Biomedical subjects
Pascal Thomas
Publications and source records attributed to Pascal Thomas.
Stage I non-small cell lung cancer: a pragmatic approach to prognosis after complete resection.
BACKGROUND: Long-term results of the surgical treatment of stage I non-small cell lung cancer (NSCLC) are disappointing. METHODS: Univariate and multivariate analyses were conducted on 515 consecutive lung resections for stage I NSCLC performed from 1990 to 1999 and identified by reviewing a database into which data were entered prospectively. Tumors were staged as stages IA (n = 147) and IB (n = 348) according to the 1997 UICC (Union Internationale Contre le Cancer) pTNM classification. RESULTS: Operative mortality rates were 6.2%, 5.3%, 2.3%, and 0% for pneumonectomy, bilobectomy, lobectomy, and lesser resections, respectively. Overall survival rate was 61.1% (55.8% to 66.5%) at 5 years. Univariate analysis identified three significant adverse prognosticators: arteriosclerosis as comorbidity, pathologic T2 status, and blood vessel invasion. Male sex (p = 0.056) and performance of pneumonectomy (p = 0.057) were at the threshold of statistical significance. At multivariate analysis, three independent prognosticators entered the model: arteriosclerosis, blood vessels invasion, and performance of pneumonectomy. CONCLUSIONS: Long-term survival of patients with completely resected stage I NSCLC was adversely influenced in a relatively balanced way by factors related to the clinical status of the patient, to the tumor, and to the treatment.
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.
Phase I trial of gemcitabine and carboplatin in metastatic non-small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie Study.
BACKGROUND: The purpose of this study was to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicity (DLT) of the 21 days carboplatin plus gemcitabine regimen in previously untreated patients with stage IV non small-cell lung cancer (NSCLC). METHODS: At least three patients were entered at each dose level. The starting dose was carboplatin AUC 4 mg/ml per min (Area Under the Curve; Calvert formula) on day 1 and gemcitabine 750 mg/m(2) on days 1 and 8. Carboplatin was increased to AUC 5 (level 3, 4) then to AUC 6 (level 5-7). Gemcitabine was increased to 875 (level 2, 3), 1000 (level 4, 5), 1250 (level 6) and finally 1500 mg/m(2) (level 7). Twenty-nine patients were entered into this phase I study. RESULTS: At dose level 6, a DLT (grade 4 thrombocytopenia) was observed in one out of six patients. At dose level 7, no DLT was observed during the first course, so the MTD was not reached. During the second course, two out of four patients presented grade 4 thrombocytopenia. None of the five patients receiving two courses at level 6 presented a DLT, so this level was retained for further phase II studies. Of the 25 patients assessable for response, five achieved partial responses with a response rate of 20% (95% CI, 7 to 41%). The median survival time was 7 months and the 1-year survival rate was 24% (95% CI, 9 to 45%). CONCLUSION: The combination of carboplatin given on day 1 and gemcitabine given on days 1 and 8 every 3 weeks seems to be an acceptable regimen. The DLT consists exclusively of severe thrombocytopenia. Despite the MTD was not reached with carboplatin AUC 6 mg/ml per min and gemcitabine 1500 mg/m(2), the recommended dose for further phase II studies is carboplatin AUC 6 mg/ml per min and gemcitabine 1250 mg/m(2).
Clinical utility of bronchoalveolar lavage cell phenotype analyses in the postoperative monitoring of lung transplant recipients.
OBJECTIVE: Bronchoalveolar lavage (BAL) fluid provides a crucial tool for investigation of the cellular component of the deep lung spaces and hence to approach the alloreactive response following lung transplantation. This study investigated whether BAL cell profiles can assist for the diagnosis of certain postoperative complications. METHODS: We conducted a retrospective analysis of both transbronchial biopsy and bronchoalveolar lavage materials in a series of 26 consecutive lung transplant recipients (LTR) in relationship with their clinical status at the time of the procedure. BAL fluid was subjected to cell morphology as well as flow cytometric phenotypic analyses. The samples were labeled as follows: normal transplant in clinically stable and healthy recipients, n=58; acute rejection (AR), n=58; infection (INF), n=31; and obliterative bronchiolitis/bronchiolitis obliterans syndrome (OB/BOS) n=27. RESULTS: Total BAL cell counts were the highest in INF. Lymphocytic alveolitis was suggestive of both acute allograft rejection and CMV viral infection, with a combined significant increased HLA-DR positive cells in AR. Alveolar neutrophilia with an increased CD4/CD8 ratio was correlated with the diagnosis of OB. The neutrophil percentages, HLA-DR and CD57 positive cells were significantly higher when an infection was present. CONCLUSION: These findings suggest that BAL cell analysis could give complementary information of histological data and further insight into immunologic events after lung allograft. A longitudinal surveillance of BAL cell profiles in an individual patient may be suggestive for a preclinical state of posttransplant acute rejection, bacterial infection and obliterative bronchiolitis.
