Surgery and Chemotherapy for Small Cell Lung Cancer in Stages I–II with or without Radiotherapy

PURPOSE: To analyze the effectiveness of surgery and chemotherapy with or without radiotherapy in the management of limited small cell lung cancer (LSCLC) in stages I and II. PATIENTS AND METHODS: 39 patients (median age 62 years) with LSCLC in stages pT1 or pT2 and pN0 or pN1 (stages IA-IIB) who had a tumor resection and systematic lymph node dissection were reviewed retrospectively. The median follow-up period was 29 months. 35 patients (90%) received a median of four cycles of a platinum-containing chemotherapy postoperatively. 16 patients (41%) received an adjuvant thoracic radiotherapy (TRT, median 50 Gy); 21 patients (54%) received a prophylactic cranial irradiation (PCI, median 30 Gy). RESULTS: The median overall survival for all patients was 47 months, resulting in actuarial 1-, 3-, and 5-year survival rates of 97%, 58%, and 49%, respectively. Distant metastases were found in 13 patients (33%) after a median of 16 months. Patients who received an adjuvant TRT showed a trend toward improved thoracic recurrence-free survival (p = 0.06) and improved overall survival (p = 0.07) compared to those treated with surgery and chemotherapy only. Brain metastasis-free survival (p = 0.01) and overall survival (p = 0.01) were improved significantly in patients who received a PCI. CONCLUSION: Surgical tumor resection may be considered for carefully selected patients. Adjuvant chemotherapy and PCI are recommended for all patients. Adjuvant TRT is currently used in patients with positive lymph nodes (pN1), because the probability of a subclinical involvement of the mediastinal lymphatic system appears to be increased in these patients.     

Endoscopic transthoracic sympathectomy: current indications and techniques

Zusammenfassung GRUNDLAGEN: Die endoskopische thorakale Sympathektomie (ETS) existiert seit 60 Jahren als effektive Therapie der primären Hyperhidrose. Nach wie vor gibt es in der medizinischen Welt teils Vorbehalte, teils Unwissen über die Methode selbst, ihre Erfolgs- und Komplikationsraten sowie Nebenwirkungen. METHODIK: Nach Einführung in die Symptome und Behandlung der primären Hyperhidrose (konservativ und chirurgisch) werden Operationsmethoden und Langzeitergebnisse der ETS-Operation vorwiegend anhand der Daten aus der eigenen Abteilung präsentiert. ERGEBNISSE: Von 1965–2001 wurden 734 Sympathikotomien (ETS2–4) und bis 2003 weitere 103 Sympathikusblockaden (ESB4) bei Patienten mit primärer palmarer und axillärer Hyperhidrose durchgeführt. Die Konversionsrate betrug 0,1 %. Seit Einführung der Video-Thorakoskopie 1991 trat kein postoperatives Horner-Syndrom auf (zuvor 2,2 %), Drainage-pflichtige Pneumothoraces waren in 1,1 % zu verzeichnen. Nach einem medianen Follow-up von 16 Jahren waren 93 % der Extremitäten trocken, 5 % fast trocken und 2 % feucht. Nebenwirkungen traten in Form von kompensatorischem Schwitzen am Stamm (55 % insgesamt, davon 5 % stark) und gustatorischem Schwitzen (33 %) auf. Seit Einführung der limitierten Sympathikusblockade auf Höhe T4 (ESB4) konnte (bei naturgemäß kurzer Nachbeobachtungszeit) das kompensatorische Schwitzen auf 8,5 % und das gustatorische Schwitzen auf 2,1 % gesenkt werden. Mit dem postoperativen Ergebnis waren 100 % der Patienten nach ESB4 zufrieden, nach ETS2–4 waren 80 % zufrieden, 14 % teilweise zufrieden und 6 % unzufrieden (meist wegen starken kompensatorischen Schwitzens). SCHLUSSFOLGERUNGEN: Die ETS-Operation bietet hohe langfristige Erfolgsraten bei niedrigen Komplikationsraten. Patienten sollten über die zu erwartenden Nebenwirkungen genau aufgeklärt werden, für unzufriedene Patienten mit starkem kompensatorischem Schwitzen besteht nun die Möglichkeit der thorakoskopischen Klip-Entfernung.     

