Treatment and survival analysis for 40-year SEER data on upper esophageal cancer.

Background: Upper esophageal cancer (UEC) is rare in both Eastern and Western countries. The epidemiological characteristics and long-term survival of UEC patients are less known. In addition, the choice of optimal treatment for UEC has been controversial. Methods: Cases of UEC (C15.3 and C15.0) arising during the period from 1973 to 2013 were identified and selected using the SEER database. Student's t-test and Pearson's chi-square test were used to compare the differences in parameters among different groups. Esophageal cancer-specific survival (ECSS) and overall survival (OS) rates were calculated by using the Kaplan-Meier method. Cox proportional hazard regression was used to analyze predictive factors. Results: In the past 40 years, the cases of UEC have gradually increased, and the proportion of adenocarcinoma (AD) has gradually increased (from 3.6% to 11.8%, p < 0.001). There has been a significant increase (1973-1982 vs. 2004-2013) in median OS (7 months vs. 10 months, p < 0.001) and median ECSS (7 months vs. 11 months, p < 0.001) among UEC patients from 1973 to 2013. For the impact of different treatments, the results showed that the ECSS and OS of surgery without radiation (SWR) and radiation plus surgery (R+S) were superior to those of radiation without surgery (RWS). Subgroup analysis showed that ECSS and OS were highest among patients treated with SWR compared with R+S and RWS for patients with localized disease. For regional disease, ECSS and OS were highest among patients with R+S compared with SWR or RWS. Among patients with regional-stage squamous cell carcinoma (SCC), OS was higher with neoadjuvant radiotherapy or adjuvant radiotherapy compared with SWR. Multivariate analysis showed that radiotherapy sequence was dependently associated with OS among patients with regional-stage SCC. Conclusion: Although the long-term survival of UEC remains poor, it has gradually increased since 1973. This should be closely related to the improvement of medical care over the past 40 years. Different treatment methods have a great influence on the long-term survival of UEC. For localized diseases, surgery may be a better choice. For regional disease, surgery plus adjuvant or neoadjuvant radiotherapy may be more beneficial to improve the long-term prognosis of UEC patients.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study.

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

Clinical and Transmission Characteristics of Covid-19 - A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department.

The outbreak of corona virus disease 2019 (Covid-19) imposes a major challenge in managing patients undergoing surgical operation. In this study, we analyzed clinical and transmission features of 25 cases of Covid-19 from a single thoracic department, including 13 patients and 12 health care staff. There were 13 males and 12 females. The median age of the patients was 61 (range: 51 to 69) years. The median age of the health care staff was 35 (range: 22 to 51) years. By the end of follow-up date (Mar. 3, 2020), there were 16 non-severe cases (64%) and 9 severe cases (36%), 5 cases were dead (20%). Nineteen (76%) of the infected cases were confirmed by SARS-CoV-2 nucleic acid test, the rest were clinically diagnosed as suspected Covid-19 cases, and 19 (76%) of the infected cases had positive exposure history. We found that COPD was significantly associated with severity and death (P=0.040, and P=0.038, respectively), and chest operation was significantly associated with death for Covid-19 patients (P=0.039). A potential "super spreader" may be the source of the transmission before the implementation of quarantine and comprehensive protection. It was concluded that Covid-19 is associated with poor prognosis for patients undergoing thoracic operation, especially for those with COPD. Implementation of comprehensive protective measures is important to control nosocomial infection.

Lymph node metastasis in Chinese patients with clinical T1 non-small cell lung cancer: A multicenter real-world observational study.

