Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis / 中华医学杂志(英文版)

BACKGROUND@#There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients.@*METHODS@#A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients.@*RESULTS@#After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy.@*CONCLUSION@#Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.

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>

Complete video-assisted thoracoscopic anatomic segmentectomy for pulmonary diseases: the early experiences / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and feasibility of video-assisted thoracic surgery (VATS) anatomic segmentectomy for pulmonary diseases.</p><p><b>METHODS</b>Between November 2009 and July 2011, 20 patients received consecutive VATS anatomic segmentectomy by single surgical group. There were 3 male and 17 female, aging from 32 to 81 years with a mean of 53 years. The patients included 12 cases of non-small cell lung cancer (NSCLC) (5 cases of bronchioloalveolar carcinoma, 6 cases of adenocarcinoma, and 1 case of squamous cell carcinoma), 7 cases of benign diseases (3 cases of bronchiectasis, 2 cases of inflammatory pseudotumor, 1 case of tuberculosis, and 1 case of sclerosing hemangioma) and 1 case of metastasis tumor. The locations of resected segments included 1 anterior segment, 3 posterior segments, 4 apical segments, and 2 superior segments in the right side; and 5 lingular segments, 3 trisegments, and 2 superior segments in the left side. Simultaneously, 3 patients with bronchiectasis underwent segmentectomy and lobectomy, 1 of 6 patients with adenocarcinoma underwent lingulectomy and thymectomy. The pathological TNM stages of 12 NSCLC patients were 9 cases of T1aN0M0, 1 case of T1bN0M0 and 2 cases of T2aN0M0.</p><p><b>RESULTS</b>Of these 20 patients, the median operative time was 155 minutes (range, 120 to 235 minutes), the median blood loss was 50 ml (range, 10 to 600 ml), the median drainage duration was 3 d (range, 1 to 6 d), and the median hospital stay was 6 d (range, 3 to 9 d). One patient who had undergone lingulectomy had a 600 ml intraoperative bleeding from lingular artery, and the bleeding was controlled by suturing the rupture under VATS. Bloody sputum occurred in 2 patients, prolonged air leak occurred in one patient for 5 days, and one patient developed subcutaneous emphysema that spontaneously resolved. No mortality was observed for 30 days after the surgery.</p><p><b>CONCLUSIONS</b>VATS anatomic segmentectomy is a feasible and safe technique with acceptable operative time, less blood loss, fewer complications, and shorter hospital stay.</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.

Analysis of lymph node metastasis in the thoracic esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the metastatic frequency in different groups of lymph nodes and its influencing factors of the thoracic esophageal squamous cell carcinoma (ESCC) in order to determine the extent of lymphadenectomy during esophagectomy.</p><p><b>METHODS</b>The clinical data of 730 patients with ESCC who underwent esophagectomy and lymphadenectomy were analyzed retrospectively.</p><p><b>RESULTS</b>Of 730 patients, 166 had metastasis to the para-esophageal lymph nodes (22.7%), 90 to the left gastric artery lymph nodes (12.3%), 67 to the lymph nodes around gastric cardia, and 15 to the subcrinal lymph nodes (2.1%). Univariate analysis showed that metastasis to the subcrinal lymph node was positively correlated with the length and differentiation of tumor (P < 0.05), but it was not correlated with any the above parameters when analyzed by multivariate analysis. The metastasis to the para-esophageal lymph node was positively correlated with the length, invasion depth and differentiation of tumor by univariate and multivariate analysis (P < 0.05). The metastasis to the lymph nodes around gastric cardia and metastasis to left gastric artery lymph nodes were positively correlated with the position and invasion depth of tumor by univariate and multivariate analysis (P < 0.05).</p><p><b>CONCLUSION</b>Lymph nodes of the para-esophagus, gastric cardia and left gastric artery usually have high frequency to harber mestastasis, therefore, it was suggested that the lymph nodes in these groups should be dissected during esophagectormy with two-field lymphadenectomy for thoracic esophageal squamous cell carcinoma. Whereas for those patients with the lesion < 3 cm in length or with tumor invasion confined within the esophageal wall or with a lesion located at the upper or lower third of the thoracic esophagus, the subcrinal lymph nodes may not be necessarily dissected.</p>

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>

Bronchial sleeve resection and reconstruction of pulmonary artery by video-assisted thoracic small incision surgery for central lung cancer: a report of 139 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and practicability between bronchial sleeve resection or reconstruction of the pulmonary artery by video-assisted thoracic small incision and routine posterolateral incision for lung cancer.</p><p><b>METHODS</b>The clinic data was analyzed retrospectively, including 139 cases in our hospital underwent sleeve lobectomy and bronchoplasty by video-assisted thoracic small incision surgery for lung cancer from January 1995 to July 2007 and 99 cases in the HUAXI Hospital of SICHUAN University underwent routine posterolateral incision from April 2000 to December 2005. All patients whose bronchus and/or pulmonary artery were involved underwent the operation and experienced the bronchial sleeve resection or reconstruction of the pulmonary artery.</p><p><b>RESULTS</b>All patients were done operation successfully with no perioperative mortality and no occurrence of anastomosis stenosis as well as fistula. The median survival period of video-assisted thoracic small incision patients and the posterolateral incision patients were 63.17 months and 42.00 months, respectively (P > 0.05). There was no sign of reperfusion injury in the reconstruction of the pulmonary artery patients. The small incisions' length was from 8 to 13 cm and the mean length was 10 cm. The routine posterolateral incisions' mean length was 30 cm. Compared to the patients underwent the routine posterolateral incision, patients underwent the operation of video assisted thoracic small incision had less operation time, less chest tube time, less hospitalization time and less postoperative shoulder joint dysfunction.</p><p><b>CONCLUSIONS</b>The bronchial sleeve resection and reconstruction of the pulmonary artery by video-assisted thoracic small incision surgery for lung cancer can finish the same work as the traditional thoracic lateral incision with less trauma and recovery time.</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>

Value of diagnosing micrometastasis by nested RT-PCR in the peripheral blood and bone marrow in non-small cell lung cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the specificity, sensitivity and their clinical significance of detecting CK19 mRNA expression by nested RT-PCR for molecular diagnosis of micrometastasis in the peripheral blood and bone marrow of patients with non-small cell lung cancer.</p><p><b>METHODS</b>CK19 mRNA expression was detected by nested RT-PCR in peripheral blood and bone marrow samples from 59 lung cancer patients, with samples of 11 benign pulmonary lesion patients and 20 healthy adults as control.</p><p><b>RESULTS</b>The sensitivity of nested RT-PCR was 10(-6). The positive rates of micrometastasis were 33.89% (20/59) in peripheral blood and 22.03% (13/59) in bone marrow, with a highly positive correlation existing between the two groups (P < 0.05). The micrometastasis in peripheral blood and bone marrow was closely correlated with the pathological classification and cell differentiation (P < 0.05) and P-TNM stage (P < 0.01). No CK19 mRNA expression was found in the samples from patients with benign pulmonary lesion or healthy adult volunteers.</p><p><b>CONCLUSION</b>The peripheral blood and bone marrow from patients with non-small cell lung cancer possesses micrometastasis that can not be detected by common methods. Nested RT-PCR technique shows favorable specificity and sensitivity in detecting the condition with definite clinical prospects.</p>