Using patients' own knowledge of early sensations and symptoms to develop an interactive, individualized e-questionnaire to facilitate early diagnosis of lung cancer.

BACKGROUND: One reason for the often late diagnosis of lung cancer (LC) may be that potentially-indicative sensations and symptoms are often diffuse, and may not be considered serious or urgent, making their interpretation complicated. However, with only a few exceptions, efforts to use people's own in-depth knowledge about prodromal bodily experiences has been a missing link in efforts to facilitate early LC diagnosis. In this study, we describe and discuss facilitators and challenges in our process of developing and initial testing an interactive, self-completion e-questionnaire based on patient descriptions of experienced prodromal sensations and symptoms, to support early identification of lung cancer (LC). METHODS: E-questionnaire items were derived from in-depth, detailed explorative interviews with individuals undergoing investigation for suspected LC. The descriptors of sensations/symptoms and the background items obtained were the basis for developing an interactive, individualized instrument, PEX-LC, which was refined for usability through think-aloud and other interviews with patients, members of the public, and clinical staff. RESULTS: Major challenges in the process of developing PEX-LC related to collaboration among many actors, and design/user interface problems including technical issues. Most problems identified through the think-aloud interviews related to design/user interface problems and technical issues rather than content, for example we re-ordered questions to be in line with patients' chronological, rather than retrospective, descriptions of their experiences. PEX-LC was developed into a final e-questionnaire on a touch-screen smart tablet with one background module covering sociodemographic characteristics, 10 interactive, individualized modules covering early sensations and symptoms, and a 12th assessing current symptoms. CONCLUSIONS: Close collaboration with patients throughout the process was intrinsic for developing PEX-LC. Similarly, we recognized the extent to which clinicians and technical experts were also important in this process. Similar endeavors should assure all necessary competence is included in the core research team, to facilitate timely progress. Our experiences developing PEX-LC combined with new empirical research suggest that this individualized, interactive e-questionnaire, developed through systematizing patients' own formulations of their prodromal symptom experiences, is both feasible for use and has potential value in the intended group.

Early symptoms and sensations as predictors of lung cancer: a machine learning multivariate model.

The aim of this study was to identify a combination of early predictive symptoms/sensations attributable to primary lung cancer (LC). An interactive e-questionnaire comprised of pre-diagnostic descriptors of first symptoms/sensations was administered to patients referred for suspected LC. Respondents were included in the present analysis only if they later received a primary LC diagnosis or had no cancer; and inclusion of each descriptor required ≥4 observations. Fully-completed data from 506/670 individuals later diagnosed with primary LC (n = 311) or no cancer (n = 195) were modelled with orthogonal projections to latent structures (OPLS). After analysing 145/285 descriptors, meeting inclusion criteria, through randomised seven-fold cross-validation (six-fold training set: n = 433; test set: n = 73), 63 provided best LC prediction. The most-significant LC-positive descriptors included a cough that varied over the day, back pain/aches/discomfort, early satiety, appetite loss, and having less strength. Upon combining the descriptors with the background variables current smoking, a cold/flu or pneumonia within the past two years, female sex, older age, a history of COPD (positive LC-association); antibiotics within the past two years, and a history of pneumonia (negative LC-association); the resulting 70-variable model had accurate cross-validated test set performance: area under the ROC curve = 0.767 (descriptors only: 0.736/background predictors only: 0.652), sensitivity = 84.8% (73.9/76.1%, respectively), specificity = 55.6% (66.7/51.9%, respectively). In conclusion, accurate prediction of LC was found through 63 early symptoms/sensations and seven background factors. Further research and precision in this model may lead to a tool for referral and LC diagnostic decision-making.

First-line afatinib vs gefitinib for patients with EGFR mutation-positive NSCLC (LUX-Lung 7): impact of afatinib dose adjustment and analysis of mode of initial progression for patients who continued treatment beyond progression.

