Tumour markers in serum, bronchoalveolar lavage and biopsy cytosol in lung carcinoma: what environment lends the optimum diagnostic yield?

BACKGROUND: The aim of this study was to assess the diagnostic yield of the tumour markers carbohydrate antigen (CA 125), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC) and specific tissue polypeptide antigen (TPS) in serum, bronchoalveolar lavage (BAL) and biopsy cytosol in a group of patients with bronchogenic carcinoma. METHODS: Serum, BAL and biopsy cytosol samples were collected in a group of 85 patients with benign or malignant pulmonary diseases. After appropriate processing, tumour markers were determined by enzyme immunoassay. The diagnostic yields (sensitivity, specificity and accuracy) in each environment (serum, BAL or biopsy) were obtained by using "ROC" curves. RESULTS: Determined individually, CA 125, NSE and SCC show the greatest diagnostic accuracy in cytosol. CEA and TPS do so in BAL. CEA is the most relevant marker in serum and BAL, and CA 125 in cytosol. When the different tumour markers are associated, they offer better overall yields for all except TPS. CONCLUSIONS: For the factors evaluated in this study, determination of CEA in BAL was clinically the most useful marker in comparison with serum and cytosol determinations, although the latter may also be helpful in certain situations. Although there is no specific tumour marker for lung cancer, the combination of several can be used to monitor most patients with lung cancer.

Papillary thyroid carcinoma: prognostic index for survival including the histological variety.

BACKGROUND: Numerous prognostic factors have been studied for survival in patients with papillary thyroid carcinoma (PTC), although there are few multivariate studies that include the histological variety of PTC. HYPOTHESIS: There are prognostic factors that influence survival in a series of patients with PTC, including the histological variety, and a new prognostic index (PI) for survival can be formulated by accounting for these factors. DESIGN: A retrospective study. SETTING: A university hospital department of surgery. PATIENTS: Between January 1970 and December 1995, 200 patients undergoing surgery for PTC were observed (mean follow-up, 8 years). MAIN OUTCOME MEASURES: A univariate analysis was done for survival rates using the Kaplan-Meier estimation method. The possible prognostic factors were evaluated using a multivariate analysis according to the Cox model. We formulated a PI and defined 3 risk groups (low, medium, and high) for mortality. RESULTS: Of the 200 patients, 175 (87.5%) are still alive. Of the 25 deaths, 19 (9.5%) were due to the tumor. The survival was 97.5% at 1 year, 92.8% at 5, 89.5% at 10, and 83.9% at 15 and 20 years. The prognostic factors obtained after the multivariate analysis were age, tumor size, extrathyroid spread, and histological variant of the PTC. The PI is calculated as follows: PI = (2 x size) + (6 x spread) + (2 x variant) + (3 x age). As for the risk groups, the low-risk group showed a mortality of 0%; the medium-risk group, 17.1%; and the high-risk group, 76.5%. CONCLUSIONS: The histological variety of PTC has prognostic value for survival in patients with PTC. As risk factors for PTC mortality, we consider an age of 50 years or older, a tumor larger than 4 cm, the existence of extrathyroid spread, and a certain histological subtype of PTC. With these risk factors, it is possible to formulate a PI and classify patients into low-, medium-, and high-risk groups for mortality.

DNA aneuploidy, S-phase fraction and nuclear p53 positivity in non-small cell lung carcinoma.

