External validation of a risk score in the prediction of the mortality after esophagectomy for cancer.

This study was designed as an external evaluation of the Steyerberg score in the prediction of different categories of postoperative mortality after esophagectomy on a large nationwide database of thoracic surgeons. Data collection was obtained from the Epithor national database encompassing the majority of thoracic procedures performed in France. We retrospectively compared the predicted to the observed postoperative 30-day (30DM), 90-day (90DM) and in-hospital mortality (IHM) rate in each decile of equal patient. Patients included in the study were operated for an esophageal cancer and Gastroesophageal junction (GEJ). Steyerberg score was determined according to its logarithmic formula obtained from a sum score including age, comorbidities, neoadjuvant treatment and hospital volume. Deviation of observed from theoretically expected number of deaths was investigated using the calibration test of Hosmer-Lemeshow. Discrimination of the score was determined using the measure of the area under the receiver operating characteristic curve (AUC) of each category of mortality. Over a 9-year period, 1039 consecutive patients underwent an esophagectomy over 42 centers. Among them, 18 centers were considered as intermediate or high-volume institutions, and 24 were low-volume institutions. There were 841 males (81%) with a mean age of 62.3 ± 10 years. Preoperative treatment was allocated to 420 patients (40%). Numbers of comorbidity was: 1 in 261 patients (25%), 2 in 264 patients (25%), 3 in 383 patients (36%) and 4 in 5 patients (1%). The 30DM, 90DM and IHM rate were, respectively, 5.6%, 9.2% and 9.6%. The main causes of postoperative deaths were related to pulmonary complications (44%), complications of the gastric interposition (28%), cardiologic and thromboembolism events (10%). For 30DM, there were significant differences between predicted/observed mortalities in four deciles, whereas there was no significant difference for 90DM and for IHM. In term of calibration, there was a fair agreement of the Steyerberg score with observed 30DM. Predictions were above 20% for seven deciles. Calibration seemed more adequate for 90DM and for IHM. Predictions were above 20% for only three deciles but deviations were not significant. In terms of discrimination, for the 30DM the Steyerberg score overpredicted, the observed mortality rate and AUC was 0.64 (CI 95%: 0.57-0.71). For the 90DM, AUC indicated 0.63 (CI 95%: 0.57-0.68). For the IHM, AUC indicated 0.63 (CI 95%: 0.58-0.68). Steyerberg scoring system seems to be a moderate risk score of the prediction of the IHM and 90DM. This score appears to have a fair discrimination for the 30DM. Nevertheless, because of its simplicity, we believe that this simple predictive score is relevant and transportable to others institution performing such surgery for benchmarking purposes. A reappraisal of the score adapted to current surgical cohort is required.

Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies.

BACKGROUND: High expression of programmed death ligand-1 (PD-L1) on tumor cells (TC) and/or on tumor-infiltrating immune cells (IC) is associated with a high response rate in patients with advanced nonsmall-cell lung cancer (NSCLC) treated with PD-L1 inhibitors. The use of a PD-L1 immunohistochemical (IHC) test in determining the responsiveness to immunotherapy has raised the question of the reliability and reproducibility of its evaluation in lung biopsies compared with corresponding resected surgical specimens. PATIENTS AND METHODS: PD-L1 expression in TC and IC was assessed in 160 patients with operable NSCLC on both whole surgical tissue sections and matched lung biopsies, by using a highly sensitive SP142 IHC assay. The specimens were scored as TC 0-3 and IC 0-3 based on increasing PD-L1 expression. RESULTS: PD-L1 expression was frequently discordant between surgical resected and matched biopsy specimens (the overall discordance rate = 48%; 95% confidence interval 4.64-13.24) and κ value was equal to 0.218 (poor agreement). In all cases, the biopsy specimens underestimated the PD-L1 status observed on the whole tissue sample. PD-L1-positive IC tumors were more common than PD-L1-positive TC tumors on resected specimens. The discrepancies were mainly related to the lack of a PD-L1-positive IC component in matched biopsies. CONCLUSIONS: Our results indicate relatively poor association of the PD-L1 expression in TC and IC between lung biopsies and corresponding resected tumors. Although these results need to be further validated in larger cohorts, they indicate that the daily routine evaluation of the PD-L1 expression in diagnostic biopsies can be misleading in defining the sensitivity to treatment with PD-L1 targeted therapy.

