[Expression of vascular endothelial growth factor D in human esophageal squamous cell carcinoma tissue and its significance].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor D (VEGF-D) in human esophageal squamous cell carcinoma (ESCC) and its significance. METHODS: The expression of VEGF-C mRNA in tumor tissues and non-cancer tissues from 39 ESCC patients in our hospital from March 2009 to February 2010 was detected by in situ hybridization (ISH) method. The expression of D2-40 was detected by immunohistochemistry,and microlymphatic vessel density (MLVD) was determined by lymphatic endothelial specific marker D2-40. The associations of VEGF-C mRNA expression with clinical data and MLVD were analyzed. RESULTS: Positive ISH VEGF-D mRNA was observed in tumor tissue samples of 22 cases (56.4%, 22/39) and non-cancer tissue sample of 1 case (2.6%, 1/39), whose difference was statistically significant (P<0.05). The expression of VEGF-D mRNA in ESCC was significantly associated with lymph node metastasis [92.9% (13/14) vs. 36.0% (9/25), P<0.05] and MLVD [(8.20±1.22) vs. (5.31±0.97), P<0.01], but not significantly associated with age, sex, pathological grade and depth of infiltration. CONCLUSION: VEGF-D can promote lymphatic metastasis of ESSC by induction of lymphangiogenesis.

Pulmonary well-differentiated fetal adenocarcinoma with platelet-derived growth factor receptor (PDGFR)α expression.

Well-differentiated fetal adenocarcinoma (WDFA) is a rare pulmonary malignancy. Biomarkers of tumor biology has rarely been studied in WDFA. Here, we report two WDFA patients. Both patients had blood-streaked sputum or mild hemoptysis at presentation. They underwent lobectomy and systematic mediastinal lymphadenectomy. Expression of PDGFRα on the plasma membrane was demonstrated by immunohistochemistry (IHC) in the resected tumor specimens. Further IHC examination showed intense immunostaining of ß-catenin in both patients but negative staining for TP53, CEA, CD56, EGFR, CK5/6, HER2, S-100, ER, PR, BCL2, and NSE. Both patients had no recurrence to date after more than 3 years of follow up. Herein, we reviewed this rare disease with special emphasis on the clinico-pathological features, treatment and potential role of PDGFRα.

Enhancing chemosensitivity in ABCB1- and ABCG2-overexpressing cells and cancer stem-like cells by an Aurora kinase inhibitor CCT129202.

Imidazopyridine CCT129202 is an inhibitor of Aurora kinase activity and displays a favorable antineoplastic effect in preclinical studies. Here, we investigated the enhanced effect of CCT129202 on the cytotoxicity of chemotherapeutic drugs in multidrug resistant (MDR) cells with overexpression of ATP-binding cassette (ABC) transporters and cancer stem-like cells. CCT129202 of more than 90% cell survival concentration significantly enhanced the cytotoxicity of substrate drugs and increased the intracellular accumulations of doxorubicin and rhodamine 123 in ABCB1 and ABCG2 overexpressing cells, while no effect was found on parental sensitive cells. Interestingly, CCT129202 also potentiated the sensitivity of cancer stem-like cells to doxorubicin. Importantly, CCT129202 increased the inhibitory effect of vincristine and paclitaxel on ABCB1 overexpressing KBv200 cell xenografts in nude mice and human esophageal cancer tissue overexpressing ABCB1 ex vivo, respectively. Furthermore, the ATPase activity of ABCB1 was inhibited by CCT129202. Homology modeling predicted the binding conformation of CCT129202 within the large hydrophobic cavity of ABCB1. On the other hand, CCT129202 neither apparently altered the expression levels of ABCB1 and ABCG2 nor inhibited the activity of Aurora kinases in MDR cells under the concentration of reversal MDR. In conclusion, CCT129202 significantly reversed ABCB1- and ABCG2-mediated MDR in vitro, in vivo and ex vivo by inhibiting the function of their transporters and enhanced the eradication of cancer stem-like cells by chemotherapeutic agents. CCT129202 may be a candidate as MDR reversal agent for antineoplastic combination therapy and merits further clinical investigation.

Extended transsternal thymectomy for the treatment of ocular myasthenia gravis.

