Impact of neoadjuvant therapy of perioperative morbidity in patients with esophageal cancer.

BACKGROUND: Conflicting results of preoperative radiochemotherapy in patients with esophageal cancer have been obtained; only patients with a complete pathological response seem to benefit from this therapy. However, there is evidence that preoperative radiochemotherapy leads to considerable postoperative morbidity. Therefore, postoperative morbidity was retrospectively investigated in 82 patients with an esophageal cancer who received preoperative radiochemotherapy. METHODS: One hundred twenty-two consecutively operated on patients were included (1991 to 2001). Preoperative radiochemotherapy was initiated in 1994 for cT >1, cNx, cM0 regardless of histology (n = 82); 36 Gy was applied (1.8 Gy daily, days 1 to 5, weeks 1 to 4), concurrently 5-fluorouracil (500 mg/m(2) days 1 to 5, weeks 1 to 4), and cisplatin (20 mg/m(2) days 1 to 5, weeks 1 and 4). Postoperative morbidity was categorized as surgery- and nonsurgery-related morbidity. Survival was calculated by the Kaplan-Meier method. Results were stratified into histology and compared with patients who were operated on only (n = 40). RESULTS: Complete pathological response after preoperative radiochemotherapy was achieved in 22%. An increase in surgery-related morbidity was observed after preoperative radiochemotherapy due to lesion of recurrent nerve (38% versus 12.5%, P = 0.009), as well as a marked difference in pulmonary morbidity (57% versus 37.5%, P = 0.05). The proportion of combined morbidity was increased after preoperative radiochemotherapy (49.4% versus 15%, P = 0.02), which led to a considerable prolongation of postoperative hospital stay (33 versus 21 days median, P = 0.0022). Patients with a longer postoperative hospital stay (>30 days; 43.2%) lived significantly shorter than patients with a shorter postoperative hospital stay (56.8%, P = 0.001). There was no statistical survival benefit in the neoadjuvant treated group. However, calculation of long-term survival revealed a significant survival advantage in patients with squamous cell cancer and a complete pathological response compared with patients without response (median 642 days versus 302, P = 0.026). CONCLUSIONS: Perioperative morbidity was significantly increased after preoperative radiochemotherapy. Long-term survival was clearly affected by the length of postoperative stay. Therefore, we need better patient selection for application of preoperative radiochemotherapy.

Influence of antiseptic agents on interleukin-8 release and transmigration of polymorphonuclear neutrophils in a human in vitro model of peritonitis.

BACKGROUND: The aim of this study was to evaluate the influence of taurolidine (TAU) and polyhexanid (POLY) on basic inflammatory reactions during peritonitis by using an in vitro model of human peritoneum. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) and human peritoneal mesothelial cells (HPMC; concentration: 2x10(5)/cm2) were brought on a collagen-coated filter insert with 3-microm pore size (HUVEC on the bottom, HPMC on the top), thus resulting in a two-chamber peritoneal model. After 5 days, confluence of the cells was reached, and HPMC were stimulated with 0.5 mL of TNF-alpha (10 microg/mL) for 4 h. Afterwards, 0.5 mL of TAU (1% and 2%) or 0.5 mL of POLY (0.1% and 0.2%) solution were added to the upper (HPMC) compartment. Polymorphonuclear neutrophils (PMN, 10(6)/mL) were placed in the lower compartment 1 h later. After 2 and 6 h, aliquots were taken from the upper compartment and transmigrated PMN were counted. Interleukin-8 (IL-8) concentrations were measured in both compartments by chemiluminescent enzyme immunometric assay. Expression of the adhesion molecules P-selectin and intercellular adhesion molecule-1 (ICAM-1) was assessed by immunohistochemistry. Controls were either TNF-alpha-stimulated HPMC without any antiseptic agents, or stimulated HPMC where TNF-alpha had been substituted by culture medium. Each experiment was performed in triplicate. RESULTS: Stimulation with TNF-alpha led to a time-dependent increase of IL-8 secretion to the apical compartment resulting in a gradient between both chambers, as well as to a time-dependent increase of PMN transmigration and expression of adhesion molecules. IL-8 gradients and PMN migration were significantly higher as compared to the other groups (p<0.05). After substitution of the stimulus by culture medium, significantly less IL-8 was measured in both compartments. PMN transmigration was almost absent (p<0.05). Addition of POLY and TAU led to comparable low IL-8 gradients with concomitant low PMN transmigration. The initially detected expression of adhesion molecules significantly decreased during the observation time. The IL-8 gradient in all groups correlated significantly with PMN transmigration (r=0.74226; p<0.0001). CONCLUSION: The diminished IL-8 response together with low PMN transmigration rates after addition of TAU and POLY may reflect either antiinflammatory effects or cellular damage.