Neoadjuvant immunotherapy plus chemotherapy and adjuvant targeted therapy in ALK-positive non-small-cell lung cancer.

Neoadjuvant therapy and adjuvant therapy for locally advanced non-small-cell lung cancer (NSCLC) with ALK fusion mutation have not been thoroughly studied. Here, a stage IIIB NSCLC patient with EML4-ALK fusion mutation receiving immunotherapy plus chemotherapy as neoadjuvant treatment followed by lobectomy plus lymph node dissection is reported. The patient achieved a pathological complete response according to pathological evaluation. The patient received adjuvant crizotinib for 3 months and achieved a disease-free survival time of 36 months.

A 50-year-old man was diagnosed with lung cancer. Surgery was not initially an option due to the seriousness of the disease. He received two cycles of treatment and the tumor became obviously smaller. Then, he received an operation. No tumor cells were discovered after detection. The patient had one gene that was not normal. Consequently, he was administered medicine for 3 months. The patient has had good health for at least 36 months.

Pleuropneumonectomy for diffuse pleural metastasis in primary lung cancer.

OBJECTIVE: The purpose of this study is to analyze a single institution experience with pleuropneumonectomy for pleural metastasis and malignant pleural effusion in primary lung cancer. MATERIALS AND METHODS: From August 1978 to August 2011, 66 consecutive patients with lung cancer underwent pleuropneumonectomy. Patients were followed-up after the operation. The quality-of-life and the survival time were recorded. RESULTS: All the 66 patients were successfully operated on, including 38 patients in early years (1978-1993) and 28 patients in recent years (1994-2011). Two patients in early years died after the operation. Post-operative complications occurred including heart arrhythmia, respiratory insufficiency and bacterial infection of residual lung, chylothoraxin and mental disorder. A total of 61 patients have been successfully followed-up and three patients in early years were lost in 1 year after the operation. Local recurrence was found in seven cases (4 in early years, 3 in recent years) and distant metastasis was found in 48 cases (29 in early years, 19 in recent years). A total of 54 patients died from tumors, seven patients survived. The actuarial 1, 2 and 3-year survival rates are 72.7%, 27.2% and 6.1% of 36 in patients of early years and 85.7%, 46.4% and 21.4% in 28 patients of recent years. The mean survival and the median survival of the total 64 patients were 20.0 ± 10.9 months and 17 months respectively. Further analysis showed that the mean survival and the median survival of the 36 patients in early years were 17.2 ± 9.7 months and 15 months, in contrast to 23.4 ± 11.3 months and 18 months of the 28 patients in recent years. CONCLUSION: Pleuropneumonectomy is an option of patients with advanced-stage lung cancer associated with uncontrolled malignant pleural fluid by conservative therapies. Strict selection of patient to be operated, careful procedures to eradicate obvious tumors and metastasis and enhanced post-operative combined therapy are beneficial to patients' long-term survival.

Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: a prospective study from China.

BACKGROUND: Early detection and diagnosis is urgent for the sake of effective treatment strategy for lung cancer. However, a convenient, economical and relatively precise method is not available. We here report a prospective study to find the possible value of the combined use of four popular tumor markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung. METHODS: Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumor group according to post-operative histological examinations. Serum levels of four tumor markers including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), Cyfra 21-1 and neuron specific enolase (NSE) were assayed for each patient. Receiver operating characteristic (ROC) curves were constructed for each tumor marker. The power of lung cancer diagnosis of each tumor marker, as well as a combination of them were analyzed and compared. RESULTS: The serum levels (median, range) of SCC, CEA, Cyfra 21-1 and NSE were 0.44 (0.01 - 35.70) ng/ml, 2.49 (0.30 - 26.78) ng/ml, 2.30 (0.82 - 73.33) ng/ml and 10.54 (0.10 - 56.41) ng/ml respectively in lung cancer group, and were 0.32 (0.01 - 0.90) ng/ml, 1.60 (0.20 - 8.93) ng/ml, 1.41 (0.72 - 4.82) ng/ml and 9.36 (6.56 - 24.24) ng/ml respectively in the benign pulmonary tumor group. The difference in each tumor marker between the two groups was significant (P < 0.05). The ROCs of SCC, CEA, Cyfra 21-1 and NSE were 0.702 (95%CI, 0.654 - 0.751), 0.611 (95%CI, 0.563 - 0.659), 0.650 (95%CI, 0.601 - 0.700) and 0.598 (95%CI, 0.542 - 0.654) respectively, indicating very low power of these four tumor markers. When a combination of SCC, CEA, Cyfra 21-1 and NSE were employed, the diagnosis power was strengthened. CONCLUSION: SCC, CEA, Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung, especially when they were assayed together for one patient.

