The role of endobronchial ultrasound-guided fine needle aspiration in the diagnosis of pleural mesothelioma.

OBJECTIVE: The aims of the present study were to investigate the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of malignant pleural mesothelioma (MPM), and to identify specific clinical settings in which this procedure can be recommended. METHODS: We retrospectively reviewed the clinical and pathological files of patients having undergone EBUS-TBNA from February 2011 to October 2014 to investigate thoracic lesions. Among 736 patients, we identified four of them with a diagnosis of MPM achieved primarily through EBUS-TBNA. The diagnosis was made on formalin-fixed paraffin-embedded cell blocks, by checking the expression of mesothelial and carcinomatous-specific markers. RESULTS: In all patients, the collected tissue was adequate, and the histological analysis in association with immunohistochemistry led us to the diagnosis of malignant pleural mesothelioma. In three patients, the diagnosis of mesothelioma was clinically suspected, as patients presented with diffuse pleural thickening. In two patients, videothoracoscopy was not possible owing to the 'dry' presentation of the pleural disease and the site of thickening. In this setting, EBUS-TBNA was considered, at a multidisciplinary consensus meeting, as the most adequate available method to obtain a histological diagnosis. CONCLUSION: EBUS-TBNA may be a valuable diagnostic technique in the field of pleural pathology in selected clinical settings. More specifically 'dry' mesothelioma forming para-tracheal nodules or masses not accessible by surgery or by computed tomography/ultrasonogaphy-guided needle biopsy constitutes a good indication to perform EBUS-TBNA.

[Thoracic adenoid cystic carcinomas]. / Cylindromes thoraciques.

Adenoid cystic carcinomas in the trachea are rare, but represent around 40% of all tracheal tumours. Other intrathoracic localisations include the carena or proximal airways. Adenoid cystic carcinoma's growth rate is slow so that it is frequently diagnosed at an advanced stage. Pathological identification may be difficult. Treatment in limited tumours is based upon surgical resection often combined to radiotherapy because of close surgical margins. Radiotherapy dose may vary between 45 and 65 Gy according to margins status. Five-year survival rates of 65-80% have been reported after surgery or surgery and postoperative radiotherapy. Among inoperable patients treated with exclusive radiotherapy for tracheal tumours (including adenoid cystic but also squamous cell carcinomas of poorer prognosis), the recommended delivered dose should be over 60 Gy. Five-year survival rate in these very heterogeneous series may vary between 12 and 27%. Local or metastatic recurrences may occur very lately. They are considered chemo-resistant and targeted therapies may prove to be effective in the future.

[Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy]. / Standards, Options et Recommandations pour la prise en charge des patients atteints d'un cancer bronchique primitif de stade I ou II traités par irradiation exclusive.

CONTEXT: The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. RESULTS: The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

[Standards, options and recommendations for the management of locally advanced non small cell lung carcinoma]. / Standards, otions et recommandationspour la prise en charge thérapeutique des patients atteints d'un cancer bronchopulmonaire primitif non à petites cellules localement avancé.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of locally advanced non small cell lung carcinoma. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations are: 1) The management of the locally advanced non small cell lung carcinoma has two main goals: firstly to obtain local control of the disease (or to at least delay local progression in order to improve the survival or relapse free survival), and secondly to prevent the development of metastases. 2) There is a consensus that locally advanced non small cell lung carcinoma should be irradiated. External beam radiotherapy should be of optimal quality and delivered at a minimal dose of 60 Gy by standard fractionation. For patients with a poor life expectancy, this can be delivered as a split-course or hypofractionated scheme. 3) Treatment for patients with a performance status of 0-1 should consist of short duration induction chemotherapy (with a least two drugs one of which must be cisplatin), combined sequentially with conventional radiotherapy. 4) Surgery is contraindicated in extensive N3 disease. Combined radio-chemotherapy (adjuvant or neoadjuvant) is not indicated outside clinical trials. Surgery is justified in stage N2 disease as good local control can be achieved. T4-N0 disease should be treated surgically with curative intent.

High-dose-rate brachytherapy as sole modality for early-stage endobronchial carcinoma.

