Circulating tumor DNA integrating tissue clonality detects minimal residual disease in resectable non-small-cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has been proven as a marker for detecting minimal residual diseases following systemic therapies in mid-to-late-stage non-small-cell lung cancers (NSCLCs) by multiple studies. However, fewer studies cast light on ctDNA-based MRD monitoring in early-to-mid-stage NSCLCs that received surgical resection as the standard of care. METHODS: We prospectively recruited 128 patients with stage I-III NSCLCs who received curative surgical resections in our Lung Cancer Tempo-spatial Heterogeneity prospective cohort. Plasma samples were collected before the surgery, 7 days after the surgery, and every 3 months thereafter. Targeted sequencing was performed on a total of 628 plasma samples and 645 matched tumor samples using a panel covering 425 cancer-associated genes. Tissue clonal phylogeny of each patient was reconstructed and used to guide ctDNA detection. RESULTS: The results demonstrated that ctDNA was more frequently detected in patients with higher stage diseases pre- and postsurgery. Positive ctDNA detection at as early as 7 days postsurgery identified high-risk patients with recurrence (HR = 3.90, P < 0.001). Our results also show that longitudinal ctDNA monitoring of at least two postsurgical time points indicated a significantly higher risk (HR = 7.59, P < 0.001), preceding radiographic relapse in 73.5% of patients by a median of 145 days. Further, clonal ctDNA mutations indicated a high-level specificity, and subclonal mutations informed the origin of tumor recurrence. CONCLUSIONS: Longitudinal ctDNA surveillance integrating clonality information may stratify high-risk patients with disease recurrence and infer the evolutionary origin of ctDNA mutations.

Curcumol Inhibits Lung Adenocarcinoma Growth and Metastasis via Inactivation of PI3K/AKT and Wnt/-Catenin Pathway.

Curcumol (Cur), isolated from the Traditional Chinese Medical plant Rhizoma Curcumae, is the bioactive component of sesquiterpene reported to possess antitumor activity. However, its bioactivity and mechanisms against lung adenocarcinoma are still unclear. We investigated its effect on lung adenocarcinoma and elucidated its underlying molecular mechanisms. In vitro, Cur effectively suppressed proliferation, migration, and invasion of lung adenocarcinoma cells A549 and H460, which were associated with the altered expressions of signaling molecules, including p-AKT, p-PI3K, p-LRP5/6, AXIN, APC, GSK3 and p--catenin, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, Cur significantly induced cell apoptosis of A549 and H460 by promoting the expression of Bax, caspase 3, and caspase 9 and suppressing the expression of Bcl-2, and arrested the cell cycle at the G0/G1 phase by lowering the levels of cyclin D1, CDK1, and CDK4. In vivo experiment revealed that Cur could inhibit lung tumor growth and lung metastasis, which were consistent with these in vitro results. In xenograft model mice, Cur strongly decreased tumor weight and tumor volume, which may be related to the downregulation of p-AKT and p-PI3K by immunofluorescence analysis. In addition, a lung metastasis model experiment suggested that Cur dramatically decreased the ratio of lung/total weight, tumor metastatic nodules, and the expressions of MMP-2 and MMP-9 in lung tissues compared with the control. Overall, these data suggested that the inhibitory activity of Cur on lung adenocarcinoma via the inactivation of PI3K/Akt and Wnt/-catenin pathways, at least in part, indicates that curcumol may be a potential antitumor agent for lung adenocarcinoma therapy.

Left upper lobectomy with bronchoplasty in uniportal video-assisted thoracic surgery for bronchial carcinoid.

A 36-year-old male smoker presented with a bronchial carcinoid in the left upper lobe (LUL) associated with bronchial occlusion of the LUL bronchus. A left upper lobectomy with bronchoplasty was performed through a 3.5 cm single-incision in video-assisted thoracic surgery (VATS). The procedure was successful and the recovery uneventful. Pathological examination revealed a carcinoid tumor with no lymph node involvement (T1bN0M0). The follow-up bronchoscopy and computed tomography (CT) scan confirmed no stenosis and no signs of recurrence.

Surgical treatment for bronchopleural fistula with omentum covering after pulmonary resection for non-small cell lung cancer.

