Bacillus-Calmette-Guérin (BCG) and 3D tumors: an in vitro model for the study of adhesion and invasion.

PURPOSE: To study adhesion, penetration and internalization of BCG and effector-cells to and into three-dimensional in vitro cell aggregates from benign and malignant urothelial origin mimicking small in vitro tumors. MATERIALS AND METHODS: Multicellular spheroids (MCS) were generated by "liquid-overlay" technique. Adhesion and penetration of viable FITC-labelled BCG into MCS from urothelial cancer cell lines and normal urothelial cells was studied by electron microscopy (TEM) and fluorescence microscopy. Spheroid growth during BCG-co-incubation was determined by light microscopy. Peripheral blood mononuclear cells (PBMC) were stimulated with BCG to generate BCG-activated-killer (BAK) cells. The infiltration of these effectors and of lymphokine-activated killer (LAK) cells into MCS was examined at different intervals by means of immunohistochemistry. The resulting cytotoxicity was judged in a 3H-l-methionine release assay. RESULTS: BCG adhered to MCS from tumor cells but not to benign cell MCS. Intracellular internalization of the bacteria was detectable in superficial tumor cell-layers (1-5) whereas BCG was not found in deeper layers. Proliferation of malignant MCS was reduced in the presence of BCG. Benign MCS showed contact inhibition growth arrest, which was not altered by BCG. BAK and LAK effector cells both infiltrated tumor cell MCS as opposed to unstimulated PBMC. In contrast to LAK cells, BAK cells did not infiltrate into benign cell MCS and were not cytotoxic towards them. CONCLUSION: With regard to the clinical situation the selective adhesion and internalization of BCG to malignant cells might explain why BCG has been rarely found in follow-up biopsies in tumor free patients. More interestingly, the selective adhesion of BCG to and infiltration of BAK effector cells into malignant cell spheroids suggests a selective mode of action of BCG.     

Patient-specific predictors of image noise in coronary CT angiography

BackgroundCoronary computed tomography (CT) angiography can be associated with high radiation exposure. Reduction of tube voltage from 120 kV to 100 kV can reduce the dose by up to 40%, but it also increases image noise.ObjectiveWe aimed to find a patient-specific predictor of image noise to determine the use of reduced tube voltage.MethodsContrast-enhanced coronary dual-source CT angiography data sets [prospectively electrocardiogram (ECG)–triggered axial and retrospectively ECG-gated spiral acquisition, rotation of 280 milliseconds, 2 × 128 × 0.6 mm collimation, 100 kV, 320 mAs] of 165 patients (age, 54 ± 13 years) for the detection of coronary artery stenoses were analyzed. Image noise was measured in the aortic root. Influence of body weight, height, body mass index, thoracic cross sectional area, as well as the area of the thoracic solid tissue were analyzed.ResultsMean image noise in the aorta was 35.1 ± 8.9 HU. Mean dose length product was 207 ± 184 cm · cGy with an average effective dose of 2.9 ± 2.6 mSv. The patient cohort was divided into tertiles according to image noise. Numerous parameters, including BMI and body weight, were significantly different between the highest and lowest tertiles. In multivariable regression analysis, the area of the thoracic solid tissue was the only independent predictor of image noise (P < 0.0001).ConclusionsThe area of the thoracic solid tissue at the level of the aortic root predicts image noise and may hence be used for the decision to reduce tube voltage from 120 kV to 100 kV.     

Iatrogenic iliac artery rupture and type a dissection after endovascular repair of type B aortic dissection

We report a case of two iatrogenic complications after endovascular repair of a type B aortic dissection treated for abdominal aortic branch ischemia. A rupture of the common iliac artery occurred first during the procedure. A type A dissection occurred 12 days later. The proximal part of the aortic endovascular graft had created a tear in the aortic wall resulting in a retrograde type A dissection. Although aortic endovascular grafting is apparently associated with less morbidity and mortality, potentially lethal complications, both acute and delayed, may arise.     

