Jean-François Regnard

Prognostic factors and long-term results after thymoma resection: A series of 307 patients

Three hundred seven cases of patients who underwent operation for thymoma (196 of whom had myasthenia gravis) were analyzed to assess the prognostic values of Masaoka clinical staging, completeness of resection, histologic classification, history of myasthenia gravis, and postoperative radiotherapy. According to the Masaoka staging system, 135 thymomas were stage I, 70 were stage II, 83 were stage III, and 19 were stage IV. According to the Verley and Hollmann histologic classification system, 67 thymomas were type 1, 77 were type 2, 139 were type 3, and 24 were type 4. Two hundred sixty patients underwent complete resection, 30 underwent incomplete resection, and 17 underwent biopsy. Postoperative radiotherapy was performed mainly in cases of invasive or metastatic thymoma. Mean follow-up was 8 years; eight patients were unavailable for follow-up. The overall 10- and 15-year survivals were 67% and 57%, respectively. In univariate analysis, three prognostic factors were established: completeness of resection, Masaoka clinical staging, and histologic classification. Furthermore, among patients with stage III thymomas, survival was significantly higher for patients with complete resection than for patients with incomplete resection (p < 0.001). Completeness of resection should therefore be taken into account in clinical-pathologic staging. We did not find any significant difference with respect to disease-free survival between patients who had postoperative radiotherapy and those who did not. In multivariate analysis, the sole significant prognostic factor was completeness of resection. On the basis of these findings, a new clinical-pathologic staging system is proposed.

SOLITARY FIBROUS TUMORS OF THE PLEURA: CLINICAL CHARACTERISTICS, SURGICAL TREATMENT AND OUTCOME

OBJECTIVE The aim of this paper is to study clinical characteristics, surgical treatment and outcome of patients with solitary fibrous tumor of the pleura operated in our institutions in a 20-year period. METHODS Clinical records of all patients operated for solitary fibrous tumors of the pleura between 1981 and 2000 were reviewed retrospectively. Tumors were classified as malignant in the presence of at least one of the following criteria: (1) high mitotic activity; (2) high cellularity with crowding and overlapping of nuclei; (3) presence of necrosis; (4) pleomorphism; otherwise they were considered as benign. RESULTS Sixty patients (mean age 55 years) were operated in this period. None had asbestos exposure. Symptoms were present in 31 cases. Surgical approaches included thoracotomy (n=53), video-assisted thoracoscopy (n=6), and median sternotomy (n=1). Tumors originated from visceral pleura in 48 cases, from parietal, mediastinal or diaphragmatic pleura in seven, two and three cases, respectively; their mean diameter was 8.5 cm. Tumors could be resected with their implantation basis in 49 patients. In the remaining 11, extended resections were performed, including lung parenchyma (lobectomy, n=4, pneumonectomy, n=2), osteomuscular chest wall structures (n=2), diaphragm (n=2), and pericardium (n=1). Two postoperative deaths (due to myocardial infarction and pulmonary embolism, respectively) occurred. Tumors were pathologically benign in 38 cases and malignant in 22 cases. Mean follow-up was 88 months. Resection was complete in all the patients with benign tumors and no recurrence occurred. Resection was considered as complete in 21/22 malignant tumors. Local recurrence was observed in two cases. Both could be successfully managed by iterative exeresis (no extended resection had been initially performed). Metastatic disease (responsible for patients death) was observed following the only incomplete resection. Actuarial 5- and 10-year survival rates were 97% for benign tumors and 89% for malignant ones. CONCLUSIONS Surgical resection provided cure in all the patients with benign tumors. As insufficiency of exeresis is associated with all recurrences in malignant tumors, completeness of resection is in our experience the best prognostic factor in these forms.

Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma

Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non-small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-γ production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression.

Aspergilloma: a series of 89 surgical cases

BACKGROUND Surgery for pleuropulmonary aspergilloma is reputed to be risky. We reviewed our results, focusing attention on the postoperative complications. METHODS During a 20-year period, 87 patients were operated on for pulmonary (86) or pleural (3) aspergillomas. Seventy-two percent of patients were complaining of hemoptysis. Eighty-nine resections were performed because there were two bilateral cases. Seventy percent of aspergillomas had developed in cavitation sequelaes from tuberculosis disease. Thirty-four patients had severe respiratory insufficiency that allowed us to perform only lobectomy (18), segmentectomy (2), or cavernostomy (14). RESULTS Thirty-seven lobectomies (five with associated segmentectomies), two bilobectomies, 21 segmentectomies, 10 pneumonectomies, and 17 cavernostomies were performed. Total blood loss exceeded 1,500 mL in 14 cases, and 71% of patients required blood transfusion. There were five postoperative deaths (5.7%), related to respiratory failure (2), infectious complication (1), pulmonary embolus (1), and cardiorythmic disorder (1). Incomplete reexpansions were frequently seen in patients undergoing lobectomies or segmentectomies. No death or major complications occurred in asymptomatic patients. During follow-up, none of the patients had recurrent hemoptysis. CONCLUSIONS Surgical resection of aspergilloma is effective in preventing recurrence of hemoptysis. It has low risk in asymptomatic patients and in the absence of underlying pulmonary disease. Incomplete reexpansion is frequent after lobectomy and segmentectomy, especially when there is underlying lung disease. Cavernostomy is an effective treatment in high-risk patients. Long-term prognosis is mainly dependent on the general condition of patients.

