Perioperative and long-term outcome of thymectomy for myasthenia gravis: comparison of surgical approaches and prognostic analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Thymectomy is an established treatment for myasthenia gravis (MG), and video-assisted thoracoscopic surgery (VATS) thymectomy has become an acceptable surgical procedure. This study aimed to compare the results of VATS thymectomy and open thymectomy and to identify the prognostic factors after thymectomy.</p><p><b>METHODS</b>The clinical data of 187 consecutive thymectomies performed between July 2000 and December 2009 were retrospectively reviewed; 75 open thymectomies and 112 VATS thymectomies. Clinical efficacy and variables influencing outcome were assessed by Kaplan-Meier survival curves and Cox proportional hazards regression analysis.</p><p><b>RESULTS</b>The operative blood loss in the VATS group was significantly less than that in the open group ((62.14 ± 55.43) ml vs. (137.87 ± 165.25) ml, P < 0.05). The postoperative crisis rate increased with the severity of preoperative MG and the prescription dose of anticholinesterase. Complete follow-up information of patients more than 12 months after the thymectomy was obtained on 151 cases, 89 cases from the VATS group and 62 cases from the open group, with a mean follow-up period of 59.3 months, range from 12 to 117 months. Complete stable remission (CSR) was the end point for evaluation of the treatment results. The overall five-year CSR rate was 57.5%. Two good prognostic factors were identified; preoperative prescription of anticholinesterase alone (P = 0.035) and non-thymomatous MG (P = 0.003). The five-year CSR rate of the ocular type of MG reached a high level of 67.4%.</p><p><b>CONCLUSIONS</b>Thymectomy can achieve good long-term CSR in MG, and VATS is an ideal alternative method. High-dose prescription of anticholinesterase and the advanced stage by Myasthenia Gravis Foundation of America (MGFA) classification have higher risks of postoperative crisis. Preoperative prescription of anticholinesterase alone and non-thymomatous MG are good prognostic factors. Thymectomy should also be considered for the ocular type of MG.</p>

The learning curve of single-direction complete video-assisted thoracoscopic surgery for lung cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the learning curve of single-direction complete video-assisted thoracoscopic surgery (cVATS) for lung cancer.</p><p><b>METHODS</b>From May 2006 to April 2009, 125 cases of cVATS for lung cancer were performed by two dedicated surgeons. Clinical data were collected prospectively and analyzed retrospectively. The patients operated by different surgeon were divided into 2 groups (group A, n = 24; group B, n = 101), and group B was further divided sequentially into 4 subgroups (B1, B2, B3 and B4) by the number of patients. The patients in group A and B were operated by the surgeons with 2-year and 5-year experience of VATS respectively. The operating time, blood loss, number of resected lymph nodes (NLN), rate of thoracotomy conversion (RTC) and postoperative complications (POC) were compared.</p><p><b>RESULTS</b>Compared with group B, the operating time of group A was significantly prolonged [(237 ± 85) min vs. (187 ± 43) min, P = 0.013], but there were no significant differences in blood loss, NLN, RTC and POC. Comparing group A with B1, the same results were got. From group B1 to B4, the operating time was gradually reduced and blood loss decreased, but the difference was not statistically significant. And in group B, there was a significant reduction of blood loss for the last 51 cases compared to the first 50 cases [(122 ± 141) ml vs. (87 ± 81) ml, P = 0.009].</p><p><b>CONCLUSIONS</b>At the early stage of cVATS resection of lung cancer, the duration of operation was longer, which it was more significant for the surgeons with short carrier of thoracoscopic experience. But the morbidity of operation related complications did not increase. The indicator of proficiency in this operation is achievement of 50 cases of complete thoracoscopic resection of lung cancer.</p>

Surgical treatment of invasive thymoma: a prognostic retrospective study / 中华外科杂志