PURPOSE: To evaluate exclusive high-dose-rate brachytherapy for localized early-stage non-small-cell bronchial carcinoma; to develop new insights in treatment-catheter positioning and tumor-volume assessment by computed tomography (CT) scan. METHODS AND MATERIALS: Between 1992 and 1996, 34 patients with non-small-cell bronchial carcinoma were treated by brachytherapy alone. All patients were medically inoperable and had contraindications for external beam irradiation. The treatment protocol was six sessions of 5 Gy over 6 weeks. The treatment catheter was placed under fiberoscopy and was positioned with the help of spacer catheters or with a surrounding plastic tube; CT scan was performed in 50% of the cases to measure the spacing between the applicator and the bronchial wall. Dose prescription was individually based on clinical and radiologic evaluation of tumor volume. RESULTS: Local disease failure occurred in 5 patients (15%). With a median follow-up of 2 years, the local control rate was 85% and the survival rate 78%. No acute toxicity was found, except one pneumothorax. CONCLUSION: Brachytherapy alone can give an optimal therapeutic ratio in small endobronchial carcinomas without radiation-induced morbidity. Such results are achieved after careful tumor volume evaluation and individualized treatment catheter positioning.

Unusual radiologic findings in the thorax after radiation therapy.

Radiation therapy is used to treat many intrathoracic and chest wall malignancies. A variety of changes may occur after radiation therapy to the thorax. Radiation therapy produces dramatic effects in the lung. Pulmonary necrosis is an uncommon, severe, late complication of adjuvant postoperative radiation therapy. Bronchiolitis obliterans with organizing pneumonia is a distinct clinicopathologic entity characterized by patchy, migratory, peripheral air-space infiltrates. Radiation therapy can also cause spontaneous pneumothorax, mesothelioma, and lung cancer. In the mediastinum, radiation therapy may cause thymic cysts, calcified lymph nodes, and esophageal injuries. Cardiovascular complications of radiation therapy are often delayed and insidious. Premature coronary artery stenosis occurs after radiation therapy to the mediastinum. Radiation therapy may also give rise to calcifications of the ascending aorta, pericardial disease, valvular injuries, and conduction abnormalities. Women who undergo thoracic irradiation before the age of 30 years have a high risk of developing a second breast cancer. Radiation-induced sarcomas are an infrequent but well-recognized complication of radiation therapy. Other chest wall injuries due to radiation therapy are osteochondroma and rib or clavicle fractures. Knowledge of the imaging features of injuries caused by radiation therapy can prevent misinterpretation as recurrent tumor and may facilitate further treatment.

[Expandable stents and composite prosthesis]. / Stents expansifs et prothèses composites.

Today, numerous expandable and mixed silicone metallic stents for trachea and bronchi are available. Among the many technical propositions, Nitinol is a new alloy with promising potential, offering the advantage of shape memory. The right stent is the one which best meets the needs of the individual stenotic situation as evaluated by endoscopy and CT. Sufficient experience has been acquired only with the Dumon stent, giving exact information about its qualities and possible complications. The new stents are thinner. Some can be inserted under fluoroscopic and fibroscopic control. They are presumed to produce fewer complications an provide answers to some still unresolved questions such as dyskinesia or stenosis on short bronchi. They appear to be more easily inserted on the tracheo-bronchial tree. More experience is needed to satisfactorily identify specific indications and contraindications. A prospective registry will be important to obtain comparative information more quickly.

Surgical treatment of hepatic and pulmonary metastases from colorectal cancers.

BACKGROUND: Selected patients with double hepatic and pulmonary metastases from colorectal cancer may benefit from operation. METHODS: From 1970 to 1995, 239 patients underwent operation for resection of pulmonary metastases from colorectal cancer at two French surgical centers. Among these patients, 43 (18%) had previously undergone complete resection of hepatic metastases and constitute the subject of this retrospective study. RESULTS: The median interval time between hepatic and pulmonary resections was 18 months. Two pneumonectomies, 5 lobectomies, 3 segmentectomies, 6 wedge resections, and 27 metastasectomies were performed. No postoperative mortality was observed. Two patients had major postoperative complications. Seven patients (16%) underwent subsequent pulmonary resection for recurrences. Twenty-one patients were still alive, 14 free of disease. The median survival from pulmonary resection was 19 months and the 5-year probability of survival was 11%. Prethoracotomy carcinoembryonic antigen blood levels and the number of pulmonary resection were found to be significant prognostic factors; the interval time between hepatic and pulmonary resection (> 36 months) was borderline significant (p = 0.06). CONCLUSIONS: Selected patients with combined hepatic and pulmonary metastases from colorectal cancer should be considered for surgical resection. Patients with normal prethoracotomy carcinoembryonic antigen levels and late metachronous pulmonary metastasis, appear to be the best surgical candidates.

