Cea and ca-19.9 as markers of colorectal neoplasms during chemotherapeutic treatment.

Carcinoembryonic antigen and CA 19.9 are markers of colorectal neoplasms, often related to tumor burden. Elevated pre-operative levels parallel disease extent and may foresee adverse prognosis. CEA and CA 19.9 may increase post-operatively, indicating tumor recurrence. Only limited data are available on the influence of chemotherapeutic treatments on these two markers, to detect chemotherapy-induced cytolysis. We measured CEA and CA 19.9 before and after a chemotherapy regimen of five days consisting of folinic acid and 5-fluorouracil in forty patients with colorectal cancer. No consistent fluctuation was detected, the examined tumor markers being related in a given patient only to tumor burden.

Fungal infections in lung transplantation. Incidence, risk factors and prognostic significance.

BACKGROUND AND AIM OF THE WORK: Fungal infections are frequent following lung transplantation and are associated with high mortality and morbidity. The study aims at 1) reporting our experience with fungal infections after lung transplantation; 2) identifying statistically significant correlations between the occurrence of fungal infections and bacterial infections, cytomegalovirus disease, rejection and steroid therapy; 3) assessing whether the presence of fungal infection has an impact on long-term survival. METHODS: 60 lung transplant recipients were studied with respect to incidence, pattern of presentation and median time to presentation of fungal infection after the transplant. Correlation analysis of the variables of interest was undertaken in 30 patients who had a minimum follow-up of 1 year following transplant. RESULTS: The prevalence of fungal infection was 44%; severe infections occurred in 5 patients (11%). The presence of Candida preoperatively was not associated with an increased risk of fungal infection. In a logistic regression analysis, a significant correlation was found between the occurrence of fungal infection and the following variables: respiratory bacterial infections (p = 0.0003), cytomegalovirus disease (p = 0.00001) and steroid therapy (p = 0.04). No statistically significant difference was found between patients who experienced a fungal infection and those who did not, either in univariate or multivariate survival analysis (p = 0.08). CONCLUSIONS: 1) fungal infections are frequent in lung transplant recipients and may be severe in more than 10% of the cases; 2) the presence of fungi preoperatively is not a contraindication to transplantation: an antifungal prophylaxis is probably indicated in such cases postoperatively; we recommend the use of the less nephrotoxic liposomal Amphotericin B by aerosol route; 3) a statistically significant association exists between fungal infections and both steroid therapy and CMV disease; this suggests that a similar antifungal prophylaxis is indicated in these clinical circumstances; 4) the presence of fungal infection is not an independent prognostic factor of long-term survival.

Clinical utility of tissue polypeptide antigen determination in lung cancer management.

In view of the fact that pulmonary malignancies still represent an important cause of tumor death and that the high rate of unsuccessful treatment may be partly due to the late clinical presentation, efforts should be spent not only to develop new and effective treatments but also to improve early diagnosis and to identify prognostic factors and parameters useful for the monitoring of the treatment. Tumor markers, if used properly, can provide a useful support for the management of patients suffering from various malignancies, including lung cancer patients. The clinical significance of one of the most widely used tumor markers, Tissue Polypeptide Antigen (TPA), has been reviewed and showed this marker to be useful to the clinician for the management of patients with pulmonary malignancy, as a complementary tool for diagnosing and staging the tumor as well as for monitoring treatment response or relapse occurrence.

Immunohistochemical detection of carcinoembryonic antigen (CEA) in non-neoplastic lung disease.

Carcinoembryonic antigen (CEA), though typically associated with malignant epithelial neoplasms, is known to be present at elevated levels even in the serum of normal individuals and of patients suffering from interstitial diseases of the lung. Few reports have addressed the question of the possible source of CEA immunoreactivity within the lung parenchyma. Two patients with elevated CEA serum levels were studied by immunohistochemistry on open lung biopsy specimens. Two different antibodies (one absorbed with non-specific cross-reacting antigen, NCA) were used. The results show that bronchiolar cells and type II pneumocytes are focally positive with both antibodies; the immunoreaction is preserved even after absorption with NCA. In agreement with experimental data on CEA synthesis in fetal bronchial cell lines, these findings indicate that interstitial lung disorders may induce abnormal CEA-like substance expression. In these cases, where no epithelial neoplasms subsequently develop, the cutoff level for CEA in serum should be raised. Bronchiolar and alveolar cells appear primarily responsible for CEA-like substance production.

Clinical significance of tumor necrosis factor in patients with bronchogenic carcinoma and benign lung diseases: a comparative study.