Results and prognostic factors in resections of primary tracheal tumors: A multicenter retrospective study

To determine long-term survival and prognostic factors, 208 patients with primary tracheal tumors were evaluated in a retrospective multicenter study including 26 centers. Ninety-four patients had squamous cell carcinoma, four had adenocarcinoma, 65 had adenoid cystic carcinoma, and 45 patients had miscellaneous tumors. The following resections were performed: tracheal resection with primary anastomosis, 165; carinal resection, 24; and laryngotracheal resection, 19. Postoperative mortality rate was 10.5% and correlated with the length of the resection, the need for a laryngeal release, the type of resection, and the histologic type of the cancer. Fifty-nine percent of patients with tracheal cancer and 43% of patients with adenoid cystic carcinomas had postoperative radiotherapy. The 5- and 10-year survivals, respectively, were 73% and 57% for adenoid cystic carcinomas and 47% and 36% for tracheal cancers (p < 0.05). Among patients with tracheal cancers, survival was significantly longer for those with complete resections than for those with incomplete resections. On the other hand, the presence of positive lymph nodes did not seem to decrease survival. Postoperative radiotherapy increased survival only in the case of incompletely resected tracheal cancers. Long-term prognosis was worsened by the occurrence of second primary malignancies in patients with tracheal cancers and by the occurrence of late pulmonary metastases in patients with adenoid cystic carcinomas.

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin.

Thyroid transcription factor-1 (TTF-1) is considered as a reliable marker for differential diagnosis in distinguishing primary adenocarcinomas of the lung from extrathoracic origins. We previously reported the first case of lung metastasis of colorectal origin, with nuclear expression of TTF-1. As most previous studies were performed on series of extrathoracic primary tumors, we raised the question of a possible role of lung microenviroment in TTF-1 expression. We investigated the rate of TTF-1 expression in lung metastases of extrathoracic adenocarcinomas and compared results of immunohistochemistry performed with different primary antibodies. Two different clones of antibodies (8G7G1/1 from Dako, SPT24 from Novocastra) raised against TTF-1 were used on 56 lung-metastatic malignant tumors, 41 from colorectal origin. A series of primary colorectal (90 cases) and primary pulmonary adenocarcinomas (86 cases) were also investigated. Four of 41 (10%) lung metastases of colorectal adenocarcinomas displayed a nuclear staining for TTF-1 with SPT24 clone. Three of the four positive cases displayed similar nuclear staining in primary and/or other extrathoracic metastatic sites as well as four of 90 (5%) primary colorectal adenocarcinomas, ruling out the role of lung microenvironment. None of them was positive with 8G7G1/1 clone. Sensitivity between two sets of antibodies was compared in 86 primary pulmonary adenocarcinomas. Nuclear staining was detected in 72 cases (84%) with Novocastras antibody and 56 cases (65%) with Dakos. Significant discordance was observed (P< 0.01). These results suggest that the diagnostic virtue of TTF-1 detection depends on the used antibodys clone. The SPT24 clone seems to have a stronger affinity for TTF-1 protein but may lead to a few positive colorectal adenocarcinomas.

Lung metastases of renal cell carcinoma: results of surgical resection.

OBJECTIVE The research was designed to evaluate the results of surgical resection of renal lung metastases. METHODS Between 1960 and 1994, 50 consecutive patients underwent resection for pulmonary metastases from renal cell carcinoma. Mean age was 59 years (range: 40-78 years). Mean time between nephrectomy and pulmonary resection was 3 years (range: 0-18 years). Nineteen patients had solitary metastase, 13 multiple unilateral, and 18 bilateral. Wedge excision was performed in 28 patients, segmentectomy in 3, lobectomy in 17, sleeve lobectomy in 1, pneumonectomy in 5 and biopsy in 3. Twelve patients had repeat resection for recurrent metastases. RESULTS The resection was complete in 45 patients. Three patients also had a complete resection of limited extra-pulmonary disease. There was one postoperative death and 3 complications. Mean follow-up was 42 months without loss of follow-up. The cause of death was always metastatic recurrent disease. Five-year survival in complete resection was 44%. Only one long survivor was observed in the case of incomplete resection in a patient who had a complete response after adjuvant immunotherapy. Five-year survival for the 12 patients with repeat resections was similar to the overall survival rate (42%). CONCLUSIONS Resection of renal lung metastases is a safe and effective treatment. No factor influenced the 5-year survival in this series except the complete resection. Extra-pulmonary metastases does not contra-indicate pulmonary resection. In selected patients, repeat resection for recurrent disease is warranted.