PURPOSE: In the randomized phase IIb LUX-Lung 7 trial, afatinib significantly improved progression-free survival (PFS) and time-to-treatment failure vs gefitinib in patients with treatment-naïve epidermal growth factor receptor mutation-positive non-small cell lung cancer. We report post hoc analyses of tolerability-guided dose adjustment for afatinib and summarize the clinical characteristics of patients who continued afatinib/gefitinib beyond initial radiological progression in LUX-Lung 7. METHODS: Patients received afatinib 40 mg/day or gefitinib 250 mg/day until investigator-assessed progression or beyond if beneficial. In case of selected treatment-related adverse events (TRAEs), the afatinib dose could be reduced by 10-mg decrements to minimum 20 mg (only dose interruptions were permitted with gefitinib). RESULTS: All randomized patients were treated (afatinib, n = 160; gefitinib, n = 159). Sixty-three patients had afatinib dose reduction (< 40 mg/day; 47 within first 6 months). Dose reduction decreased TRAE incidence/severity (before vs after; all grade/grade 3: 100.0%/63.5% vs 90.5%/23.8%). There was no evidence of significant difference in PFS for patients who received < 40 mg/day vs ≥ 40 mg/day for the first 6 months [median: 12.8 vs 11.0 months; hazard ratio 1.34 (95% confidence interval 0.90-2.00)]. Twenty-four and 26 patients continued afatinib and gefitinib, respectively, beyond progression in target lesions; median time from nadir of target lesion diameters to initial progression was 6.7 months and 5.6 months. Of these patients, ~ 70% had objective response or non-complete response/non-progressive disease in non-target lesions at initial progression. CONCLUSIONS: Protocol-defined dose adjustment of afatinib may allow patients to remain on treatment longer, maximizing clinical benefit even in the presence of radiological progression.

Optimizing diffusion-weighted magnetic resonance imaging for evaluation of lung tumors: A comparison of respiratory triggered and free breathing techniques.

PURPOSE: The aim of this study was to compare respiratory-triggered (RT) and free breathing (FB) diffusion weighted imaging (DWI) techniques regarding apparent diffusion coefficient (ADC) measurements and repeatability in non-squamous non-small cell lung cancer (NSCLC) measuring the total tumor volume. MATERIAL AND METHODS: A total of 57 magnetic resonance imaging (MRI) examinations were analyzed. DWI was obtained by a single-shot spin-echo echo-planar imaging sequence, and for each MRI examination 2 consecutive RT and 2 consecutive FB DWI sequences were performed. Two radiologists independently read the images and made measurements. For each tumor the mean ADC value of the whole tumor volume was calculated. The difference in mean ADCs between FB and RT DWI was evaluated using the paired-sample t-test. The repeatability of ADC measurements related to imaging method was evaluated by intra class correlations (ICC) for each of the FB and RT DWI pairs. RESULTS: There were no significant differences in mean ADCs between FB and RT (Reader 1 p = 0.346, Reader 2 p = 0.583). The overall repeatability of ADC measurement was good for both acquisition methods, with ICCs > 0.9. Subgroup analysis showed somewhat poorer repeatability in small tumors (50 ml or less) and tumors in the lower lung zones for the RT acquisition, with ICC as low as 0.72. CONCLUSIONS: No difference in ADC measurement or repeatability between FB and RT DWI in whole lesion ADC measurements of adenocarcinomas in the lung was demonstrated. The results imply that in this setting the FB acquisition method is accurate and possibly more robust than the RT acquisition technique.

Mutational status predicts the risk of thromboembolic events in lung adenocarcinoma.

BACKGROUND: Precision medicine promises to improve prognosis of patients affected by untreatable diseases. Patients with lung cancer (especially lung adenocarcinoma) bear an increased risk of VTE. Mutations in the EGFR and rearrangement in the ALK genes identify specific subgroups of patients. Aim of this study was to investigate the role of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status on the risk of venous thromboembolism (VTE) in lung adenocarcinoma. METHODS: A retrospective longitudinal design was used. Patients with lung adenocarcinoma diagnosed and undergoing a mutational analysis at the Karolinska University Hospital, Stockholm, Sweden between January 2009 and September 2015 were divided in three subgroups based on their mutational status (EGFR-, ALK-mutated, unexposed group). Event-free time for VTE was assessed using Cox regression analysis based on mutation status and treatment received. RESULTS: Three hundred-ten patients were included. A VTE occurred in 70 (22.6%) patients. Mutation of EGFR was associated with a decreased risk of VTE (HR 0.46, 95% CI 0.23-0.94). Treatment with tyrosine kinase inhibitors (TKI) reduced the risk of VTE compared to other treatment strategies not including TKI (HR 0.42, 95% CI 0.29-0.79). CONCLUSIONS: Our study suggests that patients with lung adenocarcinoma bearing a EGFR-mutation have a decreased risk of VTE compared with patients with other forms of lung adenocarcinoma. Targeted therapy with TKI alone or in combination with other treatments seems to reduce the risk of VTE compared to other treatments not including TKI.