The rate of development and time of transfer play different roles in influencing the viability of human blastocysts

Improved embryo culture protocols now render more feasible the possibility of obtaining human blastocysts after in-vitro fertilization. In this study we present: (i) results of blastocyst development from supernumerary embryos after co-culture on green monkey kidney epithelial cells and (ii) pregnancy rates after transfer of frozen blastocysts. In addition, we have examined the influence of the day of blastocyst freezing and the day of transfer after the luteinizing hormone (LH) peak on pregnancy and implantation rates. Of 423 supernumerary embryos, 200 developed to the blastocyst stage (47.3%). By days 5 and 6, 67% of the blastocysts had reached the blastocyst stage, and were frozen, compared to 28.5% by day 7. When we compared the cases where only blastocysts frozen on days 5 and 6 were transferred compared to those frozen and transferred on or after day 7 the pregnancy rates were 7/18 (38.9%) and 1/16 (6.2%) respectively. In contrast, when we examined the influence of the day of transfer we found that pregnancies were established from day 5 up to day 9 post LH peak. Based on these results, we suggest that every attempt should be made to increase the development rate of supernumerary embryos to the blastocyst stage, as it appears that the quality of blastocysts transferred, as shown in this study by rate of development, plays a more crucial role than the timing of transfer.      

Squamous-cell carcinoma antigen (SCC-A) values related to clinical outcome of pre-invasive and invasive cervical carcinoma.

The serum concentration of squamous-cell carcinoma antigen (SCC-A), a subfraction of tumour antigen, was determined by RIA from healthy donors (control group) and from patients with malignant cervical disease. Ninety-six percent (173/180) of the healthy patients had squamous-cell carcinoma antigen serum levels below 2 ng/ml. Ten of 70 (14.3%) patients with CIN III, 53.8% (34/62) of patients with invasive squamous-cell carcinoma stage I, 85.8% (30/35) with stage II and 96.5% (27/28) with stage III/IV had squamous-cell carcinoma antigen serum levels above 2 ng/ml. We observed that 22.5% (11/49) of patients with a tumour volume below 10 ml and 92.6% of patients with a tumour volume greater than 10 ml had squamous-cell carcinoma antigen levels above 2 ng/ml (p less than 0.005). SCC-A was correlated with recurrence or progressive disease in 90.0% of cases. Other risk factors such as depth of invasion, microscopic parametrial involvement, lymphatic and/or vascular space permeation and histological grade were not correlated with squamous-cell carcinoma antigen. Furthermore, this marker increased 4.3 +/- 2.7 months before clinical evidence of recurrence or progressive disease. We conclude that serial serum levels of squamous-cell carcinoma antigen provide a means for early detection of recurrence or progressive disease. This tumour marker might also be useful for monitoring the treatment effects and has some prognostic value.     

In Situ Thermal Denaturation of Proteins in Dunning AT-1 Prostate Cancer Cells: Implication for Hyperthermic Cell Injury

The in situ thermal protein denaturation and its correlation with direct hyperthermic cell injury in Dunning AT-1 prostate tumor cells were investigated in this study. The in situ thermal protein denaturation was studied using both Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The FTIR spectra at different temperatures show changes in protein secondary structure (from alpha helix to extended beta sheet) during in situ thermal protein denaturation within AT-1 cells. Calorimetric studies using DSC show that endothermic heat release is associated with the in situ thermal protein denaturation. Furthermore, both the secondary structure changes detected by FTIR and the calorimetric changes detected by DSC were quantified and the kinetics of the overall in situ thermal protein denaturation was derived under different heating conditions. The onset temperature where the overall in situ thermal protein denaturation is first detectable was found to be scanning rate dependent (approximately 41 degrees C at 2 degrees C min(-1) and approximately 44 degrees C at 5 degrees C min(-1)). The kinetics of the overall in situ thermal protein denaturation was derived from both DSC and FTIR measurements and was fit using kinetic and statistical models. The kinetic data determined by FTIR and DSC under the same heating conditions match well with each other. The activation energy of the overall in situ thermal protein denaturation is found to be strongly dependent on the temperature range considered (the activation energy ranges from approximately 110 kJ mol(-1) between 44 and 90 degrees C to approximately 750 kJ mol(-1) between 44 and 50 degrees C). However, its dependence on heating rate is negligible. Several denaturation peaks, including a dominant one between approximately 62 and 65 degrees C, are identifiable from both the DSC and the FTIR results. To investigate directly the relationship between thermally induced cell injury and the in situ thermal protein denaturation, both acute (propidium iodide dye exclusion, assessed 3-h postthermal treatment) and chronic (clonogenics, assessed 7-day postthermal treatment) cell injury were quantified using AT-1 cells prepared under the same conditions as for the DSC protein studies. Comparisons of the results from the cell injury studies and the DSC protein denaturation studies show that the overall in situ thermal protein denaturation correlates well with both the acute and the chronic cell injury, which suggests that overall in situ thermal protein denaturation is an important mechanism of direct hyperthermic cell injury in AT-1 cells at the macromolecular level.     

