Endoscopic laser therapy in the tracheobronchial system.

Their physical properties make lasers ideal instruments for endoscopic surgical procedures in the narrow tracheobronchial system. By the thermal effects of the Nd-YAG laser, pathological benign and, especially, malignant lesions can be destroyed under direct vision. Working without contact with the tissue, sparing the risk of bleeding and further mechanical obstruction the laser has replaced mechanical and electrical devices and cryoprobes in interventional bronchoscopy to a large extent. Thus many patients with benign lesions can be spared the risk of major thoracic surgery of the large airways. To patients suffering from tumours of the central airways the chance of long-term palliation can be given by resolution of life-threatening complications. Furthermore, by photodynamic laser therapy after application of haematoporphyrin derivatives some patients may even be cured.

Neural cell adhesion molecule expression, neuroendocrine differentiation and prognosis in lung carcinoma.

We investigated the expression of the neural cell adhesion molecule (NCAM) in a series of surgically resected lung carcinomas of various histological subtypes by means of a panel of monoclonal antibodies recognising different N-CAM epitopes. In a subgroup of 56 tumours, the results of immunostaining with MAb 123C3--the antibody studied most extensively in our material--were compared to the ultrastructure, and in 231 radically resected non-small cell carcinomas, with histological tumour type and with clinical follow-up data. N-CAM expression was not limited to neuroendocrine tumours, as assessed ultrastructurally. Non-small cell lung carcinomas positive for MAb 123C3 showed post-operative overall and disease-free survival times significantly shorter than 123C3-negative non-small cell carcinomas.

Second primary lung cancer: importance of long term follow up.

Review of histopathological and clinical data showed that 153 patients at one hospital developed a second primary lung cancer during 1980-6, 10% of all those with lung carcinoma. There were 64 synchronous tumours (interval less than one year) and 89 metachronous tumours (interval over one year). The average interval between metachronous tumours was 6.1 years. The criteria for diagnosing a second primary lung cancer were any of the following: (1) different histological type; (2) different lobe; (3) interval between the two tumours of at least three years. The incidence of second primary tumours increases with survival, and close follow up is required for their early detection.

Quantitative pathologic analysis of first and second primary cancers in double tumors of the lung.

In spite of the frequent occurrence of double tumors of the lung, pathologic reports on these tumors are rare. In this study, 34 patients with double tumors (10 metachronous and 24 synchronous) were quantitatively analyzed; in all cases, both the first and second tumors had been completely resected and had adequate archival material. One aim of the study was to investigate whether there was a difference in the malignancy of the first and second tumors, as evaluated from their pathologic features. A second question was whether the length of the disease-free interval between the first and second tumors or the survival could be predicted on the basis of any of the investigated features. It was found that the first and second tumors, whether synchronous or metachronous, were strikingly similar: there was no difference in any of the quantitative pathologic features studied (epithelial percentage, DNA index, mean nuclear area and standard deviation of the nuclear area). It was not possible to predict by either univariate or multivariate analysis from any of the parameters either the length of the disease-free interval between the first and second tumors or the survival. These quantitative pathologic similarities suggest that the malignancy of the second tumor (synchronous as well as metachronous) is not higher than that of the first tumor. Thus, in the case of metachronous tumors, the fact that most of the second tumors (60%) are detected at a higher (inoperable) stage is probably caused by inadequate follow-up and not by increased malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

The percentage of aneuploid cells is significantly correlated with survival in accurately staged patients with stage 1 resected squamous cell lung cancer and long-term follow up.

Previous studies have shown that ploidy is an important prognostic determinant in lung cancer, but in those studies followup was restricted to three years, while patients with Stage 1, 2 and 3 disease and with different histological subtypes were included. Theoretically, these factors could have influenced the findings, especially since aneuploidy strongly correlated with the stage of disease. Because of this, tumor ploidy was studied in surgically resected stage 1 (T1/2, N0M0) squamous cell lung cancer patients with a minimal followup of 6 years. All patients were accurately staged by mediastinal lymph node mapping. Fifty-two from a group of 1539 patients with lung cancer diagnosed between 1980 and 1986 inclusive, fulfilled these criteria. Of these tumors, 23 (44%) were diploid with a 6-year survival of 53% and 29 (56%) were aneuploid with a 6-year survival of 48%. Although diploidy tended to be associated with local relapse of the tumor and aneuploidy with distant metastases, the difference was not significant and neither showed a survival advantage. However, within the aneuploid tumors, there was a significant correlation between the percentage of aneuploid cells and survival, defined as event-free or time to death. Seventeen patients with a percentage of more than 10 had a worse outcome (12 died, 6 years survival 35%), than to the other 12 patients with less than 10% aneuploid cells (2 died, 6-year survival 78%) (Mantel-Cox = 6.04, P = 0.01). This implies that in patients with accurately staged and histologically proven Stage 1 squamous cell lung cancer and long-term follow up, DNA content classified as diploid and aneuploid is not a prognostic factor for survival, but the percentage of aneuploid tumor cells is correlated with the prognosis.

Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung.

47 tumor samples, 45 of which were obtained at thoracotomy for non-small cell lung cancer were examined for mutational activation of the oncogenes H-ras, K-ras, and N-ras. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. ras gene mutations were present in nine of 35 adenocarcinomas of the lung (all K-ras), in two of two lung metastases of colorectal adenocarcinomas (1 x K-ras, 1 x N-ras) and in one adenocarcinoma sample obtained at autopsy (H-ras). All K-ras and H-ras mutations were in either position 1 or 2 of codon 12, while the N-ras mutation was in position 2 of codon 61. The potential clinical significance of K-ras activation was analyzed using the combined results of this and of our earlier study (S. Rodenhuis et al., New Engl. J. Med., 317: 929-935, 1987). Lung adenocarcinomas with K-ras mutations tended to be smaller and were less likely to have spread to regional lymph nodes at presentation. With a median follow up of 10 months, survival data are still immature. None of six adenocarcinomas of nonsmokers had a K-ras mutation and only one of four who had stopped smoking more than 5 years before. We conclude that mutational K-ras activation is present in about a third of adenocarcinomas of the lung and that the mutational event may be a direct result of one or more carcinogenic ingredients of tobacco smoke. Studies involving larger numbers of patients are required to confirm the association of K-ras activation with smoking and the inverse relation with tumor progression.

HLA-B27M1M2 and high immune responsiveness to Shigella flexneri in post-dysenteric arthritis.

The heterogeneous HLA-B27 antigen is closely associated with post-infectious or reactive arthritis (ReA) and is comprised of two serologically defined variants: B27M1+M2+ and B27M1+M2-. An outbreak of dysentery (n = 120) caused by a Shigella flexneri 2a strain, which possessed cell envelope antigens with epitopes resembling B27M2, resulted in five B27M1+M2+ patients with ReA. The remaining seven B27M1+M2+, one B27M1+M2- and all but three B27-negative patients remained free of joint symptoms; the latter three displayed arthralgia. IgM, IgG and IgA serum titers were statistically raised in all patient groups, but were exceptionally and persistently high in the B27M1+M2+ patients with ReA, especially IgA, as determined in acute-phase sera and sera sampled 1 year after dysentery. B27M1+M2+ thus appears to be a marker for a subset of disease, characterized by a high immune response. It is concluded that the B27M2 epitope is not unequivocally disease-related to Shigella ReA, that B27M1+M2+ is not likely to be the only immune-response-regulating gene involved in this form of ReA and that cross-reactivity between bacterial antigenic epitopes and B27 can only be part of a multifactorial process leading to ReA and in itself not sufficient to produce ReA. The intensity of the immune response appears to be another important factor.