Comparison of routinely used intestinal biopsy forceps in dogs: an ex vivo histopathological approach.

OBJECTIVES: To compare the quality of duodenal and ileal samples obtained with different biopsy forceps. METHODS: Fifteen dogs were included in a prospective ex vivo study. After euthanasia, the duodenum and the ileum were sampled with four different forceps and evaluated according to a standardised scoring system. The biopsy forceps evaluated had alligator jaws or cups with smooth edge with or without a needle. RESULTS: The global quality of the biopsies was better in the ileum that in the duodenum regardless of the biopsy forceps. Biopsy forceps with smooth edge including a needle resulted in fewer artefacts than biopsy forceps with smooth edge but no needle in both sites and those with alligator jaws without a needle provided deeper biopsies than those with smooth edge without a needle only in the duodenum. There was no effect of the biopsy forceps type on the size of the biopsies. CLINICAL SIGNIFICANCE: Our findings may aid in choosing the appropriate type of forceps for intestinal biopsy.

FDG-PET parameters predicting mediastinal malignancy in lung cancer.

BACKGROUND: Staging of mediastinal lymph nodes in non-small cell lung cancer (NSCLC) is mandatory. The maximum Standard Uptake Value (SUVmax) obtained using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is the best non-invasive technique available for this evaluation, but its performance varies from center to center. The aim of the present study was to identify FDG-PET predictors of mediastinal malignancy that are able to minimize intercenter variability and improve the selection of subsequent staging procedures. METHOD: A multicenter study of NSCLC patients staged through FDG-PET and endobronchial ultrasonography with needle aspiration (EBUS-NA) was performed using therapeutic surgery with systematic nodal dissection as gold standard. Intercenter variability and predictive power for mediastinal malignancy of different FDG-PET measures were assessed, as well as the role of these measures for selecting additional staging procedures. RESULTS: One hundred and twenty-one NSCLC patients, of whom 94 (72%) had ≥1 hypermetabolic spots in the mediastinum, were included in the study. Mean SUVmax of the primary tumor was 12.3 (SD 6.3), and median SUVmax of the highest hypermetabolic spots in the mediastinum was 3.9 (IQR 2.4-7). Variability of FDG-PET measures between hospitals was statistically significant (p = 0.016 and p < 0.001 respectively), but lost significance when SUVmax in the mediastinum was expressed as a ratio or a subtraction from the primary tumor (SUVmax mediastinum/tumor, p = 0.083; and SUVmax mediastinum - tumor, p = 0.428 respectively). SUVmax mediastinum/tumor showed higher accuracy in the ROC analysis (AUC 0.77 CI 0.68-0.85, p < 0.001), and showed predictive power for mediastinal malignancy when using a 0.4 cutoff (OR 6.62, 95%CI 2.98-14.69). Sensitivities and negative predictive values of clinical staging through EBUS-NA attained values ranging between 57% and 92% after FDG-PET, which improved with additional techniques when the tumor had a diameter >3 cm and/or a SUVmax mediastinum/tumor ratio >0.4. CONCLUSION: The SUVmax mediastinum/tumor ratio is a good predictor of regional tumor extension in NSCLC. This measure is not influenced by intercenter variability and has an accuracy of over 70% for the identification of malignancy when using a 0.4 cutoff.

Induced sputum in the diagnosis of peripheral lung cancer not visible endoscopically.

