Intraoperative hypotension is associated with shortened overall survival after lung cancer surgery.

BACKGROUND: Intraoperative hypotension is associated with increased morbidity and mortality after surgery. We hypothesized that intraoperative hypotension might also be associated with worse long-term survival after cancer surgery. Herein, we analyzed the correlation between intraoperative hyper-/hypotension and overall survival after lung cancer surgery. METHODS: In this retrospective cohort study, 676 patients who received lung cancer surgery between January 1, 2006 and December 31, 2009 were reviewed. Intraoperative hyper- and hypotension were defined according to their correlation with long-term survival. The primary endpoint was overall survival. The association between episodes of intraoperative hyper-/hypotension and overall survival was analyzed with multivariable Cox proportional hazard models. RESULTS: Long-term follow-ups were completed in 515 patients with a median duration of 5.2 years. The estimated 5-year survival rates were 66.5, 61.3, 56.5, and 41.2% in patients with only hypertension (systolic blood pressure > 140 mmHg for ≥5 min), with both hyper- and hypotension (systolic blood pressure < 100 mmHg for ≥5 min), with neither hyper- nor hypotension, and with only hypotension during surgery, respectively. After adjusting confounding factors, intraoperative hypotension was significantly associated with shortened overall survival (compared with patients with only intraoperative hypertension, those with both hyper- and hypotension: hazard ratio [HR]1.033, 95% confidence interval [CI] 0.709 to 1.507, p = 0.864; those with neither hyper- nor hypotension: HR 0.952, 95% CI 0.608 to 1.489, p = 0.829; those with only hypotension: HR 1.736, 95% CI 1.218 to 2.475, p = 0.002). CONCLUSIONS: For patients undergoing lung cancer surgery, intraoperative hypotension, but not hypertension, was associated with shortened overall survival.

Perioperative Management May Improve Long-term Survival in Patients After Lung Cancer Surgery: A Retrospective Cohort Study.

BACKGROUND: Surgical resection is the main treatment for patients with non-small-cell lung cancer (NSCLC), but patients' long-term outcome is still challenging. The purpose of this study was to identify predictors of long-term survival in patients after lung cancer surgery. METHODS: Patients who underwent surgery for NSCLC from January 1, 2006, to December 31, 2009, were enrolled into this retrospective cohort study. The primary outcome was the survival length after surgery. Predictors of long-term survival were screened with the multivariable Cox proportional hazard model. RESULTS: Postoperative follow-up was completed in 588 patients with a median follow-up duration of 5.2 years (interquartile range, 2.0-6.8). Two hundred ninety-one patients (49.5%) survived at the end of follow-up with median survival duration of 64.3 months (interquartile range, 28.5-81.6). The overall survival rates were 90.8%, 70.0%, and 57.1% at the end of the first, third, and fifth year after surgery, respectively. Limited resection (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.08-1.98; P = .013) and large tumor size (HR, 1.29; 95% CI, 1.17-1.42; P < .001) were associated with short survival; whereas high body mass index grade (HR, 0.82; 95% CI, 0.69-0.97; P = .021), highly differentiated tumor (HR, 0.59; 95% CI, 0.37-0.93; P = .024), dissection of mediastinal lymph node during surgery (HR, 0.45; 95% CI, 0.30-0.67; P < .001), and perioperative use of dexamethasone (HR, 0.70; 95% CI, 0.54-0.90; P = .006) were associated with long survival. No association was found between perioperative use of flurbiprofen axetil and long survival (HR, 0.80; 95% CI, 0.62-1.03; P = .086). However, combined administration of dexamethasone and flurbiprofen axetil was associated with longer survival (compared to no use of both: adjusted HR, 0.57; 95% CI, 0.38-0.84; P = .005). CONCLUSIONS: Certain factors in particular perioperative dexamethasone and flurbiprofen axetil therapy may improve patients' long-term survival after surgery for NSCLC. Given the small sample size, these findings should be interpreted with caution, and randomized clinical trials are needed for further clarification.

[Prognostic analysis of 525 Chinese patients with diffuse large B cell lymphoma].

OBJECTIVE: To describe the clinical characteristics, overall survival as well as to evaluate the prognostic factors in Chinese diffuse large B cell lymphoma (DLBCL) patients. METHODS: DLBCL patients who were initially diagnosed and treated in Peking University Cancer Hospital from January 1995 to December 2008 were identified and analyzed,retrospectively.The 5-year OS rates were estimated with Kaplan-Meier. Log-rank test was used to compare the survival curves of the different groups. The multivariate analysis of prognostic factors was conducted with Cox regression model, which included all statistically significant prognostic factors in the univariate analyses. RESULTS: A total of 525 DLBCL patients were included in this retrospective analysis, of whom, 294 were male and 231 female (male:female=1.27:1). The median age at the initial diagnosis was 55 (range 16-90) years, and 37.0% (n=194) were 60 years and above. Regarding the clinical staging at the initial diagnosis, 54 patients (10.3%) were diagnosed as Stage I of the disease, 152 (28.9%) as Stage II, 117 (22.3%) as Stage III and 202 (38.5%) as Stage IV. The "B symptoms" and increased serum LDH were presented in 206 (39.2%) and 192 (36.6%) patients, respectively. A total of 197 (37.5%) patients were treated with rituximab (R). The survival follow-up continued till 31 January 2014 with a median follow-up time of 77.5 (range: 0-205) months. A total of 267 patients (50.9%) died during the follow-up period. The medial overall survival (OS) time was 84 months, and 5-year OS rate was 52.3%. There were six statistically significant prognostic factors that were identified in both univariate and multivariate analyses: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. The relative risk (RR) of these prognostic factors in the multivariate analyses were: age > 60 years / ≤ 60 years=1.380 (95%CI 1.078-1.765), male / female=1.315 (95%CI 1.025-1.687), stage III/stage I=3.034 (95%CI 1.667-5.522), stage IV/I=3.748(95%CI 2.102-6.681), with B symptoms/without B symptoms=1.278(95%CI 0.999-1.636), serum LDH increased/LDH not increased=1.351(95%CI 1.057-1.726), without R treatment / with R treatment=1.543 (95%CI 1.182-2.015).Compared with the IPI, age >50 years/ ≤ 50 years was a statistically significant factor in both univariate and multivariate analyses RR=1.478 (95%CI 1.148-1.902), P=0.002. CONCLUSION: Six factors were related to DLBCL survival: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. Compared with the IPI, several specific factors may predict a poor prognosis in Chinese DLBCL patients: male, age>50 years and the presence of "B symptoms". But this result is not conclusive until these factors are further tested.

