Long-term results in children with AML: NOPHO-AML Study Group--report of three consecutive trials.

In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.

Acute lymphoblastic leukemia in adolescents between 10 and 19 years of age in Denmark--secondary publication.

INTRODUCTION: Data seem to indicate that young adults with acute lymphoblastic leukemia (ALL) have a better survival when treated with pediatric protocols compared with adult ALL protocols. The purpose of the study was to report the clinical characteristics and outcome of all children and young adults 10-19 years of age diagnosed with ALL in Denmark between 1992 and 2001. MATERIAL: The study includes 99 patients 10-19 years of age with ALL in Denmark during a ten year period found in the complete NOPHO (Nordic Society of Pediatric Hematology and Oncology) registry and through the Danish Cancer Registry and local pathology databases. Data were retrieved by reviewing medical charts of the patients. A total of 61 children (10-14 years) treated on pediatric protocols and 38 young adults (15-19 years) were diagnosed with ALL. Data were reported as of January 1st 2005. RESULTS: There were no difference with respect to the distribution of T-ALL, CNS-leukemia, total white blood count and high risk chromosomal abnormalities between the two groups. There was a statistical significant lower event free survival (p<0.01) and lower overall survival (p<0.01) in young adults compared with 10-14 year-old children (0.38 vs 0.60 and 0.47 vs 0.67). There were more transplant-related deaths in the young adults. Higher treatment intensity in children may be an additional explanatory factor. Children received more prednisone, vincristine and high-dose methotrexate than young adults. CONCLUSION: Young adult patients with ALL might benefit from therapy with pediatric NOPHO ALL protocols.

Risk of relapse in childhood acute lymphoblastic leukemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. Nordic Society for Pediatric Hematology and Oncology.

PURPOSE: During maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), the cytotoxic metabolites of methotrexate (MTX polyglutamates) and mercaptopurine (6MP) (thioguanine nucleotides [6TGN]) accumulate intracellularly, including in erythrocytes (E-MTX and E-6TGN) with large interindividual variations. In the present Nordic Society for Pediatric Hematology and Oncology (NOPHO) study, the relation of E-MTX and E-6TGN to relapse risk was explored. PATIENTS AND METHODS: Two hundred ninety-seven patients with non-B-cell ALL, aged 1 to 14 years, on oral MTX and 6MP had E-MTX and E-6TGN levels measured three to 35 (median, eight) and three to 75 (median, nine) times, respectively. For each patient, a mean of all E-MTX (mE-MTX) and E-6TGN (mE-6TGN) measurements was calculated, as well as the product of mE-MTX and mE-6TGN (mE-MTX-6TGN), since MTX and 6MP may have synergistic action. RESULTS: For patients in remission, the median mE-MTX and mE-6TGN values were 4.7 nmol/mmol hemoglobin (Hgb) (range, 0.4 to 10.3) and 173 nmol/mmol Hgb (range, 58 to 846). With a median follow-up duration of 66 months for patients in remission, 64 patients relapsed. Cox regression analysis identified mE-MTX-6TGN and sex to be the most significant parameters to predict relapse (global P = .001). Factors that predicted a better prognosis were high mE-MTX 6TGN and female sex. Patients who had a mE-MTX-6TGN less than the product of the median mE-MTX and median mE-6TGN (813 [nmol/mmol Hgb]2) had a significantly poorer event-free survival (EFS) than did patients with higher values (5-year probability of EFS [pEFS5y], 0.70 v 0.86; P = .001). CONCLUSION: The pharmacokinetics of MTX and 6MP may have significant influence on the risk of relapse. The value of dose adjustments by E-MTX and E-6TGN remains to be determined.

No disadvantage in outcome of using matched unrelated donors as compared with matched sibling donors for bone marrow transplantation in children with acute lymphoblastic leukemia in second remission.