Superior vena cava resection with prosthetic replacement for non-small cell lung cancer: long-term results of a multicentric study.
OBJECTIVES: Superior vena cava (SVC) resection with prosthetic replacement for non-small cell lung cancer (NSCLC) is infrequently performed and oncological results are unclear. To establish a historical benchmark for this extended surgery, we have updated and reviewed data from four international centers. METHODS: Data were obtained through retrospective chart review. Prognostic factors were analyzed using first univariate techniques and subsequently multiple regression (logistic regression). Kaplan-Meier overall survival was calculated and prognostic factors examined by log-rank test and the estimation of hazard ratios using Cox regression. RESULTS: From 1985 to 2000, 28 patients underwent SVC resection with prosthetic replacement for NSCLC. During the same period, 65 patients underwent partial SVC resection. Induction treatment was performed in 25% of patients. The resection was done for T involvement in 22 patients (79%), and for N2 involvement in the remaining. There were 12 tracheal sleeve resections, four pneumonectomies, and 12 lobar or sublobar resections with or without bronchoplasty. The median clamping time was 40 min. The median diameter of the prosthesis used was No. 14. Pathological examination showed direct SVC invasion (T4) in 79% of patients, whereas N2 disease was present in 50% of patients. Median intensive care unit and hospital stay were 3 and 20 days, respectively. The postoperative morbidity and mortality were 39 and 14%, respectively. The overall 5-year probability of survival was 15% (median of 9 months, range 0-105 months). Patients who underwent partial SVC resection during the same period had a significantly higher probability of survival (P=0.03). Induction chemotherapy was associated with a significant increase of postoperative morbidity in multivariate analysis. None of the potential prognostic factors analyzed in multivariate analysis were associated with survival, but the type of resection (sleeve pneumonectomy/pneumonectomy) were borderline significant. CONCLUSIONS: SVC resection with prosthetic replacement should not be considered an absolute contraindication in patients with NSCLC; however, the poor oncological results suggest more restrictive and severe criteria of patient selection (mediastinoscopy, induction treatment, no pneumonectomy, no N2 disease).
Upregulation of chemokines in bronchoalveolar lavage fluid as a predictive marker of post-transplant airway obliteration.
BACKGROUND: The early stage of post-transplant obliterative bronchiolitis (OB) is characterized by an influx of inflammatory cells to the lung, among which neutrophils may play a role in key events. The potential for chemokines to induce leukocyte accumulation in the alveolar space was investigated. We assessed whether changes in the chemotactic expression profile could be used as sensitive markers of the onset of OB. METHODS: Serial bronchoalveolar lavage (BAL) fluids from 13 stable healthy recipients and 8 patients who developed bronchiolitis obliterans syndrome (BOS) were analyzed longitudinally for concentrations of interleukin-8 (IL-8), chemokines regulated-upon-activation and normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significantly elevated percentages of BAL neutrophils and IL-8 levels were found at the pre-clinical stage of BOS, on average 151 +/- 164 days and 307 +/- 266 days, respectively, before diagnosis of BOS. There was also early upregulation of RANTES and MCP-1 in the BOS group (mean 253 +/- 323 and 152 +/- 80 days, respectively, before diagnosis of BOS). The level of MCP-1 was consistently higher than that of RANTES until airway obliteration. BAL sICAM-1 and sVCAM-1 levels were not statistically different between the groups. CONCLUSIONS: These data support the belief that RANTES, IL-8 and MCP-1 play a crucial role in the pathogenesis of OB. The results show that relevant increased levels of such chemokines may predict BOS, and suggest that there is potential for some of these markers to be used as early and sensitive markers of the onset of BOS. Longitudinal monitoring of these chemokine signals may contribute to better management of patients at risk for developing OB, at a stage when remodeling can either be reversed or altered.
Management of an intrabronchial rupture of right main pulmonary artery: a case report.
We report a case of massive endobronchial hemorrhage following a fistula formation of the right pulmonary artery to the right mainstem bronchus in a 15-year-old girl. The fistula had occurred 39 days after the patient had undergone bilateral lung transplantation for cystic fibrosis. The post-transplantation course was remarkable for bronchial colonization by Aspergillus at the site of right bronchial anastomosis and an episode of spontaneous, self-limited hemoptysis on postoperative day 17. A massive endobronchial hemorrhage during surveillance bronchoscopy occurred 39 days after transplantation. Immediate intervention, including rigid bronchoscopy followed by surgery, was effective in saving the patient. The pathophysiologic hypothesis to explain the fistula of the right pulmonary artery to the right mainstem bronchus probably involves ischemia of the anastomosis with necrosis of the suture zone complicated by endobronchial infection with Aspergillus. Rigid bronchoscopic intervention associated with an excellent medical surgical collaboration was pivotal in successfully rescuing the patient.