Prognostic factors in patients with advanced non-small cell lung cancer : data from the phase III FLEX study

The FLEX study demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). In the FLEX intention to treat (ITT) population, we investigated the prognostic significance of particular baseline characteristics. Individual patient data from the treatment arms of the ITT population of the FLEX study were combined. Univariable and multivariable Cox regression models were used to investigate variables with potential prognostic value. The ITT population comprised 1125 patients. In the univariable analysis, longer median survival times were apparent for females compared with males (12.7 vs 9.3 months); patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 compared with 1 compared with 2 (13.5 vs 10.6 vs 5.9 months); never smokers compared with former smokers compared with current smokers (14.6 vs 11.1 vs 9.0); Asians compared with Caucasians (19.5 vs 9.6 months); patients with adenocarcinoma compared with squamous cell carcinoma (12.4 vs 9.3 months) and those with metastases to one site compared with two sites compared with three or more sites (12.4 months vs 9.8 months vs 6.4 months). Age (<65 vs ≥65 years), tumor stage (IIIB with pleural effusion vs IV) and percentage of tumor cells expressing EGFR (<40% vs ≥40%) were not identified as possible prognostic factors in relation to survival time. In multivariable analysis, a stepwise selection procedure identified age (<65 vs ≥65 years), gender, ECOG PS, smoking status, region, tumor histology, and number of organs involved as independent factors of prognostic value. In summary, in patients with advanced NSCLC enrolled in the FLEX study, and consistent with previous analyses, particular patient and disease characteristics at baseline were shown to be independent factors of prognostic value. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. © 2012 Elsevier Ireland Ltd.

Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury

Background. Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method. A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n=7) or 15 min (group 2; n=7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results. Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml. Conclusion. Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n = 35), inflamed pleura (IP, n = 12) and uninflammed pleura (UP, n = 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P = 0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P = 0.03, total MMP-2 P = 0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM. © 2003 Cancer Research UK.

GATA3 : a promising marker for metastatic breast carcinoma in serous effusion specimens

Background The utility of GATA3 as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. Methods Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from breast (30), female genital tract (13), gastrointestinal tract (7), lung adenocarcinoma (9), pancreas (1), kidney (1) and bladder (1). The breast carcinoma cases included 15 ductal carcinomas, 8 lobular carcinomas and in 7 the histology sub-type was not available. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and GCDFP-15 to compare sensitivity with GATA3. Results Positive nuclear staining for GATA3 was present in 90% (27/30) of metastatic breast carcinoma specimens. All non-breast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases showed weak positivity of benign lymphoid cells. Staining results were unambiguous as all positive cases showed intense nuclear staining in >50% of tumor cells. Mammaglobin (57%; 17/30) and GCDFP-15 (33%; 10/30) were less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only one additional case to those stained with GATA3. Conclusions GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a consideration.

Knudsen effusion measurements on Cr Mn alloys

The equilibrium partial pressures of Mn over bcc Cr--Mn alloys have been measured using Knudsen cell technique in the temp. range 1200-1500K. The alloys in particulate form were contained in thoria crucibles inside Knudsen cells made of tungsten. The rates of mass loss of each cell under vacuum was monitered as a function of time at constant temp. using a microbalance. Activities exhibit mild negative deviations from Raoult's law, contrary to indications from an earlier study using a fused salt emf technique. The Cr--Mn system is characterized by negative enthalpy and excess entropy of mixing. There is close similarity between the composition dependence of enthalpy and excess entropy. These findings suggest strong vibrational and negligible magnetic contributions to excess entropy of mixing in bcc phase at high temp. 10 ref.--AA

Sequence confirmation of the EWS-WT1 fusion gene transcript in the peritoneal effusion of a patient with desmoplastic small round cell tumor

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated neoplasm. The prognosis is poor, even if therapy is instituted promptly. and thus it is important to differentiate it from other histologically and cytologically similar-looking malignancies of the young adult. We present a case of DSRCT in a 17-yr-old male with disseminated peritoneal disease and peritoneal effusion. The cytology sample showed a malignant small round cell tumor, the classical cytological features of DSRCT, and immunohistochemistry performed in the prepared cell block exhibited an antibody expression profile in keeping with DSRCT. Further material front the effusion was prepared for RNA extraction, following which a reverse-transcriptase polymerase chain reaction (RTPCR) and sequencing of the t(l l;22)(p13;q11 or q12) were carried out. The result showed the presence of the reciprocal translocation and thus confirmed the diagnosis of DSRCT. This case shows how molecular techniques (including sequencing) call be applied to cytology in clarifying and confirming certain difficult diagnosis of undifferentiated neoplasms, DSRCT in this particular case. Diagn. Cytopathol. 2003;29:341-343. (C) 2003 Wiley-Liss. Inc.

Clozapine-induced liver injury and pleural effusion

Clozapine, whilst associated commonly with a transient and benign increase in liver enzymes, has also been associated with varying presentations of hepatitis in existing case reports. This report describes what we believe to be the first documented case of acute liver injury and pleural effusion associated with clozapine, resolving after cessation of the agent. The case supports existing literature in advocating a high index of suspicion, particularly in the 4-5 weeks following clozapine initiation, when considering nonspecific clinical symptoms and signs.

Diseases of the lungs, bronchi and pleura

UANL

Multiplane ultrasound approach to quantify pleural effusion at the bedside

To assess the accuracy of a multiplane ultrasound approach to measure pleural effusion volume (PEV), considering pleural effusion (PE) extension along the cephalocaudal axis and PE area.Prospective study performed on 58 critically ill patients with 102 PEs. Thoracic drainage was performed in 46 patients (59 PEs) and lung computed tomography (CT) in 24 patients (43 PEs). PE was assessed using bedside lung ultrasound. Adjacent paravertebral intercostal spaces were examined, and ultrasound PEV was calculated by multiplying the paravertebral PE length by its area, measured at half the distance between the apical and caudal limits of the PE.Ultrasound PEV was compared to either the volume of the drained PE (59 PE) or PEV assessed on lung CT (43 PE). In patients with lung CT, the accuracy of this new method was compared to the accuracy of previous methods proposed for PEV measurement. Ultrasound PEV was tightly correlated with drained PEV (r = 0.84, p < 0.001) and with CT PEV (r = 0.90, p < 0.001). The mean biases between ultrasound and actual volumes of PE were -33 ml when compared to drainage (limits of agreement -292 to +227 ml) and -53 ml when compared to CT (limits of agreement -303 to +198 ml). This new method was more accurate than previous methods to measure PEV.Using a multiplane approach increases the accuracy of lung ultrasound to measure the volume of large to small pleural effusions in critically ill patients.