PURPOSE: We evaluated the outcome of children with acute lymphoblastic leukemia (ALL) in second remission (2CR), comparing bone marrow transplantation (BMT) using either matched sibling donors or unrelated donors (URDs). PATIENTS AND METHODS: A total of 65 patients, aged 2 months to 20 years at BMT, with ALL in 2CR underwent allogeneic BMT at seven Nordic centers during 1990 to 1997. Of the first relapses, 85% were in bone marrow; 46% occurred on therapy, and 54%, off therapy. The preparative regimens were cyclophosphamide plus total-body irradiation +/- antithymocyte/antilymphocyte globulin, busulfan plus cyclophosphamide +/- antithymocyte/antilymphocyte globulin, or cytarabine plus total-body irradiation. Of the allografts, 37 were from HLA-matched siblings and 28 were from URDs. RESULTS: In the sibling versus URD graft recipient groups, the posttransplantation 5-year event-free survival was 39% versus 54% (P =.4), the estimated posttransplantation relapse rate was 76% versus 40% (P = not significant [NS]), and the toxic death rate was 19% versus 11% (P = NS). The incidence of significant (grade 2 to 4) acute graft-versus-host disease (GVHD) was 38% versus 64% (P <.05) and was 14% versus 32% (P <.10) for severe (grade 3 to 4) acute GVHD; the incidence of chronic GVHD was 26% versus 57% (P <.05) and was 13% versus 22% (P = NS) for extensive chronic GVHD in the sibling and URD groups. CONCLUSION: BMT with matched URD allografts offers at least equal survival for children with ALL in 2CR, as compared with allografts from matched sibling donors. URD allografts were not associated with a higher toxic mortality rate, although both acute and chronic GVHD were more frequent with URD. Indications for using matched URD allografts in ALL 2CR can be considered the same as for using matched sibling donors.

Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis in acute myocardial infarction--a pilot study: biochemical markers in acute coronary syndromes (BIOMACS II).

OBJECTIVES: This randomized, double blind, placebo-controlled pilot trial evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h. BACKGROUND: Low-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction. METHODS: In 101 patients dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20-28 h to evaluate TIMI-flow in the infarct-related artery. RESULTS: Dalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6-24 h. after start of treatment were fewer in the dalteparin group, 16% versus 38% (p = 0.04). CONCLUSIONS: When dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study.

Real-time quantitative PCR assays for deoxycytidine kinase, deoxyguanosine kinase and 5'-nucleotidase mRNA measurement in cell lines and in patients with leukemia.

The relative levels of the deoxycytidine kinase (dCK), deoxyguanosine kinase (dGK), and the 5'-nucleotidase (5'-NT) are of importance for the effect of many nucleoside analogues used in the treatment of hematological malignancies. To elucidate dCK, dGK and 5'-NT gene expressions in cell lines and in samples from patients with leukemia, we have established a real-time quantitative PCR (RQ-PCR) method. From the available dCK, dGK and 5'-NT cDNA sequences we designed specific primers and fluorogenic probes for the respective genes. The mRNA of dCK, dGK and 5'-NT was also measured by semi-quantitative RT-PCR, the enzyme activities by a radioactive substrate-based technique and Western blot was used to measure the amount of dCK and dGK protein. A MOLT-4 wild-type and its 9-beta-D-arabinofuranosylguanine (Ara-G)-resistant subline was used for the methods comparisons and the RQ-PCR assay was used in 35 samples from pediatric patients with ALL and AML. The results from RQ-PCR for the cell lines were in agreement with the semi-quantitative RT-PCR. The mRNA expression for dCK, dGK and 5'-NT (expressed as the ratio of the respective gene and the reference gene) in pediatric ALL and AML patients showed a large interindividual variability from 0.06 to 2.34, non-detectable to 0.06 and 0.04 to 0.30, respectively. These results show that the quantitative evaluation by RQ-PCR is a valuable tool in the determination of dCK, dGK and 5'-NT mRNA levels in cell lines and in clinical samples which were expressed at various levels. This rapid, convenient and specific method is suitable for further studies of these genes in clinical samples.

Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation. Nordic Society of Pediatric Haematology and Oncology (NOPHO).