Non-small Cell Lung Cancer (NSCLC) in Octogenarians in Clinical Practice.

BACKGROUND/AIM: Globally, an increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) are treated in real-life clinical practice. PATIENTS AND METHODS: This was a retrospective observational study of all elderly (≥80 years) patients with NSCLC referred to the Department of Respiratory Medicine and Allergy, Karolinska Hospital, Sweden, 2003-2010, and followed until June, 2016. RESULTS: In total, 452 patients, 216 (47.8%) men and 236 (52.2%) women, were included. The mean and median age was 83 years; 28 (6.2%) were aged 90 years or more. Current or former smokers constituted 91.1%, with men having smoked more (p<0.001). There was no difference in performance status (PS) between genders with PS 0-1 in 45.4%, PS 2 in 25.6% and PS3-4 in 29%. About a third each was diagnosed in stages 1-II, III and IV. Adenocarcinoma was most common (45.6%), 18.1% had squamous cell carcinoma, while histological diagnosis was unavailable in 23.2%. Best supportive care (BSC) was given only to 209 patients (46.2%). Potentially curative therapy was administered to 16.5% of men and 20.3% of the women with surgery performed in 35 patients (7.8%) and stereotactic body radiation therapy (SBRT) in 48 patients (10.6%). Chemotherapy was given to 51 patients (11.2%) and palliative radiotherapy to 77 (17.0%). Second-line chemotherapy was given in 4% and third-line in 1.5%. Only one patient received fourth-line. Male patients who received chemotherapy survived a mean of 281 days and for female patients it was 332 days (not significant). Median overall survival (OS) was 115 days in patients receiving BSC and 362 days in patients given any therapy. Patients who underwent surgery for stage I-II had a median OS of 5.6 years compared to 3.5 years for patients given SBRT. CONCLUSION: Treatment of NSCLC patients 80 years and older with any modality is feasible with a good PS. Survival is fairly good with surgery or SBRT.

Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial.

BACKGROUND: The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting. METHODS: This multicentre, international, open-label, exploratory, randomised controlled phase 2B trial (LUX-Lung 7) was done at 64 centres in 13 countries. Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation (exon 19 deletion or Leu858Arg) were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or web-based response system with a block size of four. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. Coprimary endpoints were progression-free survival by independent central review, time-to-treatment failure, and overall survival. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01466660. FINDINGS: Between Dec 13, 2011, and Aug 8, 2013, 319 patients were randomly assigned (160 to afatinib and 159 to gefitinib). Median follow-up was 27·3 months (IQR 15·3-33·9). Progression-free survival (median 11·0 months [95% CI 10·6-12·9] with afatinib vs 10·9 months [9·1-11·5] with gefitinib; hazard ratio [HR] 0·73 [95% CI 0·57-0·95], p=0·017) and time-to-treatment failure (median 13·7 months [95% CI 11·9-15·0] with afatinib vs 11·5 months [10·1-13·1] with gefitinib; HR 0·73 [95% CI 0·58-0·92], p=0·0073) were significantly longer with afatinib than with gefitinib. Overall survival data are not mature. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (20 [13%] of 160 patients given afatinib vs two [1%] of 159 given gefitinib) and rash or acne (15 [9%] patients given afatinib vs five [3%] of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 [9%] of those given gefitinib). Serious treatment-related adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drug-related adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drug-related hepatic and renal failure. INTERPRETATION: Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population. FUNDING: Boehringer Ingelheim.

18F-FDG PET/CT Diagnosis of Bronchopulmonary Carcinoids Versus Pulmonary Hamartomas.

