Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: a report from the childhood cancer survivor study.

BACKGROUND: Childhood cancer survivors have a sixfold increased risk of developing subsequent neoplasms when compared to the general population. We sought to describe the occurrence of melanoma as a subsequent neoplasm among adult survivors of childhood cancer. PATIENTS AND METHODS: Among 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, we calculated the cumulative incidence, standardized incidence ratio (SIR), and absolute excess risk (AER) of subsequent melanoma. Potential risk factors were assessed using a cause-specific hazards model. RESULTS: Fifty-seven melanomas (46 invasive, 2 ocular, and 9 in situ) occurred in 51 survivors. The median time to the development of melanoma was 21.0 years (range: 5.6-35.4 years) and the median age at melanoma was 32.3 years (range: 10.9-49.0 years). Initial cancer diagnoses included soft tissue and bone sarcoma (n = 15), leukemia (13), lymphoma (14), central nervous system malignancy (5), Wilms tumor (3), and neuroblastoma (1). The cumulative incidence of first subsequent melanoma at 35 years from initial cancer diagnosis was 0.55% [95% confidence interval (CI): 0.37-0.73]. The SIR of subsequent invasive malignant melanoma of the skin was 2.42 (95% CI: 1.77-3.23), and the AER was 0.10 (95% CI: 0.05-0.15) per 1,000 person-years. No statistically significant associations were found between melanoma risk and family history of cancer, demographic, or treatment-related factors. CONCLUSION: Survivors of childhood cancer have an approximate 2.5-fold increased risk of melanoma. Early screening and prevention strategies are warranted.

The chance of transition: strategies for multidisciplinary collaboration.

Many long-term childhood cancer survivors suffer from treatment-related late effects, which may occur in any organ and include a wide spectrum of conditions. Long-term follow-up (LTFU) is recommended to facilitate early diagnosis and to ensure better health outcomes. Due to the heterogeneity of these sequelae, different specialists work together in the diagnosis and treatment of these conditions. Experts from both pediatric and internal medicine are involved in age-appropriate care by providing a transition process. Hence, LTFU of childhood cancer survivors is a prototypic example of multidisciplinary care for patients with complex needs treated in a specialized setting. International collaborations of healthcare professionals and scientists involved in LTFU of childhood cancer survivors, such as the International Guideline Harmonization Group, compile surveillance recommendations that can be clinically adopted all over the world. These global networks of clinicians and researchers make a joint effort to address gaps in knowledge, increase visibility and awareness of cancer survivorship and provide an excellent example of how progress in clinical care and scientific research may be achieved by international and multidisciplinary collaboration.

Defining optic nerve tortuosity.

BACKGROUND AND PURPOSE: Optic nerve tortuosity is one of several nonmalignant abnormalities documented on MR imaging in patients with neurofibromatosis type 1 and may be related to the development of optic pathway gliomas. This study seeks an operational definition for optic nerve tortuosity. MATERIALS AND METHODS: A focus group of 3 pediatric neuroradiologists reviewed 20 MR images of the brain and orbits of patients suspected to have optic nerve tortuosity in the absence of optic pathway glioma and found 6 radiographic factors that occurred frequently. Subsequently, 28 MR images were assessed for the presence of optic nerve tortuosity, using a global assessment question that reflects a neuroradiologist's confidence in the presence of optic nerve tortuosity, and for the presence of the 6 radiographic factors, to identify a combination of these factors that best predicted a diagnosis of optic nerve tortuosity. RESULTS: We found perfect inter-rater agreement between 3 readers on the presence/absence of tortuosity in 75% of cases. Lack of congruity of the optic nerves, in more than 1 coronal section and dilation of the subarachnoid space surrounding the optic nerves, when found together are sensitive (89%) and specific (93%) for a diagnosis of tortuosity on the global scale. The absence of these 2 factors, along with absence of deviation of the optic nerve within the axial plane, provides a reliable test to exclude tortuosity. CONCLUSION: Lack of congruity of the optic nerves in more than 1 coronal section and dilation of the subarachnoid space surrounding the optic nerves together provide an operational radiographic definition of optic nerve tortuosity.

Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study.

PURPOSE: The purpose of this study was to assess the prevalence of male infertility and treatment-related risk factors in childhood cancer survivors. METHODS: Within the Childhood Cancer Survivor Study, 1,622 survivors and 274 siblings completed the Male Health Questionnaire. The analysis was restricted to survivors (938/1,622; 57.8 %) and siblings (174/274; 63.5 %) who tried to become pregnant. Relative risks (RR) and 95 % confidence intervals (CI) for the prevalence of self-reported infertility were calculated using generalized linear models for demographic variables and treatment-related factors to account for correlation among survivors and siblings of the same family. All statistical tests were two-sided. RESULTS: Among those who provided self-report data, the prevalence of infertility was 46.0 % in survivors versus 17.5 % in siblings (RR = 2.64, 95 % CI 1.88-3.70, p < 0.001). Of survivors who met the definition for infertility, 37 % had reported at least one pregnancy with a female partner that resulted in a live birth. In a multivariable analysis, risk factors for infertility included an alkylating agent dose (AAD) score ≥3 (RR = 2.13, 95 % CI 1.69-2.68 for AAD ≥3 versus AAD <3), surgical excision of any organ of the genital tract (RR = 1.63, 95 % CI 1.20-2.21), testicular radiation ≥4 Gy (RR = 1.99, 95 % CI 1.52-2.61), and exposure to bleomycin (RR = 1.55, 95 % CI 1.20-2.01). CONCLUSION: Many survivors who experience infertility father their own children, suggesting episodes of both fertility and infertility. This and the novel association of infertility with bleomycin warrant further investigation. IMPLICATIONS FOR CANCER SURVIVORS: Though infertility is common, male survivors reporting infertility often father their own children. Bleomycin may pose some fertility risk.

Imaging changes in very young children with brain tumors treated with proton therapy and chemotherapy.

SUMMARY: PT promises to reduce side effects in children with brain tumors by sparing normal tissue compared with 3D conformal or intensity-modulated radiation therapy. Information is lacking about the combined effects of PT and chemotherapy in young children. We describe imaging changes in 8 very young children with localized brain tumors who received PT after chemotherapy. Mostly transient signal abnormalities and enhancement in brain parenchyma were observed by serial MR imaging, which were consistent with radiation-induced effects on normal-appearing tissue. Correlation with PT planning data revealed that the areas of imaging abnormality were located within or adjacent to the volume that received the highest radiation dose. Radiologists should be aware of these findings in children who receive PT after chemotherapy. In this report, we describe the time course of these PT-related imaging findings and correlate them with treatment and clinical outcomes.

Utilization of donated lungs in Australia: 1989-1997.

Lung and heart-lung transplantation was first undertaken in Australia in the late 1980s and early 1990s. Although detailed data are available on Australian lung transplantation outcomes, little data are available regarding the utilization of donated lungs. This study examines donated lung utilization rates and considers various factors that may affect these rates. Australian donation and transplantation data were analyzed for the years 1989 through 1997. Results showed that 24% of overall donors were lung donors. The percentage of donors from whom at least 1 lung was transplanted increased from 6% in 1989 to 36% in 1997. Heart-lung transplantation rates changed little (2%-9%), whereas bilateral lung transplantation increased from 1% to 23% of donors. Single-lung donors accounted for 32% of lung donors in 1997. Uniform basic donor criteria and management guidelines, simple allocation mechanisms, and cooperative retrieval have evolved during this time. Close collaboration at the time of donation between units, coordinators, and ICUs has allowed early retrieval from well-managed donors.

Assessment of organ acquisition costs for an Australian public health system.