In this population-based material from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2860 children below 15 years of age were diagnosed with acute lymphoblastic leukemia (ALL) from July 1981 to June 1998. The annual incidence was 3.9/100,000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification with multidrug chemotherapy, including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. The overall event-free survival (EFS) at 5 years has increased from 56.5 +/- 1.7% in the early 1980s to 77.6 +/- 1.4% during the 1990s. The main improvements were seen in children with non-high risk leukemia. In high-risk patients, progress has been moderate, especially in children with high WBC (> or =100 x 10(9)/l) at diagnosis. During the last time period (January 1992-June 1998), only 10% of the patients have received cranial irradiation in first remission, while 90% of the patients have received pulses of high dose methotrexate (5-8 g/m2) isolated or combined with high-dose cytosine arabinoside (total dose 12 g/m2) plus multiple intrathecal injections of methotrexate as CNS-targeted treatment, not translating into increased cumulative incidence of CNS relapse.

Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes) predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92.

Inactivation of the Ink4 gene locus locus on 9p comprising the tumour suppressor gene p16ink4a and its neighbours p14ARF and p15ink4b is common in childhood acute lymphoblastic leukaemia (ALL), but the prognostic significance is controversial. DNA from 230 patients was retrospectively analysed by Southern blotting, single strand conformation polymorphism (SSCP) and sequencing techniques. The results were correlated with clinical characteristics and outcome. One hundred and ninety-four fully analysed patients, similarly treated using the Nordic NOPHO-86 or the current NOPHO-92 protocols, were included in the outcome analysis. Deletions approached a minimally deleted region between the p16ink4a and p15ink4b genes, making the p14ARF gene the most commonly deleted coding sequence. Bi-allelic deletion was associated with high white blood cell count (WBC) (P < 0.001), T cell phenotype (P < 0.001) and mediastinal mass (P < 0.001). Patients with Ink4 locus bi-allelic deletions had an inferior pEFS (P < 0.01) and multivariate analysis indicated that bi-allelic deletion of the p16ink4a and the p14ARF genes was an independent prognostic risk factor (P < 0.05). Sub-group analysis revealed a pronounced impact of deletion status for high-risk patients, ie with high WBC. Deletion-status and clinical risk criteria (WBC) could thus be combined to further differentiate risk within the high-risk group. The analysis of the Ink4 locus adds independent prognostic information in childhood ALL treated by Nordic protocols and may help in selection of patients for alternative treatment.

Combined fluorine-18-FDG and carbon-11-methionine PET for diagnosis of tumors in lung and mediastinum.

UNLABELLED: We evaluated the value of PET using 18F-fluorodeoxyglucose (FDG) and 11C-methionine, individually or in combination, to distinguish malignant from benign tumors and to identify or exclude mediastinal metastases. METHODS: Seventeen patients with a tumor in the lung or mediastinum were evaluated with 18F-FDG and 11C-methionine PET. For morphological comparison, we used CT, and all findings were confirmed by histology of surgical resection specimens (n = 16) or by cytology (n = 1). RESULTS: All tumors were visualized equally well with both tracers, and there were no false-positive results. In 2 patients with a malignant tumor, coexisting pneumonia was correctly diagnosed as an inflammatory lesion because of its wedge-like shape. PET correctly excluded hilar invasion and mediastinal lymph node metastases in 10 of 14 patients with primary lung tumor. PET identified mediastinal metastases in 4 of 4 patients. CT failed to detect mediastinal tumor spread in 2 patients and gave a false-positive reading in 2 others. Significantly higher uptake (SUV) and transport rate (slope) values were obtained from malignant than benign lesions with both tracers. No major differences were seen in either the levels of significance or accuracy when the two tracers were compared. Slope values did not add further information to what was obtained with SUV. Density correction of SUV and slope values, to avoid the influence of surrounding air as well as tumor heterogeneity, increased these differences somewhat. Both tracers distinguished malignant from benign lesions with a 93% sensitivity and an accuracy of 89%-95%, but sensitivity improved to 100% when values from both tracers were combined. CONCLUSION: Fluorine-18-FDG and 11C-methionine PET visualized all tumors equally well and detected mediastinal spread better than CT. For differentiation purposes, the problems of false-positive and false-negative PET findings could not be safely overcome in a limited number of cases either by the use of both tracers, by the additional use of slope values or by lesion density correction.

Large emphysematous bullae. Successful treatment with thoracoscopic technique using fibrin glue in poor-risk patients.

