Antoine Dujon

Survival of Patients With Resected N2 Non–Small-Cell Lung Cancer: Evidence for a Subclassification and Implications

PURPOSE Patients who suffer from non-small-cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node involvement (N2) belong to a heterogeneous subgroup of patients. We analyzed the prognosis of patients with resected N2 NSCLC to propose homogeneous patient subgroups. PATIENTS AND METHODS The present study comprised 702 consecutive patients from six French centers who underwent surgical resection of N2 NSCLC. Initially, two groups of patients were defined: patients with clinical N2 (cN2) and those with minimal N2 (mN2) disease were patients in whom N2 disease was and was not detected preoperatively at computed tomographic scan, respectively. RESULTS The median duration of follow-up was 52 months (range, 18 to 120 months). A multivariate analysis using Cox regression identified four negative prognostic factors, namely, cN2 status (P <. 0001), involvement of multiple lymph node levels (L2+; P <.0001), pT3 to T4 stage (P <.0001), and no preoperative chemotherapy (P <. 01). For patients treated with primary surgery, 5-year survival rates were as follows: mN2, one level involved (mN2L1, n = 244): 34%; mN2, multiple level involvement (mN2L2+, n = 78): 11%; cN2L1 (n = 118): 8%; and cN2L2+ (n = 122): 3%. When only patients with mN2L1 disease were considered, the site of lymph node involvement according to the American Thoracic Society numbering system had no prognostic significance (P =.14). Preoperative chemotherapy was associated with a better prognosis for those with cN2 (P <.0001). Five-year survival rates were 18% and 5% for cN2 patients treated with and without preoperative chemotherapy, respectively. CONCLUSION This study has identified homogeneous N2 NSCLC prognostic subgroups and suggests different therapeutic approaches according to the subgroup profile.

Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor

BACKGROUND Visceral pleura invasion (VPI) by non-small cell lung cancer is a factor of poor prognosis. A tumor of any size that invades the visceral pleura is classified as T2. Few studies have been conducted concerning the prognostic significance of VPI relative to other staging factors. METHODS Between April 1984 and December 1996, 1,281 patients with T1 (n = 430) and T2 (n = 851) non-small cell lung cancer underwent curative surgical resection. Adjuvant radiation therapy was performed in 455 patients. There were 176 women and 1,105 men aged 30 to 86 years (mean, 60.9 years). Five hundred nineteen pneumonectomies, 742 lobectomies, and 20 segmentectomies were performed. In all patients, a complete mediastinal lymph node dissection was performed. International staging was stage IA and B (n = 697); stage II A and B (n = 247), and stage III A (n = 337). The patients were divided into two groups according to the existence of VPI (group I without, group II with). Both groups were compared with regard to the size of the tumors, histology, associated lymph node involvement, survival rates, and cause of death. Univariate and multivariate analyses were conducted. RESULTS VPI (group II) was identified in 19.1% of the resected specimens: group I, n = 1036; group II, n = 245. The VPI was present in only 10% of non-small cell lung cancer 3 cm or less in size, reaching 33% of patients with non-small cell lung cancer larger than 5 cm (p = 0.0001). Squamous non-small cell lung cancer were significantly less accompanied by VPI (13.5%) than the other histologic categories. The VPI was associated with a higher frequency of N2 involvement (group I = 24.6%, group II = 33.4%, p = 0.01) and N2 involvement was more extensive (two or more N2 involved stations: group I = 8.2%, group II = 15.6%, p = 0.003). Actuarial survival rates were 51.8% at 5 years and 33.8% at 10 years in group I (median, 66 months), and 34.6% at 5 years and 27.9% at 10 years in group II (median, 30 months) (p = 0.000002). Long-term survival rates significantly decreased for larger tumors. Even in patients with N2 stage tumors, the difference of survival curves between the two groups was statistically significant. Cancer-related deaths were more frequent in group II and were mainly caused by distant metastases. By multivariate analysis, visceral pleura invasion proved to be a significant independent factor of poor prognosis. CONCLUSIONS The VPI is a factor of poor prognosis. Its frequent association with extensive N2 involvement supports the hypothesis that exfoliated tumor cells are drained through the pleural lymphatics by the mediastinal lymphatic pathways and then into the bloodstream. The VPI is an important prognostic factor and, as such should stimulate more studies to better select the patients who could benefit from adjuvant therapy.

Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung

BACKGROUND N1 disease represents a heterogeneous group of non-small cell lung carcinoma with varying 5-year survival rates. Specific types of N1 lymph node involvement need to be further investigated and their prognostic significance clarified. METHODS From 1984 to 1993, 1,174 patients with non-small cell lung cancer had complete mediastinal lymph node dissection: N0, 50.25% (n = 590); N1, 21.8% (n = 256); and N2, 27.95% (n = 328). The N1 subgroup cases were reviewed. Four levels of N1 nodes were identified using the New Regional Lymph Node Classification for Lung Cancer Staging. Their prognostic significances were tested and 5-year survival rates were compared with those of N0 and N2 patients of the whole group. RESULTS The overall 5-year survival rate of N1 patients was 47.5%. Survival was not related to site of the primary lung cancer, pathologic T factor, histologic type, type of resection, number of N1 station involved, nor type of N1 involvement (direct extension or metastases). Five-year survival was significantly better when N1 involvement was intralobar (levels 12 and 13, n = 102), as compared with extralobar (hilar) involvement (levels 10 and 11, n = 154): 53.6% versus 38.5% (p = 0.02). Intralobar N1 5-year survival was similar to that of N0 (53.6% vs 56.5%, p = 0.01), and extralobar 5-year survival with that of N2 (38.5 vs 28.3%, p = 0.01) when N2 was present in only one station in the ipsilateral mediastinum. CONCLUSIONS N1 disease is a compound of two subgroups: one located inside the lobes is related to N0, and the other (extralobar or hilar) behaves like an early stage of N2 disease. This offers further information for clinical, therapeutic, and research purposes.

Pulmonary Resection for Metastases of Colorectal Adenocarcinoma

BACKGROUND Surgery is a safe and effective treatment for patients with lung metastases from colorectal carcinoma. Combining chemotherapy and surgery seems to prolong survival time after metastasectomy. Our purpose was to review the effectiveness of surgery with time and evolving managements. METHODS The records of 127 patients were retrospectively analyzed. The characteristics of primary cancer, lung metastases, resections, and associated therapy were studied according to their incidence on survival. RESULTS There were 74 male and 53 female patients (mean age, 65 years); 223 operations were performed and 314 metastases were resected. Completeness of surgery (n = 117) was the main factor for prolonged survival (5- and 10-year survival, 41% and 27%, versus 0%). There was no factor of significantly better prognosis, but a tendency to higher survival rates was observed in cases of single metastasis, in patients undergoing several lung operations, and in patients in whom liver metastases were previously removed. Three of 7 patients with mediastinal lymph node involvement survived more than 5 years; 58 patients were operated on before January 2000, and 59 between January 2000 and December 2007. Five-year survival rates were 35.1% versus 63.5%, respectively (p = 0.0096), probably related to better selection with modern workup, more frequent use of chemotherapy, and repeated pulmonary resections. CONCLUSIONS Different treatment protocols were reported in the literature and in our series with time, resulting in better survival rates and a more aggressive surgical tendency. The beneficial role of such combined therapy justifies further research, including prospective trials.

Patterns of relapse of N2 nonsmall-cell lung carcinoma patients treated with preoperative chemotherapy

Although it induces a relevant reduction in the risk of both visceral metastases and locoregional recurrences, the combination of chemotherapy and surgery only marginally improves the survival of patients with Stage IIIA(N2) (International Union Against Cancer staging and classification system) nonsmall‐cell lung carcinoma (NSCLC). The purpose of the current study was to analyze the patterns of relapse in these patients.