<p><b>OBJECTIVES</b>To observe the clinical outcome of invasive thymoma, and analyze how the surgical methods, Masaoka staging, adjuvant radiotherapy and/or chemotherapy affect the prognosis.</p><p><b>METHODS</b>The clinical data of 59 surgical patients with invasive thymoma and conducted follow-up from January 2000 to December 2009 was analyzed retrospectively. There were 34 male and 25 female, aged from 18 to 72 years with a mean age of 49 years. Forty-four cases underwent radical resection while the other 15 cases underwent palliative resection or biopsy. Masaoka staging: 18 cases with stage II, 30 cases with stage III, 11 cases with stage IV. Patients with stage II didn't undergo further adjuvant radiotherapy or chemotherapy after surgery. Among the patients with stage III and stage IV, 26 patients received adjuvant radiotherapy and/or chemotherapy after surgery, while the other 15 patients did not receive any further therapy. The relationship between the prognosis and the different surgical methods, Masaoka staging, adjuvant radiotherapy and or chemotherapy was evaluated.</p><p><b>RESULTS</b>Fifty-nine patients had been followed up for 1 to 111 months with an average of 54 months. Three cases were lost with the rate of 6.1%. Nineteen patients suffered local recurrence or systemic metastasis, and 14 of them died. The 3-year and 5-year survival rates were 86.8% and 70.8% respectively. Univariate analysis indicated that patients with early Masaoka staging and who received radical resection, adjuvant radiotherapy and/or chemotherapy after surgery had better survival (P < 0.05). Multivariate analysis indicated that radical resection, adjuvant radiotherapy and or chemotherapy were the most significant prognostic factors which could remarkably improve the survival of patients (P < 0.05). For patients with resectable recurrence, reoperation could also improve survival.</p><p><b>CONCLUSIONS</b>The Masaoka staging is related to the prognosis of patients with invasive thymoma. Radical resection, adjuvant radiotherapy, chemotherapy can significantly improve the survival of patients with invasive thymoma. Reoperation can improve the survival of some patients with recurrence.</p>

The advancement of predictive diagnosis and molecular mechanism in multiple primary lung cancer / 癌症

Due to the advanced diagnostic technique and better understanding for multiple primary lung cancers (MPLC), the increasing incidence of MPLC has been reported. Very often, MPLC are misdiagnosed as metastasis because of lacking efficient molecular biomarkers for prediction and diagnosis. Studies on the molecular mechanism for tumorgenesis and progression of MPLC may therefore facilitate the discovery of biomarkers for disease diagnosis and prognosis, so that an individual and rational treatment can be achieved. We tried to further our understanding and improve the diagnostic skill for MPLC by reviewing the current status and the latest advancement of molecular markers related to MPLC.

Expression of Toll-like receptors in thymus of myasthenia gravis patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the expression of Toll-like receptors (TLRs) in thymus of myasthenia gravis (MG) patients and the relationship with clinical features.</p><p><b>METHODS</b>Thymic specimens of 36 patients received extended thymectomy for MG were divided into three groups by pathological type: 13 thymoma tissues (thymoma group) and 13 thymic tissues adjacent to thymomas (parathymoma group) from 13 cases of MG patients with thymomas, and 23 thymic tissues from MG patients without thymomas (MG nonthymoma group). Twenty-one normal thymic specimens from cardiac surgery were used as controls. The levels of TLR2-4 mRNA were examined by RT-PCR, then the levels of TLR4 mRNA were assayed by real time RT-PCR and their relationship with clinical features were analyzed.</p><p><b>RESULTS</b>The levels of TLR4 mRNA among the different groups had significant differences, while there was no difference in TLR2 and TLR3 levels. The real time RT-PCR showed that the level of TLR4 mRNA in nonthymoma group was significantly higher than that in control group(0.8544+/- 0.1200 vs 0.6851+/- 0.1524, P=0.018). And so is parathymoma group compared with the thymoma group (0.8214+/- 0.1019 vs 0.7101+/- 0.0916, P=0.005). No significant difference of TLR4 mRNA level was found between the parathymoma and nonthymoma groups. Nevertheless, the expression of TLR4 in both groups was increased compared with control group. The levels of TLR4 mRNA had positive correlation with Osserman type(R=0.609; P=0.004) .</p><p><b>CONCLUSION</b>TLR4 may play a key role in the pathogenesis of MG. It was the thymic tissues adjacent to thymomas but not thymomas themselves participated in the onset of MG.</p>