Discrepancies between FISH and immunohistochemistry for assessment of the ALK status are associated with ALK 'borderline'-positive rearrangements or a high copy number: a potential major issue for anti-ALK therapeutic strategies.

BACKGROUND: Patients with advanced lung adenocarcinomas expressing ALK rearrangements are highly responsive to crizotinib, a dual ALK/c-MET inhibitor. Immunohistochemistry (IHC) is an easy clinically and routinely applicable cost-effective assay for ALK, c-MET and ROS1 protein expression for potential treatment with crizotinib. The purpose of this study was to evaluate the percentage and the pattern of ALK-rearranged cells, the variation in the native ALK copy number, as well as ALK, c-MET and ROS1 protein expression, and their significance on outcome of crizotinib-treated lung adenocarcinoma patients. PATIENTS AND METHODS: Consecutive lung adenocarcinoma specimens (n = 176) 'double-negative' (wild-type EGFR and KRAS) were tested for ALK rearrangements/copy number alterations and for ALK, c-MET and ROS1 protein expression using automated standardized protocols. Preliminary data on the outcome of crizotinib-treated patients were recorded. RESULTS: FISH analysis identified 26/176 (15%) cases with ALK rearrangements. Seven cases had discordant results between the ALK FISH and IHC. Five cases with discordant FISH-positive/IHC-negative revealed FISH 'borderline' positivity (15%-20%). Three cases overexpressed c-MET and responded to crizotinib, and two cases with ALK-'borderline' rearranged cells only, not associated with c-MET expression, progressed under crizotinib. Two cases with discordant FISH-negative/IHC-positive revealed ALK gene amplification without associated c-MET or ROS1 protein expression. CONCLUSIONS: The discrepancies observed between the IHC and FISH data revealed unexpected biological events, rather than technical issues, which potentially can have a strong impact on the therapeutic strategy with crizotinib.

Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France).

BACKGROUND: Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment. OBJECTIVES: We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP. METHODS: IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples. RESULTS: The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively. CONCLUSIONS: This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.

Clinical value of circulating endothelial cells and of soluble CD146 levels in patients undergoing surgery for non-small cell lung cancer.

BACKGROUND: Previous studies indicate that endothelial injury, as demonstrated by the presence of circulating endothelial cells (CECs), may predict clinical outcome in cancer patients. In addition, soluble CD146 (sCD146) may reflect activation of angiogenesis. However, no study has investigated their combined clinical value in patients undergoing resection for non-small cell lung cancer (NSCLC). METHODS: Data were collected from preoperative blood samples from 74 patients who underwent resection for NSCLC. Circulating endothelial cells were defined, using the CellSearch Assay, as CD146+CD105+CD45-DAPI+. In parallel, sCD146 was quantified using an ELISA immunoassay. These experiments were also performed on a group of 20 patients with small-cell lung cancer, 60 healthy individuals and 23 patients with chronic obstructive pulmonary disease. RESULTS: The CEC count and the plasma level of sCD146 were significantly higher in NSCLC patients than in the sub-groups of controls (P<0.001). Moreover, an increased CEC count was associated with higher levels of sCD146 (P=0.010). Both high CEC count and high sCD146 plasma level at baseline significantly correlated with shorter progression-free survival (P<0.001, respectively) and overall survival (P=0.005; P=0.009) of NSCLC patients. CONCLUSIONS: The present study provides supportive evidence to show that both a high CEC count and a high sCD146 level at baseline correlate with poor prognosis and may be useful for the prediction of clinical outcome in patients undergoing surgery for NSCLC.

Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in primary lung adenocarcinoma Caucasian patients.

BACKGROUND: Non-small-cell lung carcinoma (NSCLC) patients with a BRAF(V600E) mutation benefit from targeted therapy. The usefulness of immunohistochemistry (IHC) as an alternative approach for the detection of BRAF(V600E) in NSCLC patients has not been evaluated until now. This study compared the specificity and sensitivity of IHC with other methods for the detection of BRAF(V600E) in primary lung adenocarcinoma. PATIENTS AND METHODS: BRAF mutations were analysed by DNA sequencing of a Caucasian subpopulation of selected 450 of 1509 (30%) EGFR, KRAS, PI3KA, Her2 and EML4-ALK wild-type (wt) primary lung adenocarcinomas. Detection of the BRAF(V600E) mutation was carried out by IHC using the VE1 clone antibody and compared with the results of other molecular methodologies. RESULTS: Of 450 (9%) of tumours, 40 harboured a BRAF mutation, which corresponded to either a BRAF(V600E) or a non-BRAF(V600E) mutation in 21 of 450 (5%) and 19 of 450 (4%) cases, respectively. The IHC VE1 assay was positive in 19 of 21 (90%) BRAF(V600E)-mutated tumours and negative in all BRAF(nonV600E)-mutated tumours. CONCLUSION: IHC using the VE1 clone is a specific and sensitive method for the detection of BRAF(V600E) and may be an alternative to molecular biology for the detection of mutations in NSCLC.

ALK-gene rearrangement: a comparative analysis on circulating tumour cells and tumour tissue from patients with lung adenocarcinoma.

BACKGROUND: A subgroup of anaplastic lymphoma kinase (ALK)-rearranged lung tumours can respond to ALK inhibitors. Until now, the ALK status in circulating tumour cells (CTCs) isolated from patients with lung cancer has not been characterised. We assessed the ALK status in CTCs detected in patients with lung cancer and correlated the results to the ALK status defined in the corresponding tumour tissue. PATIENTS AND METHODS: A total of 87 patients with lung adenocarcinoma showing CTCs isolated using the isolation by size of epithelial tumour cell method were screened for their ALK status both in tumour samples and in CTCs. ALK break-apart fluorescence in situ hybridisation (FISH) and immunoreactivity analyses using an anti-ALK antibody (5A4 clone) were carried out on CTCs and compared with the results obtained in the corresponding tissue specimens. RESULTS: A total of five patients showed ALK-gene rearrangement and strong ALK protein expression in CTCs and in the corresponding tumour samples. Both ALK-FISH and ALK immunoreactivity analyses show negative results in CTCs and corresponding tumour samples for 82 patients. Conclusions We demonstrated that the ALK status can be determined in CTCs isolated from patients with lung cancer by immunocytochemistry and FISH analyses. These results favour non-invasive, ALK-gene status pre-screening on a routine basis on CTCs isolated from patients with lung cancer and open new avenues for real-time monitoring for adapted targeted therapy.

Cisplatin-docetaxel induction plus concurrent 3-D conformal radiotherapy and weekly chemotherapy for locally advanced non-small cell lung cancer patients: a phase II trial.

Concurrent chemoradiotherapy (CHRT) is the standard of care for unresectable locally advanced stage III non-small cell lung cancer. However, the optimal combination remains unclear. The aim of this study was to evaluate the efficacy of 2 induction chemotherapy cycles (days 1 and 22) with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) followed by concurrent chemotherapy (weekly docetaxel-cisplatin, 20 mg/m(2)) and 3-D conformal radiotherapy for 6 weeks (66 Gy/5 fractions per week/2 Gy per fraction). The primary endpoint was the response rate. Secondary objectives were toxicity, time to progression, and overall survival. Forty-four patients were included and 40 were eligible. The mean age was 60.5 years (range 40.7-72.1), and 75% had stage IIIB disease. Six patients underwent complete R0 resection including 2 pathologic complete responses after a planned intermediate evaluation. Thirty-three patients completed CHRT. The objective response rate was 65% (95% CI 50.2-79.8). Grade 3-4 hematologic and digestive toxicities were observed mainly during the induction phase. Grade 3 esophagitis (5%) was experienced during CHRT. With a median follow-up of 38.7 months, the median progression-free survival was 28.3 months (95% CI 11.0-35.0) and the median survival rate was 31.4 months. Cisplatin-docetaxel induction followed by concurrent 3-D conformal radiotherapy and weekly chemotherapy is a feasible protocol associated with a promising response rate and acceptable toxicity.

Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method.

BACKGROUND AND OBJECTIVE: Recurrence rates after surgery for non-small cell lung cancer (NSCLC) range from 25 to 50% and 5-year survival is only 60-70%. Because no biomarkers are predictive of recurrence or the onset of metastasis, pathological TNM (pTNM) staging is currently the best prognostic factor. Consequently, the preoperative detection of circulating tumour cells (CTCs) might be useful in tailoring therapy. The aim of this study was to characterize morphologically any circulating non-haematological cells (CNHCs) in patients undergoing surgery for NSCLC using the isolation by size of epithelial tumour cell (ISET) method. METHODS: Of 299 blood samples tested, 250 were from patients with resectable NSCLC and 59 from healthy controls. The presence of CNHCs was assessed blindly and independently by 10 cytopathologists on May-Grünwald-Giemsa stained filters and the cells classified into three groups: (i) malignant cells, (ii) uncertain malignant cells, and (iii) benign cells. We assessed interobserver agreement using Kappa (κ) analysis as the measure of agreement. RESULTS: A total of 123 out of 250 (49%) patients showed CNHCs corresponding to malignant, uncertain malignant and benign cells, in 102/250 (41%), 15/250 (6%) and 6/250 (2%) cases, respectively. No CNHCs were detected in the blood of healthy subjects. Interobserver diagnostic variability was absent for CNHCs, low for malignant cells and limited for uncertain malignant and benign cells. CONCLUSION: Identification of CTCs in resectable NSCLC patients, using ISET technology and according to cytopathological criteria of malignancy, appears to be a new and promising field of cytopathology with potential relevance to lung oncology.

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer.

BACKGROUND: Carbonic anhydrase IX (CAIX) is an enzyme upregulated by hypoxia during tumour development and progression. This study was conducted to assess if the expression of CAIX in tumour tissue and/or plasma can be a prognostic factor in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays containing 555 NSCLC tissue samples were generated for quantification of CAIX expression. The plasma level of CAIX was determined by ELISA in 209 of these NSCLC patients and in 58 healthy individuals. The CAIX tissue immunostaining and plasma levels were correlated with clinicopathological factors and patient outcome. RESULTS: CAIX tissue overexpression correlated with shorter overall survival (OS) (P=0.05) and disease-specific survival (DSS) of patients (P=0.002). The CAIX plasma level was significantly higher in patients with NSCLC than in healthy individuals (P<0.001). A high level of CAIX in the plasma of patients was associated with shorter OS (P<0.001) and DSS (P<0.001), mostly in early stage I+II NSCLC. Multivariate Cox analyses revealed that high CAIX tissue expression (P=0.002) was a factor of poor prognosis in patients with resectable NSCLC. In addition, a high CAIX plasma level was an independent variable predicting poor OS (P<0.001) in patients with NSCLC. CONCLUSION: High expression of CAIX in tumour tissue is a predictor of worse survival, and a high CAIX plasma level is an independent prognostic biomarker in patients with NSCLC, in particular in early-stage I+II carcinomas.

[Thoracic surgery: the major surgical procedures]. / Chirurgie thoracique: les grandes opérations.