The diagnosis of small peripheral lung cancer is difficult to achieve by non-invasive methods. We hypothesized that in these patients induced sputum might ncrease the diagnostic yield over spontaneous sputum, representing a good diagnostic alternative in selected patients. We prospectively evaluated 60 patients with peripheral lung lesions and normal bronchoscopic evaluation. Six samples of sputum (three spontaneous and three induced with nebulization of hypertonic saline) before bronchoscopy and six samples of sputum after bronchoscopy (three spontaneous and three induced) were obtained in each subject. Forty-two out of the 60 patients included were finally diagnosed with lung cancer. Eighteen patients were diagnosed with different benign conditions of the lung. Overall, malignant cells in sputum were observed in 21 patients and in all but one, the final diagnosis of lung cancer was achieved. Only one patient with a pseudoinflammatory tumour of the lung had a false-positive result in one spontaneous sputum sample. The diagnosis of lung cancer was obtained in 18 patients with the induced sputum (43%) and in 14 patients with spontaneous sputum (31%) (P=NS). Samples of induced sputum were more adequate for cytological analysis than samples of spontaneous sputum (P < 0.001). Of 13 patients with peripheral lung neoplasms of 2 cm or less in diameter, five were diagnosed using induced sputum (38%) and only one using spontaneous sputum (8%) (P<0.05). In conclusion, induced sputum is a valuable technique for the diagnosis of peripheral lung cancer. Induced sputum gives better quality specimens and better diagnostic yield in small lesions than the spontaneous sputum and may be indicated in selected patients with disseminated disease, inoperability or severe co-morbities.

Systemic inflammatory response after bronchoalveolar lavage in critically ill patients.

Bronchoscopic bronchoalveolar lavage (BAL) may be followed by a systemic inflammatory response. Previous reports have suggested pneumonia as a predisposing condition and systemic cytokines as possible mediators. To test this hypothesis, systemic levels of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were studied before and at 12 h and 24 h after bronchoscopically guided BAL in 30 mechanically ventilated patients (median age 67 (range 54-76) yrs, simplified acute physiology score II (SAPS II) 33 (12-56)), 20 of whom had pneumonia and 10 of whom were control patients without pneumonia. Arterial oxygen partial pressure to inspired oxygen fraction ratio (Pa,O2/FI,O2), body temperature, mean arterial pressure, and cardiac frequency were recorded. The majority of patients (28/30, 93%) received antibiotic treatment prior to the procedure. Pa,O2/FI,O2 ratio was lower at 12 h compared to baseline in patients with pneumonia (baseline median 192 (range 65-256); 12 h 160 (66-190) mmHg, p<0.001) and ventilated controls (baseline 293 (205-473); 12 h 226 (153-330) mm Hg p=0.011), but returned to baseline levels at 24 h (pneumonia: 194 (92-312), p=0.991; controls: 309 (173-487) mmHg, p=0.785). No changes in other clinical variables were observed. Systemic TNF-alpha levels before BAL (pneumonia: 35 (10-88); controls: 17 (0-33) pg x mL(-1)) did not increase at 12 h (pneumonia: 35 (0-64); p=0.735; controls: 16 (0-21) pg x mL(-1), p=0.123 comparison to baseline) or 24 h (pneumonia: 31 (0-36), p=0.464; controls: 19 (0-43) pg x mL(-1), p=0.358). No changes of IL-1beta (baseline: pneumonia 0 (0-13); controls 1 (0-32) pg x mL(-1)) or IL-6 (baseline: pneumonia, 226 (9-4300); controls, 53 (0-346) pg x mL(-1)) were detected. No deterioration of clinical variables and no increase in systemic cytokine release has been observed after bronchoalveolar lavage, in critically ill patients. The potential cytokine increase is probably too small, in relation to the pre-existing inflammatory response, to yield clinical significance in this population otherwise antibiotic therapy may have been protective.

Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls.