Five patients with poor lung function (FEV1, 0.8 to 1.0 L; MVV, 27 to 36 L/min) and large emphysematous bullae were operated on. Fibrin glue was introduced into the bullae through a thoracoscope. The results have been excellent and no serious perioperative or postoperative complications have occurred. The patients have all improved clinically and are very satisfied with the results. Postoperatively, FEV1 was between 1.0 and 1.2, and MVV was 30 to 52 L. The clinical improvement was, however, larger than these figures illustrate. Our preliminary experience using this technique suggests that it can be used in patients with very low lung function with a minimal risk. We propose that all patients with severe emphysema should be screened for bullous components because improvement might be possible by operation with this minimally traumatizing technique.

Prognostic value of malignant cells in pleural lavage at thoracotomy for bronchial carcinoma.

Despite seemingly radical surgery many patients operated on for bronchial carcinoma will die from their disease. Some patients might benefit from postoperative treatment and a prognostic factor that could identify those with an increased risk for tumor relapse would be of great clinical importance. One possible such factor is the occurrence of malignant cells in pleural lavage performed at operation. To test this hypothesis 224 consecutive patients who had been operated on due to verified or strongly suspected bronchial carcinoma, preoperatively staged as stage I or II, were investigated. After opening the thorax and before manipulation or palpation of the lungs, 300 ml of physiological saline solution was installed into the pleura. After excluding patients who were not radically operated, there remained 138 patients with histologically confirmed lung cancer (carcinoids excluded) and 12.3% showed tumour cells in the washings. Two of 18 patients with metastatic lung disease ( 11%) and one of ten patients with carcinoid tumor also showed malignant cells in the lavage. The patients with lung cancer have been followed for 3 years or until death. After three years 60.2% of those without malignant cells in the pleural lavage were still alive, while this figure was 41.2% in the other group. The difference was not statistically significant. Other factors, such as spread to local lymph nodes, size of tumor, etc. were related to the occurrence of malignant cells in the pleura, and these factors were also better prognostic ones. We conclude that the clinical use of pleural lavage cytology is limited.

Allogeneic bone marrow transplantation in first remission for children with very high-risk acute lymphoblastic leukemia: a retrospective case-control study in the Nordic countries. Nordic Society for Pediatric Hematology and Oncology (NOPHO).

Among children with high-risk (HR) ALL there are subgroups with very-high-risk (VHR) features and poor prognosis despite developments in conventional chemotherapy for childhood ALL. We evaluated the outcome of VHR-ALL in children receiving allogeneic BMT (allo-BMT) in first remission (1CR) in a retrospective case-control study. In the population-based ALL material of the five Nordic countries, 22 children with VHR-ALL have undergone allo-BMT in 1CR between 1981-1991. We compared the outcome in these 22 children with 44 closely matched control patients who received conventional chemotherapy on HR-ALL protocols, as well as with a group of 405 children representing the remaining HR-ALL patients in the Nordic ALL database. The disease-free survival at 10 years was 73% in children receiving allo-BMT in 1CR, 50% in the matched controls (P = 0.02), and 59% in the remaining HR-ALL patients. The good prognosis of the allo-BMT group was due to a low relapse rate of 9%, as opposed to 41% in the group of matched controls. The superiority of allo-BMT as therapy in 1CR was mainly apparent in those with a very high WBC of > or = 100 x 10(9)/I at diagnosis; in the allo-BMT group 9/10 survived, as opposed to 8/20 of the matched controls (P = 0.03). We conclude that allo-BMT in 1CR should be seriously considered for children with a matched sibling donor and a VHR-ALL with WBC of > or = 100 and other established VHR criteria.

Allogeneic bone marrow transplantation in second remission of childhood acute lymphoblastic leukemia: a population-based case control study from the Nordic countries.