A study on selective killing effect of Hsv-tk/GCV driven by human telomerase catalytic subunit promoter on human lung cancer cell A549 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study selective killing effect of herpes simplex virus-thymidine kinase/ganciclovir (Hsv-tk/GCV) driven by human telomerase catalytic subunit (hTERT) promoter on lung cancer cell line A549 in vitro.</p><p><b>METHODS</b>(1) Expression plasmids of Hsv-tk gene driven by hTERT promoter and sv40 promoter respectively (pGL3-hTp-tk and pGL3-sv40-tk) were transfected into telomerase-positive human lung adenocarcinoma cell line A549 and telomerase-negative fetal lung fibroblast cell line MRC-5. Reverse transcription-PCR was performed to detect expression of tk gene in above transfected cell lines; (2) Inhibition effect on proliferation of above transfected cell lines treated with GCV was investigated with MTT method; (3) Influence of GCV on apoptosis and cell cycle of above transfected cell lines was investigated with flow cytometry.</p><p><b>RESULTS</b>(1) tk mRNA expression was detected in both A549 and MRC-5 transfected with pGL3-sv40-tk, also in A549 transfected with pGL3-hTp-tk, but not in pGL3-hTp-tk transfected MRC-5; (2) GCV showed significant inhibition effects on proliferation of pGL3-sv40-tk transfected A549 and MRC-5 in vitro, also on that of pGL3-hTp-tk transfected A549, but not on that of pGL3-hTp-tk transfected MRC-5; (3) Treated with GCV, apoptosis index (AI) of pGL3-sv40-tk transfected A549 and MRC-5 as well as pGL3-hTp-tk transfected A549 (21.58%, 9.35% and 23.19% respectively) increased significantly, compared with A549, MRC-5 transfected with pGL3-hTp (0.78% and 0.55% respectively) and A549, MRC-5 without plasmid transfection as blank control (2.17% and 0.60% respectively); GCV had no influence on AI of pGL3-hTp-tk transfected MRC-5 (0.88%).</p><p><b>CONCLUSION</b>tk gene driven by hTERT promoter could express selectively in lung cancer cell A549. Hsv-tk/GCV driven by hTERT promoter could selectively inhibit proliferation of lung cancer cell.</p>

nm23-H1 gene inhibits lung cancer cell invasion through down-regulation of PKC signal pathway / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the molecular mechanisms of nm23-H1 for regulating PKC signal pathway before and after transfection with nm23-H1 gene.</p><p><b>METHODS</b>Using Western-blot, Boyden-chamber, MTT and laser scanning confocal microscopy (LSCM) techniques to detect the distribution of PKC in cytosol and plasma membrane, changes of invasion and proliferation activity, PKC translocation status and changes of intracellular Ca(2+) concentration among different human pulmonary carcinoma cells with transfected or untransfected nm23-H1 gene, and changes of the three cell lines after treatment with Calphostin C, a PKC inhibitor.</p><p><b>RESULTS</b>(1) The expression of PKCalpha, PKCbeta II on L9981 and L9981-pLXSN cell membrane, which was in activated status, was remarkably higher than those in L9981-nm23-H1 cell line (P < 0.001). The expression of PKCalpha, PKCbeta II in cytosol in L9981 and L9981-pLXSN cell lines, which was in inactivated status, was lower than those in L9981-nm23-H1 cell line (P < 0.001). It means that the PKC signal pathway was activated in L9981 and L9981-pLXSN cell lines. (2) PKCalpha and PKCbeta II mainly located in nuclei and perinuclear area in L9981 and L9981-pLXSN cells, which were in active status, and the Ca(2+) concentration in these cells was obviously higher than that in L9981-nm23-H1 cell line (P < 0.01). In L9981-nm23-H1 cell line, which was transfected with nm23-H1 gene, PKCalpha and PKCbeta II mainly located in soluble cytosolic section, in an inactive status. (3) The invasion and proliferation ability of L9981 and L9981-pLXSN lung cancer cells was higher than that of L9981-nm23-H1 cell line (P < 0.001). There was no statistically significant difference between L9981 and L9981-pLXSN cell lines (P > 0.05). (4) After treated with PKC inhibitor Calphstin C, the expression of PKC and PKCbeta II in membrane in L9981 and L9981-pLXSN cell lines was down-regulated (P < 0.001), PKCalpha and PKCbeta II were mainly located in cytosolic area, mainly in an inactive status, and the Ca(2+) concentration was found to be decreased in all the three cell lines. The invasion and proliferation ability of the three lung cancer cell lines were obviously decreasing (P < 0.001). However, the invasion and proliferation ability of L9981-nm23-H1 lung cancer cell line was still lower than that of L9981 and L9981-pLXSN lung cancer cell lines (P < 0.001). There was also no significant difference between L9981 and L9981-pLXSN cell lines (P > 0.05).</p><p><b>CONCLUSION</b>The results of this study suggest that nm23-H1 gene might inhibit the invasion and metastasis of lung cancer cells by down-regulating PKC signaling pathway. The Ca(2+) in cells might be involved in this process.</p>