Prophylactic cranial irradiation in limited disease small-cell lung cancer in complete remission: a retrospective analysis.

Recently a meta-analysis showed an improved survival probability of prophylactic cranial irradiation (PCI) in limited disease small-cell lung cancer (LD SCLC) in complete remission after chemotherapy. We evaluated treatment results of PCI+ and PCI- in these patients. Whether PCI (n = 65) or no PCI (n = 37) was administered did not depend either on patients or on tumour characteristics. After 2 years the incidence of brain metastases was 11% in PCI+ patients and 51% in PCI- patients. Both disease-free survival and overall survival were significantly longer after PCI. PCI reduces the incidence of brain metastases, prolongs brain metastases-free period, and overall survival in LD SCLC patients in complete remission after chemotherapy.

Current aspects of spontaneous pneumothorax.

Although spontaneous pneumothoraces have been recognized and treated for almost 180 yrs, new aspects have emerged concerning pathogenesis, diagnostic procedures and treatment modalities. In spite of the fact that blebs and bullae are frequently found in patients with primary spontaneous pneumothorax, they seldom seem to be the actual cause of the pneumothorax. Inflammatory changes in the distal airways play an important role in the occurrence of the pneumothorax during transpulmonary pressure changes. The value of the routine use of additional expiratory chest radiographs in diagnosing pneumothoraces has been doubted in previous studies. In this review, the diagnostic yield from additional expiratory chest radiographs is analysed. The role of previous pneumothoraces at presentation and the presence of blebs and bullae are discussed in predicting future recurrences and choosing appropriate treatment for optimal cost-effectiveness. Recommendations are made regarding treatment of primary and secondary spontaneous pneumothorax.

Long-term survival after bronchial sleeve resection: univariate and multivariate analyses.

BACKGROUND: Long-term results after bronchial sleeve resection remain controversial, especially in relation to nodal involvement. In a previous report, there were no 10-year survivors among patients with N1 or N2 disease. METHODS: From 1960 to 1989, 145 patients underwent bronchial sleeve resection for a bronchogenic tumor. Follow-up was updated until the end of 1994, so the minimum follow-up was 5 years for surviving patients. A univariate analysis and a multivariate analysis were performed. RESULTS: For the whole group, 5-year, 10-year, and 15-year survival rates were 46%, 33%, and 22%, respectively. The median survival time was 53 months. Five-year and 10-year survival rates for the 71 patients with no disease were 62% and 51%, respectively; for the 58 patients with N1 disease, 31% and 10%; and for the 16 patients with N2 disease, 5-year and 7-year survival rates were 31% and 13%. There was a highly significant difference in survival between patients with no and N1 or N2 disease but not between those with N1 and N2 disease. Multivariate analysis showed only nodal stage and patient age to be significant factors in relation to survival. CONCLUSIONS: Long-term results after bronchial sleeve resection are influenced chiefly by nodal stage. A significantly lower survival is found in patients with N1 and N2 disease, and most of these patients die of distant metastases.

Bronchoscopic therapy in patients with intraluminal typical bronchial carcinoid.

OBJECTIVE: To study the efficacy of bronchoscopic therapy in patients with intraluminal typical bronchial carcinoid. DESIGN: Retrospective analysis of the data of patients with bronchial carcinoid, treated primarily with bronchoscopic techniques such as Nd-YAG laser in various hospitals in the Netherlands. SUBJECTS: Eleven patients with pulmonary complaints, ages 22 to 60 years, who were found to have intraluminal typical bronchial carcinoid. BRONCHOSCOPIC INTERVENTIONS: Six of the 11 patients received Nd-YAG laser treatments, one received Nd-YAG laser plus photodynamic therapy, and the other four had mechanical tumor removal. RESULTS: Six patients were surgically treated after bronchoscopic therapy. The resected specimens showed no residual carcinoid. Median follow-up has been 70 months (range, 9 to 170 months). Five patients were not surgically treated after bronchoscopic therapy. Follow-up has been 27 to 246 months (median, 47 months) without signs of recurrence. CONCLUSIONS: In 11 patients with typical, intraluminal, bronchial carcinoids, bronchoscopic treatment seemed to result in excellent local control, with surgical proof of cure in 6 of 11 patients. Bronchoscopic approach may provide a tissue-sparing alternative for bronchoplastic surgery in a subset of patients with typical intraluminal bronchial carcinoids.

Pneumothorax. Results of thoracoscopy and pleurodesis with talc poudrage and thoracotomy.

