Endoscopic evaluation of the esophageal cancer patient after chemoradiotherapy for persistent/recurrent cancer.

Endoscopy has an important role in the pre- and post-treatment staging of esophageal cancer. Complete pathologic response following neoadjuvant chemoradiation therapy occurs in approximately 25% of patients. However, the ability to accurately detect this preoperatively with currently available endoscopic modalities is limited such that the default pathway is for fit patients to proceed with surgical resection. This article discusses the available endoscopic modalities (primarily Esophagogastroduodenoscopy [EGD] with mucosal biopsies and endoscopic ultrasonography with or without fine needle aspiration) used for post-treatment staging of esophageal cancer. We present data regarding the benefits and limitations of endoscopic methods in assessing for residual disease. Unfortunately, endoscopic modalities are not accurate enough to identify complete pathological responsers who may avoid surgical resection.

Differential inhibition of collagenase and interleukin-1alpha gene expression in cultured corneal fibroblasts by TGF-beta, dexamethasone, and retinoic acid.

PURPOSE: Expression of the genes for collagenase and interleukin-1alpha (IL-1alpha) are induced as stromal cells become activated to the repair fibroblast phenotype after injury to the cornea. This investigation examines the mechanisms whereby expression of these genes is inhibited by transforming growth factor-beta (TGF-beta), dexamethasone (DEX), or retinoic acid (RET A). METHODS: A model of freshly isolated cultures of corneal stromal cells and early passage cultures of corneal fibroblasts was used in these studies. This model reproduces the events of stromal cell activation in the corneal wound. RESULTS: In early passage cultures of corneal fibroblasts, expression of collagenase is under obligatory control by autocrine IL-1alpha. IL-1alpha controls its own expression through an autocrine feedback loop that is dependent on transcription factor NF-kappaB. TGF-beta, DEX, and RET A were each effective inhibitors of collagenase gene expression in these cells. Furthermore, these agents have the capacity to inhibit expression of IL-1alpha and this was correlated with their ability to affect DNA-binding activity of NF-kappaB. However, TGF-beta, DEX, and RET A were also effective inhibitors of the low level of collagenase expressed by freshly isolated corneal stromal cells that cannot express IL-1alpha. CONCLUSIONS: In cells with an active IL-1alpha autocrine loop there are at least two distinct signaling pathways by which collagenase gene expression can be modulated. The results of this study demonstrate that TGF-beta, DEX, and RET A differentially inhibit collagenase and IL-1alpha gene expression. This information will be useful in the design of therapeutic modalities for fibrotic disease in the cornea and other parts of the eye.

Predictors of injury among 1638 riders in a recreational long-distance bicycle tour: Cycle Across Maryland.

To assess the incidence of and risk factors for injuries in a group of bicyclists with a well-defined exposure to bicycling, we conducted a prospective study of 1638 recreational bicyclists who rode in the 6-day 339-mile Cycle Across Maryland tour in 1994. The mean age of participants was 39 years (range, 7 to 79), and two-thirds were male. All riders wore helmets. During the tour there were 85 acute traumatic injuries (15.4 per 100,000 person-miles), 76 overuse injuries (13.7 per 100,000 person-miles), and 37 other medical problems (6.7 per 100,000 person-miles). Acute traumatic injuries were associated with a history of racing versus none (relative risk = 2.2, 95% confidence limits = 1.3, 3.7) and with inexperience, no previous Cycle Across Maryland tours versus one or more (relative risk = 1.7, 95% confidence limits = 1.04, 2.8), but not with sex, training, or prior injuries. Inexperience and lack of preride conditioning were risk factors for overuse injuries. The most common overuse injuries and medical problems were knee pain, hand or wrist numbness, foot blisters, insect stings and bites, and heat and dehydration. Study results provide exposure-based incidence rates of bicyclist injuries and suggest overuse injuries may be reduced by increased preride conditioning.