Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer.

BACKGROUND: Long-term survival in esophagectomy patients with esophageal cancer is low due to tumor-related characteristics, with few reports of modifiable variables influencing outcome. We identified determinants of overall survival, time to recurrence, and disease-free survival in this patient cohort. METHODS: Adult patients who underwent esophagectomy for primary esophageal cancer from January 5, 2000, through December 30, 2010, at our institution were identified. Univariate Cox models and multivariable logistic regression analyses were used to identify associations between modifiable and unmodifiable patient and clinical variables and outcome of survival for the total cohort and a subgroup with locally advanced disease. RESULTS: We identified 870 patients with esophageal cancer who underwent esophagectomy. The median follow-up time was 15 years, and the 15-year overall survival rate was 25.2%, survival free of recurrence was 57.96%, and disease-free survival was 24.21%. Decreased overall survival was associated with the following unmodifiable variables: older age, male sex, active smoking status, history of coronary artery disease, advanced clinical stage, and tumor location. Decreased overall survival was associated with the following modifiable variables: use of neoadjuvant therapy, advanced pathologic stage, resection margin positivity, surgical reintervention, and blood transfusion requirement. The overall survival probability 6 years after esophagectomy was 0.920 (95% CI, 0.895-0.947), and time-to-recurrence probability was 0.988 (95% CI, 0.976-1.000), with a total of 17 recurrences and 201 deaths. CONCLUSIONS: Once patients survive 5 years, recurrence is rare. Long-term survival can be achieved in high-volume centers adhering to National Comprehensive Cancer Network guidelines using multidisciplinary care teams that is double what has been previously reported in the literature from national databases.

Hyperoxia-induced changes in estradiol metabolism in postnatal airway smooth muscle.

Supplemental oxygen, used to treat hypoxia in preterm and term neonates, increases the risk of neonatal lung diseases, such as bronchopulmonary dysplasia (BPD) and asthma. There is a known sex predilection for BPD, but the underlying mechanisms are not clear. We tested the hypothesis that altered, local estradiol following hyperoxia contributes to pathophysiological changes observed in immature lung. In human fetal airway smooth muscle (fASM) cells exposed to normoxia or hyperoxia, we measured the expression of proteins involved in estrogen metabolism and cell proliferation responses to estradiol. In fASM cells, CYP1a1 expression was increased by hyperoxia, whereas hyperoxia-induced enhancement of cell proliferation was blunted by estradiol. Pharmacological studies indicated that these effects were attributable to upregulation of CYP1a1 and subsequent increased metabolism of estradiol to a downstream intermediate 2-methoxyestradiol. Microarray analysis of mouse lung exposed to 14 days of hyperoxia showed the most significant alteration in CYP1a1 expression, with minimal changes in expression of five other genes related to estrogen receptors, synthesis, and metabolism. Our novel results on estradiol metabolism in fetal and early postnatal lung in the context of hyperoxia indicate CYP1a1 as a potential mechanism for the protective effect of estradiol in hyperoxia-exposed immature lung, which may help explain the sex difference in neonatal lung diseases.

A randomized controlled trial of bupivacaine through intracostal catheters for pain management after thoracotomy.

BACKGROUND: Optimal management of pain after thoracotomy can be challenging. Continuous infusion of local anesthetic into the incision may help reduce the amount of narcotics required to control postoperative pain. To address this issue, we performed a randomized, double-blinded, controlled trial of infusion of bupivacaine versus placebo through intercostal and subcutaneous catheters after thoracotomy. METHODS: From April 2006 to June 2007, 124 patients had intercostal catheters placed at thoracotomy and connected to continuous infusion pain pumps. Each patient had catheters placed in the intercostal space near the head of the rib and subcutaneously beneath the incision; both were connected to an infusion pump through a Y connector. Patients were randomly assigned to receive placebo (normal saline solution) or 0.25% bupivacaine as a 4 cc per hour infusion for 100 hours after thoracotomy. All personnel caring for the patients were blinded to the content of the infusion. Demographic information, visual analog pain scores, and oral morphine equivalent usage was recorded for each patient. In addition to the infusion catheters, all patients had epidural analgesia that remained in place until postoperative day 3. RESULTS: There were 60 patients in the bupivacaine arm and 64 in the placebo group. Overall mean age was 64.7 years and 65 (52.4%) were men. Mean body mass index was 28.8 kg/m(2). There were no statistical differences in any demographic parameter except that there were more men in the placebo group. Pulmonary resection was performed in 100 patients, an antireflux procedure in 16, and other miscellaneous procedures in 8. There was no statistical difference in the morphine equivalent usage between the two groups. There was also no difference between the average daily pain scores between the two groups. Length of stay was not significantly different between groups: mean (SD) of 6.2 (3.4) and 6.7 (5.0) for placebo and bupivacaine, respectively (p = 0.51). There was no operative mortality, and complications occurred in 28% of patients (placebo group, 25%; bupivacaine group, 32%; p = 0.41). CONCLUSIONS: This randomized, double-blinded, controlled trial demonstrated that the infusion of local anesthetic into the subcutaneous area and around the rib fracture site in addition to epidural analgesia did not reduce the amount of narcotic usage after a thoracotomy, nor did it affect visual analog pain scores. Pain control with intercostal catheters infusing local anesthetics did not produce a measurable pain relief beyond that provided by epidural analgesia.