The most frequent thoracic surgeries are performed for the treatment of primary lung cancer and pleural mesothelioma. For lung cancer, the standard procedures are pneumonectomy and lobectomy with associated mediastinal lymphadenectomy. In order to avoid pneumonectomy, extended lobectomy with sleeve bronchoplasty and/or angioplasty can be done. When adjacent organs are involved, extended resections are accepted (chest wall, vena cava...). For small lesions (<2 cm) without lymph nodes involvement and for patients with limited respiratory function, segmentectomy is an option (results under evaluation). For the treatment of pleural mesothelioma, the accepted oncologic resection is extra-pleural pneumonectomy extended to the diaphragm and pericardium. This surgical indication requires careful evaluation of tumour staging and patient's capacities. The morbidity and mortality of these resections require comprehensive follow-up (clinical, biological (including blood gases) and radiological).

[Postoperative chest: normal imaging features]. / Imagerie du thorax post-opératoire: les aspects normaux.

Chest radiographs and CT are especially useful for the follow-up of patients after lung resection. The purpose of this paper is to illustrate normal postsurgical imaging findings that differ according to the type of surgery (pneumonectomy, lobectomy, segmentectomy and wedge resection). Anatomic changes induced by surgery affect the remaining lung, pleura and chest wall, mediastinum and diaphragm. After pneumonectomy, there is accumulation of fluid in the post pneumonectomy space, progressive chest retraction with mediastinal shift toward the operated side and elevation of the ipsilateral hemidiaphragm. After lobectomy, there is hyperexpansion of the remaining lung, mediastinal shift and intercostal space narrowing. Theses findings are different according to the delay after surgery. Knowledge of the variable imaging features is necessary to detect complications and to provide appropriate follow-up of the primary disease.

[Feasibility and efficacy of cyberknife radiotherapy for lung cancer: early results]. / Analyse de la toxicité précoce des traitements par Cyberknife des cancers pulmonaires et résultats préliminaires.

PURPOSE: High-dose robotic stereotactic irradiation can be achieved with high precision using the CyberknifeM system equipped with the Synchrony respiratory tracking device. Cyberknife irradiation can overcome some limitations of conventional radiotherapy including errors due to breathing motion and patient setup. High dose levels are of interest for tumours that have shown a dose-response relationship including lung tumours. We reviewed the treatments and outcomes for the first French patients with lung tumours treated at the Cyberknife centre of Nice. PATIENTS AND METHODS: Thirty four patients were treated between November 2006 and November 2007 at the Cyberknife centre of Nice, Centre Lacassagne, France. Thirty had untreated primary lung cancer, 4 had colorectal metastasis to the lung. We evaluated the feasibility and reliability of fiducial placement, toxicity and early outcomes. Objective tumour response was assessed on thoracic CT scan every three months. RESULTS: There was no grade 3-4 toxicity. Toxicity (11%) mainly consisted of grade 1-2 asthenia. Crude overall tumour response rate was 96% for all assessable patients and 91% at 3 and 6 months, respectively. The use of one fiducial ensured minimal toxicity (no grade III pneumothorax) while allowing reliable tumour tracking as shown by the low infield failure rate (no geographic miss). Diagnostic procedure was performed during fiducial placement when required. CONCLUSION: Early toxicity and tumour control rates from this population suggest that the use of a unique fiducial for a Cyberknife treatment was safe and effective for the treatment of selected primary and secondary lung tumours. This strategy is corroborated by similar control rates in the literature. Longer follow-up are awaited.

[Malignant struma ovarii: false positive PET image for suspected metastasis due to sarcoidosis]. / Goitre ovarien malin: faux positif du TEP-scan lié à une sarcoïdose.

Struma ovarii is an ovarian teratoma mainly composed of thyroid tissue, which can become malignant with possible peritoneal dissemination or even distant metastases. Therapeutic management follows protocols used for thyroid cancer. We report the first use of (18)F-fluorodeoxyglucose positron emission tomography (PET) in the follow-up of malignant struma ovarii with persistently elevated serum thyroglobulin level and negative diagnostic iodine 131 whole body scan after thyroidectomy and four courses of 131 iodine. Hilar and mediastinal lymph node uptake was detected but histological verification concluded that there was a false-positive localization corresponding to sarcoidosis lesions without malignant aspect.