[Diagnosis and surgical treatment for mediastinal hemangioma and lymphangioma].

OBJECTIVE: To review the experience of diagnosis and surgical treatment of the primary mediastinal hemangioma and lymphangioma. METHODS: We summarized the medical records of patients with primary mediastinal hemangioma or lymphangioma at our hospital from January 1998 to January 2009, then extracted relevant clinical data and carried out the retrospective analysis. RESULTS: There were 11 patients in the whole group. The age range was 4 - 78 years old (average: 38.9). Six patients were symptom-free and most patients had not an accurate preoperative diagnosis. All patients underwent surgical procedures. The radical excision was accomplished in 10 cases and incomplete excision in 1 case. Two cases of surgically related complications were observed. All the cases were diagnosed by postoperative histopathological examination. There were hemangioma (n = 5), lymphangioma (n = 3) and hematolymphangioma (n = 3). CONCLUSIONS: The operation should be performed once the diagnosis of hemangioma or lymphangioma is made. Radical excision should be performed to prevent a post-operative recurrence.

Effects and mechanisms of non-restrictive external stent for prevention of vein graft restenosis in a rabbit model.

BACKGROUND: Among various treatments preventing vein graft restenosis, external stent is receiving more and more attention. This study aimed to investigate the effect of non-restrictive external stent on the prevention of vein graft restenosis and the potential mechanisms of platelet-derived growth factor (PDGF) in the process of restenosis. METHODS: Thirty-six "New Zealand white rabbits" were randomly divided into two groups, stented group (group S) and control group (non-stented group, group NS). Each rabbit underwent a reversed autologous external jugular vein into common carotid artery bypass grafting. In group S, the vein grafts were surrounded by a non restrictive stent which was 6 mm in diameter (a kind of Dacron vascular prosthesis); and in group NS, there was no stent to support the vein grafts. The grafts were harvested at the first week (1W), second week (2W) and fourth week (4W) after surgery respectively. The dimensions (including the thickness and area of the intima and media, luminal area) were measured by computer-aided image analysis system, and the intimal hyperplasia ratio was defined as the percentage of the area enclosed by the internal elastic lamina occupied by the intima. RESULTS: At 1W, the difference of the thickness and area of the intima between groups S and NS was not significant (P > 0.05); at 2W and 4W, the thickness and area of the intima and the intimal hyperplasia ratio in group S were less significant than those in group NS (P < 0.05); from 1W to 4W, the thickness and area of the media in group S were smaller than those in group NS (P < 0.05). Immunocytochemistry staining of PDGF-B showed that the percentage of positive cells of intima in both two groups was peaked at 2W, and a significantly smaller percentage was detected in group S compared with that in group NS at 2W and 4W (P < 0.05); the percentage of PDGF-B positive cells of media in both two groups was also peaked at 2W, and that in group S was smaller than that in group NS from 1W to 4W (P < 0.05); and the percentage of PDGF-B positive cells of adventitia in group S was peaked at 4W, whereas the percentage of adventitia in group NS peaked at 2W, and the percentage of adventitia in group S was greater than in group NS at 4W (P < 0.05). CONCLUSIONS: Non-restrictive external stenting inhibits the hyperplasia of the intima and media of the vein grafts and reduces the thickness and area of the intima and media; Non-restrictive external stenting inhibits the synthesis of PDGF and changes its distribution, and then inhibits the hyperplasia of the intima.

[Comparison of the biodistribution and PET imaging with (11)C-PDT and (18)F-FDG in the mouse model of lung adenocarcinoma].

