Citations

Abstract Purpose: Most colorectal cancers that have high levels of microsatellite instability (MSI-H) show loss of immunohistochemical expression of proteins that participate in the DNA mismatch repair process, most often involving MLH1 and MSH2. Less commonly, a third DNA mismatch repair protein, MSH6, may also be lost as the primary event. Rarely, tumors with MSI-H show normal expression of these three proteins. The genetic deficiency leading to the MSI-H phenotype in such cases is unknown. PMS2 is another member of the DNA mismatch repair complex. Its expression is generally lost in tumors with MLH1 loss of expression. Rarely, there is selective loss of PMS2 expression. We sought to describe the frequency and clinical correlates of selective loss of expression of PMS2 with the MSI-H tumor phenotype. Experimental Design: Two thousand seven hundred nineteen colorectal cancers from both clinic- and research-based ascertainment were studied. Tumor MSI testing and immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 were conducted. Medical records were abstracted for age at diagnosis, gender, colorectal cancer site, and family history. Results: Five hundred thirty-five of the 2,719 tumors were MSI-H. Of these, 93% showed loss of expression of MLH1, MSH2, and/or MSH6. Thirty-eight showed normal expression for these proteins. PMS2 immunohistochemical staining was successful in 32 of 38 of these tumors. Of the 32, 23 showed selective loss of expression of PMS2. This was associated with young age of diagnosis and right-sided location but not with a striking family history of cancer. Conclusions: Overall, 97% of the MSI-H tumors showed loss of expression for one or more of these four mismatch repair proteins. Selective loss of expression of PMS2 was present in 72% of cases in which colorectal cancers had an MSI-H phenotype but no alteration of expression of MLH1, MSH2, and MSH6. The underlying mechanism involved cannot be determined from this study but could involve point mutations in other DNA mismatch repair genes with retention of immunohistochemical expression, somatic inactivation of PMS2, or germ line mutation of PMS2.

The National Cancer Institute’s Cancer Patient Education Network (CPEN) is composed of cancer education leaders from National Cancer Institute (NCI)-designated comprehensive and clinical cancer centers throughout the United States. Despite this commonality, the role and responsibilities of CPEN members vary across institutions. In an effort to further understand the common-alties and variances among the membership, the authors undertook a research project addressing salary and budget issues across NCI-designated cancer centers. The purpose of this study was to benchmark salaries and budgets of cancer educators at NCI-designated cancer centers; provide information to support a competitive salary range based on benchmarking with peers responsible for cancer patient education; and glean information on CPEN membership, roles, education levels, and job functions. This article highlights lessons learned and offers suggestions for using this information in a broader capacity for other cancer patient educators and patient educators in general.

OBJECTIVE To review the characteristics and determine treatment outcomes of pediatric dermoid cysts. STUDY DESIGN AND SETTING Retrospective review of the presentation, diagnosis, treatment, and outcomes of all pediatric dermoid cysts of the head and neck examined between 1980 and 2002 at Mayo Clinic. RESULTS Forty‐nine patients (59% girls) had a dermoid cyst of the head and neck. The median age at diagnosis was 22 months. The most common presenting sign was a palpable mass, noted in 100% of patients. During evaluation, approximately 25 patients (51%) had imaging studies. The most common location of the cysts was periorbital (61%), followed by the neck (18%; including 1 submental cyst). Various surgical approaches were chosen. In 2 patients (4%), the dermoid cyst had an intracranial extension. Only 1 patient experienced recurrence. The median pathologic diameter of the cysts was 1.2 cm. CONCLUSIONS Dermoid cysts are unusual neoplasms that often present in childhood, with the orbit being the area most commonly affected in the head and neck region. Imaging studies help rule out an intracranial or intraorbital extension. With complete excision, recurrence is unusual. SIGNIFICANCE Our review will assist both primary care physicians and subspecialists in diagnosing and treating dermoid cysts.

OBJECTIVE: To review dexamethasone interaction with corticotropin stimulation testing, particularly as it applies to treating septic shock. DATA SOURCES: Pertinent literature was identified through MEDLINE (1966–February 2004) using combinations of the key words dexamethasone, adrenocorticotropic hormone stimulation, and pretreat. Only articles written in the English language and evaluating human subjects were considered. Reference lists of identified articles were reviewed for additional citations. DATA SYNTHESIS: Accurate interpretation of the corticotropin stimulation test is important to identify patients with septic shock who may benefit from corticosteroid supplementation. In healthy volunteers, short-term dexamethasone administration prior to the corticotropin stimulation test may depress the baseline cortisol level, but does not inhibit the response to the corticotropin challenge. This may result in a slight increase in the difference between baseline and post-stimulation values. CONCLUSIONS: In 2 small trials in healthy adults, short-term, low-dose dexamethasone pretreatment decreased baseline cortisol levels, but values following corticotropin stimulation were unaffected. Accordingly, caution in interpreting corticotropin stimulation test results is warranted. However, the application of the findings from these studies to patients with septic shock is difficult, given the important differences in physiology between normal and septic patients. As of December 29, 2004, a dexamethasone dose >2 mg or prolonged dexamethasone therapy (>2 days, totaling 4 mg) preceding corticotropin stimulation has not been studied in any population.

Objective. To determine whether children with pallid breath-holding spells associated with bradycardia can be treated safely and successfully with permanent pacemaker implantation. Methods. The records of pediatric patients who had apparent breath-holding spells and associated bradycardia and were treated with permanent pacemaker implantation were reviewed. Results. Ten pediatric patients with apparent breath-holding spells associated with bradycardia were treated with a permanent ventricular demand pacemaker at the Mayo Clinic between 1985 and 1995. Patients had onset of symptoms between ages 6 days and 12 months and presented for evaluation between ages 12 months and 5 years. Duration of spells was 15 seconds to 10 minutes. Medications to prevent spells were unsuccessful. Electrocardiograms documented asystolic pauses of 1.7 to 24 seconds (mean: 11.9 seconds). Permanent ventricular demand pacemakers were implanted at 10 months to 5 years of age (median: 14.5 months): 9 endocardial and 1 epicardial. Three patients required pacemaker revision. At follow-up of 38 to 170 months (median: 65.5), 5 patients had complete resolution of spells, 2 had only mild color change without loss of consciousness or seizure activity, and 3 continued to have minor brief spells. Conclusions. Permanent pacemaker therapy for children with pallid breath-holding spells associated with severe bradycardia is safe, efficacious, and warranted.