Alternating radiotherapy and chemotherapy in limited disease small cell lung cancer.

In a pilot study of 29 patients treated for localized small cell lung cancer, three new approaches were introduced, i.e. an increased initial drug dose, an early alternation of chemotherapy and thoracic radiotherapy and initial accelerated and hyperfractionated irradiation. The results were interesting. However, a high rate of fatal toxicity (21%) was observed.

Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy: an early predictor of complete response and survival in patients with small cell lung carcinoma.

BACKGROUND: Serum neuron specific enolase (NSE) is the most sensitive tumor marker of small cell lung carcinoma (SCLC) at diagnosis. Its prognostic value is still debated. Thus, the authors decided to assess the predictive value, in terms of complete response and survival, of serum NSE measured before and after one cycle of chemotherapy in patients with SCLC. METHODS: Sera from 135 patients with histologically proven limited (n = 63) or metastatic (n = 72) SCLC were obtained. Clinical and biologic parameters with a known or suspected prognostic relevance were reviewed. Serum NSE was measured before chemotherapy (D1-NSE) and 28 days after its initiation (D28-NSE). The prognostic value of the parameters under study was evaluated in univariate and multivariate analyses using the Cox proportional hazards model and logistic regression analysis. RESULTS: The level of serum NSE was raised in 120 patients (88%) prior to therapy. The probability of a normal D28-NSE value was not affected by the baseline D1-NSE value. Disease extension (P = 0.0005), performance status (P = 0.0001), D28-NSE (P = 0.003), and carcinoembryonic antigen (CEA) levels (P = 0.008) were found to be predictive for survival, whereas age, gender, plasma sodium, serum protides, and D1-NSE were not. Median survival and 2-year overall survival were 15.3 months and 21% (95% confidence interval [CI], 13-31%) when D28-NSE was normal and 8.1 months and 15% (95% CI, 8-27%) when it was not (P < 0.03). Only performance status (P = 0.001), disease extension (P = 0.002), and D28-NSE (P = 0.02) were found to be independent prognostic parameters for survival in the multivariate analysis. A simple prognostic index was developed using these 3 variables. Limited disease, a normal D28-NSE value, and a normal CEA value prior to therapy were the only parameters predictive for complete response in the univariate analysis, and D28-NSE (P = 0.01) and disease extension (P = 0.0001) were found to be independent variables in multivariate analysis. A complete response to therapy occurred in 62% with a normal D28-NSE value and in only 34% in the opposite case. CONCLUSIONS: Normal serum D28-NSE is a strong, independent early predictor of both complete response to therapy and survival. This simple tool may be proposed for use in the clinic and in research, in association with an assessment of disease extension and performance status, to predict the outcome of patients with SCLC.

Should the number of pulmonary metastases influence the surgical decision?

OBJECTIVE: To assess, using a large homogeneous retrospective series, the prognostic value of the number of resected pulmonary metastases, and thus, to determine to what extent the number of resectable metastases should influence the surgical decision. METHODS: The survival analysis of all patients operated on for pulmonary metastases at a single center, the comparisons of 2 'histologic' groups (sarcoma and carcinoma) and, within each histologic group, of three subgroups with different numbers of resected metastases (1, 2-4, and > or = 5) were performed. The log-rank test was used to compare survival curves. RESULTS: Among 575 adult patients operated on with curative intent before December 1991, the first operation allowed the complete resection of a known number of histologically proven viable pulmonary metastases in 230 and 151 patients with metastases from carcinoma and sarcoma, respectively. The 5- and 10-year probabilities of survival (Kaplan-Meier) were 37 and 23%, respectively in carcinoma patients, and 31 and 28%, respectively in sarcoma patients (log-rank test: ns). Only the difference between patients with 1 versus 2-4 metastases from carcinoma proved statistically significant (P = 0.02), with 5-year survival estimates of 41 and 25%, respectively. Beside survival, the only significant difference between the subgroups of patients with different numbers of resected metastases was the mean interval between the diagnosis of pulmonary metastases and the resection of pulmonary metastases, which was significantly longer in patients with several metastases in both histologic groups. CONCLUSIONS: In patients with resectable pulmonary metastases from sarcoma or carcinoma, the number of metastases should have little influence on the surgical decision, except for delaying this decision in patients with several metastases until a significant interval, with or without treatment, has shown that metastatic disease remains resectable and confined to the lungs.

Bronchial Kaposi's sarcoma after single lung transplantation.

