Jianyong Zou

Comparative Clinical Features and Immune Responses After Extended Thymectomy for Myasthenia Gravis in Patients With Atrophic Versus Hyperplastic Thymus

BACKGROUND Although extended thymectomy is believed to be suitable for myasthenia gravis (MG) patients with hyperplastic thymus, it is not clear whether surgical treatment is indicated for MG patients with atrophic thymus. We therefore assessed the clinical features and immune responses in 175 MG patients who underwent thymectomy between 1990 and 2004. METHODS All patients underwent extended thymectomy by the transsternal approach. Clinical features, prognosis, and immune response after extended thymectomy were compared in patients with atrophic and hyperplastic thymuses. RESULTS Of the 175 patients, 47 had atrophic and 128 had hyperplastic thymuses. Although the median times to complete stable remission of the two groups were similar (4.9 versus 4.8 years; p=0.513), the median time to clinical improvement was significantly longer in patients with atrophic thymus (3.3 versus 2.3 years; p=0.005). Patients with atrophic thymus showed a greater increase in ectopic thymus in the anterior mediastinal adipose tissue. Elevated B-cell activating factor receptor, CD19, and CD21 were observed in both hyperplastic and atrophic thymuses, although serum immunoglobulin G concentration after thymectomy increased more in patients with atrophic than in those with hyperplastic thymus. CONCLUSIONS Atrophic thymus may contribute to the progression of MG. Patients with MG who have a atrophic thymus show similar postoperative prognosis as those with hyperplastic thymus, suggesting that surgical therapy should also be considered for the former subset.

Cyclooxygenase-2 up-regulates vascular endothelial growth factor via a protein kinase C pathway in non-small cell lung cancer

BackgroundVascular endothelial growth factor (VEGF) expression is up-regulated via a cyclooxygenase-2 (COX-2)-dependent mechanism in non-small cell lung cancer (NSCLC), but the specific signaling pathway involved is unclear. Our aim was to investigate the signaling pathway that links COX-2 with VEGF up-regulation in NSCLC.Material and methodsCOX-2 expression in NSCLC samples was detected immunohistochemically, and its association with VEGF, microvessel density (MVD), and other clinicopathological characteristics was determined. The effect of COX-2 treatment on the proliferation of NSCLC cells (A549, H460 and A431 cell lines) was assessed using the tetrazolium-based MTT method, and VEGF expression in tumor cells was evaluated by flow cytometry. COX-2-induced VEGF expression in tumor cells was monitored after treatment with inhibitors of protein kinase C (PKC), PKA, prostaglandin E2 (PGE2), and an activator of PKC.ResultsCOX-2 over-expression correlated with MVD (P = 0.036) and VEGF expression (P = 0.001) in NSCLC samples, and multivariate analysis demonstrated an association of VEGF with COX-2 expression (P = 0.001). Exogenously applied COX-2 stimulated the growth of NSCLCs, exhibiting EC50 values of 8.95 × 10-3, 11.20 × 10-3, and 11.20 × 10-3 μM in A549, H460, and A431 cells, respectively; COX-2 treatment also enhanced tumor-associated VEGF expression with similar potency. Inhibitors of PKC and PGE2 attenuated COX-2-induced VEGF expression in NLCSCs, whereas a PKC activator exerted a potentiating effect.ConclusionCOX-2 may contribute to VEGF expression in NSCLC. PKC and downstream signaling through prostaglandin may be involved in these COX-2 actions.

Clinical Outcome of Juvenile Myasthenia Gravis After Extended Transsternal Thymectomy in a Chinese Cohort

BACKGROUND The role of surgical treatment for juvenile myasthenia gravis (MG) remains unclear. Here, we performed a retrospective study to evaluate the predictors of clinical outcome of juvenile MG treated with extended transsternal thymectomy. METHODS A total of 141 consecutive juvenile MG patients underwent extended transsternal thymectomy at an academic hospital over a 20-year period were reviewed. Thymectomy was performed in patients resistant to pyridostigmine therapy, with generalized symptoms or ocular MG with partial response to pyridostigmine for more than 2 years. Variables potentially affecting responses to extended transsternal thymectomy were evaluated using Kaplan-Meier analysis and Cox regression modeling. Complete stable remission (CSR) is defined as asymptomatic without medication for more than 12 months. RESULTS There were 96 patients with ocular MG and 45 generalized MG, the median age at disease onset was 6 years and that at operation was 12 years. Among 135 patients with complete postoperative follow-up, 34 (25.2%) achieved CSR, 28 (20.7%) experienced pharmacologic remission, 61 (45.2%) improved, 5 (3.7%) remained stable, and 7 (5.2%) deteriorated. The results indicated the disease-onset age greater than 6 years and age at operation greater than 12 years were both positively associated with CSR responses. Postoperative steroid treatments in ocular MG and preoperative disease duration in generalized MG (>12 months) were negatively associated with CSR responses. CONCLUSIONS Extended transsternal thymectomy for Chinese juvenile MG patients has an efficacy comparable with reports from other ethnicities. Juvenile patients with disease-onset age greater than 6 years, age at operation greater than 12 years, and shorter disease duration of generalized MG are associated with favorable clinical outcomes.

