Pierre Magdeleinat

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.

Immediate and long-term results after surgical treatment of primary spontaneous pneumothorax by VATS

BACKGROUND Video-assisted thoracic surgery has recently evolved as a viable alternative to thoracotomy for spontaneous pneumothorax. METHODS A series of 163 patients with primary spontaneous pneumothorax were treated by video-assisted thoracic surgery. Seventy patients were treated for a recurrent episode, 64 patients for a persistent primary spontaneous pneumothorax, 24 patients for a contralateral episode, and 5 patients for a bilateral primary spontaneous pneumothorax. Stapling of bullae with an Endo-GIA stapler (Auto-Suture, Elencourt, France) was performed in 90% of the cases and parietal pleural abrasion was performed in each case. RESULTS One revisional lateral limited thoracotomy was required for bleeding. Six patients had a prolonged air leak; 2 of them were reoperated on by lateral limited thoracotomy. Two patients have had an incomplete reexpansion of the lung and required a reoperation. The duration of hospitalization was 6.9 +/- 3 days. With a mean follow-up of 24.5 months, three recurrences requiring a reoperation occurred; 3 other patients had a partial recurrence and healed by rest without drainage. The mean time to return to the occupational activity of the patients was 42 +/- 34 days. These results were compared with those of a previous series of 87 patients operated on by lateral limited thoracotomy. CONCLUSIONS With the development of surgical technique and video equipment, video-assisted thoracic surgery will probably become the treatment of choice of primary spontaneous pneumothorax.

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.

Presence of B Cells in Tertiary Lymphoid Structures Is Associated with a Protective Immunity in Patients with Lung Cancer

RATIONALE It is now well established that immune responses can take place outside of primary and secondary lymphoid organs. We previously described the presence of tertiary lymphoid structures (TLS) in patients with non-small cell lung cancer (NSCLC) characterized by clusters of mature dendritic cells (DCs) and T cells surrounded by B-cell follicles. We demonstrated that the density of these mature DCs was associated with favorable clinical outcome. OBJECTIVES To study the role of follicular B cells in TLS and the potential link with a local humoral immune response in patients with NSCLC. METHODS The cellular composition of TLS was investigated by immunohistochemistry. Characterization of B-cell subsets was performed by flow cytometry. A retrospective study was conducted in two independent cohorts of patients. Antibody specificity was analyzed by ELISA. MEASUREMENTS AND MAIN RESULTS Consistent with TLS organization, all stages of B-cell differentiation were detectable in most tumors. Germinal center somatic hypermutation and class switch recombination machineries were activated, associated with the generation of plasma cells. Approximately half of the patients showed antibody reactivity against up to 7 out of the 33 tumor antigens tested. A high density of follicular B cells correlated with long-term survival, both in patients with early-stage NSCLC and with advanced-stage NSCLC treated with chemotherapy. The combination of follicular B cell and mature DC densities allowed the identification of patients with the best clinical outcome. CONCLUSIONS B-cell density represents a new prognostic biomarker for NSCLC patient survival, and makes the link between TLS and a protective B cell-mediated immunity.

Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance

Compelling evidence suggests that inflammation, cell survival, and cancer are linked, with a central role played by NF-kappaB. Recent studies implicate some TLRs in tumor development based on their ability to facilitate tumor growth; however, to our knowledge, involvement of neither TLR7 nor TLR78 has yet been demonstrated. Here we have demonstrated expression of TLR7 and TLR8, the natural receptors for single-stranded RNA, by tumor cells in human lung cancer in situ and in human lung tumor cell lines. Stimulation with TLR7 or TLR8 agonists led to activated NF-kappaB, upregulated expression of the antiapoptotic protein Bcl-2, increased tumor cell survival, and chemoresistance. Transcriptional analysis performed on human primary lung tumor cells and TLR7- or TLR8-stimulated human lung tumor cell lines revealed a gene expression signature suggestive of chronic stimulation of tumor cells by TLR ligands in situ. Together, these data emphasize that TLR signaling can directly favor tumor development and further suggest that researchers developing anticancer immunotherapy using TLR7 or TLR8 agonists as adjuvants should take into account the expression of these TLRs in lung tumor cells.

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.

Results of re-resection for recurrent thymomas.