BACKGROUND: The inflammatory response has been widely investigated in patients with acute respiratory distress syndrome (ARDS) and pneumonia. Studies investigating the diagnostic values of serum cytokine levels have yielded conflicting results and only little information is available for the differential diagnosis between ARDS and pneumonia. METHODS: Clinical and physiological data, serum concentrations of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, and quantitative cultures of lower respiratory tract specimens were obtained from 46 patients with ARDS and 20 with severe pneumonia within 24 hours of the onset of the disease and from 10 control subjects with no inflammatory lung disease. Cytokine concentrations were compared between groups and determinants in addition to the diagnosis were tested. RESULTS: Serum TNF-alpha levels were significantly higher in ARDS patients (67 (57) pg/ml) than in patients with severe pneumonia (35 (20) pg/ml; p = 0.031) or controls (17 (8) pg/ml; p = 0.007). For IL-1beta and IL-6 the observed differences were not statistically significant between patients with ARDS (IL-1beta: 34 (65) pg/ml; IL-6: 712 (1058) pg/ml), those with severe pneumonia (IL-1beta: 3 (4) pg/ml, p = 0.071; IL-6: 834 (1165) pg/ml, p = 1.0), and controls (IL-1beta: 6 (11) pg/ml, p = 0.359; IL-6: 94 (110) pg/ml, p = 0.262). TNF-alpha (standardised coefficient beta = 0.410, p<0.001) and IL-1beta (standardised coefficient beta = 0.311, p = 0.006) were most strongly associated with the degree of lung injury, even when the diagnostic group was included in the statistical model. CONCLUSIONS: Serum TNF-alpha levels were higher in patients with ARDS than in those with severe pneumonia or in control subjects. Multivariate results suggest that the levels of systemic TNF-alpha and IL-1beta reflect the severity of the lung injury rather than the diagnosis.

Cytokine expression in severe pneumonia: a bronchoalveolar lavage study.

OBJECTIVE: To assess the cytokine expression (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1beta, and IL-6) in severe pneumonia, both locally (in the lungs) and systemically (in blood). DESIGN: Prospective sequential study with bronchoalveolar lavage (BAL) and blood sampling. SETTING: Six-bed respiratory intensive care unit of a 1,000-bed teaching hospital. PATIENTS: Thirty mechanically ventilated patients (>48 hrs) were allocated to either the pneumonia group (n = 20) or a control group (n = 10). INTERVENTIONS: Protected specimen brush and BAL samples for quantitative cultures, and serum and BAL fluid TNF-alpha, IL-1beta, and IL-6 levels were measured on days 1, 3, and 7. In the control group, the procedure was done on day 1 only. MEASUREMENTS AND MAIN RESULTS: Serum TNF-alpha levels were significantly higher in patients with pneumonia compared with controls (35 +/- 4 vs. 17 +/- 3 pg/mL, respectively, p = .001). IL-6 levels in serum and BAL fluid were higher in pneumonia than in control patients (serum, 837 +/- 260 vs. 94 +/- 35 pg/mL, respectively, p = .017; BAL fluid, 1176 +/- 468 vs. 234 +/- 83 pg/mL, respectively, p = .05). On days 1, 3, and 7 in patients with pneumonia, IL-1beta levels turned out to be higher in BAL fluid than in serum (71 +/- 17 vs. 2 +/-1 pg/mL on day 1; 49 +/- 8 vs. 6 +/- 2 pg/mL on day 3; and 47 +/- 16 vs. 3 +/- 2 pg/mL on day 7 for BAL fluid and serum, respectively, p < .05). No significant correlation between BAL fluid cytokine levels and lung bacterial burden was shown in presence of antibiotic treatment. Although no clear relationship was found between BAL fluid and serum cytokines and mortality, there was a trend toward higher serum IL-6 levels in nonsurvivors (1209 +/- 433 pg/mL) with pneumonia compared with survivors (464 +/- 260 pg/mL). In addition, serum TNF-alpha and IL-6 correlated with multiple organ failure score (r2 = .36, p = .004 for both) and with lung injury score (r2 = .30, p = .01, and r2 = .22, p = .03, for TNF-alpha and IL-6, respectively). CONCLUSIONS: The present study describes the lung and systemic inflammatory response in severe pneumonia. The lung cytokine expression seems to be independent from the lung bacterial burden in the presence of antibiotic treatment. Because of the limited sample size, we did not find a clear relationship between serum and BAL fluid cytokine levels and outcome.

Role of glucocorticoids on inflammatory response in nonimmunosuppressed patients with pneumonia: a pilot study.

