Guanchao Jiang

Knockdown of mutant K-ras expression by adenovirus-mediated siRNA inhibits the in vitro and in vivo growth of lung cancer cells.

The ras mutation, which is observed in 20-30% of human non-small cell lung cancers (NSCLCs), is one of common genetic alterations and has been proposed to be a prognostic factor in lung cancer. Oncogene ras appears to be essential for tumor progression and maintenance. Several therapeutic agents have been developed to inhibit ras, such as FTIs and antisense oligonucleotides. A new tool for blocking oncogenes in cancer cells has emerged with the discovery that RNA interference can specifically silence expression of endogenous human genes. In the current study, we used small interfering RNA (siRNA) directed against mutant K-ras to determine the anti-tumor effects of decreasing the levels of this protein in lung cancer cell lines. Adenovirus-mediated siRNA (AdH1/siK-rasV12) against K-rasV12 markedly decreased K-rasV12 gene expression and inhibited cellular proliferation of NSCLC H441 cells that express the relevant mutation (K-ras codon 12 GGT→GTT), but produced minimal growth inhibition on NSCLC H1650 cells that lack the relevant mutation. Pre-treatment with AdH1/siK-rasV12 completely abrogated subcutaneous engraftment of H441 cells, as compared with a 100% tumor take in animals that received control vector-treated tumor cells. The in vivo effect of AdH1/siK-rasV12 treatment was further examined by intratumoral injections after tumor induction. Preexisting tumor growth was reduced by 45% by a single intratumoral injection. Three or five repeat injections resulted in complete tumor regression in eight of ten nude mice. Further, 23.12% of AdH1/siK-rasV12 treated H441 cells underwent apoptosis, as compared with 6.13%, and 8.27% in untreated and control vector-treated cells, respectively. These results indicate that adenovirus-mediated siRNA can specifically and efficiently target factors whose expression is altered in malignancy and may have the potential as a therapeutic modality to treat human lung cancer.

Thoracoscopic enucleation of esophageal leiomyoma: a retrospective study on 40 cases

Esophageal leiomyoma is the most common benign esophageal tumor. Thoracoscopic enucleation is currently a preferred approach to most of these lesions. We present our experiences of enucleation of these tumors using thoracoscopic approach. A retrospective review of 40 patients who underwent enucleation of esophageal leiomyoma from 1997 to 2007 in our institute was conducted. Presenting symptoms, operative approach, tumor size, tumor shape, outcomes, and indication for this approach were analyzed. Forty patients were identified. Postoperative histopathology confirmed the leiomyoma in all patients. The thoracoscopic enucleation was completed in 34 cases, and the operation was converted to open procedure in six cases. Reasons for conversion included too small tumors to be visualized in two cases, thoracic cavity adhesion in one case, and the too large tumors in three cases. The median operating time was 70 min (50 to 210 min). Mean tumor size was 3.7 cm (0.5-10 cm). There were no major postoperative complications. Symptoms especially dysphasia were relieved postoperatively. Short- and long-term follow-up was satisfactory with none of the patients having tumor recurrences or other problems. Thoracoscopic enucleation of esophageal leiomyoma is technically safe and effective. It is currently the best choice for management of esophageal leiomyoma 1 to 5 cm in diameter. It can also be tried on a tumor larger than 5 cm, although the possibility of conversion to thoracotomy increases along with tumor growing and surrounding the esophagus.

Learning curves and long-term outcome of simulation-based thoracentesis training for medical students

BackgroundSimulation-based medical education has been widely used in medical skills training; however, the effectiveness and long-term outcome of simulation-based training in thoracentesis requires further investigation. The purpose of this study was to assess the learning curve of simulation-based thoracentesis training, study skills retention and transfer of knowledge to a clinical setting following simulation-based education intervention in thoracentesis procedures.MethodsFifty-two medical students were enrolled in this study. Each participant performed five supervised trials on the simulator. Participants performance was assessed by performance score (PS), procedure time (PT), and participants confidence (PC). Learning curves for each variable were generated. Long-term outcome of the training was measured by the retesting and clinical performance evaluation 6 months and 1 year, respectively, after initial training on the simulator.ResultsSignificant improvements in PS, PT, and PC were noted among the first 3 to 4 test trials (p < 0.05). A plateau for PS, PT, and PC in the learning curves occurred in trial 4. Retesting 6 months after training yielded similar scores to trial 5 (p > 0.05). Clinical competency in thoracentesis was improved in participants who received simulation training relative to that of first year medical residents without such experience (p < 0.05).ConclusionsThis study demonstrates that simulation-based thoracentesis training can significantly improve an individuals performance. The saturation of learning from the simulator can be achieved after four practice sessions. Simulation-based training can assist in long-term retention of skills and can be partially transferred to clinical practice.

