Manuel Díez

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.

Prognostic significance of serum CA 125 antigen assay in patients with non-small cell lung cancer.

Background. The serum levels of CA 125 tumor‐associated antigen in patients with lung cancer have been previously related to TNM stage, histologic type, and survival rate. In the current study, the prognostic information provided by the CA 125 antigen assay was analyzed.

Prediction of recurrence in B–C stages of colorectal cancer by p53 nuclear overexpression in comparison with standard pathological features

This study investigated the predictive value of p53 nuclear overexpression on recurrence of colorectal adenocarcinomas compared with established prognostic pathological features. Sixty-one paraffin-embedded sections from primary tumours were examined by immunohistochemistry. Specific nuclear staining was detected in 27 (44.2%) cases. Positivity was more frequent in tumours with venous invasion (76.9%) (P = 0.06) and in rectal cancer (68.4%) (P = 0.06). After a median observation time of 46 months, p53-positive tumours exhibited a higher percentage of recurrence (40.7% vs 11.7%) (P = 0.03), and a higher likelihood of relapse at 5-year follow-up (46% vs 13%) (P = 0.006). Among the pathological variables analysed, only the extent of bowel wall invasion showed a relationship with recurrence. After adjustment for the other covariates in a Coxs regression model, p53 overexpression was the only factor showing independent prognostic significance (hazard ratio: 4.96; 95% Confidence Interval (CI): 1.47-16.71) (P = 0.012). The results of this study show that nuclear p53 protein overexpression has higher predictive value than standard pathological variables.

Time‐dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma

This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma.

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.

Serum CEA, CA125, and SCC antigens and tumor recurrence in resectable non-small cell lung cancer

Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CA125 were determined pre- and postoperatively in non-small cell lung cancer patients (NSCLC) to assess the relationship between serum levels and postoperative recurrent disease. Ninety-five patients who underwent curative surgical resection were included (TNM stages I, II, IIIa). CEA and CA125 were determined by solid-phase enzyme-immunoassay, SCC by radio-immunoassay. Tumor relapse was detected in 41 patients (43%): 16 (39%) with locoregional disease and 25 (61%) with disseminated disease. The overall 36-month disease-free survival rate was 42%. The sensitivity for recurrence was 58% for CEA, 53.6% for CA125, and 51.2% for SCC; 87.8% of patients showed at least one elevated marker. The sensitivity of CEA and CA125 increased significantly in patients with preoperative serum concentrations above the cut-off: 86.6% versus 42.3% (p < 0.01), and 93% versus 18% (p < 0.01), respectively. Preoperative CA125 above 15 U/ml identified a high-risk group of patients: a lower 36-month disease-free survival rate (0%) versus 56%) (p < 0.001), a 3.02-fold higher risk of recurrence (p < 0.05), and a 6.22-fold higher risk of disseminated failure (p < 0.001). The identification of CEA and CA125 producer-tumors, based on preoperative serum values, enhances the clinical performance of a postoperative surveillance program in surgically treated NSCLC. Preoperative serum CA125 is a prognostic factor to identify patients at high risk of postoperative tumor recurrence.

Evaluation of serum carcinoembryonic antigen monitoring in the follow-up of colorectal cancer patients with metastatic lymph nodes and a normal preoperative serum level.

The value of serial serum carcinoembryonic antigen (CEA) assay in the follow-up of colorectal cancer patients with metastatic lymph nodes and normal (≤ 5 ng/ml) preoperative CEA levels, was examined in this study. Thirty-eight patients were studied and compared with 22 patients with elevated CEA levels. The overall sensitivity of CEA for the diagnosis of recurrence was 36%. Postoperative CEA was strongly influenced by the site of recurrence. CEA monitoring showed the best results in patients who developed hepatic metastases (sensitivity 60%, specificity 94%, positive predictive value 60%, and negative predictive value 94%), and was ineffective for the detection of locoregional or pulmonary metastases. The results indicate that elevation of CEA in the postoperative course of these patients is an indicator of the presence of hepatic metastases. Postoperative CEA monitoring should not be omitted in Dukes C patients with normal preoperative levels, and is more reliable for the detection of liver metastases.

Evaluation of the SENIC risk index in a Spanish university hospital.

OBJECTIVE To assess the performance of the Study of the Efficacy of Nosocomial Infection Control (SENIC) risk index for the evaluation of the risk of surgical-site infection (SSI) in a country other than the United States, having a different health system. SETTING 350-bed university hospital in Spain belonging to the National Health System (Insalud). DESIGN Observational cohort study of 1,019 patients who underwent consecutive surgery from January to December 1992. Surgical-infection risk factors assessed by the traditional wound-classification system (clean, clean-contaminated, contaminated, and dirty-infected wound) and by the SENIC risk index (length of intervention more than 2 hours, more than three discharge diagnoses, abdominal surgery, and contaminated or dirty-infected wound) were compared by forward logistic regression. RESULTS The SENIC risk index showed a greater ability to predict SSI than the traditional wound-classification system. The study carried out in our institution reproduced the estimators provided by the SENIC study in the United States. The SENIC risk index provided a stepwise increase in SSI rates, according to the number of factors present, for every traditional wound-classification group. In the case of clean wounds, the incidence of surgical infection (per 100 interventions) increased (1.5, 2.4, 5.3, and 50; P<.001) for patients having from zero to three risk factors of the SENIC risk index. CONCLUSIONS This study shows that the SENIC risk index results are reproducible, and the index can be used to compare rates of wound infection across countries with different health systems than the United States.

Continent colostomy by means of a new one-piece disposable device

A study was established concerning a continent colostomy system consisting of a new one-piece disposable plug. Twenty patients participated: 13 men and 7 women, who ranged in age from 35 to 87 years. All patients had an end colostomy located on the left lower quadrant. The colostomy age ranged from 2 months to 7 years. Of the 20 participants, 17 found the new procedure to be safer and more comfortable, as well as a considerable improvement for their quality of life. The other three patients found no advantage in its use. In no case was there any perception of local, secondary, or general adverse effects owing to its use. Taking into consideration that the use of this new device does not require any type of special conditioning, we consider that it can contribute to the better quality of life of a colostomy patient, the one best able to evaluate the worthiness of its use.