BACKGROUND: Approximately 8.3-15.9% of patients with clinical stage I non-small cell lung cancer are subsequently shown to have lymph node metastasis. However, the clinical characteristics of patients with lymph node metastasis in China are not fully understood. METHODS: This is a multicenter retrospective analysis of pathological T1 non-small cell lung cancer patients who underwent surgical resection from 2 January 2014 to 27 December 2017. Clinical and pathological information was collected with the assistance of the Large-scale Data Analysis Center of Cancer Precision Medicine-LinkDoc database. The clinical and pathological factors associated with lymph node metastasis were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 10 885 participants (51.6% women; 15.3% squamous cell carcinoma) were included in the analysis. The median age was 60.0 years (range 12.9-86.6 years). A total of 1159 patients (10.6%) had metastases in mediastinal nodes (N2), and 640 patients (5.9%) had metastasis in pulmonary lymph nodes (N1). Most patients had T1b lung cancer (4766, 43.8%). Of the patients, 3260 (29.9%) were current or former smokers. The univariate and multivariate analyses showed that younger age, squamous cell carcinoma, poor differentiation, larger tumor size, carcinoembryonic antigen level ≥5 ng/mL, and vascular invasion (+) were significantly associated with higher percentages of lymph node metastases (P < 0.001 for all). CONCLUSION: This real-world study showed the significant association of lymph node metastasis with age, tumor size, histology and differentiation, carcinoembryonic antigen levels, and status of vascular invasion. Female patients with T1a adenocarcinoma in the right upper lobe barely had lymph node metastasis.

Modular 3-cm uniportal video-assisted thoracoscopic left upper lobectomy with systemic lymphadenectomy.

Uniportal video-assisted thoracoscopic lobectomy for non-small-cell lung cancer is accepted worldwide, with incisions ranging from 4 to 6 cm. We believed in less invasive and more precise that uniportal video-assisted thoracoscopic lobectomy could be. Therefore, we performed modular uniportal thoracoscopic lobectomy with systemic lymphadenectomy on left upper lobe using a 3-cm-diameter port. And the modular surgical route was arranged in seven modules. Anesthesia, patient positioning and instruments play an important role in the surgery. From October 2014 to June 2015, 96 patients underwent this modular surgery and all patient were discharged uneventfully with no postoperative deaths. Compared with multi-port VATS, the operation time were longer than multiport video-assisted thoracoscopic surgery (VATS) (164.70±12.50 vs. 160.70±11.60 min, P>0.05), and the mean lymphadenectomy station was 6.00±0.77, and the mean lymphadenectomy number was 17.58±5.33. There is no significant difference on lymphadenectomy. Thus, modular uniportal video-assisted thoracoscopic lobectomy with systemic lymphadenectomy on left upper lobe using a 3-cm-diameter port is a safe, feasible, and less painful technique for select patients with lung disease.

Clinical analysis of thoracoscopic surgery combined with intraoperative autologous blood transfusion in the treatment of traumatic hemothorax.

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

Expression and significance of hypoxia inducible factor-1α and lysyl oxidase in non-small cell lung cancer.

OBJECT: To detect expression of hypoxia inducible factor-1α (HIF-1α) and lysyl oxidase (LOX) in non-small cell lung cancer (NSCLC) and explore their roles in prognosis. METHODS: The mRNA levels of HIF-1α and LOX were investigated by real-time reverse-transcriptase polymerase chain reaction in 40 cases of tumour and paired normal tissues. In addition, protein expression of HIF-1α and LOX was examined by immunohistochemistry in 82 cases of tumour and 45 paired normal tissues. The relationship between HIF-1α or LOX and clinicopathologic characteristics, as well as the correlation between HIF-1α and LOX, were also examined. Kaplan-Meier survival curves and the log-rank test were used to analyze progression-free survival. RESULTS: HIF-1α or LOX mRNA levels in tumor tissues was significantly higher than those in paired normal tissues (p<0.01). Positive HIF-1α or LOX protein expression in tumor tissues was noted in 46/82 (56.1%) and 49/82 (59.8%) of the cases, respectively, being significantly higher than those in paired normal tissues (p<0.05). There was significant correlation between the expression of HIF-1α or LOX and tumor size, lymph node metastasis and pathological stage (p<0.05). The expression of HIF-1α and LOX had a significant inverse impact on survival of patients with NSCLC. CONCLUSION: HIF-1α and LOX may play a pivotal role in the development of NSCLC, and may act in synergy to promote the progression of NSCLC.

Association of preoperative serum IGF- I concentration with clinicopathological parameters in patients with non-small cell lung cancer.