PURPOSE: Radiological characterization of pulmonary tumors may be difficult and invasive. Needle biopsy may produce false-negative results. 18F-FDG PET/CT is an established noninvasive procedure for lung tumor characterization and staging. This study was aimed at differentiating bronchopulmonary carcinoids from hamartomas and typical from atypical bronchopulmonary carcinoids by means of 18F-FDG PET/CT. PATIENTS AND METHODS: In a retrospective analysis of 118 patients, with surgically resected pulmonary carcinoid tumors and hamartomas, 87 of those selected had also undergone 18F-FDG PET/CT preoperatively and constituted the study population. To better assess the tracer accumulation, especially in small lesions, the 18F-FDG uptake (SUV) in the tumors was corrected for partial volume effect by applying recovery coefficients corresponding to the respective various specific tumor volumes, as extrapolated from those obtained from experiments in a NEMA phantom. RESULTS: The SUVmax was higher in the pulmonary carcinoids (mean, 3.9) than in the hamartomas (mean, 1.4; P ≤ 0.00001) and higher in the subgroup of peripheral carcinoids than in hamartomas (P ≤ 0.00001). The SUVmax was similar for the atypical and typical carcinoids, 5.0 and 3.8, respectively, because of the large variation in the data (P = 0.11). CONCLUSIONS: Using PET measurements of the 18F-FDG uptake (SUVmax) in the tumors, corrected for partial volume effects, it was possible to differentiate the carcinoids from the hamartomas, but the clinically more aggressive atypical carcinoids could not be differentiated from the typical carcinoids.

Chemotherapy Treatment of Elderly Patients (≥70 Years) with Non-Small Cell Lung Cancer: A Seven-Year Retrospective Study of Real-Life Clinical Practice at Karolinska University Hospital, Sweden.

An increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue; so we performed a retrospective study of our patients to demonstrate how elderly patients with NSCLC are treated in real-life, clinical practice. All patients aged ≥70 years with NSCLC at our department were reviewed retrospectively. In total, 1059 patients (50.8% of all NSCLC patients). Of these patients, 243 (22.9%) received chemotherapy, 164 (70.4%) of whom were treated with a platinum doublet using carboplatin. Second- and third-line chemotherapy were given to 31.4% and 13.9% of patients, respectively. Median overall survival was 289 and 320 days for male and female patients, respectively. Patients with performance status (PS) 0 experienced significantly better survival than patients with PS1 or PS 2: 410, 314, and 204 days, respectively. Age was of less importance, with patients aged 70-79 years versus those aged ≥80 years. Treatment of elderly NSCLC patients with chemotherapy is feasible if they have a good PS and appears to prolong survival. In this study, we found no significant differences in survival either between age groups or genders.

Pemetrexed and gemcitabine versus carboplatin and gemcitabine in non-small cell lung cancer: a randomized noninferiority phase II study in one center.

BACKGROUND: The standard treatment for non-small cell lung cancer (NSCLC) stages IIIb and IV is a platinum compound combined with a third-generation cytotoxic agent. We decided to conduct a phase II study to assess whether the platinum compound could be replaced with pemetrexed with similar results and without an increase in side effects. METHODS: Consecutive eligible patients were randomized to either the standard arm of gemcitabine plus carboplatin (GC) or the experimental arm of gemcitabine plus pemetrexed (GP). RESULTS: Fifty evaluable patients were enrolled in the GC arm, and 44 received GP. There were 10 partial responses in the GC arm and 16 in the GP arm. With GC, mean survival was 9 months compared with 15 months with GP. The side effects were similar in both groups. CONCLUSION: Pemetrexed can replace platinum compounds in the first-line treatment of stage IIIb and IV NSCLC without increasing the side effects. A trend toward better survival was observed in the patients receiving pemetrexed instead of a platinum compound, and this should be studied further.

Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007.

BACKGROUND: The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004-2007. METHODS: Routinely collected population-based data were obtained on all adults (15-99 years) diagnosed with lung cancer in 2004-2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. RESULTS: Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. CONCLUSIONS: There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved.

One year after endoscopic sinus surgery in polyposis: asthma, olfaction, and quality-of-life outcomes.