[Evolution of pain during respiratory rehabilitation after major lung resection]. / Évolution de la douleur en soins de suites et rééducation après résection pulmonaire majeure.

INTRODUCTION: Lung resection for cancer is the cause of significant postoperative pain. The aim of this study was to determine whether pulmonary rehabilitation could induce a resurgence of pain. METHODS: In 2014 and 2015, pulmonary rehabilitation was offered to all patients referred to our institution after lung resection for cancer. Patients were assessed at entry and departure for nociceptive pain, neuropathic pain (DN4), for quality of life using questionnaire EORTC QlQ-C30 and for anxiety and depression (HAD questionnaire). Pain was studied before and after the sessions of cycloergometer, gym and massages. RESULTS: During the period, 99 patients were admitted to our institution following lung resection for cancer. Medians changed during pulmonary rehabilitation from 3 to 1 for nociceptive pain (p<0.001), 3 to 3 for DN4 (NS), 50 to 67 for the quality of life score (p<0.001), 7 to 5 for the anxiety (p<0.001) and 5 to 3 for depression (p<0.0001). Pain remained stable during the sessions of cycloergometer and gym, and decreased during massage. Patients undergoing thoracotomy or video-assisted thoracic surgery evolved identically. CONCLUSION: Postoperative pulmonary rehabilitation after lung resection for cancer was not harmful. It was associated with a decrease in nociceptive pain and was without effect on neuropathic pain.

["Therapeutic" pleural surgery]. / La chirurgie pleurale "thérapeutique".

Renewed interest in carcinological pleura surgery for the treatment of mesothelioma has resulted from an increased incidence of the tumor and also better control of postoperative mortality for an operation with a dramatic reputation. Techniques include pleurectomy, pleurodecrotication and wide pleuropneumectomy. To achive isolated resection of the parietal pleura or a combined resection of the parietal and visceral pleura with more or less wide resection of the diaphragm and pericardium. Indications depend on the tumor extension and the patient's status. Mortality, particularly for wide pleuropneumectomy is no well controlled by well-trained teams and is to the order of 5%. The rate of local recurrence is to the order of 10% and can warrant use of local treatments such as intrathoracic hyperthermic chemotherapy. Median survival for operated mesothelioma is 19 months with a 46% five-year survival for the tumors with the best prognosis. At the present time, radical surgical resection is the basis of local treatment for pleural mesothelioma.

[Impact of pulmonary rehabilitation after lung resection for cancer on patients' level of anxiety and depression]. / Impact de la réhabilitation respiratoire sur l'anxiété et la dépression après chirurgie thoracique pour cancer.

INTRODUCTION: Pulmonary rehabilitation (PR) for patients undergoing lung resection for cancer remains controversial. We studied the effects of PR, its impact on quality of life and the level of anxiety and depression. METHODS: In 2011 and 2012, PR was offered to all patients referred to our institution after lung resection for cancer. Patients were evaluated between admission and discharge by a 6 minutes walking test (6MWD), a Visual Analogue Pain Intensity Scale, a quality of life questionnaire (EORTC QLQ C30) and by the Hospital Anxiety and Depression Scale (HAD). The same questionnaires were mailed 6 months after completing PR. RESULTS: Between early 2011 and late 2012, 133 patients were admitted to our institution following lung resection for cancer. Of these, 59 (44%) patients completed PR and returned their questionnaires 6 months after discharge. During PR of these 59 patients, the mean quality of life score increased from 56.3 to 65.9 (P<0.05), the median anxiety score decreased from 5.5 to 4 (P<0.05) and that of depression from 3 to 2 (P<0.05). At 6 months post-discharge, the mean quality of life score remained stable at 66.3 (P=0.8), the median anxiety score reverted to 6 (P<0.05) and the median depression score reverted to 4.5 (P<0.05). CONCLUSION: This observational study during PR, showed that quality of life and the levels of anxiety and depression were improved at the end of the course. After returning home, the average quality of life score remained stable but the level of anxiety and depression increased.