A retrospective study was performed of the evaluable data in 710 patients with a spontaneous pneumothorax. The male:female ratio was 3.4:1. A thoracoscopy was performed in 622 patients. The two main therapeutic strategies were pleurodesis with talc poudrage (n = 356) and thoracotomy (n = 248). The success rate of talc poudrage was 88 percent, and in the group failures who have undergone surgery afterwards, we found unexpected bullous structures in 20 of 37 patients. The success rate of operation (bullectomy, pleurectomy, or resection) was 97 percent. Our conclusion is that aggressive therapy in spontaneous pneumothorax is acceptable, with a high success rate with very few complications. The diagnostic thoracoscopic evaluation needs to be in experienced hands, especially to inspect the apical lobes with the Valsalva maneuver.

A twenty-five-year follow-up of ninety-three resected typical carcinoid tumors of the lung.

From 1965 to 1990, 93 patients (57 women and 36 men) with typical bronchopulmonary carcinoids were operated upon. Patient ages ranged from 17 to 78 years, the mean age being 45.5 years. Central carcinoids were symptomatic in 80% of the patients. A correct preoperative diagnosis was made in 54 of 64 (84%) patients. Peripheral carcinoids were usually asymptomatic and a correct diagnosis was established in 4 of 29 patients (14%). The prognosis in the group of patients with bronchopulmonary carcinoids treated surgically was excellent. Seven patients died from nonrelated causes. The 5-, 10-, and 15-year survival rates for the remaining 86 patients are 100%. Only one patient died as a result of the tumor after 17 years and another patient is known to have had distant metastasis 9 years after resection. There was no hospital mortality. In the last decade a lung parenchyma-preserving attitude was adopted. Whenever possible, bronchoplastic surgery was applied for central carcinoids and resection of one segment or less was used for peripheral carcinoids. This approach was possible in 30 of 50 patients (60%). Nine patients were treated with preoperative endobronchial neodymium:yttrium-aluminum-garnet laser resection to facilitate a lung-preserving surgical resection. The prognosis of patients for whom a lung-preserving approach was adopted was as good as that of those with conventional resections. Involvement of regional lymph nodes (nine patients, 9.7%) or positive resection margins (two patients, 2.1%) had no influence on prognosis. We conclude that lung-preserving resections are often facilitated by preoperative neodymium:yttrium-aluminum-garnet laser treatment in central obstructing carcinoids.

[ACTH-producing small-cell lung carcinoma]. / ACTH-producerend kleincellig longcarcinoom.

Small-cell lung cancer may be accompanied by hypercortisolism due to secretion of adrenal stimulating peptides. This occurs almost exclusively in case of extensive disease. The neuroendocrine cell, from which these tumours may originate, plays an important part in the production of these peptides. Four patients are described with small-cell lung cancer and clinical presentation of hypercortisolism, particularly manifesting itself with hypokalaemia.

Effects of cytokines on beta-adrenoceptor function of human peripheral blood mononuclear cells and guinea pig trachea.

In asthma, a beta-adrenoceptor dysfunction may be the consequence of an active disease state rather than a fundamental abnormality. In the present study the possible involvement of T lymphocytes in beta-adrenergic impairment was investigated by studying the effects of lymphocyte-derived mediators of beta-adrenoceptor function of human peripheral blood mononuclear cells (PBMCs) and guinea pig trachea. Supernatants of phytohemagglutinin- or concanavalin A-activated PBMCs from either persons with asthma or healthy persons inhibited isoprenaline stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production of PBMCs after 20 hours of preincubation. These supernatants also inhibited beta-adrenoceptor function of PBMCs from patients with asthma to the same extent. The isoprenaline stimulated cAMP production of PBMCs was not altered after a 2-hour preincubation period with human interleukin-1 (IL-1), IL-2, IL-3, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN-gamma). In contrast, after 20 hours of preincubation, stimulated cAMP production of PBMCs was significantly diminished, with 63% by IL-1 (40 U/ml, p less than 0.01), with 36% by IL-2 (100 U/ml, p less than 0.05), with 37% by IFN-gamma (1000 U/ml, p less than 0.05), and with 21% by GM-CSF (100 U/ml, p less than 0.05). Preincubation of guinea pig tracheal segments with IL-1, IL-2, IL-4, or GM-CSF during 1 or 3 days did not affect the EC50 values or the maximal relaxation of isoprenaline dose response curves.

[Tracheobronchial lesions after closed thoracic injuries]. / Les lésions trachéobronchiques lors des traumatismes fermés du thorax.

We report the clinical picture and the outcome after medical and surgical treatment of eleven patients who had a traumatic rupture of the tracheobronchial tree between 1971 and 1990. The lesions occurred after a blunt chest trauma. All patients but one had evidence of extrapulmonary air leak on admission; one patient complained of hemoptysis. Seven patients underwent a fibroscopy on admission, which confirmed the rupture. One of them was operated immediately for tracheal rupture; four presented a small lesion which was medically treated; two were operated later on for secondary stenosis. Four patients didn't undergo a fibroscopy at first examination, one of them being asymptomatic. All four were operated secondarily. Of the six patients operated for secondary stenosis, three were operated within one month after the accident. This reflects the importance of other priorities at the initial stage. Of the three patients operated later on two didn't have a fibroscopy and it is impossible to assess the importance of the primary lesion. For the last patient operation was delayed because of the peripheral location of the lesion. The long term evolution was satisfactory in all cases.