Pyrrolidine dithiocarbamate attenuates nuclear factor-ĸB activation, cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic epithelial cells.

BACKGROUND: The nuclear factor-κB (NF-κB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. We sought to examine the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. METHODS: The phosphorylation of IκB, expression of nuclear p65 protein and NF-κB DNA binding in endometriotic epithelial cells (EECs), endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs) were detected by Western blot analysis and electrophoretic mobility shift assay. Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT-PCR and Western blot analysis. Prostaglandin E(2) (PGE(2)) production of EECs was measured by ELISA. RESULTS: PDTC in the absence or presence of tumor necrosing factor-α (TNF-α) showed stronger inhibitory effects on IκB phosphorylation, expression of nuclear p65 protein and NF-κB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-α-induced expressions of COX-2 at gene and protein levels, as well as a reduction of PGE(2) synthesis. CONCLUSION: PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

Pyrrolidine dithiocarbamate inhibits nuclear factor-κB pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells.

The activation of nuclear factor-κB (NF-κB) has been implicated in the development and progression of endometriosis. The aim of this study is to investigate the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in endometriotic ectopic stromal cells (EcSCs), endometriotic eutopic stromal cells (EuSCs) and normal endometrial stromal cells (NESCs) were detected by electrophoretic mobility shift assay and western blot analysis. Adhesion, migration, invasion and apoptosis of EcSCs were observed by means of adhesion, migration, invasion and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling assay, respectively. Gene and protein expressions of CD44s, matrix metalloproteinase (MMP)-2, MMP-9 and survivin in EcSCs were measured by RT-PCR and western blot analysis. The results showed that PDTC in the absence or presence of interleukin (IL)-1ß showed stronger inhibitory effects on NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in EcSCs than those in EuSCs or NESCs. PDTC enhanced apoptosis, and suppressed IL-1ß-induced cellular adhesion, migration and invasion of EcSCs. Pretreatment of EcSCs with PDTC attenuated IL-1ß-induced expressions of CD44s, MMP-2, MMP-9 and survivin at gene and protein levels. All these findings suggest that PDTC induces apoptosis and down-regulates adhesion, migration and invasion of EcSCs through the suppression of various molecules. Therefore, PDTC could be used as a therapeutic agent for the treatment of endometriosis.

Application of the nuclear factor-κB inhibitor pyrrolidine dithiocarbamate for the treatment of endometriosis: an in vitro study.

This study demonstrated that pyrrolidine dithiocarbamate (PDTC), a potent nuclear factor-κB inhibitor, showed stronger inhibitory effects on nuclear factor-κB activation in endometriotic stromal cells than in normal endometrial stromal cells as determined by electrophoretic mobility shift assay and Western blot analysis. Pretreatment of endometriotic stromal cells with PDTC attenuated tumor necrosis factor-α-induced expressions of CD44s, matrix metalloproteinase-9, and vascular endothelial growth factor whereas reversed tumor necrosis factor-α-reduced expressions of tissue inhibitor of metalloproteinase-1 revealed by reverse transcriptase polymerase chain reaction and Western blot analysis, suggesting that PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

Real-time quantitative RT-PCR detection of disseminated endometrial tumor cells in peripheral blood and lymph nodes using the LightCycler System.

OBJECTIVE: Some endometrial cancer patients without clinical evidence of extrauterine spread die as a result of recurrence even after curative operation. These recurrences may arise from occult tumor cells that are not detected by conventional methods. The goal of this study was to develop a quantitative method for the detection of disseminated tumor cells (DTCs) in the peripheral blood (PB) and lymph nodes (LNs) of patients with endometrial cancer. METHODS: Ninety-eight PB samples from 30 patients and 218 LNs from 14 patients were studied. Real-time quantitative analysis was performed using a LightCycler instrument and a TaqMan probe for cytokeratin 19 (CK19) as a marker gene. RESULTS: This method resulted in the reproducible quantitation of 10 to 10(6) MCF-7 cells (CK19-expressing breast cancer cell line) per 10(6) peripheral blood nucleated cells. CK19 mRNA expression was detected in 28 PB samples and in 62 LNs. Only three preoperative PB samples and one postoperative PB sample (from four patients) and 33 LNs (from six patients) were PCR-positive. The PCR-positive rate of LNs was higher in patients with pathologically metastatic (path-positive) LNs than in patients with path-negative but PCR-positive LNs. Furthermore, the CK19 mRNA background expression rate was higher in the LNs of path-negative but PCR-positive patients than in LNs of path-negative and PCR-negative patients. CONCLUSIONS: Real-time qRT-PCR with TaqMan probes is a sensitive, specific and rapid method for the detection of DTCs in PB and LNs. Additional studies with larger numbers of patients and adequate follow-up would be of benefit.