This study compares allogeneic BMT with conventional chemotherapy for childhood ALL in second remission. Seventy-five children were transplanted between July 1981 and December 1995. For each patient two control patients matching the following criteria were selected from the Nordic database of ALL: (1) time of diagnosis, (2) T vs. non-T ALL, (3) site of relapse, (4) initial risk group, (5) sex and (6) relapse < or > or =6 months after cessation of therapy. The minimal time of follow-up was 24 months. Mortality rate in CR2, leukemic relapse rate and the proportion in continued second remission were 16/75 (21%), 22/75 (29%) and 37/75 (50%), respectively. P2.-EFS for the BMT group was significantly better than that for the control group (0.40 vs. 0.23, P = 0.02). Children transplanted for bone marrow relapses in particular had a higher P2.-EFS (0.35 vs. 0.15 for the control group, P<0.01). Also, children grafted for early BM relapses had a higher P2.-EFS (0.32 vs. 0.11 for the control group P = 0.01). The outcome was similar when children were transplanted after early or late relapse. Also, there was no difference in outcome between the BMT and the chemotherapy group for children with late relapses. We conclude that allogeneic BMT with an HLA-identical sibling donor or other family donor should be performed in children relapsing in bone marrow during therapy or within 6 months of discontinuing therapy.

Dynamic vectorcardiography for early diagnosis of acute myocardial infarction compared with 12-lead electrocardiogram. BIOMACS Study Group.

BACKGROUND: The aim of the study was to assess the diagnostic accuracy of multilead continuous vectorcardiography (VCG) for early diagnosis of acute myocardial infarction (AMI) in patients admitted to hospital because of suspicion of AMI. VCG was compared with resting 12-lead electrocardiogram (ECG) on admission. METHODS: In a multicentre study, 107 patients with chest pain (< or = 12 h) were included. The diagnosis of AMI was on the basis of World Health Organization criteria. Continuous VCG was recorded for 12-24 h and the data were evaluated blindly at 2 and 6 h of recording and after the completion of recording (12-24 h). RESULTS: AMI was diagnosed in 74 patients. The VCG recording had a diagnostic accuracy of 71% after 2 h and 86% after both the 6 h and the completed VCG recording. Compared with ECG on admission, the VCG recording after 6 h showed a significantly greater sensitivity: 86% compared with 62% (P < 0.01). In patients with non-diagnostic ECG on arrival (n = 55), VCG after 6 h had a diagnostic accuracy of 85%, a sensitivity of 82% and a specificity of 89%. CONCLUSIONS: VCG might be useful for early diagnosis of AMI, especially in patients with non-diagnostic ECG.

Possible reasons for the prognostic value of troponin-T on admission in patients with ST-elevation myocardial infarction.

BACKGROUND: In patients with acute myocardial infarction and ST-segment elevation, increased troponin-T (TnT) on admission implies an increased mortality. OBJECTIVE: To elucidate the underlying mechanisms of the prognostic value of TnT. METHODS AND RESULTS: One hundred and one patients were included and all received thrombolytic treatment. The patients were compared according to TnT level on admission (cut-off 0.1 microg/l). Elevation of TnT was associated with long-term mortality and also with longer delay, more episodes of chest pain during the last 24 h and fewer noninvasive signs of reperfusion at 90 min. In the group with elevated TnT, the coronary angiography at 24 h showed a strong trend towards lower patency in the infarct-related artery. TnT was also associated with increased infarct size if a higher cut-off level (0.43 microg/l) was used. In univariate analysis, elevated TnT, longer delay, repeated chest pain, Q-waves on admission and reduced left ventricular (LV) function were significantly associated with long-term mortality. In multivariate models, only reduced LV function and less than TIMI (thrombolysis in myocardial infarction) grade 3 flow turned out to be significant independent risk factors. CONCLUSIONS: The prognostic value of TnT level on admission regarding long-term mortality was confirmed and seems mainly to be explained by its association with longer delay and recent myocardial damage, but its association with reduced effect of thrombolytic treatment, larger infarct size and impaired LV function might also be of importance.

Dynamic changes of the QRS complex in unstable angina pectoris.

Despite intensive medical treatment to control chest pain, about one-third of patients with unstable angina have an unfavourable outcome within a period of 1 to 2 months. Holter monitoring can identify patients with silent myocardial ischaemia that are at a high risk of sustaining a major cardiovascular event. The present paper describes the use of dynamic, continuous, computerized on-line vectorcardiography for real-time monitoring of QRS-complex and ST-segment changes in patients with unstable coronary disease. In many patients a pattern of frequent repetitive episodes of QRS change was observed, with or without concomitant ST change. Whereas no patient had episodes of ST-vector change without also having episodes of significant QRS change, 15 patients had several episodes of QRS changes without any episode of significant ST change. The number of episodes of significant increase of the QRS vector difference correlated weakly but significantly with the number of episodes of significant ST-vector magnitude change (r = 0.34, p less than 0.05). The present study suggests that myocardial ischaemia will influence the QRS complex as well as the ST segment. The mechanism behind the QRS changes observed is not clear but episodes of QRS change without ST change or chest pain, may reflect sudden depressions of left ventricular function, as has been reported by others to occur in patients with coronary artery disease. Dynamic vectorcardiography offers the opportunity to monitor all parts of the QRST complex in real time.