Surgical management of pleuropulmonary tuberculosis.

To define the current indications for surgical management of pleuropulmonary tuberculosis and analyze the results of operative procedures, the records of 59 patients operated on between January 1987 and December 1993 were reviewed. Three patient categories were defined. Group I patients (n = 25) underwent operation for diagnostic purposes: solitary mediastinal node or mediastinal adenopathy associated with pulmonary lesions (n = 10), pulmonary infiltrates (n = 4), pulmonary nodules or masses (n = 10), or chronic pleurisy (n = 1). Postoperative mortality and morbidity rates in this group were both 4%. Group II patients (n = 18) underwent operation for active lesions: intrapulmonary cavity (n = 6), destroyed lung parenchyma (n = 6), or chronic loculated pleural effusion (n = 6). Postoperative morbidity and mortality rates were 16.6% and 5.5%, respectively. Group III patients (n = 16) underwent operation for a complication of therapy or for sequelae of previously "cured" tuberculosis: calcified pyothorax (n = 8), empyema (n = 2), fistulized nodes (n = 2), bronchiectasis (n = 3), or aspergilloma (n = 1). Morbidity and mortality rates in this group were 31.25% and 12.5%, respectively. Surgery continues to have both diagnostic and therapeutic indications for management of pleuropulmonary tuberculosis, despite the morbidity and mortality rates associated with operative procedures.

Management of pleural effusion of cirrhotic origin.

STUDY OBJECTIVE: To determine the indications and limitations of surgical videothoracoscopy for management of pleural effusion, an infrequent and often recurring complication of cirrhotic ascites whose pathogenesis involves direct passage of ascitic fluid into the pleural space through minute defects in the diaphragm. DESIGN/SETTING/PATIENTS/INTERVENTIONS: Eight cirrhotic patients with ascites and recurrent pleural effusion underwent surgical videothoracoscopy to localize and close any diaphragmatic defects and to achieve pleurodesis by application of talc. MEASUREMENTS AND RESULTS: Diaphragmatic defects were localized and closed in six patients; postoperative mean volume and duration of drainage were, respectively, 0.408 +/- 0.157 mL and 7.6 +/- 1.75 days. None of these six patients developed recurrent pleural effusion (follow-up, 7 to 36 months). In the 2 patients in whom no defect was found, drainage had to be maintained for 15 days and 18 days (drainage volumes, 3 and 4 L). At hospital discharge, both patients had a stable recurrent effusion occupying the lower third of the cavity. CONCLUSIONS: Utilization of videothoracoscopy appears particularly indicated for these fragile patients when medical therapy fails. The procedure's efficacy is immediate and durable once defects are identified and closed. If the technique proves unsuccessful, it does not hinder subsequent use of other methods.

Ciliary beat frequency in human bronchi and bronchioles.

STUDY OBJECTIVE: This study aimed to determine the differences between ciliary beat frequencies of respiratory ciliated cells from peripheral bronchioles and from proximal bronchi in humans. DESIGN: Measurements were made from resected lungs. Ciliated cells were harvested by brushing the mucosa of each site immediately after surgery. Brushings with a cytology brush were performed on normal areas of the resected cartilaginous bronchus for proximal samplings and through a peripheral bronchiole close to the visceral pleura for peripheral samplings. For each site, at least 12 different measurements were made at 22 degrees C using an image analysis system. RESULTS: A highly significant difference between proximal bronchi (mean, 7.1 Hz; SD, 1.29) and peripheral bronchioles (mean, 4.6 Hz; SD, 1.39) (p < 0.0001) was found. CONCLUSION: Thus, cilia from peripheral bronchioles beat at a 35% lower beat frequency than cilia from proximal bronchi.