Isolated tumor cells in bone marrow predict reduced survival in node-negative non-small cell lung cancer

Background. It recently became evident that isolated tumor cells undetectable by conventional tumor staging are frequently present in bone marrow of patients with apparently localized non-small cell lung cancer (NSCLC). The clinical relevance of this minimal hematogenous tumor cell dissemination is under vigorous debate.

Methods. For tumor cell detection in the bone marrow, we used monoclonal antibody CK2 against the epithelial intermediate filament protein cytokeratin 18. The influence of a positive bone marrow finding on clinical outcome was studied in 139 patients with NSCLC postoperatively staged as pT_1–4, pN_0–2, M₀, and R₀ after a median follow-up of 66 months (range 48 to 74 months).

Results. Cytokeratin-18-positive cells in bone marrow were demonstrated in 83 (59.7%) patients at the time of primary surgery and in 6 of 12 representative patients analyzed twice 3 to 18 months after surgery. In patients without histopathological lymph node metastases (pN₀; n = 66), the occurrence of 2 or more tumor cells in bone marrow at primary surgery was a strong and independent predictor for overall survival (p = 0.007) in univariate analysis. The multivariate analysis showed a 2.8 times increased risk for shorter survival in patients with disseminated tumor cells versus patients without such cells. Four of the 6 patients with a positive cytokeratin status after surgery developed a tumor recurrence 11 to 44 months after the operation, while none of the patients with a negative bone marrow at all time intervals showed a tumor relapse.

Conclusions. Minimal residual bone marrow involvement is an independent prognostic factor for overall survival in patients with node-negative NSCLC, which may help to identify patients in need of an adjuvant systemic therapy. The postoperative persistence or reappearance of tumor cells in bone marrow indicates that these are not only shedded cells but rather represent true micrometastasis.     

Mediastinal staging (take home messages)

Mediastinal lymph-node involvement is still the major prognostic factor in NSCLC. Currently, cervical mediastinoscopy is the gold standard of mediastinal lymph-node staging. However, less invasive methods such as transbronchial or transoesophageal FNA are becoming more popular and might replace or adjunct mediastinoscopy under certain circumstances. It has been clearly shown that FDG PET is more accurate than CT for the detection of mediastinal lymph-node metastases. However, a positive finding on the PET scan implies that these lymph nodes have to be examined by invasive methods (e.g. mediastinoscopy). It has been demonstrated that PET might be useful in order to detect non-symptomatic distant metastases. The method of pathological analysis of the lymph nodes is critical for the correct determination of the N stage.     

Short- and long-term hemodynamic effects of intra-aortic balloon support in ventricular septal defect complicating acute myocardial infarction

In patients with an infarct-related ventricular septal defect, an intra-aortic balloon pump provides immediate and long-term hemodynamic improvement, resulting in an enhanced effective cardiac output and a reduced left-to-right-shunt and shunt flow ration. In patients who can be stabilized or remain stable, there is no habituation to the effects of the intra-aortic balloon pump; thus, later surgical closure of the ventricular septal defect might be possible in some patients.     

Protection against lethal pneumococcal septicemia in pigs is associated with decreased levels of interleukin-6 in blood.

Injection of type 6b pneumococci into pigs results in a sharp rise in levels of interleukin-6 (IL-6) in blood, with an average peak value of 7,700 U/ml at 4 h and mortality in five of seven of these animals. Pretreatment at -24 h with the monocyte activator MTP-PE prevents this strong increase in IL-6 (peak value, 1,000 U/ml) and reduces mortality to zero of six animals. This suggests that MTP-PE, in addition to activating monocytes, protects animals by preventing the harmful increase of cytokines such as IL-6.     

Preterm birth reduction after clotrimazole treatment during pregnancy

OBJECTIVE: We have previously found an association between the combination of topical and vaginal clotrimazole treatment during pregnancy and a decreased prevalence of preterm births in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities. Thus the objective of this secondary analysis in the expanded data set was to evaluate potential confounders and to examine the possible interaction of clotrimazole with other drugs. STUDY DESIGN: Medically recorded birth weight/gestational age, in addition the prevalence of preterm birth and low birthweight infants of newborn infants without birth defects born to mothers with or without clotrimazole treatment during pregnancy were compared in the expanded control data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. RESULTS: The 17-year data set included 38,151 newborn infants and 8.1% were born to mothers who received clotrimazole treatment during pregnancy. There was an increase in mean gestational age among the exposed relative to the unexposed, resulting in a significant (34-64%) reduction in the prevalence of preterm births. This finding could not be explained by confounders and/or interaction with other drugs. CONCLUSION: The protective effect of clotrimazole for preterm birth was confirmed. We conclude that the protective effect of topical clotrimazole during pregnancy may be attributable to the beneficial effect of clotrimazole in the restoration of the abnormal colonization of the female genital organs and its known antibacterial and/or antiprotozoal effect.     

Multimodale Therapie des nicht-kleinzelligen Bronchialkarzinoms

Die Behandlung des nicht-kleinzelligen Bronchialkarzinoms (NSCLC) wird vom Tumorstadium bestimmt. Bei Patienten mit einem Bronchialkarzinom ohne Fernmetastasen sollte eine Behandlung in enger Kooperation zwischen Onkologen, Radiotherapeuten und Thoraxchirurgen stattfinden. Die Resektabilit?t wird vom Thoraxchirurgen bestimmt. Die Anwendung der Therapiemodalit?ten erfolgt in Abh?ngigkeit vom lokoregion?ren Lymphknotenbefall. Im Fall von Fernmetastasen (Stadium IV) ist lediglich eine palliative Behandlung mit einer Lebenserwartung von im Median 6–12 Monaten m?glich.     

Initial management of children with newly diagnosed idiopathic thrombocytopenic purpura in the Nordic countries

AIM: To describe the management practices of newly diagnosed childhood idiopathic thrombocytopenic purpura (ITP) in the Nordic countries. METHODS: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0-14 years and at least one platelet count < 30 x 10(9)/L. RESULTS: 506 children from 98 departments were registered. A diagnostic bone marrow aspiration was obtained within 14 days in 33%. Platelet and/or red blood cell transfusion was given in 11%. 287 children (57%) received platelet-enhancing therapy with intravenous immune globulin (IVIG) or corticosteroids within 14 days of diagnosis, IVIG being the first line choice in over 90% of the cases. There were noticeable national differences in the management. The decision to start drug treatment within two days of diagnosis was influenced mainly by the platelet count. Neither early treatment nor response to treatment changed the risk of chronic disease. CONCLUSION: This study has shown a great variation in the management practices of children with newly diagnosed ITP. Prospective studies are required to produce evidence-based recommendations for this patient group.