Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.     

Differential parental communication with adolescents who are disabled and their healthy siblings

Purpose: To examine the levels of parental communication and differential conversational styles with adolescents who are disabled and their healthy siblings, to better understand why the adolescent who is disabled has a higher risk of psychosocial problems during the transition into adulthood.

Methods: Families who had a disabled adolescent and at least one other adolescent who was not disabled were videorecorded during dinner at home. Twenty adolescents (12 girls and 8 boys) and their families participated. Analyses were conducted on the 392 interactions.

Results: Not only did the healthy adolescents participate in family interactions at higher frequencies than the adolescents who were disabled F(1, 383) = 14.00, p < .001, but the interactions were also more meaningful with healthy adolescents, F(2, 383) = 5.25, p < .01. Furthermore, healthy siblings had significantly greater conversational control than did their siblings with disabilities, χ² [1] = 14.36, p < .001. Parents responded more negatively when adolescents who were disabled initiated a topic in comparison with their response to the healthy siblings, F(2, 69) = 5.44, p < .01. Finally, adolescents with disabilities were ignored more often than their healthy siblings, z = −3.75, p < .001, and they did not monopolize the conversation as often as did their healthy siblings, z = −3.91, p < .001.

Conclusion: These results suggest that adolescents who are disabled may be at a disadvantage when engaged in family interactions in contrast with their healthy siblings.     

Effects of mixed-action kappa/mu opioids on cocaine self-administration and cocaine discrimination by rhesus monkeys.

kappa-Opioid agonists may functionally antagonize some behavioral effects of cocaine, but the role of mixed kappa/mu receptor activity is unclear. The effects of three mixed kappa/mu agonists (MCL-101, (-)cyclorphan, and Mr2034) and one kappa-selective agonist (enadoline) on cocaine self-administration and cocaine discrimination were compared in rhesus monkeys. Acute treatment with all kappa agonists dose dependently reduced cocaine-maintained responding and produced a downward shift in the cocaine self-administration dose-effect curve (0.001-0.32 mg/kg/inj, i.v.). During 7 days of chronic treatment, (-)cyclorphan (0.0032-0.032 mg/kg/h) and MCL-101 (0.0032-0.032 mg/kg/h) each dose dependently reduced cocaine self-administration maintained by a dose near the peak of the cocaine self-administration dose-effect curve. MCL-101 (0.032 mg/kg/h) produced selective and sustained decreases in cocaine self-administration, whereas (-)cyclorphan (0.032 mg/kg/h) had selective but transient effects. In addition, these mixed kappa/mu agonists produced fewer side effects (some salivation) than the kappa-selective agonist (sedation, salivation, emesis). However, none of these kappa agonists substituted for or antagonized cocaine's discriminative stimulus effects in monkeys trained to discriminate cocaine (0.4 mg/kg, i.m.) from saline. Thus, kappa and mixed kappa/mu-opioid agonists may reduce cocaine self-administration without altering cocaine's discriminative stimulus effects. Mixed kappa/mu agonists appear to offer some advantages over selective kappa agonists as potential treatments for cocaine abuse.     

Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study.

OBJECTIVE: The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. PATIENTS AND METHODS: Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m(2) per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. RESULTS: Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% +/- 7.6% and 64.8% +/- 8.1%, respectively. Radiologic review showed that 4% of patients were wrongly included. Review of radiotherapy technical files demonstrated a correlation between the presence of a major protocol deviation and treatment failure. The 5-year recurrence-free survival rate of patients included in this study with all optimal quality controls of histology, radiology, and radiotherapy was 71.8% +/- 10.5%. In terms of sequelae, 31% of patients required growth hormone replacement therapy and 25% required special schooling. CONCLUSION: Reduced-dose craniospinal radiation therapy can be proposed in standard-risk medulloblastoma provided staging and radiation therapy are performed under optimal conditions.     

Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis.

PURPOSE: To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis. PATIENTS AND METHODS: Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses. RESULTS: Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNFalpha, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011). CONCLUSION: Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication.     

The Role of Self-Beliefs in Predicting Postschool Outcomes for Deaf Young Adults

The aim of this study was to explore the role of self-beliefs in predicting postschool outcomes for deaf young adults in transition from secondary settings. Three self-level constructs were explored: self-concept, self-determination, and expectations about the future. This study utilized data from the National Longitudinal Transition Study-2 (NLTS2) that collected longitudinal data from youths with disabilities across the nation, 550 of which were deaf or hard of hearing and met the selection criteria in this study. This study examined the relationships between these deaf adolescents’ self-beliefs and actual future achievements that were reached as they transitioned to adult life, in three domains: life, employment, and education. Despite the generally positive self-beliefs of deaf individuals, which were, in some cases, related to postschool outcomes, the self-beliefs assessed in this study did not emerge as comprehensive predictors of postschool attainments. Findings suggest that for deaf individuals, successfully navigating transitions to adult life involves dimensions beyond individual agency. Positive self-beliefs are clearly a part of successfully attaining postschool outcomes, but deaf individuals may not have full access to equitable opportunities to capitalize on these beliefs.