Ana Gómez

Catamenial pneumothorax caused by diaphragmatic endometriosis

We are grateful to Ms. Chieko Yoshida, Mr. Toshihiko Kanno, Ms. Mieko Kosuga, and Ms. Mutsuko Izumi for their technical assistance. R E F E R E N C E S 1. Jacobson MJ, LoCicero J. Endobronchial treatment of lung carcinoma. Chest 1991;100:837-41. 2. Marasso A, Gallo E, Massaglia GM, Onoscuri M, Bernardi V. Cryosurgery in bronchoscopic treatment of tracheobronchial stenosis. Chest 1993;103:472-4. 3. Petrou M, Goldstraw P. The management of tracheobronchial obstruction: a review of endoscopic technique. Eur J Cardiothorac Surg 1994;8:436-41. 4. Themelin D, Duchatelet P, Boudaka W, Lamy V. Endoscopic resection of an endobronchial hypernephroma metastasis using polypectomy snare. Eur Respir J 1990;3:732-3. 5. Gerasin VA, Shafirovsky BB. Endoscopic electrosurgery. Chest 1988;93:270-4.

Clinical value of p53, c‐erbB‐2, CEA and CA125 regarding relapse, metastasis and death in resectable non‐small cell lung cancer

The prognostic value of p53 and c‐erbB‐2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non‐small cell lung cancer (NSCLC) patients with resectable tumors. Four end‐points were used: lung cancer death, first relapse (either locoregional or metastasis), loco‐regional recurrence and metastasis development. Standard statistical survival methods (Kaplan‐Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose‐response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung‐cancer recurrence. They can add useful information regarding the complex nature of prognosis.

Value of Serum Neuron-Specific Enolase in Nonsmall Cell Lung Cancer

To assess the prognostic value of pretreatment serum neuron-specific enolase (NSE) in nonsmall cell lung cancer (NSCLC), levels were measured in 84 NSCLC patients, 40 healthy controls, and 20 patients with benign pulmonary diseases. NSE concentration was higher in NSCLC (11.7 +/- 10.8 ng/ml) (mean +/- SD; median = 9.7 ng/ml) than in the two control groups (p < 0.001). Serum NSE was neither related with the tumor-node-metastasis (TNM) stage, nor with histologic subtype. At a cutoff value of 15 ng/ml, NSE had a sensitivity of 27.3% and a specificity of 96%. Patients with a preoperative NSE level < 15 ng/ml showed significantly longer 24-month survival than those whose initial levels were > 15 ng/ml (70 vs, 47%; p < 0.05), and this was confirmed after stratifying by TNM stage. Likelihood of tumor relapse in I, II, and IIIa TNM stages showed similar behavior. These findings suggest that NSE could be used as an adjunctive prognostic test in NSCLC patients.

Methylation profiling in non-small cell lung cancer: Clinical implications

The aim of this study was to identify a panel of methylation markers that distinguish non-small cell lung cancers (NSCLCs) from normal lung tissues. We also studied the relation of the methylation profile to clinicopathological factors in NSCLC. We collected a series of 46 NSCLC samples and their corresponding control tissues and analyzed them to determine gene methylation status using the Illumina GoldenGate Methylation bead array, which screens up to 1505 CpG sites from 803 different genes. We found that 120 CpG sites, corresponding to 88 genes were hypermethylated in tumor samples and only 17 CpG sites (16 genes) were hypomethylated when compared with controls. Clustering analysis of these 104 genes discriminates almost perfectly between tumors and normal samples. Global hypermethylation was significantly associated with a worse prognosis in stage IIIA NSCLC patients (P=0.012). Moreover, hypermethylation of the CALCA and MMP-2 genes were statistically associated to a poor clinical evolution of patients, independently of TNM tumor stage (P=0.06, RR=2.64; P=0.04, RR=2.96, respectively). However, hypermethylation of RASSF1 turned out to be a protective variable (P=0.02; RR=0.53). In conclusion, our results could be useful for establishing a gene methylation pattern for the detection and prognosis of NSCLC.

Synthesis of novel functionalized monocyclic 2-azetidinones from N,N'-diaryl-α-diimines and lithium ester enolates

Abstract Reaction of the glyoxal diimine 1a with lithium ester enolates 2a-b gave 4-imino-2-azetidinones 3a-c in excellent yields. The biacetyl diimine 1b only reacted with the enolate 2a to yield the 4-imino-2-azetidinone 3d and the 5-methylene-2-pyrrolinone 8 depending on the experimental conditions. In addition, various reactions of compounds 3 and of some derivatives, including two new examples of intramolecular β-lactam ring-opening, are described and discussed.

