Radiation-Induced Malignant Gliomas: Is There a Role for Reirradiation?

PURPOSE: To review the literature regarding the role of radiotherapy (RT) in the treatment of patients with radiation-induced malignant gliomas (RIMGs). METHODS AND MATERIALS: A PubMed search of English-language articles dealing with RIMG was performed, yielding 52 articles with 92 patients available for review. RESULTS: Initial tumor types treated with RT included brain tumor in 37 patients (40%), acute lymphoblastic leukemia in 33 (36%), benign disease in 11 (12%), and other in 11 (12%). Median time from RT to development of an RIMG was 8.75 years (range, 2.5-61 years). The RIMG occurred within 10 years after RT in 81% of patients with acute lymphoblastic leukemia/lymphoma, 59% of patients with brain/other, and 18% of patients with benign conditions (p = 0.002). Type of RIMG was glioblastoma in 69 (75%) and anaplastic astrocytoma in 23 (25%). One-, 2-, and 5-year overall survival rates were 29.3%, 7.3%, and 0% for patients with glioblastoma and 59.7%, 30.3%, and 20.2% for patients with anaplastic astrocytoma. For the 85 patients with data regarding treatment for RIMG, 35 underwent reirradiation to a median dose of 50 Gy (range, 30-76 Gy). For patients undergoing reirradiation, 1-, 2- and 5-year overall survival rates were 58.9%, 20.5%, and 6.8%. For those not undergoing reirradiation, they were 15.1%, 3%, and 0% (p = 0.0009). CONCLUSIONS: The RIMG appeared earlier in patients treated for leukemia and lymphoma and latest for those treated for a benign condition. Patients who underwent reirradiation for RIMG have longer survival times compared with those not receiving RT.     

Hypoxia-induced human endonuclease G expression suppresses tumor growth in a xenograft model

We have developed a hypoxia-inducible gene therapy approach for the expression of the mature form of human endonuclease G to facilitate cell death in hypoxic regions of the tumor. The chimeric therapeutic gene is placed under the control of a hypoxia response element based promoter and contains a translocation motif linked in frame to an oxygen-dependent degradation domain and the endonuclease G gene. Transient expression of the chimeric therapeutic gene in breast and prostate cancer cell lines resulted in efficient cell death under hypoxia-mimetic conditions. Stable MDA-MB-435 cells expressing the chimeric therapeutic gene under 1% O2 showed an increase in stable HIF-1alpha protein levels and synthesis of the endonuclease G protein in a time-dependent manner. In normoxic conditions, these stable transgenic cells exhibited no change in growth rate, invasion and motility when compared to parental cells. Moreover, xenografts generated using the transgenic cells exhibited highly significant suppression of tumor growth in a preclinical cancer model compared to the parental cell line. Thus, the hypoxia-modulated endonuclease G expression has the potential to be used as a gene-based-therapy system to kill malignant cells within hypoxic regions of tumors.     

The detection and significance of melanoma micrometastases in sentinel nodes

Sentinel node (SN) biopsy in melanoma patients is an accurate and minimally invasive method of staging and determining prognosis in patients with early-stage disease, and of identifying those patients who may benefit from complete regional lymph node dissection. Careful identification, removal and pathological assessment of SNs is critical to the accuracy of the technique and deficiencies in any of these steps may result in a false-negative biopsy. Pathologists should examine multiple sections from each SN, stained routinely with haematoxylin-eosin and immunohistochemically for melanoma-associated antigens. However, the most appropriate staining and sectioning protocol is not clear from the available evidence. While it appears that more extensive sectioning protocols detect more melanoma, failure rates and false-negative rates of the procedure do not appear to be significantly worse than with less extensive sampling protocols. Micromorphometrical parameters of melanoma deposits in SNs (such as their size, maximal tumour penetrative depth, microanatomical location and percentage nodal cross-sectional area) have been shown to be predictive of regional non-SN involvement and of clinical outcome. Classifying and measuring these parameters can be difficult, depending on the nature and distribution of the tumour deposits in the SN. Because the positive SNs have been removed in all patients included in studies assessing the clinical significance of tiny SN melanoma micrometastases, the likely therapeutic effect of the SN biopsy itself and/or any complete lymph node dissection, as well as lead time bias, are important confounding factors that must be considered when interpreting these studies. Limited data from some retrospective studies with relatively short follow-up suggest that some melanoma metastases may not be clinically relevant, but other studies imply a likely clinical significance of even very small SN metastases. Until there is unequivocal evidence from prospective randomised clinical trials with long term follow-up for the prognostic significance (or lack thereof) of very small SN tumour deposits, it is probably prudent to treat patients with such deposits as SN-positive.     

