Low tumor interleukin-1ß expression predicts a limited effect of adjuvant platinum-based chemotherapy for patients with completely resected lung adenocarcinoma: An identification and validation study.

INTRODUCTION AND OBJECTIVES: Adjuvant platinum-based chemotherapy for completely resected non-small cell lung cancer is associated with modest improvement in survival; nevertheless, no validated biomarker exists for predicting the benefit or harm of adjuvant platinum-based chemotherapy. MATERIALS AND METHODS: We simultaneously measured 27 cytokines in operative tumor specimens from a discovery cohort (n = 97) by multiplex immunoassay; half of the patients received adjuvant platinum-based chemotherapy, and the other half were observed. We tested possible prognostic and predictive factors in multivariate Cox models for overall survival (OS) and relapse-free survival (RFS), and a tree-based method was applied to detect predictive factors with respect to RFS. The results were validated in an independent validation cohort (n = 93). RESULTS: Fifty-two of 97 (54 %) patients in the discovery cohort and 50 of 93 (54 %) in the validation cohort received adjuvant chemotherapy; forty-four (85 %) patients in the discovery cohort and 37 (74 %) in the validation cohort received four cycles as planned. In patients with low IL-1ß-expressing tumors, RFS and OS were worse after adjuvant chemotherapy than after observation. The limited effect of adjuvant chemotherapy for patients with low IL-1ß-expressing tumors was confirmed in the validation cohort. Additionally, RFS and OS were prolonged by adjuvant chemotherapy only in patients with high IL-1ß-expressing tumors in the validation cohort. CONCLUSIONS: This study identified and validated low tumor IL-1ß expression as a potential biomarker of a limited response to adjuvant platinum-based chemotherapy after complete resection of pulmonary adenocarcinoma. This finding has the potential to inform adjuvant treatment decisions.

[Histopathological research laboratories in translational research : Conception and integration into the infrastructure of pathological institutes]. / Histopathologische Forschungslabors in der translationalen Forschung : Konzeption sowie Integration in die Infrastruktur pathologischer Institute.

A systematic review of histopathology from experimental animal systems is an essential part of up-to-date biomedical research. Pathologists at university hospitals are especially and increasingly challenged by these specialized and time-consuming duties. This article presents and analyzes a new laboratory structure of comparative experimental pathology-jointly lead by veterinary and human pathologists-which might solve this problem. The focus is on the establishment and full integration of this laboratory structure into a local, regional, and nationwide biomedical research cluster. A detailed comparison with an established structure of routine histopathology laboratories discusses merits and benefits as well as disadvantages.

[Spindle-cell osteosclerotic bone lesion with MDM2 amplification]. / Spindelzellige osteosklerotische Knochenläsion mit MDM2-Amplifikation.

This case report presents an osteosclerotic bone lesion in a 49-year-old man with MDM2 amplification. The final diagnosis shows metastasis to the bones from stomach cancer. In primary bone tumours, the MDM2 amplifications observed have been described for many other tumour entities as well, and therefore do not exclude bone metastasis from a carcinoma.

Sphere-enhanced microwave ablation (sMWA) versus bland microwave ablation (bMWA): technical parameters, specific CT 3D rendering and histopathology.

PURPOSE: This study was designed to compare technical parameters during ablation as well as CT 3D rendering and histopathology of the ablation zone between sphere-enhanced microwave ablation (sMWA) and bland microwave ablation (bMWA). METHODS: In six sheep-livers, 18 microwave ablations were performed with identical system presets (power output: 80 W, ablation time: 120 s). In three sheep, transarterial embolisation (TAE) was performed immediately before microwave ablation using spheres (diameter: 40 ± 10 µm) (sMWA). In the other three sheep, microwave ablation was performed without spheres embolisation (bMWA). Contrast-enhanced CT, sacrifice, and liver harvest followed immediately after microwave ablation. Study goals included technical parameters during ablation (resulting power output, ablation time), geometry of the ablation zone applying specific CT 3D rendering with a software prototype (short axis of the ablation zone, volume of the largest aligned ablation sphere within the ablation zone), and histopathology (hematoxylin-eosin, Masson Goldner and TUNEL). RESULTS: Resulting power output/ablation times were 78.7 ± 1.0 W/120 ± 0.0 s for bMWA and 78.4 ± 1.0 W/120 ± 0.0 s for sMWA (n.s., respectively). Short axis/volume were 23.7 ± 3.7 mm/7.0 ± 2.4 cm(3) for bMWA and 29.1 ± 3.4 mm/11.5 ± 3.9 cm(3) for sMWA (P < 0.01, respectively). Histopathology confirmed the signs of coagulation necrosis as well as early and irreversible cell death for bMWA and sMWA. For sMWA, spheres were detected within, at the rim, and outside of the ablation zone without conspicuous features. CONCLUSIONS: Specific CT 3D rendering identifies a larger ablation zone for sMWA compared with bMWA. The histopathological signs and the detectable amount of cell death are comparable for both groups. When comparing sMWA with bMWA, TAE has no effect on the technical parameters during ablation.