Insulin-like growth factor-I (IGF-I) is a mitogenic and anti-apoptotic factor. Serum IGF-I concentration is related to some cancer risk and tumor progression. The aim of this research was to study the association of preoperative serum IGF-I concentration with clinicopathological parameters and prognosis of non-small cell lung cancer (NSCLC). Preoperative serum IGF-I concentration was measured in 80 consecutive patients with NSCLC who underwent radical lung cancer resection, and 45 patients with benign pulmonary lesion (BPL) by using enzyme linked immunosorbent assay (ELISA). The results showed that the serum IGF-I concentration was elevated and correlated with clinicopathological parameters and overall survival (OS) in NSCLC patients. Serum IGF-I concentration was significantly higher in patients with NSCLC than in those with BPL. The IGF-I concentrations were significantly higher in NSCLC patients with ≥T2, N1-3, and in IIIA-IV but not in those with

Thoracoscopic lobectomy versus open lobectomy in stage I non-small cell lung cancer: a meta-analysis.

The objective of the present meta-analysis was to evaluate the survival, recurrence rate, and complications in patients with stage I non-small cell lung cancer (NSCLC) who received video-assisted thoracoscopic surgery (VATS) or open lobectomy. A literature search was conducted on June 31, 2012 using combinations of the search terms video-assisted thoracic surgery, open thoracotomy, lobectomy, and non-small-cell lung cancer (NSCLC). Inclusion criteria were: 1) Compared video-assisted thoracic surgery (VATS) lobectomy with open lobectomy. 2) Stage I NSCLC. 2) No previous treatment for lung cancer. 4) Outcome data included 5-year survival rate, complication, and recurrence rate. Tests of heterogeneity, sensitivity, and publication bias were performed. A total of 23 studies (21 retrospective and 2 prospective) met the inclusion criteria. VATS was associated with a longer 5-year survival (odds ratio [OR] = 1.622, 95% confidence interval [CI] 1.272 to 2.069; P<0.001), higher local recurrence rate (OR = 2.152, 95% CI 1.349 to 3.434; P = 0.001), similar distant recurrence rate (OR = 0.91, 95% CI 0.33 to 2.48; P = 0.8560), and lower total complication rate (OR = 0.45, 95% CI 0.24 to 0.84; P = 0.013) compared to open lobectomy. VATS was also associated with lower rates arrhythmias, prolonged air leakage, and pneumonia but it did not show any statistical significance. Patients with stage I NSCLC undergoing VATS lobectomy had longer survival and fewer complications than those who received open lobectomy.

Use of a pedicled omental flap in the treatment of chest wall tuberculosis.

The most effective way to treat the chest wall tuberculosis is to fill the residual space with a muscle flap after complete resection of the lesion. However, in some situations a muscle flap cannot be used. The greater omentum has been widely used for reconstruction and the treatment of infections. We describe our technique of using a pedicled omental transposition flap in the management of chest wall tuberculosis for closing the dead space created by excision of the lesion.

Effects of TGF-ß signaling blockade on human A549 lung adenocarcinoma cell lines.

Transforming growth factor ß (TGF-ß) is overexpressed in a wide variety of cancer types including lung adenocarcinoma (LAC), and the TGF-ß signaling pathway plays an important role in tumor development. To determine whether blockade of the TGF-ß signaling pathway can inhibit the malignant biological behavior of LAC, RNA interference (RNAi) technology was used to silence the expression of TGF-ß receptor, type II (TGFßRII) in the LAC cell line, A549, and its effects on cell proliferation, invasion and metastasis were examined. Three specific small interfering RNAs (siRNAs) designed for targeting human TGFßRII were transfected into A549 cells. The expression of TGFßRII was detected by Western blot analysis. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The invasion and metastasis of A549 cells were investigated using the wound healing and Matrigel invasion assays. The expression of PI3K, phosphorylated Smad2, Smad4, Akt, Erk1/2, P38 and MMPs was detected by Western blot analysis. The TGFßRII siRNA significantly reduced the expression of TGFßRII in A549 cells. The knockdown of TGFßRII in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis. In addition to the Smad-dependent pathway, independent pathways including the Erk MAPK, PI3K/Akt and p38 MAPK pathways, as well as the expression of MMPs and VEGF, were inhibited. In conclusion, TGF-ß signaling is required for LAC progression. Therefore, the blockade of this signaling pathway by the down-regulation of TGFßRII using SiRNA may provide a potential gene therapy for LAC.

Lobectomy by video-assisted thoracoscopic surgery (VATS) for early stage of non-small cell lung cancer.

