Inverted urothelial carcinoma: a series of 12 cases with a wide morphologic spectrum overlapping with the large nested variant.

The current series presents 12 cases of invasive urothelial carcinoma (UC) with inverted growth pattern that fulfill the architectural criteria of the recently described "large nested" variant of UC, but which display a wider spectrum of morphologic and cytologic changes. All cases had an associated component of usual invasive UC, and 10 had an associated surface papillary component. Although many areas within the tumors were indistinguishable from a noninvasive endophytic growth pattern, at least some had an irregular ragged contour, and all showed haphazard arrangement with variable amount of intervening stroma at least focally. Inflammatory stromal reaction was noted in 11 cases, and desmoplasia and retraction artifact were present in 8 cases each. Although major areas showed mild atypia, many tumors showed marked hyperchromasia, prominent nucleoli, marked irregular nuclear membranes, and brisk mitotic activity. Final pathological stage on cystectomy specimens was T2 in 4 cases, T3 in 2 cases, and T4 in 3 cases. In 3 cases, lymph node metastases were documented histologically. Review of the literature shows that the "large nested," "inverted," "endophytic," and "inverted papilloma-like" variants of invasive UC are interrelated entities and should probably be considered as one variant with a wide spectrum of cytoarchitectural features. They should also be separated from the "nested" variant with which they rarely coexist and which shows different characteristics at the morphologic level.

Subcellular distribution of a fluorescence-labeled combi-molecule designed to block epidermal growth factor receptor tyrosine kinase and damage DNA with a green fluorescent species.

To monitor the subcellular distribution of mixed epidermal growth factor (EGF) receptor (EGFR)-DNA targeting drugs termed combi-molecules, we designed AL237, a fluorescent prototype, to degrade into a green fluorescent DNA damaging species and FD105, a blue fluorescent EGFR inhibitor. Here we showed that AL237 damaged DNA in the 12.5 to 50 mumol/L range. Despite its size, it blocked EGFR phosphorylation in an enzyme assay (IC(50) = 0.27 mumol/L) and in MDA-MB468 breast cancer cells in the same concentration range as for DNA damage. This translated into inhibition of extracellular signal-regulated kinase 1/2 or BAD phosphorylation and downregulation of DNA repair proteins (XRCC1, ERCC1). Having shown that AL237 was a balanced EGFR-DNA targeting molecule, it was used as an imaging probe to show that (a) green and blue colors were primarily colocalized in the perinuclear and partially in the nucleus in EGFR- or ErbB2-expressing cells, (b) the blue fluorescence associated with FD105, but not the green, was colocalized with anti-EGFR red-labeled antibody, (c) the green fluorescence of nuclei was significantly more intense in NIH 3T3 cells expressing EGFR or ErbB2 than in their wild-type counterparts (P < 0.05). Similarly, the growth inhibitory potency of AL237 was selectively stronger in the transfectants. In summary, the results suggest that AL237 diffuses into the cells and localizes abundantly in the perinuclear region and partially in the nucleus where it degrades into EGFR and DNA targeting species. This bystander-like effect translates into high levels of DNA damage in the nucleus. Sufficient quinazoline levels are released in the cells to block EGF-induced activation of downstream signaling. Mol Cancer Ther; 9(4); 869-82. (c)2010 AACR.

Validation and properties of the verbal numeric scale in children with acute pain.

Although the verbal numeric scale (VNS) is used frequently at patients' bedsides, it has never been formally validated in children with acute pain. In order to validate this scale, a prospective cohort study was performed in children between 8 and 17years presenting to a pediatric emergency department (ED) with acute pain. Pain was graded using the VNS, the visual analogue scale (VAS), and the verbal rating scale (VRS). A second assessment was done before discharge. We determined a priori that in order to be valid, the VNS would need to: correlate with the VAS (concurrent validity); decrease after intervention to reduce pain (construct validity); and be associated with the VRS categories (content validity). The VNS interchangeability with the VAS, its minimal clinically significant difference, and test-retest reliability were also determined. A total of 202 patients (mean age: 12.2+/-2.6years) were enrolled. The VNS correlated with the VAS: r(ic)=0.93, p<0.001. There were differences in the VNS before versus after interventions (p<0.001), and between VRS categories (mild versus moderate, p<0.001; moderate versus severe, p<0.001). The 95% limits of agreement (interchangeability) between VNS/VAS were outside the a priori set limit of +/-2.0: -1.8, 2.5. The VNS minimal clinically significant difference was 1. The VNS had good test-retest reliability with 95% limits of agreement of -0.9 and 1.2. In conclusion, the VNS provides a valid and reliable scale to evaluate acute pain in children aged 8-17years but is not interchangeable with the VAS.

Practice variation after implementation of a protocol for migraines in children.

The objective of this study was to evaluate the changes that occurred in the treatment of migraine over a 10-year period in a pediatric emergency department (ED) after the implementation of a protocol. The method employed was a comparative retrospective chart review of children diagnosed with migraine in an ED. The two study periods were 1996-1997, and 2006-2007. A protocol suggesting a specific approach was implemented in the ED in 1999. The primary outcome was the medications used in the ED. There were 182 visits for migraine in 2006-2007 compared with 144 visits in 1996-1997. More patients were treated in the ED in 2006-2007 compared with 1996-1997: 50 versus 30%, a difference of 20% (95% confidence interval: 9, 30). The treatments used were also different. In conclusion, a variation in the treatment of migraine was observed over a 10-year period in a pediatric ED after the implementation of a treatment protocol.

Clinical outcomes of children treated with intravenous prochlorperazine for migraine in a pediatric emergency department.

BACKGROUND: Prochlorperazine is the only treatment that has been studied so far in a randomized controlled trial and found to reduce pain at 1 h in children with migraine who presented to an emergency department (ED). OBJECTIVE: To evaluate the rate of treatment failure associated with prochlorperazine used in children with severe migraine in a pediatric ED. METHODS: This study was a retrospective chart review of patients < 18 years of age who visited the ED of a tertiary care pediatric hospital between November 2005 and June 2007. All patients diagnosed with migraine by the emergency physicians were included in the study. Charts were evaluated by a data abstractor blinded to the study hypothesis using a standardized datasheet. Inter-rater agreement was measured. Prochlorperazine treatment failure was defined as either administration of further rescue therapy, a hospitalization, or a return visit to the ED within 48 h for symptom recurrence or side effects from the medication. RESULTS: Prochlorperazine was administered in 92 episodes of migraine, including 43 confirmed by a pediatric neurologist; all received diphenhydramine to prevent akathisia. A total of 13 (14%) of these patients had a treatment failure: 8 patients received one or more further rescue therapies after the administration of prochlorperazine; 5 patients were hospitalized, including 3 who had received further rescue therapy; and 3 patients returned to the ED within 48 h due to symptom recurrence. CONCLUSION: There was a treatment failure rate of 14% with the use of prochlorperazine in association with diphenhydramine for severe migraine in children seen in a pediatric ED.