An incidental persistent falcine sinus with dominant straight sinus and hypoplastic distal superior sagittal sinus

An incidental persistent falcine sinus was detected in an otherwise normal brain on MRI in a 12-year-old girl who underwent imaging after clinical suspicion of acute disseminated encephalomyelitis. The falcine sinus was associated with a hypoplastic posterior third of the superior sagittal sinus and a dominant straight sinus. Generally, atresia or hypoplasia of the straight sinus is associated with a persistent falcine sinus in postnatal life; otherwise, the falcine sinus disappears before birth. We discuss the embryological basis for such an association in this case.     

Serious injuries from dishwasher powder ingestions in small children

AIMS: To describe patterns and severity of caustic injuries sustained from dishwasher powder ingestion and highlight need for national safety standards. METHODS: Retrospective chart review of admissions for caustic ingestion to Starship Children's Hospital from January 2003 to January 2005 and review of New Zealand National Poisons Centre data. RESULTS: Between January 2003 and January 2005, the National Poisons Centre recorded 610 dishwashing powder ingestions, with 88% of children less than 2 years old. Twenty-three children were admitted to Starship Children's Hospital following caustic ingestion, of whom 11 were identified as having ingested dishwasher powder (9 boys and 2 girls) and were aged 11 to 30 months (mean 17.5). Five children (45%) were admitted to the Paediatric Intensive Care Unit over 4 months (October 2004 to January 2005), requiring intubation for airway control. Two children needed tracheostomy. Three of the 11 children (27%) required repeated oesophageal dilatation, and two underwent gastrostomy formation. One brand of dishwasher detergent and container type was implicated in over half of the cases. CONCLUSIONS: Dishwasher detergents are highly corrosive substances that cause potentially life-threatening injuries and ongoing morbidity. The recent surge of incidents may be related to change in product constituents or non-compliance with New Zealand safety standards. Efforts to limit product alkalinity, legislative requirement of Child-Resistant Packaging and public education may reduce injuries from these common household substances.     

Role of impacted cerumen in hearing loss

We performed a study to determine if cerumen in the ear canal causes significant hearing loss and to ascertain if there is any correlation between the amount of cerumen and the degree of hearing loss. Our study was conducted on 109 ears in 80 patients. The results indicated that impacted cerumen does cause a significant degree of conductive hearing loss. We found no significant correlation between the length of the cerumen plug and the severity of hearing loss. Nor did we find any significant correlation between the presence of impacted cerumen and variables such as age, sex, ethnicity, or affected side.     

The distribution of D2/D3 receptor binding in the adolescent rhesus monkey using small animal PET imaging

PET imaging of the neuroreceptor systems in the brain has earned a prominent role in studying normal development, neuropsychiatric illness and developing targeted drugs. The dopaminergic system is of particular interest due to its role in the development of cognitive function and mood as well as its suspected involvement in neuropsychiatric illness. Nonhuman primate animal models provide a valuable resource for relating neurochemical changes to behavior. To facilitate comparison within and between primate models, we report in vivo D2/D3 binding in a large cohort of adolescent rhesus monkeys. Methods: In this work, the in vivo D2/D3 dopamine receptor availability was measured in a cohort of 33 rhesus monkeys in the adolescent stage of development (3.2–5.3 years). Both striatal and extrastriatal D2/D3 binding were measured using [F-18]fallypride with a high resolution small animal PET scanner. The distribution volume ratio (DVR) was measured for all subjects and group comparisons of D2/D3 binding among the cohort were made based on age and sex. Because two sequential studies were acquired from a single [F-18]fallypride batch, the effect of competing (unlabeled) ligand mass was also investigated. Results: Among this cohort, the rank order of regional D2/D3 receptor binding did not vary from previous studies with adult rhesus monkeys, with: putamen > caudate > ventral striatum > amygdala  substantia nigra > medial dorsal thalamus > lateral temporal cortex  frontal cortex. The DVR coefficient of variation ranged from 14%–26%, with the greatest variance seen in the head of the caudate. There were significant sex differences in [F-18]fallypride kinetics in the pituitary gland, but this was not observed for regions within the blood-brain barrier. Furthermore, no regions in the brain showed significant sex or age related differences in DVR within this small age range. Based on a wide range of injected fallypride mass across the cohort, significant competition effects could only be detected in the substantia nigra, thalamus, and frontal cortex, and were not evident above intersubject variability in all other regions. Conclusion: These data represent the first report of large cohort in vivo D2/D3 dopamine whole brain binding in the adolescent brain and will serve as a valuable comparison for understanding dopamine changes during this critical time of development and provide a framework for creating a dopaminergic biochemical atlas for the rhesus monkey.     

Laryngeal metastasis from a rectal carcinoma

Metastases to the larynx from distant primaries are rare. We report a case of a laryngeal metastasis from a rectal carcinoma.