Video-assisted thoracoscopic surgery (VATS) provides a new approach for treating early-stage lung cancer. Lobectomy by VATS has many advantages over conventional thoracotomy, such as shorter recovery time, less postoperative pain, and faster resumption of a normal lifestyle. However, there is still much debate on the role of VATS in lobectomy for the treatment of lung cancer. Concerns regarding safety, the extent of mediastinal lymph node dissection, and long-term survival have made some surgeons apprehensive of its validity for lung cancer. In this paper, we review the development of thoracoscopy, the present status of VATS for early stage of non-small cell lung cancer (NSCLC), and comparison between VATS and open thoracotomy in the management of NSCLC.

Upright position mechanical ventilation: an alternative strategy for ALI/ARDS patients?

Use of body positioning to improve oxygenation in mechanically ventilated patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has been well documented. However, neither prone position ventilation nor side lying ventilation has been reported to improve the survival. Whether there is a body position superior to routine supine position or other positions as therapeutic adjunct for ventilated patients with ALI and ARDS? We propose the hypothesis that upright position ventilation may be helpful to improve oxygenation and benefit patients with ALI/ARDS. According to the existing physiologic and pathophysiologic data of upright position investigation, we suppose that improvement of V/Q matching, increased functional residual capacity, alveolar recruitment, accelerated diaphragm recovery, early gastric emptying and enteric feeding may be a potential protect mechanism of upright position ventilation. Whether this can be translated into improvement in patient outcome should be further tested in clinical trial.

Expression of cytochrome P450 arachidonic acid epoxygenase 2J2 in human tumor tissues and cell lines.

BACKGROUND AND OBJECTIVE: Cytochrome P450 arachidonic acid epoxygenase 2J2 (CYP2J2) is a new metabolic pathway of arachidonic acid. However, its biological effects, especially pathophysiologic significance in human beings, remain to be further recognized. This study was to determine the expression of CYP2J2 in human tumor tissues and cell lines. METHODS: The expression of CYP2J2 mRNA and protein in 130 specimens of human carcinoma and related adjacent normal tissues, four specimens of inflammatory pseudotumor tissues, eight human tumor cell lines and two normal cell lines (as control) was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blot and immunohistochemistry. RESULTS: CYP2J2 was highly expressed in 101 (78%) carcinoma tissues, but was not detected in adjacent normal tissues and inflammatory pseudo-tumor tissues. Its mRNA level was obviously correlated to its protein level (r = 0.613, p < 0.01). Immunohistochemistry analysis showed the same results as RT-PCR and western blot. Furthermore, CYP2J2 was only expressed in cancer cells but not in interstitial and inflammatory cells. CYP2J2 was highly expressed in all carcinoma cell lines, but not in two normal cell lines. CONCLUSION: CYP2J2 is highly and selectively expressed in human tumor tissues and cell lines and may be a novel biomarker of human tumors.

Molecular cloning, characterization and three-dimensional modeling of porcine nectin-2/CD112.

Nectin-2, also known as poliovirus receptor-related 2 or CD112, has been identified in many animals and plays a crucial role in cell recognition and adhesion. Here we report the identification of two porcine Nectin-2 (poNectin-2) isoforms. The open reading frame (ORF) of 1440 nucleotides (nt) of poNectin-2alpha encodes 479 amino acids (aa). poNectin-2delta gene consists of 1620nt of ORF with 539aa. The deduced aa sequences of poNectin-2alpha and poNectin-2delta gene exhibit high identity with human (74% and 79%) and mouse (71% and 76%) orthologs, respectively. The ectodomains of deduced poNectin-2 protein share the structural feature of mammalian Nectin-2, including a conserved cysteine skeleton important for the formation of the three-dimensional structure. RT-PCR analysis showed that the mRNA of both poNectin-2 isoforms was broadly expressed in various tissues and cells. poNectin-2 gene was mapped to chromosome 6q21. Information from this study will help to elucidate the Nectin-2 pathway in xenotransplant immunity.

[Promotive effects of epoxyeicosatrienoic acids (EETs) on proliferation of tumor cells].