Outcome after lung cancer surgery. Factors predicting early mortality and major morbidity.

OBJECTIVE: This study was undertaken to assess mortality, complications and major morbidity during the first 30 days after lung cancer surgery and to estimate the significance of presurgical risk factors. METHODS: The study was based on all patients referred for surgery for primary lung cancer from 1 January 1987 to 1 September 1999. There were in total 616 patients with primary lung cancer. Three-hundred and ninety-four were men and 222 women. Postoperative events studied were divided into major and minor complications or death during the first 30 days after surgery. The significance of risk factors for an adverse outcome (defined as death or major complication in the first 30 days postoperatively) was assessed by uni- and multivariate logistic regression analyses. RESULTS: During the study period an increasing number of women and of patients older than 70 years underwent surgery. Overall 30-day mortality was 2.9, 0.6% after single lobectomy and 5.7% after pneumonectomy. Major complications occurred in 54 patients (8.8%). Fifty-eight patients (9.5%) had an adverse outcome during the first 30 days. Male gender, smoker, FEV(1)< or =70% of expected value, squamous cell carcinoma and pneumonectomy were risk factors predicting adverse outcome in the univariate model. Pneumonectomy and FEV(1)< or =70%, were the only independently significant factors for adverse outcome. Only pneumonectomy was independently associated with an increased risk for early death. CONCLUSION: Our results show low mortality and morbidity after lung cancer surgery. However, patients with reduced lung capacity and those undergoing pneumonectomy should be treated with great care, as they run a considerable risk of major complications or death during the first 30 days postoperatively. Older age (>70 years) does not appear to be a contraindication to lung cancer surgery, but patients in this group should undergo careful preoperative evaluation.

Complete sequence of p53 gene in 20 patients with lung cancer: comparison with chemosensitivity and immunohistochemistry.

In this study the entire p53 complementary DNA has been sequenced in 20 non-small cell lung carcinomas (NSCLC) and the results correlated with chemosensitivity, immunohistochemistry and clinical data. Ten patients had mutations in p53, 8 missense mutations and 2 nonsense mutations. The method discovered two mutations never described previously and two other mutations that have never been described before in connection with NSCLC tumours. Chemosensitivity data, according to a short-term assay (FMCA), indicated that tumours with p53 mutation were more resistant to cisplatin and cyclophosphamide. Immunohistochemical studied demonstrated a 70% concordance between over-expression of p53 protein and mutation in p53. No conclusions or trends could be drawn from the immunohistochemical studies of Bcl-2 and Bax.

Standard computer programs in statistical analysis of survival in childhood lymphoblastic leukemia.

A material comprising all children in Sweden with acute lymphoblastic leukemia diagnosed in the years 1973-80 was analysed statistically. The total number of children was 505. Studies were made of 38 different variables, using frequency tables, cross tables, life table studies (1) and linear regression analysis according to Cox's method (2,4). Chi-square tests and log rank tests were included in the methods. The combination of life-table studies and linear regression analysis proved to be of value in assessing the significance of different parameters and treatment programs with regard to prognosis. The aim of this paper is to present a method for analysis of a patient material with use of standard computer programs. The results of the total analysis will be published elsewhere (3).

Clinical and surgical staging of Hodgkin's disease.

Staging laparotomy was performed in 36 patients with Hodgkin's disease. The surgical procedure changed the stage in 14 cases or 36% and also revealed subdiaphragmatic disease in 14 patients. Mixed cellularity and nodular sclerosis were the main histopathological types, contributing 44% and 42%, respectively, of the whole material. Postoperative complications occurred in 8 cases (22%)--none was fatal. The average hospital stay was 9.5 days, the longest being 22 days.