Tumor Necrosis Factor (TNF) was determined in the serum of 72 lung carcinoma patients. Twenty-four healthy subjects younger than 50 years and 10 healthy subjects older than 70 years were considered as control group. TNF was also measured in 20 patients with stage I sarcoidosis and in 15 patients with pulmonary fibrosis. The marker was detected in 32% of cases in the neoplastic group, in 37.5% of disease confined to the chest and in 25% of advanced disease cases. A large proportion of TNF-positive samples was found in sarcoidosis (30%), and even larger in pulmonary fibrosis (66.6%). TNF was also present in healthy subjects older than 70 (40%). We conclude that TNF is not specific of malignancy, being demonstrable in other benign pulmonary diseases and even in the course of physiological aging.

Tumor markers and lung cancer: guidelines in a cost-limited medical organization.

The aim of our study was to evaluate the cost of the tumor marker assays most widely used in pneumological practice and the effectiveness of the percentage of DRG-based reimbursements absorbed by these assays. For this purpose we assessed the cost of lung tumor marker assays in Emilia Romagna compared to the DRG-based reimbursement of inpatients affected by lung diseases in whom the use of tumor markers is indicated. As an example, we evaluated the cost/effectiveness of the CEA assay in the differential diagnosis of 68 pleural effusions from 46 patients (20 benign diseases, 26 malignant). Because the CEA assay was not a substitute for cytology when this was not diagnostic, 41.3% of the resources were not efficiently spent. If the marker assay had been performed only in cases with negative cytology, we could have spared 14 of 46 tests. Moreover, since the expense lies predominantly in the cost of reagents (81.23%), we suggest as a routine procedure to collect and store samples for tumor marker assay in all cases; the test should be performed in a selected population of patients with negative cytology and "suspect" clinical outcome.

TAF test in primary esophageal carcinoma: comparison with other tumor markers.

An ELISA method for the determination of circulating specific HSV-TAA antibodies has recently become available (TAF test). The presence of TAF was tested in serum of 154 patients with primary esophageal carcinoma, collected in three institutions. The overall TAF-test positivity rate was 57.1%, being significantly lower in stage IV than in stage III patients. The concordance rate between TAF and CEA, ferritin, TPA, SCC and TATI was low, suggesting that TAF is probably independent of the other tumor markers evaluated. The clinical role of TAF-test determination in patients with esophageal carcinoma is currently under evaluation.

Disappearance curves of tumor markers after radical surgery.

CEA serum levels were sampled from 15 patients with lung carcinoma, 12 patients with colon carcinoma, and 5 patients with gastric carcinoma before and after radical excision of the malignancy. In addition, TPA serum levels were measured in 7 patients with lung carcinoma and CA 19.9 serum levels in 9 patients with colon carcinoma, before and after curative surgery. Irrespective of the primary malignancy, a CEA half-life of approximately 3 days was calculated. The normalization time was related to the preoperative level of the marker, being longer when the preoperative CEA level was > 20 ng/ml. The TPA half-life was slightly longer than 1 day, ranging from less than 1 day to more than 3 days, with a normalization time of about 20 days. The CA 19.9 half-life was slightly longer than 1 day with variations from less than 1 day to about 3 days. Many factors, especially associated inflammatory processes and hepatic clearance imbalances, may influence marker kinetics in the postoperative period. A correct evaluation of the clinical significance of tumor marker half-life after radical surgery will require a larger number of patients as well as careful and prolonged follow-up.

Effect of lung resection on pulmonary function. A comparative study in different surgical procedures.

The effect of lung surgery on respiratory function has been investigated in 40 patients considering separately the three main procedures (pneumonectomy, lobectomy and thoracotomy alone) to ascertain if the resected lung and the volume removal can influence this function in the immediate postoperative period. The patients were submitted to spirometry and arterial gas analysis preoperatively and during 9 days postoperation; the tests controlled were VC, FEV1, TV and RR. No significant difference has been noticed among various surgical procedures.

Respiratory function during oxygen administration in chronic obstructive pulmonary disease.

Patient with severe chronic obstructive pulmonary disease (COPD) can develop respiratory muscle weakness and fatigue. Arterial hypoxemia can predispose to this condition. To assess whether O2 administration improved respiratory muscle function and respiratory pattern in COPD 11 patients with chronic hypoxemia were examined. Each patient was first submitted to respiratory function studies, including lung volumes, in normal and recumbent position, respiratory frequency, Ti/Te, Ti/Tot, maximal inspiratory and expiratory pressures (Pimax, Pemax) and arterial gas analysis breathing room air. All these tests were repeated during oxygen Administration through a nasal cannula. The arterial PO2 improved from 50 +/- 7 mmHg to 81 +/- 28 mmHg but the breathing pattern, Pimax and Pemax as well as lung volumes remained unchanged. It is concluded that oxygen, in short term administration, doesn't influence respiratory pattern and muscle function.

Clinical importance of tumour markers in the diagnosis of squamous-cell carcinoma of the esophagus.