OBJECTIVES: Surgical resection currently offers the best option for managing non-small cell lung carcinoma (NSCLC) but its efficiency is limited by subsequent tumor recurrence. We evaluated whether flow cytometric study and the p53 gene staining pattern may be useful in this respect. DESIGN AND METHODS: We took biopsy samples of 40 patients with operable NSCLC to study the frequency of aneuploidy, proliferative activity, and alterations in the p53 tumor suppressor gene and compared them with clinicopathological parameters such as age, gender, smoking, histological type, tumor size, and degree of differentiation. To study DNA content, the nuclei were analyzed by flow cytometry using a FACS flow cytometer (Becton-Dickinson) equipped with an argon ion laser, with a propidium iodide excitation of 488 nm. We used the immunohistochemical technique for p53 analysis in samples of paraffin-embedded tissue corresponding to the same patients from whom fresh tissue was taken. RESULTS: Nuclear p53 staining was detected in 66.7% of the samples; 69.4% of the cases revealed aneuploid DNA histograms and 59% presented with an S phase fraction of more than 12%. Comparison with clinicopathological parameters showed that p53 protein was associated significantly with histological classification (p = 0.04), gender (p = 0.01), and smoking (p = 0.04). CONCLUSIONS: Immunodetection of p53 overexpression and DNA ploidy in the bronchial epithelium may be a useful tool in any future multifactorial analysis in such tumors for identifying previous lesions that may progress to malignancy.

Tumor markers in lung cancer: does the method of obtaining the cut-off point and reference population influence diagnostic yield?

OBJECTIVES: The aim of this study was to evaluate the clinical usefulness of the tumor markers CA125, CEA, NSE, SCC, and TPS in a group of patients with lung cancer. We estimated the influence of the method for choosing the cut-off point and of considering as a reference population either healthy controls or patients with some form of non-neoplastic pulmonary disease (NNPD). DESIGN AND METHODS: The tumor markers were determined using enzyme immunoassay techniques, and their diagnostic yield was evaluated using ROC curves and their correlation with the percentages between false and true positives. The diagnostic parameters of the tumor markers are presented in 116 patients with lung cancer and compared with a group of 25 healthy controls and another group of 80 patients with some form of NNPD. We determined on the one hand the cut-off points resulting from the best sensitivity-specificity balance in the ROC curves and on the other those resulting from considering a specificity of 95%. With the two cut-offs we studied the different diagnostic parameters: sensitivity, specificity and accuracy or area below the ROC curve. RESULTS: Optimum diagnostic yield is obtained when we choose the cut-off point determined by the best balance of sensitivity and specificity in the ROC curves and take a healthy population as a reference group. The cut-off values for CA125, CEA, NSE, SCC, and TPS were 24 U/mL, 2.8 ng/mL, 9.8 ng/mL, 1.6 ng/mL, and 67.8 U/L, respectively. CONCLUSIONS: Our results suggest that in future studies on tumor markers, a group of healthy subjects should be used as a reference population and ROC curves should be used to obtain the optimum cut-offs.

Results of surgical treatment of epidermoid carcinoma of the thoracic esophagus.

During 1979 to 1991, 125 patients with epidermoid carcinoma of the thoracic esophagus were admitted to our General Surgery unit. The average age was 60.1 years; 94.4 percent of the patients were male. The mean duration of symptoms was 3.65 months. The most frequent symptom was dysphagia in 97.19 percent, followed by weight loss in 64.48 percent. The most frequent location was the middle one-third in 58.4 percent. The tumor was well differentiated in 27.2 percent, moderately well differentiated in 41.6 percent and poorly differentiated in 31.2 percent. By preoperative staging, 1 patient was stage I, 24 were stage II, 86 were stage III and 14 were stage IV. The operability rate was 76 percent and the resectability rate was 48.8 percent. Resection was "curative" in 42.62 percent and palliative in 57.37 percent. Radiation therapy and chemotherapy were used only in those patients who did not undergo resection. All of the patients in whom resection was possible underwent a single-stage esophagogastrectomy. The postoperative mortality rate was 20 percent, but only 11.54 percent if we only consider those patients who underwent "curative" resection. The most frequent causes of mortality were respiratory complications and anastomotic leakage. The five year overall survival rate was 5.99 percent. In the resected group, the five year survival rate was 8.82 percent and in patients in whom resection was considered "curative," the rate was 20.86 percent.