Video-Assisted Thoracoscopic Left Cardiac Sympathetic Denervation: A Reliable Minimally Invasive Approach for Congenital Long-QT Syndrome

BACKGROUND The purpose of this study was to assess the feasibility and long-term effect of video-assisted thoracoscopic left cardiac sympathetic denervation for congenital long-QT syndrome. METHODS From December 2002 to May 2007, 11 patients who could not tolerate or who were refractory to beta-blocker therapy received video-assisted thoracoscopic left cardiac sympathetic denervation. Under general anesthesia, the pleural cavity was entered through three 1.5-cm incisions in the left subaxillary area. The left thoracic sympathetic chain was identified, and the lower one third of the left stellate ganglion, together with T(2) to T(5) sympathetic chain, was resected. RESULTS The mean operative time was 40.9 +/- 7.7 minutes. Blood loss was minimal. The mean postoperative stay was 6 +/- 1.4 days. There were no major perioperative complications apart from mild ptosis of the left upper eyelid in 1 patient who subsequently recovered shortly after the procedure. The mean follow-up time was 37.0 +/- 26.3 months. Seven of the patients are totally free of cardiac events and report good quality of life. One patient experienced decreased syncopal events from 5 or 6 times per year to 2 or 3 times per year. One patient still experiences syncopal events 3 to 4 times a year, but with shortened duration to several seconds. One patient reports syncope 10 times per year. Only 1 patient died, early in the second year after surgery. In conclusion, the overall efficacy rate (that is, reduction in syncopal episodes) is 81.8% (9 of 11) and the mortality rate, 9.1% (1 of 11). CONCLUSIONS Video-assisted thoracoscopic left cardiac sympathetic denervation is a simple and minimally invasive technique that results in good long-term benefits in patients with congenital long-QT syndromes.

Development and Validation of a Clinical Prediction Model for N2 Lymph Node Metastasis in Non-Small Cell Lung Cancer

BACKGROUND The true incidence of occult N2 lymph node metastasis in patients with clinical N0 non-small cell lung cancer (NSCLC) remains controversial. Estimation of the probability of N2 lymph node metastasis can assist physicians when making diagnosis and treatment decisions. METHODS We reviewed the medical records of 605 patients (group A) and 211 patients (group B) with computed tomography-defined N0 NSCLC that had an exact tumor-node-metastasis stage after surgery. Logistic regression analysis of group As clinical characteristics was used to estimate the independent predictors of N2 lymph node metastasis. A prediction model was then built and internally validated by using cross validation and externally validated in group B. The model was also compared with 2 previously described models. RESULTS We identified 4 independent predictors of N2 disease: a younger age; larger tumor size; central tumor location; and adenocarcinoma or adenosquamous carcinoma pathology. The model showed good calibration (Hosmer-Lemeshow test: p = 0.96) with an area under the receiver operating characteristic curve (AUC) of 0.756 (95% confidence interval, 0.699 to 0.813). The AUC of our model was better than those of the other models when validated with independent data. CONCLUSIONS Our prediction model estimated the pretest probability of N2 disease in computed tomography-defined N0 NSCLC and was more accurate than the existing models. Use of our model can be of assistance when making clinical decisions about invasive or expensive mediastinal staging procedures.

Highly expressed SLC35F2 in non-small cell lung cancer is associated with pathological staging.

Homo sapiens solute carrier family 35 member F2 (SLC35F2) is highly homologous to the lung squamous cell cancer-related gene, LSCC3, which is highly expressed in lung squamous cell tumour tissues. However, the clinical implication of the SLC35F2 gene in tumour development and progression remains unclear. An affinity-purified polyclonal antibody raised against the human SLC35F2 peptide was used in the immunohistochemical analysis of a non-small cell lung cancer (NSCLC) tissue microarray of human NSCLC (n=129). SLC35F2 protein was also analysed with the same antibody using Western blotting. Total RNAs were extracted from tumour tissues (n=43) and from laser-dissected tumour cells (n=9). SLC35F2 gene expression was detected by fluorescent real-time quantitative PCR and compared to the expression in the corresponding adjacent normal lung tissues. It was found that both the SLC35F2 protein (by IHC analysis) and the SLS35F2 gene transcripts (by Q-PCR analysis) were expressed at significantly higher levels in the NSCLC tumour tissues than in the corresponding adjacent normal lung tissues (p<0.001 and =0.015, respectively). There was a significant correlation between the SLC35F2 transcript and pathological staging (r=0.219, p=0.029), although the correlation between SLC35F2 protein and the staging was not significant (r=0.175). SLC35F2 was highly expressed in NSCLC tissues and the levels of expression, in particular the levels of the SLC35F2 transcript, were associated with NSCLC pathological staging. SLC35F2 appears to have a significant prognostic value in NSCLC.