Management of superior sulcus tumors: experience with 139 cases treated by surgical resection.

BACKGROUND The management of non-small cell carcinomas of the lung involving the superior sulcus remains controversial. The goal of this retrospective study was to evaluate the role of surgery, radiotherapy, and chemotherapy for the treatment of superior sulcus tumors, to define the best surgical approach for radical resection, and to identify factors influencing long-term survival. METHODS Between 1983 and 1999, 139 patients underwent surgical resection of superior sulcus tumors in seven thoracic surgery centers. According to the classification of the American Joint Committee, 51.1% of cancers were stage IIB, 13.7% stage IIIA, 32.4% stage IIIB, and 2.9% stage IV. RESULTS The resections were performed with 74.1% using the posterior approach and 25.9% using an anterior approach. A lobectomy was accomplished in 69.8% of the cases and a wedge resection in 22.3%. Resection of a segment of vertebrae or subclavian artery was performed, respectively, in 19.4% and 18% of the cases. Resection was complete in 81.3% of cancers. The overall 5-year survival rate was 35%. Preoperative radiotherapy improved 5-year survival for stages IIB-IIIA. Surgical approach, postoperative radiotherapy, or chemotherapy did not change survival. CONCLUSIONS The optimal treatment for superior sulcus tumors is complete surgical resection. The surgical approach (anterior/posterior) did not influence the 5-year survival rate. Preoperative radiotherapy should be recommended to improve outcome of patients with a superior sulcus tumor.

Thoracoscopic excision of mediastinal bronchogenic cysts: results in 20 cases

BACKGROUND We present our experience with thoracoscopic resection of mediastinal bronchogenic cysts in adults. METHODS From November 1990 to September 1993, 20 patients with mediastinal bronchogenic cysts were operated on by thoracoscopy. The average cyst size was 4.9 cm, and the largest diameter was 10 cm. Ten cysts were located in the middle mediastinum and 10 in the posterior mediastinum. Two cysts were complicated. RESULTS Thirteen bronchogenic cysts were resected completely by thoracoscopy. We had to convert thoracoscopy into thoracotomy because of bleeding in two cases and because of major adhesions to vital structures in five cases. There were no operative deaths and no postoperative complications. Mean hospital stay was significantly less in the completely thoracoscopically treated group. Long-term follow-up (range, 4.5 to 7.5 years) showed no late complications and no recurrence. CONCLUSIONS Preoperative complications, intraoperative injuries, and major adhesions to vital structures seem to be the only unfavorable conditions to thoracoscopic treatment of bronchogenic cysts. This study found encouraging results for thoracoscopic excision of mediastinal bronchogenic cysts in selected patients.

Complications of video-assisted thoracic surgery: A five-year experience

BACKGROUND Although thoracoscopy was originally described in 1910, recent developments in video-assisted surgical techniques and endoscopic equipment has expanded the application of video-assisted surgical procedures in the field of thoracic surgery. METHODS In an effort to define both high-risk patients for video-assisted thoracic procedures and high-risk video-assisted thoracic surgical procedures, we reviewed the experience of four surgical institutions from June 1991 through May 1995. We looked specifically at complications resulting from the 937 video-assisted thoracic procedures performed during this period. RESULTS Perioperative incidents or complications occurred in 35 patients (3.7%), and 116 procedures (12.4%) were converted to a thoracotomy. The in-hospital mortality rate was 0.5%, and death occurred principally in patients operated on for malignant pleural effusion. The overall incidence of postoperative complications was 10.9%, and the most prevalent complications were prolonged air leak (6.7%) and pleural effusion (0.7%). CONCLUSIONS The incidence of complications was acceptable and, except for that of prolonged air leak, did not differ significantly from that resulting from analogous open procedures. Video-assisted thoracic surgery appears safe and particularly useful for some indications. However, the possibility of dramatic life-threatening perioperative complications requiring emergency conversion to thoracotomy justifies the fact that only trained thoracic surgeons should perform video-assisted thoracic surgical procedures.