In order to evaluate the diagnostic value of three tumour markers, CEA, CA 19-9 and TA4-scc, 50 patients affected by squamous-cell carcinoma of the esophagus were studied together with 70 normal controls and 22 patients affected by benign esophageal pathologies. The three tumour markers were assessed in all patients and data were evaluated statistically in order to reveal their sensitivities, specificities and diagnostic values. It was concluded that further studies should be carried out on the marker TA4-scc given its high specificity and sensitivity towards esophageal neoplasias at a relatively early stage.

Pulmonary function in the patients submitted to lung exeresis.

The effects of lung surgery on respiratory function were investigated in 80 patients; 17 patients were submitted to left pneumonectomy (LPN); 11 patients were submitted to right pneumonectomy (RPN); 7 patients underwent a left upper lobectomy (LUL); 16 patients a left lower lobectomy (LLL); 17 patients were submitted to right upper lobectomy (RUL); 12 patients underwent right lower lobectomy (RLL). All patients were submitted to spirometry and arterial blood gas analysis. The effects of lung surgery on respiratory function depends upon the extent of the resected tissue.

Pulmonary function in patients with pleural effusion of varying magnitude and fibrothorax.

Pulmonary function was studied in sixty patients with pleural effusion and seventy patients with fibrothorax. The patients with pleural effusion were divided into three groups according to the extent of the effusion. The patients were submitted to spirometry and arterial blood gas analysis. The effects of pleural effusion on pulmonary function is evaluated with regards to the size of effusion. Small-size pleural effusion little affects arterial oxygen tension. Pleural effusion and fibrothorax have a similar pattern of pulmonary function.

Videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease.

OBJECTIVE: Interstitial lung diseases (ILD) require lung biopsy for the diagnosis in more than 30% of patients. Open lung biopsy (OLB) was generally considered the most reliable method of biopsy and tissue diagnosis. This study tests the diagnostic accuracy and safety of the videothoracoscopic lung biopsy (VTLB) in the diagnosis of ILD. METHODS: During the last 5 years, 58 patients were submitted to VTLB under general anesthesia. The mean age was 49.6 +/- 12.0 years (range 21-69). All the biopsies were performed by an endostapler EndoPath 30 or 45. Conversion to minithoracotomy was necessary in only one patient because of extensive pleural sinfisis. All the specimens were sent to the microbiology and pathology department for microbiological and histopathological diagnosis. One chest-tube (28F) was positioned and connected to a drainage-system and placed on suction. RESULTS: The histopathological diagnosis was obtained for all patients and therefore the diagnostic accuracy of the procedure was 100%. No postoperative haemothorax occurred and only two patients experienced a prolonged air-leakage (3.4%). The median duration of the chest-drain was 3 days (range 1-7) and the median hospital stay was 4 days (range 2-7). CONCLUSION: VTLB provides adequate specimen volume for histopathologic diagnosis and achieves a very high diagnostic accuracy (100% in our series). The postoperative morbidity and mortality rates are lower than those related to OLB. We conclude that VTLB is an effective and safe procedure in the diagnosis of ILD.

CYFRA 21-1 determination in patients with non-small cell lung cancer: clinical utility for the detection of recurrences.

The aim of this study was to evaluate serial determinations of CYFRA 21-1 in the follow-up of patients treated surgically for non-small cell lung cancer in order to predict the risk of tumour recurrence. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 57 patients with operable non-small cell lung cancer (NSCLC): 25 with squamous cell carcinoma (SqCC), 20 with adenocarcinoma (AC), 12 with large cell carcinoma (LCC) and 30 with non-malignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified in 44% of all patients with NSCLC. The diagnostic specificity of the assay was 97%. Positive CYFRA 21-1 levels was observed in 30% of stage I, 33% of stage II, and 55% of stage IIIa. Statistically significant differences were obtained between stages I and IIIa, II and IIIa, but not between stages I and II. During follow-up recurrence was observed in 19 of 57 (33%) NSCLC patients. Recurrence-free survival probability for patients with elevated serum CYFRA 21-1 levels before surgery was 52% (13/25), versus 81% (26/32) for patients with normal serum CYFRA 21-1 levels (p < 0.01). In 15 patients with increased trend for CYFRA 21-1, elevated serum CYFRA 21-1 levels preceded (13 patients) or coincided (2 patients) with the clinical detection of tumour recurrence, providing a predictive value of an increased trend of 87%. In the multivariate analysis the association of the increase of CYFRA 21-1 level with a higher risk of recurrence is statistically significant (p < 0.001).

Tumor markers kinetic in malignant lung neoplasms.

