Publications

Cardiovascular risk factors impair endothelium-dependent vasodilation as well as other functions of the endothelium, thereby predisposing the patient to atherosclerosis and its overt clinical manifestations. Loss of endogenous estrogen also leads to reduced bioavailability of endothelium-derived nitric oxide. In premenopausal women, the impairment of endothelial function develops within 1 month of surgical ovariectomy and is reversed by the administration of exogenous 17 beta-estradiol. Exogenous estrogen administration restores endothelial function by enhancing nitric oxide synthesis through genomic and nongenomic mechanisms and by reducing oxidative stress and nitric oxide breakdown. The effect of progesterone on endothelial function is still under investigation. In animal studies, medroxyprogesterone acetate (MPA) counteracts estrogen's beneficial effects on endothelial function and on coronary plaque size. In humans, however, the addition of progesterone to estradiol does not appreciably attenuate estrogen-associated endothelium-dependent vasodilation. Secondary prevention trials with conjugated equine estrogen plus MPA have no proven benefit in reducing coronary events, progression of angiographic coronary atherosclerosis, or incidence of cerebrovascular events. This suggests that beneficial effects of estrogen on endothelial function are counterbalanced by detrimental effects, perhaps because of proinflammatory and prothrombotic actions. The selective estrogen receptor modulators are currently under investigation as agents that might retain the favorable, without possessing the unfavorable, effects of estrogen on the vascular system.

The capsaicin-sensitive vanilloid receptor (VR1) was recently shown to play an important role in inflammatory pain (hyperalgesia), but the underlying mechanism is unknown. We hypothesized that pain-producing inflammatory mediators activate capsaicin receptors by inducing the production of fatty acid agonists of VR1. This study demonstrates that bradykinin, acting at B2 bradykinin receptors, excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid. This finding identifies a mechanism that might be targeted in the development of new therapeutic strategies for the treatment of inflammatory pain.

BACKGROUND

Data suggest that preoperative chemoradiation improves survival in patients with stage II and III esophageal tumors. Whether preoperative therapy increases postesophagectomy morbidity and mortality has not been determined. This study evaluates our postoperative results after chemoradiation therapy.

METHODS

From 1989 through 1998, 120 consecutive patients underwent chemoradiation therapy followed by esophagectomy at our institution. The medical records for these patients were reviewed to determine patient age, sex, race, cell type, operative technique, complications, deaths, and length of hospital stay (LOS).

RESULTS

There were 106 (88%) men and 14 (12%) women with a mean age of 58 (32 to 77) years. White patients predominated (114 of 120, 95%); 98 (82%) had adenocarcinoma and 22 (18%) had squamous cell carcinoma. Operative technique was transhiatal in 91 (76%) patients, three-incision in 23 (19%), Ivor-Lewis in 4 (3%), and thoracoabdominal in 2 (2%). There was 1 death. Complications developed in 44 (37%) patients; 59% (13 of 22) of squamous cell carcinoma patients and 32% (31 of 98) of adenocarcinoma patients developed complications. Respiratory complications occurred in 32% (7 of 22) of squamous cell carcinoma patients and in 3% (3 of 98) of adenocarcinoma patients. Mean length of stay after surgery was 15 days (range 7 to 163).

CONCLUSIONS

Postesophagectomy results after chemoradiation therapy are comparable to those reported after esophagectomy alone. Squamous cell carcinoma patients are nearly twice as likely to develop postoperative complications and are more likely to have respiratory complications than adenocarcinoma patients.