Noninvasive visualization of coronary arteries using contrast-enhanced multidetector CT: influence of heart rate on image quality and stenosis detection

OBJECTIVE: Although multidetector CT (MDCT) with retrospectively ECG-gated image reconstruction has been shown to permit noninvasive visualization of the coronary arteries, the 125-250 msec required for image acquisition frequently causes motion artifacts. We investigated the influence of a patient's heart rate on the presence of motion artifacts and on accuracy of stenosis detection on contrast-enhanced MDCT. MATERIALS AND METHODS: In 100 patients, MDCT was performed, and ECG-gated cross-sectional images were retrospectively reconstructed. From the 10 data sets obtained for each patient (reconstructed at 0-90% of the cardiac cycle in increments of 10%), we chose the best data set for every coronary artery. The images of the arteries were evaluated for occurrence of artifacts and the presence of high-grade stenosis (diameter reduction exceeding 70%) or occlusions. MDCT results were compared with coronary angiographic findings. RESULTS: Of the 400 coronary arteries, 115 (29%) could not be evaluated because of motion artifacts (n = 84) or other reasons (n = 31). Overall, 51 (49%) of 104 stenoses were revealed on MDCT. For detecting stenosis in those arteries that we could evaluate, MDCT had a sensitivity of 91% (51 of 56 stenoses detected) and a specificity of 89%. As the heart rate increased, the number of arteries that could be evaluated decreased, and overall sensitivity for stenosis detection decreased from 62% (heart rate < or = 70 beats per minute) to 33% (heart rate > 70 beats per minute). CONCLUSION: MDCT can reveal coronary stenoses, but the usefulness of MDCT as an aid in accurately evaluating stenoses decreases as a patient's heart rate increases.     

Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging

Dynamic contrast agent-enhanced perfusion magnetic resonance (MR) imaging provides physiologic information that complements the anatomic information available with conventional MR imaging. Analysis of dynamic data from perfusion MR imaging, based on tracer kinetic theory, yields quantitative estimates of cerebral blood volume that reflect the underlying microvasculature and angiogenesis. Perfusion MR imaging is a fast and robust imaging technique that is increasingly used as a research tool to help evaluate and understand intracranial disease processes and as a clinical tool to help diagnose, manage, and understand intracranial mass lesions. With the increasing number of applications of perfusion MR imaging, it is important to understand the principles underlying the technique. In this review, the essential underlying physics and methods of dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging are described. The clinical applications of cerebral blood volume maps obtained with perfusion MR imaging in the differential diagnosis of intracranial mass lesions, as well as the pitfalls and limitations of the technique, are discussed. Emphasis is on the clinical role of perfusion MR imaging in providing insight into the underlying pathophysiology of cerebral microcirculation.     

Alveolar recruitment improves ventilatory efficiency of the lungs during anesthesia

PURPOSE: The goal of this study was to analyze the effect of positive end-expiratory pressure (PEEP), with and without a lung recruitment maneuver, on dead space. METHODS: 16 anesthetized patients were sequentially studied in three steps: 1) without PEEP (ZEEP), 2) with 5 cm H(2)O of PEEP and 3) with 5 cm H(2)O of PEEP after an alveolar recruitment strategy (ARS). Ventilation was maintained constant. The single breath test of CO(2) (SBT-CO(2)), arterial oxygenation, end-expiratory lung volume (EELV) and respiratory compliance were recorded every 30 min. RESULTS: Physiological dead space to tidal volume decreased after ARS (0.45 +/- 0.01) compared with ZEEP (0.50 +/- 0.07, P < 0.05) and PEEP (0.51 +/- 0.06, P < 0.05). The elimination of CO(2) per breath increased during PEEP (25 +/- 3.3 mL.min(-1)) and ARS (27 +/- 3.2 mL.min(-1)) compared to ZEEP (23 +/- 2.6 mL.min(-1), P < 0.05), although ARS showed larger values than PEEP (P < 0.05). Pa-etCO(2) difference was lower after recruitment (0.9 +/- 0.5 kPa, P < 0.05) compared to ZEEP (1.1 +/- 0.5 kPa) and PEEP (1.2 +/- 0.5 kPa). Slope II increased after ARS (63 +/- 11%/L, P < 0.05) compared with ZEEP (46 +/- 7.7%/L) and PEEP (56 +/- 10%/L). Slope III decreased significantly after recruitment (0.13 +/- 0.07 1/L) compared with ZEEP (0.21 +/- 0.11 1/L) and PEEP (0.18 +/- 0.10 1/L). The angle between slope II and III decreased only after ARS. After lung recruitment, PaO(2), EELV, and compliance increased significantly compared with ZEEP and PEEP. CONCLUSION: Lung recruitment improved the efficiency of ventilation in anesthetized patients.     