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.

Extended use of diagnostic anterior mediastinotomy: intrapericardial exploration and evaluation of resectability of left-sided bronchogenic carcinoma.

From June 1987 to June 1990, an anterior mediastinotomy with opening of the pericardium was performed in 11 patients (mean age 67.8 years) to evaluate resectability of left-sided centrally located bronchogenic carcinoma. In 3 patients (27.3%), extensive intrapericardial involvement was found which precluded complete resection. Intrapericardial extension without complete invasion of the pulmonary vessels was present in 2 patients (18.2%) who subsequently underwent an intrapericardial pneumonectomy. In 6 patients (54.5%), no intrapericardial tumour was present. There was no perioperative mortality. One patient required redrainage of the pleural cavity because of a postoperative pneumothorax. In total, 4 patients (36.4%) underwent intrapericardial pneumonectomy, 6 (54.5%) were treated by radiotherapy and 1 (9.1%) by chemotherapy. In left-sided, centrally located tumours, opening the pericardium during anterior mediastinotomy yields additional information about the degree of tumour invasion and the feasibility of performing an intrapericardial pneumonectomy. In this way, an exploratory thoracotomy is avoided and the risk of irresectability is greatly reduced.

K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung.

BACKGROUND: The capability of activated oncogenes to induce malignant transformation of immortalized cells in vitro has suggested that they have a similar role in the pathogenesis of human tumors. We previously found that activation of the K-ras oncogene by a point mutation in codon 12 occurs in about one third of human lung adenocarcinomas. METHODS: We studied the clinical importance of this oncogene-activation in 69 patients with lung adenocarcinoma in whom complete resection of the tumor was possible. The polymerase chain reaction was used to amplify ras-specific sequences of DNA isolated from frozen or paraffin-embedded tumor samples. Ras point mutations were subsequently detected and classified with the use of mutation-specific oligonucleotide probes. RESULTS: Nineteen of the tumors harbored a point mutation in codon 12 of the K-ras oncogene. There was no association between the K-ras point mutation and the age at diagnosis, sex, or presence of previous or concurrent neoplasms. Tumors positive for K-ras point mutations tended to be smaller and less differentiated than those without mutations. The K-ras codon-12 point mutation was a strong (and unfavorable) prognostic factor: 12 of the 19 patients with K-ras point-mutation-positive tumors died during the follow-up period, as compared with 16 of the 50 patients with no mutation in the K-ras oncogene (P = 0.002). This difference in prognosis was also reflected in the duration of disease-free survival (P = 0.038) and in the number of deaths due to cancer (P less than 0.001). CONCLUSIONS: The presence of K-ras point mutations defines a subgroup of patients with lung adenocarcinoma in whom the prognosis is very poor and disease-free survival is not usually long despite radical resection and a small tumor load.

Complications of endobronchial neodymium-Yag (Nd:Yag) laser application.

Endobronchial Nd:Yag laser therapy is an excellent tool to reopen the central airway(s) in patients with severe respiratory symptoms caused by endobronchial tumor growth. Rigid bronchoscopy should be the method of choice. Usually general anesthesia is necessary. Complication rate depends on the condition of the patient, the localization of the tumor, patient selection criteria, method of endoscopy, method of anesthesia, method of laser energy application, and last but not least, the operator's skills and the treating team's cooperation. A very careful monitoring of the patient's condition during and after the operative procedure is mandatory. Only when all these conditions are fulfilled can endobronchial Nd:Yag laser therapy have a great benefit for the patient with a low grade, acceptable complication rate.

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.

Resection of more than 10 lung segments. A 30-year survey of 30 bronchiectatic patients.

A series of 30 bronchiectatic patients, treated by bilateral resection of 11, 12, or 13 lung segments, has been followed up for 30 years. The progress of the patients is analyzed and the results of treatment are evaluated. Ten patients required further resections for persisting collapse, kinking of the apical segment of a lower lobe, or because the previous resection had been too limited. The long-term results of these extensive bilateral resections in our group of patients are excellent. The quantitative function, more than 20 years after the last resection, lies markedly above the predicted value for the number of remaining segments. The qualitative function did not deteriorate over the years. It is clear that extensive bilateral bronchiectasis does not, per se, constitute a contraindication to resection, provided that at least six normal segments can be preserved.