Recent Publications by CFE Educators

BACKGROUND

Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels.

OBJECTIVES

We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures.

METHODS

We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms "radiation" AND "heart" AND "disease," OR "radiation" AND "stroke," OR "radiation" AND "circulatory" AND "disease." Radiation exposures had to be whole-body, with a cumulative mean dose of 0.5 Sv, or at a low dose rate ( 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries.

RESULTS

Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia.

CONCLUSIONS

Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).

The U.S. population is undergoing a dramatic shift in demographics, with a rise in the proportion of elderly Americans. Given an increased prevalence of thyroid disease and malignancy with age, understanding the safety of thyroid surgery in this age group is increasingly pertinent. There remains disagreement regarding the clinical outcomes of elderly patients after thyroidectomy and the applicability of single-institution cohorts to the population at large. This paper reviews the epidemiology of thyroid disease in the elderly, current surgical indications and practice patterns, and the clinical and economic outcomes of elderly patients with thyroid disease after surgical intervention.

Hemophagocytic syndrome (HPS) arises secondary to genetic, rheumatologic, neoplastic, and infectious causes. We discuss a patient whose presentation was consistent with systemic infection but was discovered to have HPS of unknown etiology. The presenting symptoms, as well as unremarkable malignancy and rheumatologic workups, led to the pursuit of an infectious cause, but the patient was ultimately discovered to have an occult anaplastic large-cell lymphoma (ALCL). This case demonstrates the diagnostic challenges that result from infectious mimicry in the context of HPS-first, in distinguishing noninfectious HPS from the systemic inflammation that can result from a widespread infectious process, second, in the identification of the precipitating cause of HPS. While evidence of these challenges has been suggested by the limited literature on HPS and ALCL, our case illustrates the diagnostic dilemma that arises when tissue biopsy does not quickly reveal an etiology. It is important that all physicians be aware that HPS can mimic infection and be prepared to redirect the workup when an infectious etiology for HPS cannot be identified.

PURPOSE

Adults with complications from previous hypospadias surgery experience various problems, including urethral stricture, persistent hypospadias and urethrocutaneous fistula. Innate deficiencies of the corpus spongiosum and multiple failed operations makes further management challenging.

MATERIALS AND METHODS

We reviewed our prospective urethroplasty database of men who presented with complications of previous hypospadias surgery. Patients were included in study if they had greater than 6 months of followup. Our surgical management was defined as an initial success if there were no urethral complications. The overall success rate included men with the same result after additional treatment.

RESULTS

A total of 50 men had followup greater than 6 months (median 89) and were included in study. These 50 patients presented with urethral stricture (36), urethrocutaneous fistula (12), persistent hypospadias (7), hair in the urethra (6) and severe penile chordee (7). Patients underwent a total of 74 urethroplasties, including stage 1 urethroplasty in 19, a penile skin flap in 11, stage 2 urethroplasty in 11, urethrocutaneous fistula closure in 9, permanent perineal urethrostomy in 6, excision and primary anastomosis in 6, a 1-stage buccal mucosa onlay in 4, tubularized plate urethroplasty in 3, combined techniques in 3 and chordee correction in 1. In 25 men (50%) treatment was initially successfully. Of the 25 men in whom surgery failed 18 underwent additional procedures, including 13 who were ultimately treated successfully for an overall 76% success rate (38 of 50).

CONCLUSIONS

Managing problems from previous hypospadias surgery is difficult with a high initial failure rate. Additional procedures are commonly needed.

Medullary thyroid cancer (MTC) represents an aggressive form of thyroid malignancy. Some may occur spontaneously or can be associated with Multiple Endocrine Neoplasia syndromes, or Familial Medullary Thyroid Cancer syndrome. In these patients, the protooncogene RET (rearranged during transfection) is mutated. In patients who have unresectable or metastatic disease, the long term prognosis is poor. New treatments for this disease have focused on the use of targeted agents that inhibit the receptor tyrosine kinase of RET. One of these treatments, Vandetanib (Caprelsa, Astra Zeneca), recently has received approval from the Food and Drug Administration for the treatment of patients with progressive locally advanced and/or metastatic disease. This review highlights the studies that led to the drug's approval, and discusses on the potential financial costs of treatment and side effects of this therapy. The main clinical studies evaluating Vandetanib for the treatment of other solid tumors will also be reviewed.

Lipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as therapeutics for MS.

BACKGROUND

Patients receiving lithium therapy are at elevated risk of developing hyperparathyroidism. In lithium-associated hyperparathyroidism (LAH), the incidence of multiglandular disease (MGD) is unclear, and the need for routine bilateral cervical exploration remains controversial. Therefore, in LAH patients, surgical approaches, pathologic findings, cure rates, and factors associated with persistent or recurrent disease were investigated.

METHODS

Retrospective analysis of 27 patients with LAH undergoing parathyroidectomy with the intraoperative parathyroid hormone (PTH) assay.

RESULTS

The median postoperative follow-up was 7 months; 17 patients had >6 months follow-up. Cervical exploration was unilateral in 9, bilateral in 18 (3 were converted from unilateral). Sixteen patients (62%) had MGD, 12 with four-gland hyperplasia and 4 with double adenomas. Ten patients (38%) had a single adenoma. Twenty-five (93%) of 27 patients had initially successful surgery. Of the 17 patients with >6 months follow-up, two had persistent disease and two experienced recurrent disease. All patients with a single adenoma remain free of disease. Three (75%) of four patients with persistent/recurrent disease had MGD and were receiving lithium at the time of surgery. Patients with persistent/recurrent disease were older (p = 0.01) and had experienced a longer duration of hypercalcemia (p = 0.04).

CONCLUSIONS

LAH patients have a high incidence of MGD, and bilateral exploration is frequently necessary. With access to the intraoperative PTH assay, it is reasonable to initiate a unilateral approach because many patients will harbor single adenomas and can be reliably rendered normocalcemic. Patients with MGD remain at higher risk of persistent/recurrent disease.