BACKGROUND: Bronchopleural fistula is an especially severe complication with a high mortality rate. We investigated the efficiency of our surgical treatments for this severe complication. METHODS: From January 2007 to December 2009, standard surgical resections and systematic lymph node dissections for non-small cell lung cancer (NSCLC) were performed on 1178 patients at our institution. Eight patients developed bronchopleural fistulas during the postoperative follow-up period, and received reoperations. Seven patients underwent additional pneumonectomies, and the omental flap, which was mobilized using a transdiaphragmatic harvesting technique through the usual thoracotomy, was used to cover postpneumonectomy bronchial stump. The other patient, who had received right side pneumonectomy and systemic lymph node dissection, received omental flap stuffing and covering without reclosure of the stump or carinal plasty. RESULTS: Bronchopleural fistulas after standard surgical resections and systematic lymph node dissections for NSCLC were observed in eight patients (0.68%) in our study. The period between pulmonary resection and the appearance of bronchopleural fistula ranged from eight to 19 days (median 11 days). Repairing of the bronchial fistula was successful in all eight patients and no development of late fistula was found during the follow-up period. Postoperative hospital stay for undergoing omentoplasty to repair the bronchial fistula ranged between 11 and 23 days (median 15 days). There were no complications related to the omentoplasty procedure. CONCLUSION: Transdiaphragmatic harvesting technique of omental flap through a thoracotomy is safe and technically feasible. Surgical treatment for postoperative bronchopleural fistula with omental flap covering is effective.

[Lung auto-transplantation technique in the treatment for stage III central lung cancer].

OBJECTIVE: To assess the feasibility and benefit of lung auto-transplantation technique in surgical treatment for stage III central lung cancer. METHODS: From Aug 2000 to June 2007 eight patients, who were proved to be malignant pathologically through fiber-bronchoscope before operations and could not tolerate pneumonectomy, underwent lung auto-transplantations. The "cutdown" lower lobe was flushed with heparin solution at 20 degrees C. Since the length of resected bronchus or pulmonary artery involved by tumor was too long to perform tension-free anastomosis, we transplanted the inferior pulmonary vein to the proximal stump of the superior pulmonary vein. The bronchus and pulmonary artery were anastomosed in turn. Then radical hilar and mediastinal lymphadenectomy was performed. RESULTS: No anastomotic stoma fistula occurred in these 8 patients. Until Jan 2008, six of the eight patients who underwent lung autotransplantations, had been free of tumor recurrence for 7-90 months with good quality of life. And the median time was 33 months. Radioisotope scanning of the replanted lobes of three patients revealed normal perfusion 18, 24 and 72 months postoperatively. One patient received resection of the replanted lobe because of pulmonary vein thrombus on the 2nd day after transplantation, and died of respiratory failure caused by pulmonary relapse on 15th month postoperatively. Another patient died of brain metastases 31 months postoperatively. CONCLUSION: Lung auto-transplantation is an alternative technique for pulmonary preservation for patient with stage III centrally placed lung cancer, whose cardio-pulmonary functions is too poor to undergo pneumonectomy.

Carinal resection and reconstruction in surgical treatment of bronchogenic carcinoma with carinal involvement.

BACKGROUND: Carinal resection and reconstruction is technically demanding. The aim of this study is to discuss the clinical value of carinoplasty in the surgical treatment of bronchogenic carcinoma involving carina. MATERIALS AND METHODS: From 1982 to 2006, 41 cases of centrally placed bronchogenic carcinoma invading the carina were treated with carinal resection and reconstruction in our hospital. Among the 41 patients, 25 patients simultaneously underwent additional cardiovascular plasty operations besides carinoplasty. There were 12 different types of carinal resection and reconstruction in our group. RESULTS: In this group, there was one perioperative death due to anastomotic leakage. This patient died 2 weeks postoperatively. Arrhythmia occurred in 12 patients, atelectasis in eight patients, and pneumonia in five patients. Five patients had to be assisted with mechanical ventilation because of pulmonary function failure. Anastomosis stenoses were found in three patients 3 to 6 months postoperatively and were resolved by stent insertion. Thirty-one patients were diagnosed with tumor recurrences after operations. Progression-free survival was 75.6% at 1 year, 43.9% at 3 years, and 22.0% at 5 years; the overall actuarial survival was 75.6% at 1 year, 46.3% at 3 years, and 26.8% at 5 years. Survival was better in patients with N0-1 disease than those with N2 disease (37.0% versus 7.1% at 5 years). CONCLUSION: Carinoplasty for bronchogenic carcinoma involving carina is feasible with acceptable morbidity and mortality if patients are selected carefully. Preoperative evaluation of the mediastinum is crucial for treatment selection.