BACKGROUND & OBJECTIVE: Epoxyeicosatrienoic acids (EETs) are generated from arachidomic acid by cytochrome P450(CYP). Previous studies revealed very strong and selective expression of CYP expoxygenase in human cancer tissues, but almost none in adjacent normal tissues. This study was to investigate the promotive effect of EETs on proliferation of tumor cells and the possible mechanisms. METHODS: Four tumor cell lines, Tca-8113, A549, Ncl-H446 and HepG2, were treated with different concentrations of EETs (8,9-EET, 11,12-EET and 14,15-EET) for 12, 24, 48 and 72 h, respectively. Cell proliferation was measured using the MTT assay. The effect of exogenous EETs on cell cycle of Tca-8113 cells was assessed by flow cytometry. Signal transduction inhibitors of PI3K (LY294002), MAPKK (PD98059), MAPK (apigenin) and PKC (H7) were used to block EETs-induced cell proliferation. Expressions of the total protein and phosphorylated ERK1/2 and Akt were determined by Western blot. RESULTS: EETs promoted proliferation of tumor cells compared with the control and vehicle group in a dose-and time-dependent manner (P<0.01). Incubation of tumor cells with EETs markedly increased the cell number at S/G2-M phase. The percentages of Tca-8113 cells at S and G2-M phases were (49.7+/-7.5%) vs. (17.2+/-9.7%) (P<0.01) and (21.0+/-5.3%) vs. (4.9+/-7.3%), respectively(P<0.01) with and without the treatment of 11,12-EET. EETs incubation significantly enhanced phosphorylation of MARK as well as PI3K/Akt in tumor cells. LY294002, PD98059, apigenine and H7 reduced the stimulative effect of EETs on cell proliferation. CONCLUSION: EETs possess the promotive effect on proliferation of tumor cells via activation of MAPK and PI3K/Akt signal pathways.

[Surgical treatment for tumors of trachea, carina and main bronchus].

OBJECTIVE: To review the experience in surgical treatment for tumors of trachea, carina and main bronchus. METHODS: From Jan. 1996 to Jun. 2004, 27 patients with tumor of trachea, carina or main bronchus underwent surgery including resection and reconstruction of trachea in 8, right/left pneumonectomy and carinal resection and reconstruction in 9 (6/3), right sleeve upper lobectomy and carnial resection with reconstruction of trachea and carina in 2, carina resection and reconstruction in 3, tumor removal through tracheal windows in 5. CPB (cardiopulmonary bypass) was used in 2 patients during surgery. RESULTS: There were 3 peri-operative deaths caused by acute respiratory failure in 2 and severe postoperative bleeding in 1 case. After follow-up of more than 6 months, no death or post-operative complication occurred. CONCLUSION: Resection and reconstruction for patients with tumor of trachea, main bronchus or carina can be performed with excellent results using effective surgical and anaesthetic methods with or without CPB assistance.

[Cardiac valve MCSF-1 and its receptor expression changes in Staphylococcus aureus induced infective endocarditis].

OBJECTIVE: To explore the cellular immunology mechanism of infective endocarditis (IE), we investigated the effects of Staphylococcus aureus (S. aureus) on MCSF-1 and its receptor (c-fms) gene expression in cardiac valves. METHODS: Thirty-two rabbits were divided into 4 groups: mitral or tricuspid valve artificial lesions with 5 x 10(4) CFU or 5 x 10(6) CFU S. aureus injection. Control rabbits (n = 7) received 5 x 10(6) CFU S. aureus injection. IE after operation were confirmed by naked eyes and electron microscope observations. MCSF-1, c-fms in mitral and tricuspid valves were detected by RT-PCR. RESULTS: Twenty-six rabbits survived the operation and 14 rabbits developed IE (2 with 5 x 10(4) CFU and 12 with 5 x 10(6) CFU S. aureus injection) one day post operation. S. aureus injection alone did not induce IE. Compared to control rabbits, MCSF-1 mRNA was significantly upregulated and c-fms mRNA significantly downregulated after 5 x 10(4) CFU S. aureus injection with heart valve artificial lesion in mitral valves or tricuspid valves. MCSF-1 expression in mitral valves was further increased while remained unchanged in tricuspid valve after 5 x 10(6) CFU S. aureus injection compared to that in 5 x 10(4) CFU S. aureus injection group. CONCLUSION: High dose bacterial invasion and heart valves lesion were the main factors for inducing infective endocarditis. Development of infective endocarditis was associated with valve MCSF-1/c-fms expression changes in this rabbit model.