Kaposi's sarcoma (KS) has been reported in 6% of malignancies of solid organ transplant recipients. Most of the observations have been in recipients of renal allografts but, so far, KS has not been described in lung transplantation. We report a case of bronchial KS occurring in a black patient 6 months after single lung-transplantation. Skin lesions were absent and, interestingly, KS lesions were observed solely in the trachea and the native lung. Following reduction of the immunosuppressive regimen a complete remission was obtained 1 year later. Up to the present time, this clinical remission is very encouraging, but close surveillance remains necessary to detect rejection episodes or the reappearance of KS following manipulation of the immunosuppressive therapy.

[New therapeutic strategies and current research in inoperable locally advanced non small-cell lung cancers (stage IIIB)]. / Stratégies thérapeutiques récentes et voies de recherche actuelles dans les cancers du poumon inopérables (stade IIIB) non à petites cellules.

Treatment of patients with inoperable locally advanced non small-cell lung cancer (NSCLC) remains disappointing with less of 5% of patients alive at 5 years. Both initial local control and circumvention of concomitant undetectable metastatic chemoresistant cells are the critical targets for the oncologists in charge of this disease. Results of a recent meta-analysis including 22 randomized studies comparing standard treatment (i.e. radiotherapy) to sequential chemoradiotherapy have undoubtabely well defined the role of cisplatine-containing chemotherapy in stage IIIB NSCLC, even if the 5 year survival benefit remains modest. However, high complete response rates and prolonged overall survival were observed with combinations of new promising chemotherapy regimens and new fractionated radiation schedules in several phase II studies. These results have to be corroborated by prospective randomized trials. Integration of more aggressive and more toxic strategies such as radical surgery in these initial inoperable locally advanced NSCLC are evaluating. Around these conventional therapies, the stage IIIB NSCLC represent a favoured target to elaborate innovative therapeutic approaches based on emergence of biotherapies as recombinant cytokines, antitumoral vaccine and gene therapy programs. The contribution of these new therapeutic options opens new directions in the therapeutic strategy and leads to hope a new promising era in the management and outcome of patients with these tumors.

Lung resection for recurrence after pneumonectomy for metastases.

Resection of pulmonary recurrences after pneumonectomy for metastases is exceptional. Nevertheless in carefully selected patients surgery on the residual lung might be successfully performed. From January 1987 to February 1996, 5 patients underwent metastasectomy on single lung after pneumonectomy performed for the same metastatic disease. There were 3 male and 2 female with a mean age of 38 years at the time of surgery on single lung. All patients had a FEV1 > 40%. One patient (n degree 1) had 2 consecutive operations (wedge resections) on the right lower lobe followed 17 months later by right inferior lobectomy for metastases of soft tissue sarcoma. Three patients had only an operation on the residual lung (patient n degree 2 had 2 wedge resections for carcinoma; patient n degree 3 had 7 wedge resections for carcinoma; patient n degree 4 had 6 wedge resections for osteogenic sarcoma). The last patient (n degree 5) had 2 wedge resections on the right upper lobe and a large wedge resection on the right lower lobe for metastases of malignant corticosurrenaloma using a cardiopulmonary femoro-femoral by-pass without cardiac arrest. She postoperatively developed a right lower lobe venous infarction treated subsequently with a completion right lower lobectomy. She died in the postoperative course from cardiorespiratory insufficiency. The other patients had an uneventful postoperative course. Two patients (n degree 2 and n degree 4) died of their disease 14 and 12 months respectively after the surgery on the residual lung; by contrast 2 patients (40%) (n degree 1 and n degree 3) are still alive without recurrences 36 and 27 months after the last resection. In selected patients aggressive surgery for metastases on the residual lung can be successfully performed but the benefits in terms of long-term disease-free survival remain to be determined.

[Optimization of combined radiotherapy and chemotherapy in treatment of non-small cell lung carcinoma]. / Optimisation de l'association radiothérapie et chimiothérapie dans les carcinomes bronchiques non à petites cellules.