BACKGROUND The treatment of recurrent thymomas remains controversial. PATIENTS The place for re-resection was retrospectively studied in 28 consecutive patients operated on during the last 40 years. The initial Masaoka staging of the thymoma was stage I, 4; stage II, 8; stage III, 11; and stage IVa, 3. Postoperatively, 14 have had radiation therapy, 1 chemotherapy, and 13 no adjuvant treatment. Seven patients had development of recurrences, 15 had pleuropulmonary metastases, 5 had both, and 1 had thoracotomy scar recurrence. Nineteen patients had a complete resection and 9 an incomplete one. RESULTS Most local recurrences appeared after resection of stage I or II thymomas. On the other hand, in patients with stage III or IV thymomas pleural or pulmonary metastases mainly developed. No local recurrence occurred in patients who initially received postoperative radiation therapy. Five-year and 10-year survival rates were 51% and 43%, respectively, for the overall population. Among the 19 patients with complete resection, only 3 patients had a subsequent recurrence; 1 of them could be reoperated on and is still alive and free of disease. CONCLUSIONS Thymoma recurrences often appear as a locoregional rather than a hematogenous spread. Reresection can be recommended in selected patients.

Resection of pulmonary metastases from sarcoma: can some patients benefit from a less invasive approach?

BACKGROUND Although video-assisted metastasectomy has been proposed for some solitary metastases, its value has not been investigated in patients with pulmonary metastases from sarcoma for which open resection remains the usual approach. METHODS In all, 113 consecutive patients underwent curatively intended lung resection for metastases from sarcomas. Of these 113 patients, 31 were selected for a thoracoscopic wedge resection (group TS). These patients were compared with 29 patients operated on by thoracotomy but whose features could have made them possible candidates for a thoracoscopic resection (group TT). Follow-up was complete for all patients (mean follow-up, 34 months). RESULTS No mortality occurred. No morbidity was observed in group TT, and 1 complication occurred in group TS. The mean postoperative hospital stay was 3.7 days for group TS and 6.2 days for group TT (p < 0.0001). Overall survival rates at 1, 3, and 5 years were, respectively, 87.4%, 70.9%, and 52.5% in group TS, and 82.3%, 63.6%, and 34% in group TT (p = 0.20). Disease-free survival rates at 1 and 3 years were, respectively, 50.5% and 26.4% in group TS and 60% and 24.8% in group TT (p = 0.74). Local recurrence occurred in 1 patient in each group. Survival without a homolateral recurrence (i.e., in the operated lung) at 1 and 3 years was 66.7% and 44.4% in group TS and 83.5% and 45% in group TT, respectively (p = 0.54). CONCLUSIONS In selected patients with a maximum of two pulmonary nodules, thoracoscopic resections yield survival rates similar to open resections while being less invasive and preserving the patients ability to undergo possible repeat operations.

Surgical treatment of lung cancer invading the chest wall: results and prognostic factors

BACKGROUND The study was performed to assess prognostic factors in patients with lung cancer invading the chest wall treated by surgery. METHODS We reviewed retrospectively clinical records of all patients operated on for lung cancer invading chest wall structures between 1984 and 1998. RESULTS Two hundred one patients were operated on in this 14-year period. One hundred thirty-seven lobectomies, 55 pneumonectomies, and 9 wedge resections were performed. Extrapleural resection (when invasion was limited to the parietal pleura) and chest wall resection (in the case of invasion of deeper structures) were combined with pulmonary resection in 79 (39%) and 122 (61%) cases, respectively. Pathologic TNM stages were T3N0 in 116 (57.5%) cases, T3N1 in 52 (26%), T3N2 in 27 (13.5%), and T4N0-N1 in 6 (3%). A complete resection was achieved in 167 (83%) cases. Fourteen postoperative deaths (7%) occurred. One hundred thirty-nine patients (74%) underwent postoperative radiotherapy. Actuarial 5-year survival was 24% and 13% after complete and incomplete resection, respectively (p < 0.05). Actuarial 5-year survival after complete resection was 25% in T3N0 patients, 20% in T3N1, and 21% in T3N2. In completely resected patients, univariate and multivariate analyses identified three independent prognostic factors: nodal involvement, depth of parietal invasion, and age. Radiation therapy did not improve survival if a complete resection was possible. CONCLUSIONS Completeness of resection, nodal involvement, depth of invasion, and age affect survival of patients with lung cancer invading the chest wall. N2 disease should not be considered a contraindication to surgery.