Indications for conversion of thoracoscopic to open thoracotomy in video-assisted thoracoscopic lobectomy

Backgroud:  The study aims to discuss indications for conversion to thoracotomy in completely thoracoscopic lobectomy.

Propensity-matched comparison of video-assisted thoracoscopic with thoracotomy lobectomy for locally advanced non–small cell lung cancer

Objective: We evaluated whether video‐assisted thoracoscopic lobectomy for locally advanced non–small cell lung cancer could be performed safely and with acceptable long‐term outcomes by our improved technique and compared with standard thoracotomy lobectomy in a well‐balanced population. Methods: Patients with clinical stage II and III A non–small cell lung cancers who received lobectomy were reviewed. Video‐assisted thoracoscopic lobectomies were all performed with Wangs technique by the surgeons who had overcome the learning curve and achieved proficiency. By using propensity‐matched analysis, perioperative outcomes and long‐term survival were compared. Results: Matching based on propensity scores produced 120 patients in each group. Conversion rate to thoracotomy was 11.7%. After thoracoscopic lobectomy, hospital length of stay was shorter compared with thoracotomy (9.2 vs 12 days; P = .014) despite similar rates of postoperative complications (30/125 [25%] vs 34/125 [28.3%]; P = .56). Disease‐free survival (49.1% vs 42.2%; P = .40) and overall survival (55.0% vs 57.1%; P = .73) at 5 years were similar between groups. Although advanced pathologic stage (hazard ratio [HR], 2.018; 95% confidence interval [CI], 1.330–3.062) and no postoperative chemotherapy (HR, 1.880; 95% CI, 1.236–2.858) were independently associated with increased hazard of death in multivariable Cox regression at each time point in follow‐up, thoracoscopic lobectomy was not (HR, 1.075; 95% CI, 0.714–1.620; P = .73). Conclusions: With continued experience and optimized technique, video‐assisted thoracoscopic lobectomy can be performed in the majority of cases without compromising perioperative outcomes and oncologic efficacy.

Sympathicotomy for Palmar Hyperhidrosis: The Association between Intraoperative Palm Temperature Change and the Curative Effect

PURPOSE To investigate the association between intraoperative palm temperature change and the curative effect of sympathicotomy. METHODS 49 patients with palmar hyperhidrosis were treated with bilateral endoscopic sympathicotomy. Ipsilateral palm temperature was monitored before and at 3-5 min increments after the sympathetic trunk was transected. The maximum temperature elevation (Tmax) was calculated and used to evaluate the effect on postoperative cure rates. RESULTS Forty-nine patients underwent 98 sympathicotomies. There were 77 T4 sympathicotomies, 15 T4 + T5 sympathicotomies, and six T3 sympathicotomies due to pleural adhesions or neurovascular proximity. The Tmax was ≤1°C in 49 (50.0%), 1-1.5°C in 17 (17.3%), and >1.5°C in 32 (32.7%) palms. Ninety-two palms of 46 patients were followed with complete efficacy, and three patients were lost to follow up. Cure was achieved in 86 palms (93.4%). Of the 71 palms which underwent T4 sympathicotomy, cure was achieved in 67 palms (94.3%). In those palms which did not achieve cure, the Tmax was less than 1°C in each case, while in palms with a Tmax ≤1°C, 32 of 36 (88.9%) were cured. CONCLUSION There is an association between intraoperative palmar temperature change and curative effect. However, palmar temperature change cannot be used to predict cure or guide surgical approach.

Applications of indocyanine green based near-infrared fluorescence imaging in thoracic surgery

Near-infrared (NIR) fluorescence guided surgery is an emerging technique. This technique uses the combination of dyes and NIR imaging devices to expand the visible spectrum. Thus it can provide more anatomic and functional information, and may facilitate a more complete resection of cancer, or better protection of important normal structures. Recently, significant progress has been made in the field of NIR fluorescence guided thoracic surgery. This may lead to better prognosis and health-economic outcomes. In this article, the current studies of indocyanine green (ICG) based NIR fluorescence guided thoracic surgeries are reviewed. The applications are classified into four categories, which are applications based on blood supply, lymphatic drainage, the enhanced permeability and retention (EPR) effect, and the other mechanisms.