OBJECTIVE: The objective of this study was to compare the biodistribution and PET imaging of (11)C-PDT and (18)F-FDG in a mouse model of lung adenocarcinoma, and to evaluate the value of (11)C-PDT as a new tracer for PET imaging of lung cancer. METHODS: Twenty four lung adenocarcinoma-bearing mice were randomly divided into two groups, 12 each. The mice received (11)C-PDT or (18)F-FDG injection i.v. respectively. The biodistribution of (11)C-PDT or (18)F-FDG in the mice was measured with a well-gamma detector at 60 min after injection. The PET imagings of mice were performed using either of the two tracers. RESULTS: Considerable uptake of the both radioactive tracers in the tumors was observed. The tumor uptake of (11)C-PDT [(0.65 +/- 0.20)%ID/g] was significantly lower than that of (18)F-FDG [(7.44 +/- 1.56)%ID/g, P < 0.01]. In the (11)C-PDT group, the highest uptake was observed in the liver, kidney and blood in a successively declining order, while the highest uptake of (18)F-FDG was seen in a order of heart, tumor and kidneys. The tumor/muscle ratio of (11)C-PDT uptake was relatively high (2.02 +/- 0.56), but still lower than that of (18)F-FDG (2.95 +/- 0.49, P < 0.01). All values of other tumor/organ ratios (T/NT) of (11)C-PDT uptake were < 2. High radioactive uptake was showed in the tumor and abdominal organs on PET images in the tumor-bearing mice injected with (11)C-PDT, and (18)F-FDG uptake was showed in the heart, tumor and abdominal organs. The tumor PET images with (11)C-PDT and (18)F-FDG were all clear. CONCLUSION: The uptake of (11)C-PDT in lung cancer is higher than that in muscle tissues, and pulmonary cancers can be detected by PET imaging. (11)C-PDT may be a promising PET tracer for lung cancers.

Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials.

INTRODUCTION: The survival effectiveness of neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) is still unclear based on the study of most up-to-date literatures. This article contributes to this problem by conducting an updated meta-analysis. METHODS: Based on Burdett et al's (J Thorac Oncol 2006;1:611-621) systematic review, this meta-analysis was conducted. Articles were searched electrically. The possible survival benefit of neoadjuvant chemotherapy was assessed by hazard ratio (HR) in terms of overall survival. A subgroup meta-analysis with only stage III NSCLC was also conducted. The software of Review Manager was used for data management. RESULTS: Thirteen randomized control trials, 6 of which were new ones, were included into this meta-analysis. The overall survival of NSCLC patients in neoadjuvant chemotherapy arm were improved significantly, comparing with those in surgery-alone arm (combined HR = 0.84; 95% confidence interval, 0.77-0.92; p = 0.0001). When only patients with stage III NSCLC were considered, the result was similar (combined HR = 0.84; 95% confidence interval, 0.75-0.95; p = 0.005). CONCLUSION: Neoadjuvant chemotherapy, as an addition of surgery, would significantly improve the overall survival of operable NSCLC patients, including patients with stage III NSCLC.

[Expression of EYA2 in non-small cell lang cancer].

OBJECTIVE: To identify the expression of Drosophila Eyes Absent Homologue 2 (EYA2) in non-small cell lung cancer (NSCLC) and to investigate its correlation with clinical parameters. METHODS: 59 fresh specimens of lung cancer and paired normal lung tissue were obtained from 59 NSCLC cases treated in the department of thoracic surgery in our hospital from June 2006 to October 2007. Western blotting and immunohistochemistry were used to assay the specimens with goat anti-human EYA2 polyclone antibody. Clinicopathological parameters were collected and the correlation with EYA2 expression was subsequently analyzed. RESULTS: The expression of EYA2 was detected in cytoplasm and nucleus of the cancer cells, but mostly in cytoplasm. Western blotting and immunohistochemistry showed the expression of EYA2 in NSCLC was increased and correlated with pathological type, but not with gender, age, pTNM stage, histological differentiation and lymph node metastasis. EYA2 expression was significantly up-regulated in adenocarcinoma, while not changed in lung squamous cell carcinoma. CONCLUSION: The results of this study suggest that expression of EYA2 in lung adenocarcinoma is augmented. EYA2 is likely participating in the development of lung adenocarcinoma as a transcriptional activator.

[Biodistribution and positron emission tomography imaging of 11C-acetate in murine model of lung carcinoma].