Lung autotransplantation technique in the treatment for central lung cancer of upper lobe.

AIM: To assess the feasibility and benefit of lung autotransplantation technique in surgical treatment for central lung cancer of upper lobe which could not tolerate pneumonectomy. METHODS: From August 2000 to August 2006 seven patients, who were proved to be malignant pathologically through fiber-bronchoscope before operation and could not tolerate pneumonectomy, underwent lung autotransplantations. Double-sleeve resection of the right upper and middle bilobectomy (or left upper lobectomy) and involved pulmonary artery was performed firstly. Because the length of resected bronchus or pulmonary artery involved by tumor was too long to perform tension-free anastomosis, we transplanted the inferior pulmonary vein to the proximal stump of the superior pulmonary vein. The bronchus and pulmonary artery were anastomosed in turn. Then radical hilar and mediastinal lymphadenectomy was performed. RESULTS: Until August 2006, among the seven patients who underwent lung autotransplantations, five patients had been free of tumor recurrence for 2 to 73 months with good quality of life. Radioisotope scanning of the replanted lobe of one patient revealed normal perfusion 6 years postoperatively. One patient received resection of the replanted lobe because of pulmonary vein thrombus on the second day after transplantation, and died of respiratory failure caused by pulmonary relapse on 15th month postoperatively. Another patient died of brain metastases 31 months postoperatively. No anastomotic stoma fistula occurred in these seven patients. CONCLUSION: Lung autotransplantation is an alternative technique for pulmonary preservation for patients with centrally placed tumor of the upper lobe, whose pulmonary function is too poor to undergo pneumonectomy.

[Experience of carinal resection and reconstruction in the treatment of carinal tumor and bronchogenic carcinoma].

BACKGROUND: Carinal resection and reconstruction is an emphasis in surgical treatment of carinal tumor and bronchogenic carcinoma involving carina. The aim of this study is to discuss the clinical value of carinoplasty in lung cancer surgery. METHODS: From 1982 to 2004, 41 cases of central bronchogenic carcinoma that invaded the carina accepted carinal resection and reconstruction in this hospital. Of the 41 patients, 25 patients underwent simutaneously additional cardiovascular plasty operation besides carinoplasty. There were 12 different types of carinal resection and reconstruction in this series. RESULTS: There was 1 perioperative death (because of anastomotic leakage) in this group. Arrhythmia occured in 12 patients, atelectasis in 6 patient and pneumonia in 5 patients. Five patients were assisted ventilation through breathing machine because of pulmonary function failure. The 1-, 3-, and 5-year survival rates were 76.21%, 47.23% and 26.83% respectively. CONCLUSIONS: The carinoplasty is a good method to treat central bronchogenic carcinoma which invaded the carina. With this method lung cancer tissue can be resected maximally, meanwhile, it can save pulmonary function of patient maximally. Postoperative multi-modality therapy is helpful to increase postoperative survival rate and improve quality of life.

[Surgical treatment for locally advanced lung cancer invading heart and great vessels].

BACKGROUND: To summarize the surgical treatment for locally advanced lung cancer invading heart and great vessels. METHODS: One hundred and eighteen cases of lung cancer accepting cardiovascular plasty operation from 1980 to 2001 were reviewed. RESULTS: The operations included partial resection of left atrium in 38 cases, pulmonary artery resection and restruction in 48 cases, replacement or partial resection of superior vena cava in 25 cases, partial resection of pulmonary conus in 3 cases, and lober replantation in 4 cases respectively. There was no perioperative death, and the 1-, 3-, 5- and 10 year survival rate was 72.68%, 55.20%, 28.62% and 20.36% respectively. CONCLUSIONS: Cardiovascular plasty in the surgical treatment of locally advanced lung cancer invading heart or great vessels can remarkably increase the long-term survival and improve the life quality of the patients.