Effects of ischemic preconditioning on ischemia/reperfusion-induced arrhythmias by upregulatation of connexin 43 expression

BackgroundThe susceptibility of hypertrophied myocardium to ischemia-reperfusion injury is associated with increased risk of postoperative arrhythmias. We investigate the effects of ischemic preconditioning (IP) on post-ischemic reperfusion arrhythmias in hypertrophic rabbit hearts.MethodsThirty-three rabbit models of myocardial hypertrophy were randomly divided into three groups of 11 each: non-ischemia-reperfusion group (group A), ischemia-reperfusion group (group B), and ischemic preconditioning group (group C). Another ten healthy rabbits with normal myocardium served as the healthy control group. Rabbit models of myocardial hypertrophy were induced by abdominal aortic banding. Surface electrocardiogram (ECG) was recorded and Curtis-Ravingerova score was used for arrhythmia quantification. Connexin 43 (Cx43) expression was assessed by immunohistochemistry.ResultsRatios of heart weight to body weight and left ventricular weight to body weight increase significantly in the three groups compared with the healthy control group (p < 0.05). Arrhythmia incidence in group C is significantly lower than group B (p < 0.05). Curtis-Ravingerova score in group C is lower than group B (p < 0.05). Cx43 expression area in group A is smaller by comparison with the healthy control group (p < 0.05). Cx43 expression area and fluorescence intensity in group B are reduced by 60.9% and 23.9%, respectively, compared with group A (p < 0.05). In group C, Cx43 expression area increases by 32.5% compared with group B (p < 0.05), and decreases by 54.8% compared with group A (p < 0.05).ConclusionsThe incidence of ischemia/reperfusion-induced arrhythmias in hypertrophic rabbit hearts decreases after IP, which plays an important protecting role on the electrophysiology of hypertrophied myocardium by up-regulating the expression of Cx43.

Preoperative serum fibrinogen is an independent prognostic factor in operable esophageal cancer.

In order to fully elucidate the association between serum fibrinogen and prognosis of esophageal cancer, we examined serum fibrinogen concentrations in 1512 patients who underwent esophagectomy by the Clauss method. The impact of fibrinogen on overall survival and disease-free survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models. Hyperfibrinogenemia was significantly associated with older age, male gender, smoking, alcohol consumption, weight loss, advanced pathological T stage and lymph node metastasis. Patients with hyperfibrinogenemia exhibited poor OS (HR=1.20, 95%CI: 1.04-1.38, P=0.012) and DFS (HR=1.18, 95%CI: 1.03-1.35, P=0.019). Subgroup analysis further exhibited an significant association between hyperfibrinogenemia and poor OS (P<0.001), DFS (P<0.001) in esophageal squamous cell carcinoma (P<0.001) and early pathological stage (I-II) (P=0.001). Collectively, this study indicates that preoperative serum fibrinogen is an independent prognostic factor for survival in esophageal cancer.

Frequency of EGFR mutations in lung adenocarcinoma with malignant pleural effusion: Implication of cancer biological behaviour regulated by EGFR mutation

Objective A retrospective single-centre study to compare the clinical features of patients with lung adenocarcinoma with and without epidermal growth factor receptor (EGFR) mutations. Methods Pretreatment medical records of patients with lung adenocarcinoma were reviewed. DNA was extracted from paraffin wax-embedded tumour tissue for analysis of EGFR mutations. Malignant pleural effusion (MPE) was diagnosed by cytopathological testing of pleural fluid. Results EGFR mutations (19-Del and L858R) were recorded in 81/283 patients (28.6%). MPE was found in 42/283 patients (14.8%). In patients with stage IV disease, the frequency of EGFR mutations was higher in those with MPE than in those without MPE. EGFR mutations were independently associated with female sex, no history of smoking and presence of MPE. Conclusions There was a positive association between EGFR mutation and the presence of MPE. EGFR mutations may play an important role in the formation of MPE.