OBJECTIVE: To investigate the biodistribution and positron emission tomography (PET) imaging of 11C-acetate (11C-AC) in a murine model of pulmonary carcinoma, and to evaluate the use of 11C-AC for diagnosis of malignant tumor. METHODS: A total of 30 T739 mice underwent subcutaneous injection of mouse pulmonary adenocarcinoma cells of the line LA-795 to establish adenocarcinoma models and then were randomly divided into five equal groups. Four groups underwent intravenous injection of 11C-acetate through the caudal vein, killed 5, 10, 20, and 30 minutes later respectively, underwent PET, and then their organs and tumors were isolated. The mice in the control group underwent injection of 11F-fluorodeoxyglucose (18F-FDG) and were killed 60 min later. The biodistribution of 11C-AC and that of 18F-FDG were measured with well-gamma detector. The ratios of the levels of percentage activity of injection dose per gram of tissue between the tumor and normal tissues (T/NT ratios), were calculated. RESULTS: In the biodistribution study of 11C-AC, considerable radioactive uptake of tumor was observed, and much radioactivity was showed in kidney, liver, and spleen. The ratios of tumor/blood, tumor/muscle, and tumor/lung were all above 2. 0. The tumor PET images with 11C-AC as tracer were as clear as that with 18F-FDGas tracer. The 11C-AC standard uptake value (SUV) of the tumors was 2.8 +/- 0.8, significantly lower than that of 18F-FDG (5.3 +/- 1.6, P <0.01). CONCLUSION: 11C-AC can be used in PET imaging of pulmonary malignancy. The optimized imaging acquisition time point is 20 min after injection. It may become a complementary tracer in the cases with unsatisfying 18F-FDG images.

[Diagnosis and surgical treatment of the primary mediastinal teratoma].

OBJECTIVE: To review the experience of diagnosis and surgical treatment of the primary mediastinal teratomas. METHODS: The clinical data of forty-nine cases with teratoma were retrospectively analysed from March 1996 to March 2006. RESULTS: Based on history, physical examination, chest X-ray, CT scan and magnetic resonance, the diagnosis of forty-eight cases were confirmed before surgery. Surgical procedures were performed in all cases. Forty-six patients were subjected to radical excision, two patients to partial excision and one patient to exploratory operation. Among all the cases, Wedge resection of the lung was performed in eight cases, partial pericardium excision in six cases. There was no surgically related mortality or complications in any patients. The diagnosis of teratoma was confirmed by postoperative histopathological examination. No relapse occurred during follow-up. CONCLUSIONS: History, physical examination and radiological imaging are the main diagnostic means for the primary mediastinal teratoma. Surgical resection is an effective therapy. Early diagnosis and correct selection of operation according to the characteristic of the tumor are important to therapy.

[Diagnosis and surgical treatment of mediastinal tumors and cysts: analysis of 343 cases].

OBJECTIVE: To review the experience of diagnosis and surgical treatment of mediastinal tumors and cysts. METHODS: The clinical data of 343 cases with mediastinal tumors and cysts who underwent operation from March 1996 to April 2005, 208 males and 135 females, aged 40.5 +/- 16.1, were analyzed. RESULTS: No specific symptom and sign was found among the patients. Tumor of Thymus accounted for 42.24%. 300 of the 343 patients were subjected to radical excision, and 25 patients to partial excision. The diagnosis of all the patients was confirmed by postoperative histopathological examination. Surgically related complications were observed in 9 cases. CONCLUSION: Tumor of thymus is the commonest mediastinal tumors. Early operation is necessary provided there is no contraindication thereto.

[Results of myasthenia gravis treated with thymectomy].

OBJECTIVE: To evaluate the effectiveness of thymectomy for myasthenia gravis (MG) and the relative risk factors for postoperative myasthenic crisis. METHODS: The clinic data of 78 cases with MG who underwent thymectomy from June 1985 to June 2005 were analyzed retrospectively. The relative risk factors of postoperative myasthenic crisis were analyzed and the differences between new and old region of perioperative management were compared. RESULTS: The symptom of MG was complete remission in 21 cases, significantly improved in 38 cases, improved in 11 cases and unchanged in 8 cases, respectively. The symptom duration before operation, preoperative serum level of anti-acetylcholine receptor antibody, Osserman stage and pathological type of thymoma were independent relative risk factors for postoperative myasthenic crisis. The new region of perioperative management was significant better than the old one. CONCLUSION: Surgical treatment shows significant clinical benefits for patients with MG.

[The application of stapling device in surgery of carcinoma of the esophagus and cardia].