BACKGROUND: The optimal treatment for ocular myasthenia gravis (OMG) remains controversial. We conducted a review of the long-term clinical outcomes of Chinese patients with OMG after extended transsternal thymectomy (ETT) to determine the efficacy of this procedure as a treatment for OMG. METHODS: We reviewed the cases of 115 consecutive patients with OMG who underwent ETT at our Myasthenia Gravis Research Center between January 2006 and December 2008. Extended transsternal thymectomy was done in patients who had thymoma, resistance to pyridostigmine therapy, or relapse after immunosuppressive therapy. The patients' postoperative responses were defined as strict complete remission (SCR), consisting of an asymptomatic status without medication for more than 12 months; general complete remission (GCR), consisting of an asymptomatic status with low-dose single-drug therapy or without medication for more than 12 months; or improvement, consisting of fewer symptoms or less of a need for medication than before surgery. RESULTS: The overall complication rate was 7.8%. None of the patients experienced a myasthenic crisis, progression to generalized myasthenia gravis, or mortality. Hyperplasia of the thymus was present in 106 of the 115 patients (92.2%). Among 110 patients on whom follow-up was done postoperatively, 29 (26.4%) were in SCR, 64 (58.2%) showed improvement, 7 (6.4%) remained unchanged, and 10 (9.1%) had a worsening of their conditions. Kaplan-Meier analysis revealed rates of GCR of 41.8% at 24 months and 47.3% at 48 months after surgery, and rates of SCR of 24.5% at 24 months and 26.4% at 48 months. Both univariate analysis and multivariate Cox regression analysis revealed that only preoperative duration of illness was positively associated with GCR (p < 0.001). CONCLUSIONS: The results of the review indicate that ETT is a safe and effective treatment for OMG, especially in patients with illness of shorter duration.

[Notch1 expression in esophageal squamous cell carcinoma and its relation with microvascular angiogenesis].

OBJECTIVE: To observe Notch1 expression in esophageal squamous cell carcinoma (ESCC) and investigate its relation with microvascular angiogenesis in the tumor. METHODS: Tissue slices of 40 cases ESCC (cancer group) and 8 cases normal esophagus tissues (normal group) were obtained to analyze the expression of Notch1 and vascular endothelial growth factor (VEGF) using immunohistochemistry and estimate the microvessel density (MVD) in the tumor. RESULTS: Notch1 expression was significantly lower in the cancer group than in the normal group (P<0.05). In the cancer group, Notch1 expression was higher in highly differentiated than in poorly differentiated tumors (P<0.05) regardless of tumor infiltration or lymph nodes metastasis (P>0.05). VEGF expression and MVD were significantly higher in cancer group than in normal group, and showed significant differences between tumors with different differentiation degrees, infiltration and lymph node metastasis (P<0.05). Correlation analysis showed that Notch1 expression was inversely correlated to VEGF expression. CONCLUSION: Notch1 may be an anti-oncogene in ESCC and affects cell differentiation in early stage of the malignancy. Abnormally low expression of Notch1 in ESCC may be one of the upstream factors to induce high expression of VEGF and increased MVD. The Notch1 pathway might play a key role in microvascular angiogenesis in ESCC.

Serum protein profiles in myasthenia gravis.

BACKGROUND: The diagnosis of myasthenia gravis (MG) remains challenging. We performed a proteome-wide search for potential serum protein diagnostic markers for MG using surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry (TOFMS). METHODS: Proteomic spectra from 80 MG patients and 80 healthy individuals were generated by SELDI. Samples from 56 MG patients and 56 healthy individuals in the training set were analyzed to set up the decision tree. Samples from 24 MG patients and 24 healthy individuals were used for cross-validation testing. RESULTS: The SELDI TOFMS analysis generated 101 peaks, representing differentially expressed proteins between 1000 and 20000 Da. Among them, 9 peaks were down-regulated and 30 others were up-regulated in the MG sera compared with the controls. The decision tree used the peak at M4168.94 Da and M1122.57 Da as splitters in the classification process. In the training set, 112 samples were classified as MG or control group, with a sensitivity of 100% and specificity of 89.3%; the 10-fold cross-validated analysis identified the optimal decision tree with the lowest relative cross-validated cost of 0.080. In the test set, the decision tree generated was able to identify 20 of 24 MG patients and 21 of 24 healthy individuals with a sensitivity of 83.3% and a specificity of 87.5%. CONCLUSIONS: SELDI TOFMS is a useful tool for the detection and identification of potential serum biomarkers that can diagnose MG with high sensitivity and specificity.

Aneurysmal bone cyst in the first rib.

Aneurysmal bone cyst is a benign tumor of the skeletal system that rarely occurs in ribs. We report two cases of aneurysmal bone cyst in the first rib. The first patient was a 21-year-old woman with an aneurysmal bone cyst in the left first rib that was resected with an L incision. The second patient was a 42-year-old man with an aneurysmal bone cyst in the right first rib that was resected with a posterolateral incision but recurred 1 year later. An en bloc resection was performed, without recurrence to date. We also review this disease with emphasis on the etiology, clinicopathology, and treatment approaches.

[Effect of thoracic duct ligation during transthoracic esophagectomy on the prevention of post-operative chylothorax in different tumor locations].