Available data on the cost of organ acquisition in Australia's socialized public health systems are minimal. The purpose of this study was to determine the cost for organ acquisition by a state transplant service, and to provide (1) an assessment of acquisition costs within one Australian public health system, (2) a baseline for future cost assessments, and (3) an indication of cost-effectiveness in international terms. Between July and December 1993, 51 kidneys, 21 livers, and 15 hearts were provided for transplantation in the system. Data collected during this period were used to calculate the acquisition cost for each transplanted organ. Direct and indirect costs were included in the calculations. The distribution of costs incurred for organ acquisition were direct, 67%; indirect, 14%; and organ-specific, 19%. Of the total direct costs, aircraft charter accounted for 75%, or 50% of the total acquisition costs. The provision of an organ by a donor coordination service accounted for 20% of the total costs, or a mean of A$783 (US$563) per organ. This study provides a baseline for organ acquisition cost in the Australian healthcare system. The geographic and demographic nature of Australia imposes the largest single cost factor (i.e., air charter), which highlights the need for alternative retrieval and transport systems of organs wherever possible. The acquisition costs reported in this study indicate that the system is cost-effective in international terms.

Age: an indicator of willingness to donate?

Answers to the question about consent for organ donation on the Queensland Transport Driver's Licence Database were reviewed to determine if age is an indicator of willingness to donate. As of November 1994, the database contained records on 1,969,382 persons (54% male, 46% female), accounting for 86.7% of the population 17 years of age or older. Fifty-four percent had answered yes to the question; 46% had indicated no or had not answered. The data were divided into three groups, males only, females only, and males plus females, and then subgrouped by age. The number of subjects who had not answered the question was included in the number who had answered no. In the males-plus-females group, the percentage of yes answers by age remained relatively constant (56%-62%) for persons 17 to 49 years old but decreased to 39% for persons 70 years old. The data for males only and females only showed a similar decrease. Slightly more females than males had answered yes among persons 17 to 49 years old (mean difference, 5%; range, 1%-8%). This difference decreased with age. A higher willingness to donate in the younger age groups may augur well for the future. The data indicate that more attention must be given to persons 50 years of age and older to increase their awareness of their ability to donate.

The Heats of Combustion of Polytetrafluoroethylene (Teflon) and Graphite in Elemental Fluorine.

Bomb calorimetric measurements are reported for the combustion in fluorine of polytetrafluoroethylene (Teflon) and graphite-polytetrafluoroethylene mixtures. Mass spectrometric examination of the product gases showed CF4 to be the only major product with C2F6(g) present in only very small amounts. The completeness of combustion of the graphite was determined by chemical analysis of combustion residues and found to range from 97 to better than 99 percent. From the combustion data, the heats of formation Δ H f 298 ° [ CF 4 ( g ) ] and Δ H f 298 ° [ C 2 F 4 ( solid polymer ) ] were determined to be -222.87 ±0.38 kcal mol-1 and -197.82 ±0.39 kcal (gfw C2F4)-1, respectively. The uncertainties are estimates of the overall experimental errors. A previously reported value for the heat of formation of AlF3(c) is adjusted to be consistent with the present work. An evaluation of other data on CF4 is presented. The heat of formation of CF4(g) is combined with other work to derive the heats of formation of HF solutions at three specific concentrations.

The Heat of Formation of Boron Carbide.

The standard heat of combustion in fluorine of a boron carbide sample having the composition B4.222C was determined from the heats of combustion of polytetrarluoroethylene and of boron carbide-polytetrafluoroethylene mixtures. The energy of the combustion reaction was measured in an isothermal-jacket bomb calorimeter. From the experimental data, we calculate -17.1 kcal mol-1 for the heat of formation of boron carbide. By combining all probable errors, we estimate our overall experimental uncertainty to be 2.7 kcal mol-1. The value for the heat of formation of boron carbide is for the phase represented by the formula B4.222C.

Studies in Bomb Calorimetry. A New Determination of the Energy of Combustion of Benzoic Acid in Terms of Electrical Units.