The Vista system: a new bipolar resection device for endourological procedures: comparison with conventional resectoscope

OBJECTIVE: Conventional transurethral resection of the prostate (TURP) uses a monopolar electrocautery system in which the current passes from the active electrode through the patient's body towards the return plate and may cause distant negative effects. In this study a new developed resection device, the Vista system, using a bipolar electrocautery system and 0.9% sodium chloride solution for irrigation, was evaluated in an ex-vivo model. METHODS: The modified model of the isolated blood perfused kidney was used to determine cutting qualities, ablation rate, blood loss and coagulation depth of the bipolar resectoscope. After ablating the renal tissue of a perfused kidney in a surface area, blood loss was semiquantitatively determined. Afterwards samples were taken and processed for histological evaluation of the coagulation depth. We compared the new bipolar resection device against a conventional monopolar resectoscope. RESULTS: We found good cutting qualities of the bipolar resectoscope although it is more difficult to start a cut. The ablation rate is determined by the width of the electrode and is similar to the standard device (30 cm(2)/min). The bleeding is reduced with increasing output powers (26.13 +/- 6.15 g/min (level 5); 20.49 +/- 5,47 g/min (level 6); 13.16 +/- 5,47 g/min (level 7); 10.43 +/- 4.76 g/min (level 8) and lower compared to a conventional monopolar resectoscope (17.08 +/- 4.47 g/min). The coagulation depth increases with higher output powers but is reduced compared to the standard device (118 +/- 22 microm (level 5); 121 +/- 23 microm (level 6); 141 +/- 62 microm (level 7); 163 +/- 30 microm (level 8) versus 287 +/- 57 (monopolar resectoscope)). CONCLUSION: Our results with the bipolar resection device for TURP suggest that it may offer an alternative to conventional TURP. As active and the return electrode are placed on the resectoscope, high current densities are achieved locally and complications caused by distant negative effects of the current are theoretically reduced in vivo. Furthermore the risk of TUR syndrome is theoretically eliminated by using physiological sodium chloride solution for irrigation. To prove the clinical significance of our ex-vivo findings, clinical studies including large numbers of patients have to be performed.     

Importance of adrenal incidentaloma in patients with a history of malignancy

BACKGROUND: Adrenal incidentaloma presents a frequent finding in patients with a history of malignancy. This study was carried out to determine whether imaging techniques can discriminate between a malignant and a benign adrenal tumor and subsequently select candidates for adrenal surgery. METHODS: Beginning in July 1995, oncologic patients with adrenal incidentaloma underwent abdominal ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and [ 18 ]fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET). Consecutively in all patients adrenalectomy was performed. Histologic findings were compared with the imaging results. RESULTS: In 42 patients, 33 to 79 years old (mean age, 58 years), 44 adrenal lesions were detectable. Two patients presented with bilateral adrenal masses. At operation, 43 adrenal resections and 3 biopsies were performed. Histologic examination revealed 31 metastases (71%) and 13 adrenal adenomas (29%). In metastases the sensitivity of ultrasonography, CT, MRI, and 18-FDG-PET was 66%, 81%, 100%, and 100%, respectively. For adrenal adenoma, the sensitivity of ultrasonography, CT, MRI, and 18-FDG-PET was 46%, 39%, 100%, and 54%, respectively. CONCLUSIONS: In oncologic patients with indeterminate adrenal tumors MRI and 18-FDG-PET provide accurate differentiation between metastases and benign adenomas. Positive results of these 2 imaging modalities are highly suggestive for metastatic disease. In cases of negative MRI and 18-FDG-PET results the adrenal lesion corresponds to a benign adenoma that needs no surgical intervention.     

Absence of donor CD40 protects renal allograft epithelium and preserves renal function

Blocking the CD40‐CD154 pathway prevents allograft rejection and induces donor‐specific tolerance in various experimental models. However, the translation to clinical studies has been hampered by unexpected thromboembolic complications of CD154‐blocking antibodies. Thus, blocking CD40 instead is now considered as an alternative strategy. Here, we evaluated the role of donor CD40 in allospecific T‐cell responses in vitro and in an in vivo model for renal transplantation. Fully MHC‐mismatched allografts from CD40‐deficient donors displayed better renal function than wild type. These functional data correlated with a lower level of apoptosis in renal tubular epithelial cells and higher expression of PD‐L1, which is most probably because of a reduced Th17 response in recipients of a CD40‐deficient donor. This hypothesis was supported in vitro, where donor CD40 expression was important for the induction of direct allospecific T‐cell responses. Especially the induction of Th17 cells was critically dependent on donor CD40. IL‐17A in conjunction with interferon‐γ in turn rendered renal tubular epithelial cells to a more costimulatory state by upregulating CD40 and downregulating PD‐L1 expression. In conclusion, CD40 blockade not only reduces the allospecific T‐cell responses, but might also lead to protection of tubular epithelium from apoptosis and thereby preserve kidney allograft function.