities, surgical techniques, medical therapy, and supportive care. Awareness among pediatricians, general practitioners, and emergency physicians is warranted, with a focus on high-risk groups for early detection among childhood cancer patients.

Permanent I-125 brain stem implants in children.

Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.

Constitutional balanced translocations in alveolar rhabdomyosarcoma.

Chromosomal analysis of tumor tissue from two children with alveolar rhabdomyosarcoma revealed t(1;5)(q32;q31) and t(1;22)(q21;q11.2) in all metaphases examined, respectively. Peripheral blood lymphocytes carried the same cytogenetic abnormality as that of the tumor cells in both patients. Parental lymphocytes were karyotypically normal in the patient with t(1;22), indicating a de novo constitutional translocation, but t(1;5) was paternally inherited in the other patient. The presence of constitutional translocations in these two children might have contributed to the development of alveolar rhabdomyosarcoma.

Langerhans cell histiocytosis: an exploratory epidemiologic study of 177 cases.

There is little information available regarding epidemiologic risk factors for Langerhans cell histiocytosis (LCH). An exploratory investigation was conducted using information obtained from parents of 177 cases of LCH diagnosed before 21 years of age (median 2 years). Utilizing data available from the Children's Cancer Group, LCH cases were compared to two matched control groups including 614 patients diagnosed with a variety of childhood cancers and 318 community controls. Questionnaire data included information on demographics, prenatal and perinatal factors, complications in the neonatal period, environmental exposures, family medical history, and childhood exposures. Factors found to be statistically significantly associated with an increased risk of LCH included: maternal urinary tract infection during the index pregnancy, feeding problems during infancy, and blood transfusions during infancy. Use of supplemental vitamins was associated with a significantly decreased risk of LCH. Results from this exploratory study provide a basis for speculation on potential etiologic risk factors for LCH. Future epidemiologic investigations of LCH need to consider the presenting disease characteristics in assessing possible etiologic factors.

Resistance to inhibitors of S-adenosyl-L-homocysteine hydrolase in C1300 murine neuroblastoma tumor cells is associated with increased methionine adenosyltransferase activity.

Adaptive changes occurring in C1300 murine neuroblastoma cell lines developed for resistance to nucleoside analogue inhibitors of S-adenosyl-L-homocysteine hydrolase (AdoHcyase, EC 3.3.1.1) were investigated. Two drug-resistant cell lines, rMNB-MDL-7-2 and rMNB-Deaz-7-2, were established from wild-type C1300 neuroblastoma cells (wMNB) following incubation with the AdoHcyase inhibitors (Z)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (MDL 28,842) and 3-deazaneplanocin A, respectively. The nucleoside analogue concentration required to inhibit cellular proliferation by 50% (IC50) was 3.2 x 10(2) to 4.3 x 10(3) fold higher in the resistant cells when compared with the wMNB cell line. The proliferation rates of the resistant cell lines under in vitro or in vivo conditions were significantly lower than the wMNB cell line. In contrast to wMNB, both resistant cell lines had slower doubling times in tissue culture (22% longer) and smaller tumor weights (55% smaller) 14 days after implantation in A/J mice. No significant differences in AdoHcyase activity were noted between the resistant and wild-type cell lines. The resistant cell lines had concentrations of S-adenosyl-L-methionine that were five times higher and methionine adenosyltransferase (MAT, EC 2.5.1.6) activities that were two to four times greater than the wMNB phenotype. These data indicate that neuroblastoma tumor cell resistance to AdoHcyase inhibitors is associated with an adaptive increase in MAT activity. This cellular response facilitates methylation by elevating intracellular concentrations of the methyl donor S-adenosyl-L-methionine, thereby sustaining tumor cell viability in the presence of MDL 28,842 and 3-deazaneplanocin A.

Spontaneous subcutaneous emphysema.

Subcutaneous emphysema is an unusual complication of bronchiolitis. The investigators describe a patient with bronchiolitis who developed extensive subcutaneous emphysema. Despite an alarming appearance, the patient recovered with symptomatic care and observation. Review of the literature shows a multitude of causes of subcutaneous emphysema. The vast majority of cases resolve without intervention.

Intraspinal Wilms' tumor metastases.

BACKGROUND: Intraspinal Wilms' tumor metastasis is rare, and is associated with a high mortality rate. METHODS: The authors reviewed the clinical course of two patients with Wilms' tumor in whom extradural metastasis developed. In addition, a review of the literature and of patients entered in the National Wilms' Tumor Studies was performed to determine the clinical presentation, treatment, and outcome of other patients with Wilms' tumor with intraspinal metastases. RESULTS: Both of the patients initially had abdominal pain without neurologic deficits. Despite therapy, paraplegia secondary to cord compression from recurrent epidural metastases developed in one patient, although a third remission has been achieved with further chemotherapy. the second patient remains in disease-free remission 25+ months after surgical resection of the extradural spinal tumor, adjuvant chemotherapy and radiation therapy, and autologous bone marrow transplantation. Review of the literature and of the patients entered in the National Wilms' Tumor Studies revealed an additional 27 patients with Wilms' tumor with this pattern of metastasis. Only four were disease-free at the time of this report. CONCLUSIONS: The authors' experience stresses the importance of early recognition and treatment of this complication of Wilms' tumor and demonstrates that intensive multimodality therapy can result in long-term disease-free remission.

Intraspinal hematomas in hemophilia.