BACKGROUND: No studies about correlation between post-operative half-life of tumor markers and prognosis in lung cancer exist in literature. The aim of our study was to determine the half-life of CEA, TPA, NSE and CYFRA 21-1 in postoperative period after surgery of bronchogenic carcinoma, and to correlate it with the prognosis and survival of the patients. METHODS: From March 1997 to March 1998, 35 patients with bronchogenic carcinoma were studied (29 males and 6 females, mean age 64.9 years, range 51-77 and 61.0 years, range 52-77 respectively). The mean follow-up for males was 125.70 days (from 30 to 198) after surgery and for females 125.79 days (from 30 to 180). CEA and NSE were tested by immunoenzymatic automated method, whereas TPA and CYFRA 21-1 were assayed by immunoradiometric techniques. For each patient both the dismission curve and the half-life of considered markers were calculated during follow-up. RESULTS: A statistically significant difference was found for preoperative values of TPA (p = 0.027) and CYFRA 21-1 (p = 0.025) between SqCLC and adenocarcinoma. The preoperative levels of markers were higher in patients who would develop a relapse, even if statistical significance was not reached. CEA half-life was of 1.4 days, while in patients with a history of relapse or metastatic spreading was 4.5 days. No differences were revealed concerning CYFRA 21-1 between the two groups. CONCLUSIONS: Seriate determination of some markers (CEA and TPA in particular) during postoperative follow-up after surgery for bronchogenic carcinomas can be a useful prognostic tool. Longer follow-up would provide additional informations in order to determine individual predictive threshold between poor and good prognosis.

[ Correlation between histopathologic and scintigraphic findings (employing 67Ga) in relation to the surgical indication for bronchial carcinoma (author's transl)]. / Correlazione tra reperto anatomo-patologico e scintigrafico (impiego di 67Ga) in rapporto all'indicazione chirurgica del carcinoma bronchiale

Following the investigation on the correlation between scintigraphic pictures and histopathologic findings in 66 patients with suspected bronchial carcinoma, 84% of the scannings were positive and the data relative to the so-called "false negative" cases was analyzed. The presence of hilar or mediastinal lymph node metastases, histologically ascertained in about one-third of the patients, appeared significant; and a restricted accumulation of the radio-element was evident in 70.5% of the cases. In 10 of the cases with negative scintigraphic findings, pictures of reactive or hyperplastic lymphadenitis (almost all radiologically relievable) were obtained. Therefore, if it cannot be logically concluded that the negative scintigraphic findings at the mediastinal level indicate the absence of metastases in the lymph nodes, thus indicating surgery (or preventive mediastinoscopy), positive finding seem to be synonymous with extrapulmonary diffusion of the neoplastic process, with direct implication in determining the operability of the patient.

TA 4-SCC versus CEA sensitivity for lung cancer.

The sensitivity of a new tumor marker, TA 4-SCC, for lung tumors is examined and compared with the performance of the already established CEA. TA 4-SCC sensitivity is only moderate (30%), and it presents no significant differences among the various histologic types of lung cancer. In addition, unlike CEA, TA 4-SCC is present in large amounts in the serum of many stage I and II patients. In fact, its sensitivity in still curatively operable tumors reaches 30% compared to 10% with CEA.

[Usefulness of the determination of CA 19-9 in the follow-up of patients with gastroenteric neoplasms in comparison to CEA]. / Considerazioni sulla utilità del dosaggio del CA 19-9 nel follow-up di pazienti portatori di carcinoma gastroenterico in confronto al CEA.

28 cases of carcinoma of the digestive tract were studied in order to assess the value of assaying a new tumour marker (CA 19-9) on monitoring the postoperative course of neoplasia. CEA, a tumour antigen of more certain dependability was assayed at the same time. In the case series examined it was found useful to monitor both antigens since although CA 19-9 is less sensitive then CEA in cancers of the large intestine, it is more sensitive in carcinomas of the stomach and pancreas. These early data will have to be confirmed on larger samples but in general terms they do indicate the value of the combined monitoring of this new antigen and CEA in the follow-up of patients given surgery for carcinoma of the digestive tract.

[Bronchial carcinoma in subjects under 40]. / Il carcinoma bronchiale nei soggetti di età inferiore a 40 anni.

We investigated a series of 30 patients younger than 40 years with histologically proven bronchogenic carcinoma. Most patients were symptomatic for a mean duration of 3 months before examination. The most common cell types were squamous carcinoma in 10 patients, oat cell carcinoma in 9 patients, and adenocarcinoma in 5 patients. The disease was categorized as Stage I in 3 patients, Stage II in 3, Stage III in 17, and Stage IV in 7. Ten patients underwent resection, whereas 3 patients were inoperable at surgery. The average length of survival for the nonoperated patients was 4.2 months (range 1 to 16 months). The mean survival for the surgically treated patients was 23.3 months (range 0 to 84 months). Extent of resection did not have any statistical significance in the survival rates which were mainly affected by staging of disease.