Preoperative Carcinoembryonic Antigen Level as a Prognostic Indicator in Resected Primary Lung Cancer

The aim of this study was to evaluate the prognostic significance of elevated preoperative carcinoembryonic antigen (CEA) levels in cases of resected primary lung cancer. Between 1985 and 1989, 152 patients with tumors and CEA levels above 10 ng/mL underwent operation. One hundred twenty-five of them underwent resection of their tumors and the other 27 underwent exploratory thoracotomy only. Fifty-two percent of cancers were adenocarcinomas and 33% were epidermoid. Forty-two resected tumors were classified as stage I, 29 as stage II, 45 as stage IIIa, 7 as stage IIIb, and 2 as stage IV. The 3-year actuarial survival rate was 54% for patients with stage I tumors, 28% for those with stage II, 18% for those with stage IIIa, 44% for those with stage IIIb, and 0% for those with stage IV tumors. The 5 year actuarial survival was 40% for those with stage I tumors, 28% for those with stage II, 7% for those with stage IIIa, and 0% for those with stage IIIb tumors. Preoperative CEA levels increased from stage I to stage IIIa (p < 0.05). However, based on preoperative CEA levels we were not able to predict resectability, because levels were not significantly different between stage IIIa and exploratory thoracotomy-only groups. Adenocarcinoma was not significantly associated with higher CEA levels than was epidermoid, except in stage IIIa disease (p < 0.05). We found a critical unfavorable level of prognostic significance at 30 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Genomic Profiles Specific to Patient Ethnicity in Lung Adenocarcinoma

Purpose: East-Asian (EA) patients with non–small-cell lung cancer (NSCLC) are associated with a high proportion of nonsmoking women, epidermal growth factor receptor (EGFR)-activating somatic mutations, and clinical responses to tyrosine kinase inhibitors. We sought to identify novel molecular differences between NSCLCs from EA and Western European (WE) patients. Experimental Design: A total of 226 lung adenocarcinoma samples from EA (n = 90) and WE (n = 136) patients were analyzed for copy number aberrations (CNA) by using a common high-resolution SNP (single nucleotide polymorphism) microarray platform. Univariate and multivariate analyses were carried out to identify CNAs specifically related to smoking history, EGFR mutation status, and ethnicity. Results: The overall genomic profiles of adenocarcinomas from EA and WE patients were highly similar. Univariate analyses revealed several CNAs significantly associated with ethnicity, EGFR mutation, and smoking, but not to gender, and KRAS or p53 mutations. A multivariate model identified four ethnic-specific recurrent CNAs—significantly higher rates of copy number gain were observed on 16p13.13 and 16p13.11 in EA tumors, whereas higher rates of genomic loss on 19p13.3 and 19p13.11 were observed in tumors from WE patients. We identified several potential driver genes in these regions, showing a positive correlation between cis-localized copy number changes and transcriptomic changes. Conclusion: 16p copy number gains (EA) and 19p losses (WE) are ethnic-specific chromosomal aberrations in lung adenocarcinoma. Patient ethnicity should be considered when evaluating future NSCLC therapies targeting genes located on these areas. Clin Cancer Res; 17(11); 3542–50. ©2011 AACR.

Prognostic factors and results after surgical treatment of primary sarcomas of the lung

BACKGROUND Primary sarcoma of the lung is a rare tumor. Our purpose was to study survival after resection and prognostic factors, which have been rarely reported. METHODS In a 24-year period, we performed 20 complete resections and three exploratory thoracotomies only for primary lung sarcomas. One patient declined operation. Mean diameter of resected tumors was 9 cm (range, 4 to 18 cm). There were eight stage IB, eight stage IIB, one stage IIIA, and three stage IIIB. Sixty percent of patients with resected tumors received adjuvant therapy. Age, sex, resectability, tumor size, histologic cell type, stage, and adjuvant therapy were analyzed as predictors of survival. RESULTS No postoperative deaths occurred. All 4 patients who had no resection died within 15 months. The 5- and 10-year actuarial survival after complete resection was 48%. The 5- and 10-year actuarial survival in stage IB was 83%, whereas the 4-year actuarial survival in stage IIB was 30% (p < 0.05). Complete resection and stage of disease were the sole significant prognostic factors. CONCLUSIONS Complete resection of primary sarcoma of the lung, when feasible, can achieve prolonged survival, although almost half of the patients died of metastasis within 2 years of operation. Adjuvant therapy needs to be investigated.