OBJECTIVE: To evaluate the application of circular stapler in upper digestive tract reconstruction. METHODS: We present a retrospective review of 3322 patients with Carcinoma of esophagus and cardia undergoing a stapled esophagogastric anastomosis from August 1980 to September 2004. There were 2642 males and 680 females with age ranged from 28 to 83 years old. Carcinoma of esophagus was present in 2312 patients and carcinoma of gastric cardia in 1010 patients. The anastomosis was performed in the cervical region in 102 cases, thoracic apex in 147 cases, up aortic in 1838 cases and below aortic in 1235 cases. RESULTS: Anastomotic leakage occurred in 18 patients with an overall incidence of 0.54%, including thoracic leakage in 11 cases and cervical leakage in 7 cases. nine patients were dead because of the thoracic leakage, and the mortality of thoracic leakage was 81.8%. Benign anastomotic stricture was found in 66 patients with a rate of 2.0%, and instrumental failure occurred in 36 patients with a rate of 1.1%. CONCLUSION: Circular stapler can be used safely and reliably in upper digestive tract surgery, and the stapled anastomosis is an effective technique to reduce the incidence of anastomotic leakage.

[An experimental research on inhibitory action of skeletal muscle conditioned medium on metastases of lung carcinomas].

BACKGROUND & OBJECTIVE: Malignant tumors spread and metastasize in the majority of the organs, but are very rare in skeletal muscles. This study was conducted to explore the effect of organic microenvironment of skeletal muscles on the proliferation of pulmonary large cell carcinomas with different metastatic potential and to investigate the mechanism of the rarity of metastases in skeletal muscles. METHODS: Primary culture of newborn Wistar rat skeletal muscle cells was established, and the murine skeletal muscle conditioned medium(MMCM)was prepared to test its effect in vitro on pulmonary large cell carcinomas with different metastatic potential (PLA-801C with lower potential and PLA-801D with relatively higher potential) by MTT assay. Adriamycin was used as positive control for MMCM; murine benign renal cells BHK-21 were used as negative control for lung carcinoma cells. RESULTS: Proliferation of tumor cell lines of both PLA-801C and PLA-801D was significantly restrained when cultured with MMCM, while BHK-21 cells were not affected(P< 0.05). Compared with PLA-801C (significant only in primary MMCM), PLA-801D showed significantly decreased proliferation even when cultured in higher reciprocal of MMCM dilution(1/16 of primary MMCM). CONCLUSION: Skeletal muscle cells could selectively inhibit the proliferation of cancerous cells in vitro while benign cells are not affected. Tumor cells with higher metastatic potential are more sensitive to this effect.

[Results of unilateral lung volume reduction surgery in twenty-five patients with chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the effectiveness of unilateral lung volume reduction surgery (LVRS) in patients with chronic obstructive pulmonary disease (COPD). METHODS: The follow-up data of 25 patients with COPD who had underwent unilateral LVRS between January 1996 to December 2002 in department of thoracic surgery, China-Japan friendship hospital were analyzed retrospectively. The operative target was determined by pre-operative CT and pulmonary ventilation-perfusion (V/Q) scintigraphy. LVRS was performed in 21 patients through video assisted thoracoscopy surgery (VATS) or VATS with adjuvant small lateral thoracotomy. In 4 patients LVRS was performed through posterolateral thoracotomy. Destroyed pulmonary tissue was resected by liner stapler or Endo GIA. To evaluate the effectiveness of unilateral LVRS, the changing of dyspnea score, pulmonary function and the quality of life were analyzed. RESULTS: The postoperative follow-up interval range was 2 years. The mean postoperative FEV(1) increased by (35 +/- 9)%, and six minute walking distance (6MWD) increased by (88 +/- 22)%. For dyspnea score, among 16 patients with a preoperative grade of IV, 4 patients improved to grade I, 12 improved to grade II; among 9 patients with a preoperative grade of V, 1 improved to grade I, 1 improved to grade II, 4 improved to grade III, and the other 3 improved to grade IV. Karnofsky score increased by (44 +/- 10) in average. One and two year survival rates was 96% and 92%, respectively. There was no perioperative death in this group, and the total postoperative morbidity was 32%. CONCLUSIONS: Unilateral LVRS shows significant clinical benefits for the majority of patients with COPD. It is associated with lower operative mortality and morbidity, and has a wide range of indications. The key points of the operation are to resect dysfunctional lung tissues as much as possible and to prevent pulmonary air leak. Preoperative and postoperative breathing training plays a very important role in the postoperative recovering of lung function.