Multiple Lung Cancers Prognosis : What About Histology?

BACKGROUND Among multiple lung cancers (MLC), some may have similar histologic classification. Demonstrating that the second tumor is a metastasis would change the stage and consequently the management. Our purpose was to reconsider this consequence. METHODS We reviewed 234 patients (194 male and 40 female, from 37 to 83 years of age) with synchronous and metachronous non-small cell MLC. Surgery consisted of a potentially curative complete resection with lymphadenectomy. Patients with similar histologic MLC (considered as metastasis) were compared with those with different histologic classification in terms of MLC chronology, type of resection, pT and pN, stage, and overall survival. RESULTS There were 116 metachronous (ipsilateral, n = 48; contralateral, n = 68) and 118 synchronous MLCs (bilateral, n = 10; same lobe, n = 57; other lobe, n = 51). Pneumonectomy was performed in 77 patients, lobectomy in 103, and lesser resection in 54. Histologic classification was similar in 57.9% of patients and different in 42.1%. The 5-year survival rates tended to be lower in patients with synchronous MLCs (23.4% versus 31.6%; p = 0.07). They were higher when synchronous MLCs were located in the same lobe than if they were located in another lobe (29.9% versus 15.6%; p = 0.022). Whatever the type of MLC, the 5-year survival rates were not correlated with similar or different histologic classification. CONCLUSIONS Our analysis supports that surgery is safe and warranted in MLC patients even if synchronous MLCs present ominously. Changing the staging by establishing the diagnosis of metastasis is probably an important issue warranting further biologic research, but according to our results this diagnosis must not in any case preclude surgery.

Chylothorax complicating pulmonary resection

BACKGROUND Chylothorax complicating pulmonary resection (CCPR) is infrequent and surgical treatment is for the most part avoided. The purpose of this study is to analyze the clinical and therapeutic characteristics of this complication. METHODS From March 1981 to June 2001, 26 cases of CCPR (24 men and 2 women; mean age 57 years) were treated in two departments of thoracic surgery. Twenty-five cases complicated lung resection for lung cancer (lobectomy n = 14, bilobectomy n = 3, pneumonectomy n = 8) and 1 case followed lobectomy for a benign lesion. Medical history, location, and characteristics of the chylothorax, lymphography, and clinical evolution after medical or surgical therapy were studied. RESULTS Medical history was never predictive of CCPR. Chylothorax was right sided in 18 cases and left sided in 8 cases. The total amount of chyle ranged from 1.9 L to 27.9 L per patient with a mean of 7.9 L (pneumonectomy 12.3 L and lobectomy 6.3 L). In 15 patients (pneumonectomy n = 2 and lobectomy n = 13) mean quantity of daily chyle was 0.3 L. All these patients recovered with conservative therapy except for 2 patients who underwent drainage and talc slurry (n = 1) and video-assisted lysis of adhesions (n = 1). In the remaining 11 patients (pneumonectomy n = 6 and lobectomy n = 5) mean quantity of daily chyle was 1 L. The chylous leak was seen at lymphography (n = 4), during reoperation (n = 2), or at lymphography and reoperation (n = 3). The location was clearly identified at the level of thoracic duct tributaries in all cases. In 4 postlobectomy cases (4 of 7), surgery was not performed because of the therapeutic usefulness of lymphography. Reoperation was necessary in 6 cases (postpneumonectomy n = 5, postlobectomy n = 1) and consisted of duct ligation (n = 2), leak/suture (n = 3), and fibrin glue (n = 1). CONCLUSIONS CCPR is rare and appears to respond well to medical treatment owing to the fact that the thoracic duct is generally patent as the leak is due to injury of its tributaries. When surgery is considered, lymphography may help to select cases in which conservative medical therapy should be continued. However, in a small number of cases, usually after pneumonectomy, surgery remains mandatory.