The heat of combustion of NBS Standard Sample 39i of benzoic acid under standard bomb conditions has been determined in terms of electrical units. A value of -26,434.0 J g-1 was obtained. The total uncertainty in our determination is estimated to be ±3.3 J g-1. The uncertainty due to random errors was 1.7 J g-1 and is based on the appropriate factors for the Student t distribution at the 95 percent confidence limits for eleven determinations of the energy equivalent of the calorimeter and six determinations of the heat of combustion of benzoic acid. The principal systematic error, neglect of surface temperature correction for our calorimeter, has been assigned a value of ±2.6 J g-1 until more reliable estimates of the correction can be made. Particular emphasis was placed on improving the precision of a calorimetric measurement over those previously obtained in this laboratory by the use of more sensitive auxiliary measuring equipment and more accurate procedures to evaluate the corrected temperature rise.

The Heat of Combustion of Beryllium in Fluorine.

An experimental determination of the energies of combustion in fluorine of polytetrafluoroethylene film and powder and of mixtures of beryllium with polytetrafluoroethylene gives for reaction (1) Δ H 25 C ° = - 1022.22 kJ mol-1 (-244.32 kcal mol-1) with an overall precision of 0.96 kJ mol-1 (0.23 kcal mol-1) at the 95 percent confidence limits. The total uncertainty is estimated not to exceed ±3.2 kJ mol-1 (±0.8 kcal mol-1). The measurements on polytetrarluoroethylene give for reaction (2a) and reaction (2b) Δ H 25 ° C ° = - 10369.7 and -10392.4 Jg-1, respectively. Overall precisions expressed at the 95 percent confidence limits are 3.3 and 6.0 Jg-1, respectively. (1) Be ( c ) + F 2 ( g ) = BeF 2 (  amorphous  ) (2a) C 2 F 4 ( polymer powder ) + 2 F 2 ( g ) = 2 CF 4 ( g ) (2b) C 2 F 4 ( polymer film ) + 2 F 2 ( g ) = 2 CF 4 ( g ) Be2C and Be metal were observed in a small carbonaceous residue from the combustion of the beryllium-polytetrafluoroethylene mixtures. Methods of analysis for these substances were developed. Gases resulting from the solution of the solid residues in aqueous KOH were analyzed for H2 and CH4 by differential absorption in molecular sieves at low temperatures.

Fluorine Flame Calorimetry III. The Heat of Formation of Chlorine Trifluoride at 298.15 K.

The standard heat of formation of chlorine trifluoride (gas) at 298.15 K has been determined to be - 164.65 kj mol-1 (-39.35 kcal mol-1) with an overall experimental uncertainty of 5.14 kj mol-1 (1.23 kcal mol-1). This value is derived from the enthalpies of the following reactions which were measured directly in a flame calorimeter operated at 1 atm pressure and 303.5 K, together with data from previous investigations. ClF 3 ( g ) + 2 H 2 ( g ) + 100 H 2 O ( 1 ) → [ HC 1 ⋅ 3 HF ⋅ 100 H 2 O ] ( 1 ) ( 1 / 2 ) Cl 2 ( g ) + 1 / 2 H 2 ( g ) + [ 3 HF ⋅ 100 H 2 O ] ( 1 ) → [ HC 1 ⋅ 3 HF ⋅ 100 H 2 O ] ( 1 ) The enthalpy of formation of [HC1‧100H2O](l) was also measured. The average Cl - F bond energy in chlorine trifluoride is calculated to be 160.1 kj mol-1 (38.26 kcal mol-1).

A modification of the primary nasal correction in the rotation-advancement unilateral cleft lip repair.

Primary correction of the unilateral cleft lip nasal deformity remains a challenge to the cleft surgeon. We wish to present a method of primary nasal correction utilizing presurgical orthopedics with the Latham dentomaxillary advancement appliance, concomitant rotation-advancement cleft lip repair, gingivoperiosteoplasty, and immediate correction of the nasal cartilage distortion with an "open technique" utilizing the rotation-advancement incisions. Direct elevation and suture fixation of the cleft side alar cartilage is performed as well as recreation of the normal upper lateral/lower lateral cartilage relationship, repair of nasal web, and release of the vestibular lining utilizing an L-flap pedicled to the alar base. Details of the operative technique, observations of unilateral cleft nasal anatomy as visualized with the "open technique," and preliminary results are illustrated in patients followed as long as 5 years.