OBJECTIVE: Nasal polyposis is a disease known to be associated with asthma. The long-term effects of surgical treatment on lower airways have not been sufficiently studied. STUDY DESIGN: One-year follow-up of a double-blind, randomized, placebo-controlled study. SETTING: The study was conducted at the Karolinska University Hospital, Stockholm, Sweden. SUBJECTS AND METHODS: Fifty-one patients, age 18 years or older, with nasal polyposis and asthma were evaluated 1 year after endoscopic sinus surgery (ESS). Outcomes included dyspnea/cough scores, mean daily peak expiratory flow rate, spirometry, butanol test, olfaction scores, peak nasal inspiratory flow, polyp scores, and health-related quality of life (SF-36). RESULTS: The short-term postsurgery improvements in asthma symptom scores, daily peak expiratory flow rate, all nasal parameters including olfaction, and quality-of-life scores were generally maintained 1 year after ESS. CONCLUSION: Endoscopic sinus surgery had beneficial long-term effects on asthma, olfaction, and quality of life in patients with nasal polyposis. This is the first study to show long-term benefits of ESS on butanol tests in patients with nasal polyposis.

Swine dust exposure is a model for rapid induction of non-allergic neutrophil inflammation in the nasal mucosa of healthy volunteers, and the symptoms as well as the microcirculation are modified by nasal lavage.

BACKGROUND: The pathophysiological mechanism of non-allergic rhinitis is not clear and there is a lack of models in healthy volunteers. It has previously been shown that swine dust exposure is an excellent method for inducing inflammatory changes in the lower airways. We have shown earlier that exposure to swine dust increases the histamine sensitivity of the nasal mucosa as measured by rhinostereometry. In this study the aim was to investigate the effects of swine dust exposure on nasal symptoms as well as the microcirculation. Furthermore, the effect on nasal lavage was investigated. METHOD: Seventeen subjects were exposed to swine dust during a three-hour period of work in a swine house. Nasal symptoms and the nasal mucosal response to histamine before and after exposure to swine dust were evaluated by laser Doppler flowmetry and nasal lavage. RESULTS: Exposure to swine dust increased nasal symptoms and levels of neutrophils, IL-8 and albumin. The increase in nasal symptoms and the microcirculation were modified by nasal lavage. CMBC correlated inversely with an increase in albumin (p = 0.018, R = -0.95). CONCLUSIONS: Swine dust exposure is a useful model for inducing nasal inflammation in healthy volunteers. Furthermore, nasal lavage modifies subjective as well as objective parameters, which should be considered when designing studies. Nasal lavage may be useful in the treatment of workers in a swine dust environment.

Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group.

PURPOSE: This phase III study compared overall survival in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) when treated with single-agent gemcitabine versus gemcitabine/carboplatin. Secondary objectives were to compare response, time to progression, toxicity, and quality of life. PATIENTS AND METHODS: Chemotherapy-naive patients received either gemcitabine alone (1,250 mg/m2 on days 1 and 8; gemcitabine arm) or with carboplatin (area under the curve 5 on day 1; GC arm) every 21 days. RESULTS: Demographics and disease characteristics of 334 randomly assigned patients were comparable on both arms. An intent-to-treat analysis showed significantly better overall survival (log-rank P = .0205) and 2-year survival (15% v 5%; P = .009) favoring the GC arm. Per Cox multivariate analysis, only two covariates, treatment arm (GC v G) and baseline performance status (0 or 1 v 2), independently influenced survival. Per-protocol analyses showed significantly longer median time to progression (5.7 v 3.9 months; P = .0001) and significantly higher objective response rate (29.6 v 11.3%; P < .0001) in the GC arm. Grade 3 to 4 leucopenia and thrombocytopenia were significantly more pronounced in the GC arm (P for both variables < .001) but importantly without associated increases in fever, infection, bleeding, or hospitalizations. There was no discernible difference in global quality-of-life patterns between treatment arms. CONCLUSION: In advanced NSCLC, gemcitabine/carboplatin therapy resulted in significant survival benefit compared with single-agent gemcitabine without undue increase in toxicity.

Imaging of regional lymph node metastases with 99mTc-depreotide in patients with lung cancer.

