Florentino Hernando

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.

Heterotopic gastric mucosa in the upper esophagus ("inlet patch") : a rare cause of esophageal perforation

We report the case of a 21-yr-old woman who presented with a perforation of an upper esophageal ulcer on a patch of gastric-type mucosa. Despite surgical closure of the perforation and reinforcement with a pleuro-muscular flap the patient developed an esophageal leakage and died in the postoperative period. Heterotopic gastric mucosa in the upper esophagus is usually an asymptomatic abnormality, discovered incidentally during endoscopic studies carried out for some other reason; however, complications secondary to the inlet patch acid secreting capacity can arise, and this has to be kept in mind to elude life-threatening conditions.

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.

3p21, 5q21, and 9p21 allelic deletions are frequently found in normal bronchial cells adjacent to non-small-cell lung cancer, while they are unusual in patients with no evidence of malignancy.

Molecular cytogenetic and loss of heterozygosity (LOH) analyses of non‐small‐cell lung cancer (NSCLC) have shown frequent allelic deletions in a variety of chromosomes, such as 1p, 3p, 5q, 8p, 9p, 11p, 11q, and 17p. Allelic loss at 3p21, 9p21, and 5q21 has also been reported in premalignant epithelial lesions of the bronchus and in normal bronchial cells. These findings suggest that a tissue field of somatic genetic alterations precedes the histopathological phenotypic changes of carcinoma. LOH at chromosomal regions 3p21, 5q21, 9p21, and 17p (TP53) was looked for in the peritumoural normal bronchial cells from 30 archival surgically resected tumours. Microdissected normal bronchial cells from 20 benign cytological smears were also added to the study. Matched populations of lymphocytes, tumour cells, and normal bronchial cells adjacent to the tumour were microdissected from paraffin‐embedded tissues, while matched populations of normal bronchial cells and inflammatory cells were microdissected from benign cytological smears (bronchial brushings). Polymerase chain reaction (PCR) amplification was performed utilizing the specific markers D5S346, D3S1300, D9S157, D9S171, and TP53. Within the NSCLC tumour cells, LOH was more frequently found at the 5q21 locus (72% of the informative cases), the 3p21 locus (47%), 9p21 (48%), and 17p (33%). Within the peritumoural normal bronchial cells, LOH at 5q21 was found in 37.5% of the cases, 22% showed LOH at 3p21, 27% at 9p21, and 13% at 17p (TP53). LOH was also detected in one case, in normal bronchial cells obtained from cytological smears at one locus (5q21). In conclusion, normal bronchial mucosa adjacent to NSCLC has frequent allelic losses at 3p21, 5q21, and 9p21, while LOH at these loci is unusual in normal bronchial cells obtained from cytological smears from patients with no evidence of malignancy. LOH at these loci may be present before the onset of the malignant growth. LOH studies may supplement the histopathological evaluation of bronchial cells to detect genotypic alterations in both cytological and biopsy specimens. Copyright

Quantitative analysis of carcinoembryonic antigen, squamous cell carcinoma antigen, CA 125, and CA 50 cytosolic content in non-small cell lung cancer.

Background. The cytosolic content of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC), CA 125, and CA 50 antigens in non‐small cell lung cancer (NSCLC) is analyzed in this study. The aim was to ascertain the relationship between tumor marker content and the clinicopathologic aspects of this neoplasm.

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.

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.

Use of possible synergistic expression of p53 and p185 as a prognostic tool for stage I non-small-cell lung cancer.

Abstract. The possible interaction between the quantified overexpression of the oncoproteins p53 and p185 was evaluated. These proteins have already been independently defined as prognostic factors in non-small-cell lung cancer (NSCLC). p53 and p185 levels were determined in stage I patients (n= 40) from a sample of 102 NSCLC sufferers who underwent surgery for precocious disease during the period October 1991 to June 1994. The resected tumors were histologically classified and included 15 adenocarcinomas (37.5%), 1 large-cell carcinoma (2.5%), and 24 epidermoid (60%) carcinomas. The p53 concentration of tumor specimens was determined by luminescence immunoanalysis and was defined as positive if it was above the minimum value detectable by the method (0.01 ng/mg). The p185 protein was quantified by enzyme-linked immunoassay, and the 80th percentile of the frequency distribution was used as the reference cutoff value (348.8 U/mg). Survival and disease-free-survival (DFS) rates were estimated at 24 months after intervention. There were no significant differences in survival or DFS of patients with adenocarcinoma-type tumors for subjects with independent p185 values < 348.8 U/mg and those showing values ≥ 348.8 U/mg. Neither were there differences observed between patients with positive and negative p53 values. In patients with epidermoid-type tumors the cumulative survival was significantly higher in p53-negative than in p53-positive patients (p= 0.03) and was also higher in patients with p185 levels < 348.8 U/mg than in those with values ≥ 348.8 U/mg (p= 0.00001). These patients showed no significant differences with respect to recurrence rate. The possible synergistic behavior of p53 and p185 levels as a prognostic factor was evaluated in patients with epidermoid-type tumors. p53-negative and p53-positive patients were grouped according to a p185 level of less than or more than 348.8 U/mg. Significant differences were seen in both survival rates and DFS between groups. Individual analysis of relative risks showed an increased risk of death and greater recurrence rate in patients with p185 levels ≥ 348.8 U/mg and a greater recurrence rate in patients with p53-positive values. Multivariate analysis established that the multiplicative, synergistic, prognostic effect of p53 and p185 was not significant. The existence of a significant, synergistic, prognostic effect of the p185 and p53 proteins in NSCLC could not be proven. However, a greater prognostic potential of the quantified overexpression of p185 with respect to that of p53 was established. An additive effect in the prognostic potential of both proteins was also observed (stratified analysis).