Comparative pulmonary functional recovery after Nuss and Ravitch procedures for pectus excavatum repair: a meta-analysis

BackgroundPectus excavatum (PE) is a common chest wall malformation, with surgery being the only method known to correct the defect. Although the Nuss and Ravitch procedures are commonly used, there is no consensus as to whether surgical repair improves pulmonary function. We therefore investigated whether pulmonary function recovers after surgical repair, and if recovery is dependent on the type of procedure or time after surgery.MethodsLiterature searches were performed using PubMed, EMBASE, Health Periodicals Database, and CNKI (Chinese National Knowledge Index) from January 1990 to December 2007. The following keywords were used: pectus excavatum, chest wall deformity, funnel chest, pulmonary function, respiratory, lung function, and pectus severity index. The primary outcome of interest was possible changes in pulmonary function following surgical repair.ResultsMeta-analysis of 23 studies showed that, although there was evidence of statistically significant heterogeneity among studies (Chi-square, 17.11, p < 0.05), changes in pulmonary functional indices, including forced expiratory volume over 1 s (FEV1), forced vital capacity (FVC), vital capacity (VC), and total lung capacity (TLC), were similar 1 year after the Ravitch and Nuss procedures. Several years after surgery and bar removal, however, the changes in pulmonary functional indices significantly favored the Nuss procedure.ConclusionsPulmonary function tends to improve after the surgical correction of pectus excavatum. Although the Nuss procedure was not significantly better 1 year after surgery, long-term postoperative pulmonary function improvement was significantly better after bar removal.

Aurora-A is a novel predictor of poor prognosis in patients with resected lung adenocarcinoma

BACKGROUND The Aurora-A (Aur-A) gene, a key regulator of mitosis, has been proved as an oncogene in a variety of cancers. The Aur-A overexpression has been proved correlated with aggressiveness of cancer cells. However, the frequency of Aur-A protein overexpression, as well as its association with clinicopathologic parameters and prognosis remain unclear in lung adenocarcinoma (ADC). This study tried to clarify the clinical significance of Aur-A in patients with resected lung ADC. PATIENTS AND METHODS A total of 142 informative patients with surgically resected lung ADC and 20 normal lung tissues were enrolled. Western blot and immunohistochemistry (IHC) were utilized to assess protein expression of Aur-A. RESULT The expression of Aur-A was elevated in most of tumor tissues compared with the adjacent tissues by western blot. The IHC results showed that Aur-A protein was over-expressed in 98 of 142 (69.0%) tumor sections, while Aur-A was low-expressed in all normal lung sections. A positive correlation between Aur-A overexpression rate and ascending pathologic stages was observed (P<0.05). Kaplan-Meier analysis demonstrated that patients with Aur-A high expression had significantly inferior survival compared to those with Aur-A low expression. Both overall survival (OS) and disease-free survival (DFS) of positive overexpression patients were shorter than the negative group (P=0.036, P=0.041, respectively). Multivariate analysis confirmed that Aur-A expression, as an independent and significant factor for both DFS and OS, could predict a poor prognosis in patients with resected lung ADC (P=0.022, P=0.049, respectively). CONCLUSIONS Aur-A was overexpressed in lung ADC and overexpression of Aur-A might be a novel predictor for poor prognosis and potential therapeutic target in lung ADC.

Intravenous flurbiprofen for post-thymectomy pain relief in patients with myasthenia gravis

BackgroundPost-thymectomy pain in myasthenia gravis (MG) patients can inhibit breathing and coughing. Inappropriate usage of analgesics may exacerbate respiratory inhibition and even cause myasthenic crisis. Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used to control moderate postoperative pain and is not associated with respiratory inhibition. We hypothesized that flurbiprofen may provide post-thymectomy pain relief without increasing the risk of complications in MG patients.MethodsTwo hundred MG patients underwent extended thymectomy from March 2006 to December 2010 and were randomly allocated to a flurbiprofen group (110 patients, 50 mg intravenous flurbiprofen axetil) or a control group (90 patients, 100 mg intramuscular tramadol) as postoperative analgesia. Visual analog scale (VAS) pain score, heart rate, blood pressure, respiratory rate, pulse oximetry (SpO2), and adverse effects were recorded before and up to 24 h after drug administration.ResultsThere were no significant differences in the preoperative clinical characteristics of the flurbiprofen and control (tramadol) groups. Both flurbiprofen and tramadol significantly alleviated post-thymectomy pain (p < 0.05 for both), but patients in flurbiprofen group had significantly lower VAS pain scores at 0.5 h, 2 h, 4 h, and 8 h after surgery (p < 0.05 for all times). There were no significant post-thymectomy changes of heart rate, respiratory rate, mean arterial blood pressure, or SpO2 in either group at all time points.ConclusionsPost-thymectomy intravenous administration of flurbiprofen axetil provides safe and effective analgesia for MG patients.

Primary cardiac osteosarcoma in a 42-year-old woman

We describe here a 42-year-old woman who was admitted to hospital with a pedunculated mass in her left atrium. She was diagnosed with a primary cardiac osteosarcoma with special immunohistochemical characteristics. Echocardiography and computed tomography can be used to differentiate cardiac osteosarcomas from routine intracardiac tumors. The patient was treated by surgical removal of the mass. Two years later, she has shown no evidence of disease recurrence. We discuss primary osteosarcomas in the cardiac cavity and their management.