Reproductive health among cancer survivors is an important quality of life issue. Certain cancer therapies have known fertility risks. There is an existing cohort of adolescents and young adults (AYA) cancer survivors that, seen less frequently in clinical care settings than active patients, are likely not having discussions of fertility and other reproductive health issues. A survivor or healthcare provider can easily assume that the window of opportunity for fertility preservation has passed, however emerging research has shown this may not be the case. Recent data demonstrates a close relationship between fertility and other late effects to conclude that ongoing assessment during survivorship is warranted. Some fertility preservation procedures have also been shown to mitigate common late effects. This review explores the link between late effects from treatment and common comorbidities from infertility, which may exacerbate these late effects. This review also highlights the relevance of fertility discussions in the AYA survivorship population.
Neutrophil-mediated lung injury is a potential complication of trauma and sepsis. Concomitant with trauma and sepsis, there is an immediate and sustained systemic elevation of catecholamines including epinephrine. In the absence of trauma or sepsis, we examined whether epinephrine contributes to the accumulation of neutrophils in the lung. Eight- to 12-week-old male CF-1 mice were injected i.p. with 0.2 mL of normal saline or epinephrine (0.1-5.0 mg/kg). An unmanipulated control group was included to examine the stress of i.p. injection. Animals were sacrificed at predetermined time points, and lung and spleen were harvested. PMN accumulation was assessed by using a myeloperoxidase (MPO) assay, which is an indirect marker for neutrophil presence. Morphometric analysis of lung tissue was performed by a pathologist blinded to the groups. Increasing epinephrine doses resulted in a significantly increased accumulation of pulmonary neutrophils compared with normal saline. The stress of normal saline injection also resulted in a significantly greater pulmonary neutrophil accumulation than unmanipulated controls. The effects of epinephrine on pulmonary neutrophil accumulation were greatest at 2 h, but they were not significantly different from saline-injected controls by 12 h. These results correlated with histological analysis. There were no significant differences in spleen MPO activity between groups, suggesting an organ-specific mechanism of epinephrine-induced pulmonary neutrophil sequestration. In the absence of trauma, shock, or infection, epinephrine results in the accumulation of neutrophils in murine lungs. The finding that "injection stress" increased lung neutrophil sequestration suggests the possibility that this mechanism may be physiologically relevant. Thus, epinephrine release in trauma may set the stage for development of neutrophil-mediated acute lung injury.
We report two cases of unusual extraneural metastasis in patients with embryonal tumors without central nervous system disease progression and prolonged survival. The first patient presented at 16 years of age with atypical teratoid rhabdoid tumor of the cervical spine. The tumor was confirmed to have loss of INI1, SMARCB1 deletion of exons 1–3, and heterozygous deletion of 22q11.2. The patient received treatment initially per ACNS0333 with high dose chemotherapy and tandem autologous transplants. The patient developed a biopsy-confirmed liver metastasis six months from diagnosis and, subsequently, had disease progression including liver metastases, bony lesions, muscle involvement, and lung nodules. Two and a half years from diagnosis the patient has still not had a relapse in the CNS. The second patient presented with medulloblastoma isolated to the posterior fossa at 11 years of age and was treated on SJMB03 protocol with craniospinal irradiation and high dose chemotherapy. He had his first recurrence in the temporal lobe three years post treatment. He had multiple recurrences in the brain over the next five years treated with re-resections, adjuvant chemotherapy, and gamma knife radiotherapy. He then developed cervical lymphadenopathy, bony lesions, liver lesions, and lung nodules. Cervical lymph node biopsy confirmed medulloblastoma. Next generation sequencing from recurrent tumor showed somatic mutations in p53, KDM6A, and PPP2R1A. Fourteen years from treatment, he has now developed a temporal lobe lesion. These cases are notable for prolonged survival despite widely metastatic disease and genomics predicting poor prognosis as well as metastatic disease disproportionate to CNS disease.
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