The aim of the study was to assess the potential role of glucocorticoids (GC) in modulating systemic and pulmonary inflammatory responses in mechanically ventilated patients with severe pneumonia. Twenty mechanically ventilated patients with pneumonia treated at a respiratory intensive care unit (RICU) of a 1,000-bed teaching hospital were prospectively studied. All patients had received prior antimicrobial treatment. Eleven patients received GC (mean+/-SD dose of i.v. methylprednisolone 677+/-508 mg for 9+/-7 days), mainly for bronchial dilatation. Serum and bronchoalveolar lavage fluid (BALF) tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and C-reactive protein levels were measured in all patients. The inflammatory response was attenuated in patients receiving GC, both systemically (IL-6 1,089+/-342 versus 630+/-385 pg x mL(-1), p=0.03; C-reactive protein 34+/-5 versus 19+/-5 mg x L(-1), p=0.04) and locally in BALF (TNF-alpha 118+/-50 versus 24+/-5 pg x mL(-1), p= 0.05; neutrophil count: 2.4+/-1.1 x 10(9) cells x L(-1) (93+/-3%) versus 1.9+/-1.8 x 10(9) cells x L(-1) (57+/-16%), p=0.03). Four of the 11 (36%) patients receiving GC died compared to six (67%) who were not receiving GC (p=0.37). The present pilot study suggests that glucocorticoids decrease systemic and lung inflammatory responses in mechanically ventilated patients with severe pneumonia receiving antimicrobial treatment.

Lung inflammatory response in pneumonia.

In normal conditions, alveolar macrophages (AMs) are the main cells that respond to bacteria that reach lower airways. However, if the microbial inoculum is too high or too virulent to be stopped by AM alone, these cells recruit polymorphonuclear neutrophils (PMN) into the alveoli from the vascular compartment. Cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8), secreted by the AM are able to attract PMN enhanced for phagocytosis, ready to destroy the invading pathogens. However, excessive cytokine production has deleterious effects, with a systemic inflammatory response (sepsis) that can lead to multiorganic failure and death. Other cytokines, such as interleukin-10 (IL-10) balance this response, attenuating several inflammatory mechanisms. The inflammatory lung response in pneumonia has been well studied in animals, and more recently in humans, using bronchoalveolar lavage to measure some inflammatory mediators (TNF-alpha, IL-1 beta, IL-6, IL-8). From these studies, it seems that: 1) the inflammatory response to pneumonia is compartmentalized for most cytokines (in contrast to adult respiratory distress syndrome (ARDS)), except for IL-6 which is a general marker of inflammation. On the other hand, C-reactive-protein is an acute-phase protein synthesized by the liver through the stimulus of IL-6 that may also be an easy-to-measure marker of inflammation that is directly related to IL-6; 2) some of these cytokines may be useful as prognostic indices; 3) there is no clear relationship between the local lung bacterial burden and the intensity of the inflammatory response; and 4) the administration of granulocyte colony-stimulating factor (G-CSF) is a promising therapeutic approach that is still under clinical investigation. In the future, it is probable that the therapeutic goal in severe pneumonia will be to find the exact point at which inflammation is beneficial but not deleterious. The measurement of the inflammatory response may serve for this purpose.

[Epidemic Kaposi's sarcoma in women: presentation of 4 cases]. / Sarcoma de Kaposi epidémico en mujeres: presentación de 4 casos.

Epidemic Kaposi's sarcoma is the neoplasm most frequently manifested in infection by the human immunodeficiency virus. Its prevalence is considerably higher among homosexual males than among intravenous drug users with practically exclusive infection in this sex. Four cases of Kaposi's sarcoma in women with the human immunodeficiency virus are described. Two of these subjects were intravenous drug users and the other two were heterosexually promiscuous as the only conduct of risk for acquiring infection by the human immunodeficiency virus. Kaposi's sarcoma was the form of presentation of the syndrome of acquired immunodeficiency syndrome in these four patients.