PURPOSE: To report the results of CEBI 140 and 142 trials. These trials were aimed at improving the local control in stage III non-small cell carcinoma with concomitant chemotherapy and radiotherapy in the CEBI 140 trial, and with concomitant chemotherapy and radiotherapy followed by local excision in the CEBI 142 trial. MATERIAL AND METHODS: Thirty-four patients presenting with stage III non-small cell lung carcinoma were included into the CEBI 140 trial from December 1989 to December 1992. Patients were treated with a combination of daily cisplatin (6 mg/m2 per day, 144 mg/m2 in total), vindesine once a week (2.5 mg/m2, 15 mg/m2 in total) and bifractionated radiotherapy (60 Gy/48 fractions/6 weeks) followed by two cycles of cisplatin 120 mg/m2 (at d18 and d45 after completion of radiochemotherapy) and three cycles of vindesine (6 mg/m2 at d24, d31, and d38 after completion of radiochemotherapy). Twenty-eight patients presenting with stage IIIB non-small cell carcinoma-were included into the CEBI 142 trial since January 1993. Patients received a combination of cisplatin (100 mg/m2 at d1 and d24, 200 mg/m2 in total), vinblastine (4 mg/m2 at d1 and d24, 8 mg/m2 in total), 5-fluorouracil in continuous infusion (1,000 mg/m2 from d1 to d3, and from d24 to 26, 6,000 mg/m2 in total) and bifractionated radiotherapy (two series of 21 Gy/14 fractions/9 days, 11 days apart) followed by a new evaluation and surgical excision. RESULTS: In the CEBI 140 trial, all patients received a complete course of radiotherapy, but the dose of cisplatin was decreased in 27% of the cases, and the dose of vindesine in 88%. There were two toxicity-related deaths. Three months after completion of the protocol, there were 50% of complete responders. The overall survival rates at 1, 2 and 3 years were 53, 33, and 11%, respectively, and disease-free survival rates 21 11, and 11%, respectively. In the CEBI 142 trial the immediate tolerance was good. Twenty-one patients (75%) underwent surgical resection. Four tumors could not be resected. Resection was histologically incomplete in one case, and complete in the 16 remaining cases. With a median follow-up of 14 months, ten patients were alive and disease-free. CONCLUSION: Preliminary results of the CEBI 142 trial are encouraging. More patients and longer follow-up are needed for definitive conclusion. It would be of interest to implement a randomized trial comparing the CEBI 142 scheme and classical radiation therapy.

Completion pneumonectomy for lung metastases: is it justified?

OBJECTIVE: To evaluate the postoperative outcome and long-term results of patients who underwent iterative and extended pulmonary resection leading to completion pneumonectomy for pulmonary metastases. METHODS: From January 1985 to December 1995, 12 patients (mean age 45 years) underwent completion pneumonectomy for pulmonary metastases. These patients represent 1.5% of all pulmonary metastases operated on. There were 5 sarcoma and 7 carcinoma patients. Before completion pneumonectomy, 8 patients had only one pulmonary resection (wedge resection, 2; segmentectomy, 2; lobectomy, 4), 3 patients had two operations and finally, 1 patient had multiple bilateral wedge resections and 1 lobectomy. The median interval time between the last pulmonary resection and completion pneumonectomy was 13.5 months (range 1-24 months). RESULTS: There were 10 left and two right completion pneumonectomies. Three patients had an extended resection (1 carina; 1 chest wall; 1 pleuropneumonectomy). Intrapericardial dissection was used in 3 patients. Two patients died within 30 days of the operation: 1 died of postoperative complications (8.3%) whereas the other died of rapidly evolving metastatic disease. The remaining 10 patients had an uneventful postoperative course. Only 1 patient is still alive and free of disease 69 months after completion pneumonectomy. One patient is alive with disease, another was lost to follow-up; 9 patients died of metastatic disease. The median survival time after completion pneumonectomy was 6 months (range 0-69 months). The estimated 5-year probability of survival was 10% (95% CI: 2-40%). CONCLUSIONS: Indications for both iterative and extended pulmonary resection for PM may be discussed only in highly young selected patients; the extremely poor outcome of our subgroup of patients should lead to even more restrictive indications of CP for pulmonary metastatic disease.

Completion right lower lobectomy for recurrence after left pneumonectomy for metastases.

Resection of pulmonary recurrences on the residual lung after pneumonectomy for metastases is exceptional. A 37-year-old woman was submitted to left extended pleuro-pneumonectomy after left leg amputation for fibrosarcoma. At 43 months later, a wedge resection on the right lower lobe was performed followed 32 months later by a further wedge resection in the same lobe. A completion right lower lobectomy for a new recurrence was performed 17 months after the last pulmonary resection. The patient did not develop postoperative complications. She is still alive and free of disease 10 years and 9 months after pneumonectomy and 36 months after completion lobectomy on the residual lung. In highly selected patients, aggressive surgery for metastases on the residual lung can be successfully performed and it can improve survival.