TLR4 gene variants modify endotoxin effects on asthma

BACKGROUND: Environmental exposure to endotoxin might have a crucial role in immune maturation and development of asthma. OBJECTIVE: The aim of this study was to investigate whether the effect of endotoxin concentration in settled house dust on asthma is modified by the presence of variation in the TLR4 gene. METHODS: We performed a cross-sectional study within the German follow-up of the European Community Respiratory Health Survey. Multivariate logistic regression analysis and nonparametric effect estimates (S-Plus) were applied to examine the association between endotoxin exposure and diagnosed asthma, related clinical symptoms, and bronchial hyperreactivity (BHR) stratified for noncarriers and carriers of G299/I399 polymorphism in the TLR4 gene. RESULTS: In the noncarrier group (n = 279), the prevalence of asthma was significantly increased with elevated endotoxin levels in house dust with adjusted odds ratio 6.24 (95% CI, 1.33-29.17) in the second tertile, and 4.54 (95% CI, 0.94-21.96) in the third tertile compared with the lowest endotoxin tertile. The carriers of the polymorphisms (n = 55) showed a nonsignificant trend to have a lower risk of asthma (crude odds ratio, 0.67; 95% CI, 0.06-8.06 for the second tertile and 1.33; 95% CI, 0.17-10.58 for the third tertile). We found a similar association for wheeze and endotoxin exposure that was also attenuated in subjects with G299/I399 polymorphisms. CONCLUSIONS: The G299/I399 polymorphisms were associated with a modified response to endotoxin, but the functional relationship still needs clarification.     

Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite

Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti‐asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail. Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model. Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post‐mortem (48 h post‐challenge) for histology and immunohistochemical analyses. Results Immunizations with 50 μg house dust mite induced an allergen‐specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG₁ but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post‐challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late‐phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post‐challenge, representing 10 to 33% of BAL leucocytes in allergen‐challenged allergic sheep compared to 0 to 3% in allergen‐challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4⁺ T cells and were more activated than lymphocytes in blood. There was significant down‐regulation of CD62L (L‐selectin) and CD49d (VLA‐4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM‐1 (ligand for VLA‐4) was up‐regulated on blood vessels of allergen‐challenged lungs. Eosinophils, CD4⁺ T cells and CD45R⁺ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge. Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma.     

CA 125 in seminal plasma: correlation with semen parameters

Ovarian cancer marker CA 125 was measured in human seminal plasma,and the concentrations ranged between 22 and 1149 U/ml, andbetween 39 and 4711 U/ejaculate. This very high patient-to-patientvariability was in contrast to a much lower within-patient variability,which was comparable to that of other semen parameters. No significantdifferences in CA 125 concentration were found in seminal plasmafrom normospermic patients, patients with male factors, vasectomizedmen, and in aliquots of samples which led to a pregnancy, viaartificial insemination or in-vitro fertilization. The seminalplasma CA 125 concentration was not correlated with sperm count,motility and morphology. In contrast, seminal plasma CA 125concentrations correlated with the age of the patient (P <0.001) and inversely with the volume of the ejaculate (P <0.001). These correlations were independent of each other. CA125 did not correlate with the prostatic marker zinc, but diddo so with the seminal vesicle marker fructose and the epididymalmarker carnitine.     

Evolution of sleep and sleep EEG after hemispheric stroke

The evolution of subjective sleep and sleep electroencephalogram (EEG) after hemispheric stroke have been rarely studied and the relationship of sleep variables to stroke outcome is essentially unknown. We studied 27 patients with first hemispheric ischaemic stroke and no sleep apnoea in the acute (1-8 days), subacute (9-35 days), and chronic phase (5-24 months) after stroke. Clinical assessment included estimated sleep time per 24 h (EST) and Epworth sleepiness score (ESS) before stroke, as well as EST, ESS and clinical outcome after stroke. Sleep EEG data from stroke patients were compared with data from 11 hospitalized controls and published norms. Changes in EST (>2 h, 38% of patients) and ESS (>3 points, 26%) were frequent but correlated poorly with sleep EEG changes. In the chronic phase no significant differences in sleep EEG between controls and patients were found. High sleep efficiency and low wakefulness after sleep onset in the acute phase were associated with a good long-term outcome. These two sleep EEG variables improved significantly from the acute to the subacute and chronic phase. In conclusion, hemispheric strokes can cause insomnia, hypersomnia or changes in sleep needs but only rarely persisting sleep EEG abnormalities. High sleep EEG continuity in the acute phase of stroke heralds a good clinical outcome.