OBJECTIVE: To investigate the effect of thoracic duct ligation during transthoracic esophagectomy on preventing post-operative chylothorax in different tumor locations. METHODS: Between March 2003 and June 2007, 243 patients with thoracic esophageal carcinoma underwent esophageal resection in our hospital. All the cases were divided into five groups according to tumor localization, including cervical, upper middle, middle, lower middle and lower sections. Each was then subdivided into 2 groups: with and without intraoperative thoracic duct ligation. Statistical analysis was carried out to evaluate the relevance between ligation and non-ligation of the thoracic duct during esophagectomy and the incidence of post-operative chylothorax. RESULTS: A total of 8 cases of post-operative chylothorax was recorded and the incidence was 3.3%. Incidence with respect to tumor location was as follows: cervical section: ligation subgroup 3 cases and non-ligation subgroup 5 cases; upper middle section: no one for both ligation and non-ligation subgroups; middle section: ligation subgroup 0/26 and non-ligation subgroup 1/28 (3.6%); lower middle section: ligation subgroup 1/39 (2.6%) and non-ligation subgroup 1/35 (2.9%); lower section: ligation subgroup 1/37 (2.7%) and non-ligation subgroup 2/44 (4.5%). Logistic regression analysis revealed no significant difference between ligation and non-ligation subgroup in the prevention of post-operative chylothorax (P>0.05). CONCLUSION: Thoracic duct ligation as preventive measure can not decrease the incidence of chylothorax secondary to esophagectomy.

Surgical intervention for advanced valvular heart disease in 227 cases.

BACKGROUND: Although the results of surgical treatment in cardiac valve disease continue to improve, the postoperative mortality rate and the rate of complications in patients with advanced valvular heart disease (AVHD) are still very high. We did this retrospective study to summarize the surgical experience of heart valve replacement for patients with AVHD and discuss effective ways to improve the surgical outcome. METHODS: From January 1994 to October 2003, surgical procedures of heart valve replacement were performed on 227 (136 men and 91 women) patients with AVHD in our Department of Cardiothoracic Surgery. The clinical data of all patients were collected and analysed. Patients' age ranged from 10 years to 77 years. In preoperative cardiac function grading, 157 cases were NYHA III and 70 cases NYHA IV. Fifty-one patients had had cardiac operations. The ultrasonic cardiac graphs showed that 145 patients suffered from moderate or severe pulmonary hypertension and 73 had combined giant left ventricle. Mitral valve replacement was performed in 32 cases, aortic valve replacement in 90, tricuspid valve replacement in 1, combined mitral and aortic replacement in 103 and combined mitral and tricuspid replacement in 1. Nineteen patients also received surgical corrections for other minor abnormalities during the operations. A logistic model was established to evaluate the influence of perioperative factors on the mortality rate. RESULTS: The operative mortality rate was 13.2% (30/227). The main causes of death included multiple organ dysfunction syndrome (MODS), low cardiac output syndrome and ventricular fibrillation. From the results of the binary noncounterpart multivariate logistic regression, the following statistically significant factors were found to influence the operative mortality rate: redo operation, age >/= 55 years, preoperative NYHA cardiac function grading, extracorporeal circulation time >/= 120 minutes and postoperative usage of GIK (glucose, insulin and potassium) solution. All factors were risk ones except postoperative application of GIK. The Hosmer-Lemeshow goodness of fit coefficient of this model was 0.976. CONCLUSIONS: The risk factors associated with postoperative mortality rate in the patients with AVHD were redo operation, age >/= 55 years, preoperative NYHA cardiac function grading and extracorporeal circulation time >/= 120 minutes. Postoperative usage of GIK acted as a kind of metabolic therapy and will improve the recovery for patients with AVHD. Active perioperative management and care will play a very important role in reducing the operative risk and improving the short term outcome of surgical treatment for the patients with AVHD.

[Diagnosis and surgical treatment of primary cardiac tumors].

OBJECTIVE: To study the clinical characteristics, diagnosis, and surgical treatment of primary cardiac tumors. METHOD: The clinical features and surgical results in 126 cases (1971-2000) of primary cardiac tumors were analyzed retrospectively. RESULTS: Among the 121 patients with benign tumors were treated surgically, 6 had recurrence of the pathologically confirmed intracardiac myxoma in a period of 1 to 7 years after surgery, and all were cured after reoperation. Follow-up of these patients showed satisfying long-term survival. In the other 5 malignant cases, 1 died during the perioperative period, and the others died of progressive heart failure, cardiac tamponade and cardiac rupture, respectively, within 10 months after the final diagnosis. CONCLUSION: The symptoms of primary cardiac tumor are diverse and complex, and echocardiography, CT, MRI are instrumental for a definite early diagnosis. In case of benign tumors, operation usually produces good results, but for malignant tumors characterized by rapid progression, earlier surgical removal in combination with other therapeutic modalities may improve the prognosis.