We report herein a case of a intraspinal hematoma in a 9-year-old boy with factor IX deficiency. Replacement of factor IX resulted in resolution of symptoms. The most frequent presentations of intraspinal hematomas are neck or back pain, paresis, sensory impairment, and urinary retention. Intraspinal hematomas may have devastating sequelae, including hemiplegia and quadriplegia. The occurrence or development of sequelae are related to the length of time between onset of symptoms and factor replacement. Whenever the physician suspects intraspinal hematoma, immediate replacement should be given to obtain levels of 80-100% prior to any imaging studies. Factor levels should be maintained at 30-50% for 10-14 days while the patient is monitored closely with serial neurological examinations. Most patients respond to factor replacement, but laminectomy should be considered for intractable or progressive cases.

Effect of rearing regimens on pullet growth and subsequent laying performance.

Treatments consisted of eight pullet dietary regimens: high protein with low, medium, or high ME; low protein with high ME, step-up protein, and diets with gradually decreasing protein levels and increasing ME levels with deficient methionine and TSAA levels, recommended methionine levels (TSAA-deficient), or recommended methionine and TSAA levels. Two additional regimens were introduced at 20 wk by selecting light and heavy birds, from caged birds maintained under high protein, medium ME conditions. Laying performance was measured from 20 to 64 wk. During the rearing period, birds fed the low energy and the methionine-deficient regimens consumed less energy (P less than .05). Body weight at 8 wk was affected by initial protein levels (P less than .05), but such effect was not seen after 16 wk of age. Birds on the step-up protein regimen consumed less feed during the laying period but also produced less egg mass (P less than .05). Birds with heavier body weights at 20 wk had better laying performance than birds with lighter body weights (P less than .05). A rearing regimen (0 to 20 wk) that resulted in a total protein intake of 1,140 g and a total ME intake of 20.0 Mcal was shown to control final pullet body weight and maximize laying performance; although at higher ME intake (21.5 Mcal) no detrimental effect was seen.

Effect of environmental stress on the ascorbic acid requirement of laying hens.

An experiment with a factorial arrangement of treatment (3 by 2 by 2 by 2) was conducted to determine the effect of ascorbic-acid supplementation (0, 100, and 200 ppm) on the performance of two commercial layer strains housed at a density of either 3 or 4 birds per cage and relative humidities (RH) of 40% or 60%. The hens were subjected to a continuous heat stress of 31.1 degrees C for the 3-mo experimental period. As a comparison with an unstressed control group, an additional group of hens was housed at 23.9 degrees C and 40% RH and was fed the diet without ascorbic-acid supplementation. Mortality was reduced by ascorbic-acid supplementation. Shell weight per unit surface area showed a small increase with the added ascorbic acid. Values (in Haugh units) were increased by ascorbic-acid supplementation at the 200 ppm level and by the lower relative humidity. The higher RH reduced egg production by 4.16% and changed feed efficiency from 2.29 to 2.45 g of feed intake per gram of egg mass. There were differences in blood pH, blood CO2, blood HCO3-, and blood and adrenal ascorbic-acid levels due to the housing temperature. The higher RH produced blood-chemistry changes that were typical of respiratory alkalosis, which has been shown to occur in layers at high temperatures. Higher cage density, on the other hand, showed no change in the HCO3 level; but blood pCO2 was increased while blood pH was decreased. These results demonstrate that ascorbic-acid supplementation can be effective in reducing laying-hen mortality due to environmental stress and has small influences on egg quality.

Effects of radiation on ovarian function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group has assessed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and pubertal development in 97 long-term female survivors of childhood acute lymphoblastic leukemia (ALL). All patients received identical induction and maintenance therapy with either 18 or 24 Gy of radiation therapy (RT) to one of the following fields: cranial, craniospinal, or craniospinal plus 12 Gy abdominal RT including the ovaries. Thirty-six percent (35 patients) were found to have above normal levels of FSH and/or LH. The percentages of elevated values for RT fields were 93% for craniospinal plus abdominal RT, 49% for craniospinal RT, and 9% for cranial RT (P less than .001). A dose-response relationship was observed between 18 Gy and 24 Gy in females receiving only craniospinal RT (P = .01). Craniospinal plus abdominal RT and abnormal FSH/LH levels were significantly associated with lack of pubertal development and delayed onset of menses. Duration of maintenance chemotherapy was not associated with abnormal gonadotropin levels or the development of secondary sexual characteristics. Additional follow-up of this cohort is needed to establish the ultimate pubertal development and fertility of these patients.

The effect of a purified water-soluble fraction of a Fusarium roseum 'Graminearum' culture on reproduction of white Leghorn females.

White Leghorn females (36 weeks old) in egg production were individually fed a purified water-soluble fraction residue remaining from the water extract and a crude culture of Fusarium roseum 'Graminearium'. Each fraction was fed at 3% of the diet for 6 weeks followed by 2 weeks with a control diet. Hens were inseminated weekly with .05 ml of pooled semen from males given control diets. The purified water-soluble fraction increased feed consumption during the test periods. During the posttest period, hens fed test diets consumed less feed than those fed a control diet. All test diets did not affect body weight change during the test periods. There was a significant increase in body weight of hens on the diet containing 3% crude culture and a marked decrease in body weight of hens fed the purified water-soluble fraction during the posttest period. Egg production and egg weight were not affected by treatments during the test and posttest periods. Fertility was reduced by the crude culture of F. roseum 'Graminearum' during the 6-week test. Hatchability of fertile eggs was significantly reduced by the purified water-soluble fraction and the crude culture of F. roseum 'Graminearum'. Hatchability rapidly increased when these toxic diets were replaced with control diets. The majority of embryo mortality occurred during 5 days of incubation. The major mycotoxins responsible for reduced hatchability of fertile eggs appeared to be water soluble components of F. roseum 'Graminearum' and not trichothecenes or zearalenone.