Prognostic Value of Flow Cytometric DNA Analysis in Non-Small-Cell Lung Cancer: Rationale of Sequential Processing of Frozen and Paraffin-Embedded Tissue

Abstract. The objective of this study was to determine the prognostic information provided by flow cytometric DNA analysis in non-small-cell lung cancer. Lung samples of 132 consecutive patients submitted to surgery were prospectively processed. When no aneuploid populations were detected in fresh frozen samples, the process continued as a second step in paraffin-embedded tissue, consuming all the tumor available. The influence of ploidy on the postoperative outcome was studied by both a univariate and a multivariate analysis. Aneuploidy was found in 81 patients (61.4%). Fourteen patients showed no aneuploidy in fresh frozen samples; and only after further analysis in paraffin-embedded tissue was abnormal DNA detected. Overall, the 36-month survival was 69% for the diploid group and 24% for the aneuploid group (p = 0.0006). Including subjects submitted to complete tumor removal (stages I, II, and IIIA) in a multivariate analysis adjusted for TNM stage and histologic type, bearers of aneuploid tumors exhibited a higher risk of relapse (hazard ratio 2.65; CI 95% 1.5–4.66;p = 0.004) or death (hazard ratio 2.17; CI 95% 1.08–4.39;p = 0.032) than patients with diploid tumors. DNA ploidy resulted an independent prognostic factor of survival and tumor relapse in completely resected non-small-cell lung cancer. Sequential analysis of fresh and paraffin-embedded samples can help avoid the bias due to intratumoral DNA content heterogeneity. DNA ploidy could be an useful parameter in any future multifactorial analysis of outcome in such tumors.

Nodular pulmonary amyloidosis in a patient with rheumatoid arthritis

We describe a 67-year-old white woman with a long-standing active rheumatoid arthritis who refused treatment. Chest roentgenograms performed in 2000 revealed a pulmonary nodule in the mid-left lung. Progression of the nodule was followed annually by computerized tomography (CT). In the last CT in 2002, we observed multiple nodules in both lungs in the absence of lymph gland involvement. The patient was operated by videothoracoscopy to resect one of the pulmonary nodules. Pathological examination of the excised tissue revealed amyloid A-type (AA) amyloidosis. Although pulmonary amyloidosis is rare in patients with systemic AA amyloidosis, we recommend that this possibility be considered when confronted with a patient with these characteristics.

More than one pulmonary resections or combined lung-liver resection in 79 patients with metastatic colorectal carcinoma.

The way to select patients who will benefit from surgical resection of pulmonary metastases of colorectal carcinoma (CRC) remains unclear.

Differential Expression of Senescence and Cell Death Factors in Non-Small Cell Lung and Colorectal Tumors Showing Telomere Attrition

Objective: The main aim of this work is to investigate the expression of factors related to senescence and cell death pathways in non-small cell lung cancers (NSCLCs) and colorectal cancers (CRCs) in relation to telomere status. Methods: We analyzed 158 tissue samples, 36 NSCLCs, 43 CRCs, and their corresponding control tissues obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. Expression of factors related to senescence, cell death pathways, transformation and tumorigenesis was investigated using arrays. Results were validated by real-time quantitative PCR. Results: Considering tumors with telomere shortening, expression for BNIP3, DAPK1, NDRG1, EGFR, and CDKN2A was significantly higher in NSCLC than in CRC, whereas TP53 was overexpressed in CRC with respect to NSCLC. Moreover, compared to nontumor samples, DAPK1, GADD45A, SHC1, and TP53 were downregulatedin the group of NSCLCs with telomere shortening, and no significant differences were found in CRC. Conclusions: In NSCLC, the failure of pathways which involve factors such as DAPK1, GADD45A, SHC1, and TP53, in response to short telomeres, could promote tumor progression. In CRC, the viability of these pathways in response to short telomeres could contribute to limiting tumorigenesis.

Localización de nódulos pulmonares con arpón guiado por TC previa a cirugía videotoracoscópica

Fundamento Localizacion de nodulos pulmonarescon arpon guiado por tomografiacomputarizada previa a cirugia videotoracoscopica. Pacientes y metodos Se coloco un arponguiado por tomografia computarizada en 22nodulos pulmonares tinendo la pleura visceralcon azul de metileno. Inmediatamentese realizo cirugia videotoracoscopica. Resultados Se localizaron y resecaron correctamentetodos los nodulos, sin complicacionessignificativas. Conclusion La localizacion con arpon y azulde metileno, en casos seleccionados de nodulospulmonares perifericos, permite la resecciontoracoscopica de lesiones de dificilacceso.