PURPOSE: The aim of this study was to evaluate the clinical usefulness of scintigraphy with 99mTc-depreotide in the assessment of loco-regional nodal spread in patients with suspected lung cancer in comparison with computed tomography (CT). METHODS: Eighty-six patients were investigated with single-photon emission computed tomography (SPECT) of the thorax after i.v. injection of 740 MBq 99mTc-depreotide. The results were evaluated in conjunction with a thoracic CT scan in all 86 patients with 204 lymph node stations. The scintigraphic results were correlated with cytological (38), histological (20) or clinical-radiological (146) findings and compared with CT. The quantitative evaluation of depreotide uptake was performed on 48 cytologically or histologically verified nodal stations from 28 patients by SPECT using region of interest analysis with four different reference regions. RESULTS: 99mTc-depreotide scintigraphy for all 204 investigated lymph node stations had a sensitivity of 99% and a negative predictive value of 98% in determining lymph node involvement. Scintigraphy and CT showed the same level of accuracy, 76.4%. CT findings had a higher positive predictive value but a lower negative predictive value compared to 99mTc-depreotide scintigraphy. The quantitative evaluation of depreotide uptake in lymph nodes using vertebra as a reference region showed that a cut-off level of 0.56 excludes malignant involvement of lymph nodes, while a cut-off level of 1.66 excludes benign disease in lymph nodes. About 73% of all investigated lymph node stations showed uptake values between these cut-off levels. CONCLUSION: Absence of 99mTc-depreotide uptake on scintigraphic imaging can exclude regional lymph node involvement with a high degree of probability and may be useful in clinical practice. The quantitative evaluation of depreotide uptake in regional lymph nodes did not increase the diagnostic accuracy of the method in general but did elucidate the lymph node status in some patients.

Accumulation of Tc-99m depreotide (NeoSpect) in axillary sweat glands.

Tc-99m depreotide (NeoSpect) is a radiolabeled somatostatin analog introduced recently for scintigraphic imaging of patients with lung cancer. Eighteen patients were examined 2 to 4 hours after administration of 740 MBq mCi Tc-99m depreotide. In 13 patients (72.2%) bilateral symmetric activity corresponding to the large, deep apocrine sweat glands of the axillae was present. This observation is clinically relevant regardless of its reason or mechanism. It is important to be aware of this reason for activity in the axillae when assessing lymph node involvement not only in patients with lung cancer but also in breast cancer patients using scintigraphy with Tc-99m depreotide.

Nasal and bronchial histamine responsiveness in pollen-exposed patients with seasonal rhinitis.

In a previous study, we found an increased nasal responsiveness as measured by rhinostereometry and histamine challenge out of season in a sample of 12 patients suffering mainly from hay fever. The aim of the present study was to investigate whether airway responsiveness in these patients was further increased after direct pollen exposure, after a single nasal pollen provocation as well as by repeated exposure during the pollen season. In spite of increased allergic symptoms, the basal degree of nasal mucosal swelling was unchanged before histamine challenge under these circumstances. After histamine challenge, nasal mucosal swelling was increased in the same way over the seasons. Also bronchial responsiveness was unchanged during the pollen season. It correlated to frequent sneezing following nasal histamine challenge during the season (p = 0.0071, r = -0.74). We interpret the results as an indication of a continuos airway inflammation regardless of season in these patients with pollen allergy, with acute symptoms added on direct exposure to the allergen.

Modulation of plasma levels of soluble adhesion molecules and nitric oxide in healthy volunteers by exposure to swine dust.

Short-time exposure to swine dust causes an intense airways inflammation and symptoms of systemic inflammation in healthy volunteers. Here, we sought to study whether this response involved signs of endothelial cell activation. Peripheral blood cell counts and plasma levels of sE-selectin, sP-selectin, sICAM-1, interleukin-8, nitrite and nitrate were measured in blood samples from 17 healthy subjects before and after a 3-hr exposure to swine dust in a swine confinement building. Dust exposure induced a 3-fold increase of blood neutrophil p = 0.0009) and 1.5-fold increase of monocyte counts (p = 0.0047). IL-8 was detected in 15 individuals after exposure (p = 0.001). Endothelial cell markers such as sICAM and nitrate increased by 10 and 34% resp. (p = 0.011 and 0.017), whereas sE-selectin remained unchanged and sP-selectin was reduced by 15% (p = 0.031). Thus, short time exposure to swine dust induced a systemic inflammatory response with evidence of endothelial and inflammatory cell activation.