[Severe bilateral keratomalacia]. / Schwere bilaterale Keratomalazie.

In contrast to developing countries, xerophthalmia is rather rare in developed countries. Malnutrition (e.g. in mentally deficient or psychiatric patients), chronic liver diseases (e.g. due to alcoholism), or bowel surgery can be reasons for vitamin A deficiency in developed countries. The prodromal stage of hypovitaminosis A is characterized by nyctalopia, which often manifests subclinically. Longer lasting and severe cases of vitamin A deficiency may be complicated by the occurrence of keratinizing metaplasia in the cornea and conjunctiva, xerosis, keratomalacia or blindness.

[Frozen section diagnostics in visceral surgery. Liver, bile ducts and pancreas]. / Schnellschnittdiagnostik in der Viszeralchirurgie : Leber, Gallenwege und Pankreas.

Intraoperative examination of specimens from the liver, bile ducts, gallbladder and pancreas are widely used in routine fresh frozen section diagnostics. The main clinical requests focus on diagnosis of masses of unknown dignity as well as evaluation of surgical margins in oncological resections. In addition, assessment of organ quality for transplantation is also often required.

Super-micro-bland particle embolization combined with RF-ablation: angiographic, macroscopic and microscopic features in porcine kidneys.

PURPOSE: To describe angiographic, macroscopic and microscopic features of super-micro-bland particle embolization in combination with RF-ablation in kidneys. Thereby, a special focus was given on the impact of the sequence of the different procedural steps. MATERIALS AND METHODS: In ten pigs, super-micro-bland particle embolization combined with RF-ablation was carried out. Super-micro-bland embolization was performed with spherical particles of very small size and tight calibration (40 ± 10 µm). In the left kidneys, RF-ablations were performed before embolization (I). In the right kidneys, RF-ablations were performed after embolization (II). The animals were killed three hours after the procedures. Angiographic (e.g. vessel architecture), macroscopic (e.g. long and short axes of the RF-ablations) and microscopic (e.g. particle distribution) study goals were defined. RESULTS: Angiography detected almost no vessels in the center of the RF-ablations in I. In II, angiography could not define the RF-ablations. Macroscopy detected significantly larger long and short axes of the RF-ablations in II compared to I (52.2 ± 3.2 mm vs. 45.3 ± 6.9 mm [P<0.05] and 25.1 ± 3.5mm vs. 20.0 ± 1.9 mm [P<0.01], respectively). Microscopy detected irregular particle distribution at the rim of the RF-ablations in I. In II, microscopy detected homogeneous particle distribution at the rim of the RF-ablations. Microscopy detected no particles in the center of the RF-ablations in I and II. CONCLUSION: The sequence of the different procedural steps of super-micro-bland particle embolization combined with RF-ablation impacts angiographic, macroscopic and microscopic features in kidneys in the acute setting.

Microwave ablation of porcine kidneys in vivo: effect of two different ablation modes ("temperature control" and "power control") on procedural outcome.

PURPOSE: This study was designed to analyze the effect of two different ablation modes ("temperature control" and "power control") of a microwave system on procedural outcome in porcine kidneys in vivo. METHODS: A commercially available microwave system (Avecure Microwave Generator; MedWaves, San Diego, CA) was used. The system offers the possibility to ablate with two different ablation modes: temperature control and power control. Thirty-two microwave ablations were performed in 16 kidneys of 8 pigs. In each animal, one kidney was ablated twice by applying temperature control (ablation duration set point at 60 s, ablation temperature set point at 96°C, automatic power set point; group I). The other kidney was ablated twice by applying power control (ablation duration set point at 60 s, ablation temperature set point at 96°C, ablation power set point at 24 W; group II). Procedural outcome was analyzed: (1) technical success (e.g., system failures, duration of the ablation cycle), and (2) ablation geometry (e.g., long axis diameter, short axis diameter, and circularity). RESULTS: System failures occurred in 0% in group I and 13% in group II. Duration of the ablation cycle was 60±0 s in group I and 102±21 s in group II. Long axis diameter was 20.3±4.6 mm in group I and 19.8±3.5 mm in group II (not significant (NS)). Short axis diameter was 10.3±2 mm in group I and 10.5±2.4 mm in group II (NS). Circularity was 0.5±0.1 in group I and 0.5±0.1 in group II (NS). CONCLUSIONS: Microwave ablations performed with temperature control showed fewer system failures and were finished faster. Both ablation modes demonstrated no significant differences with respect to ablation geometry.

Renal artery embolization combined with radiofrequency ablation in a porcine kidney model: effect of small and narrowly calibrated microparticles as embolization material on coagulation diameter, volume, and shape.

The purpose of this study was to evaluate the effect of renal artery embolization with small and narrowly calibrated microparticles on the coagulation diameter, volume, and shape of radiofrequency ablations (RFAs) in porcine kidneys. Forty-eight RFAs were performed in 24 kidneys of 12 pigs. In 6 animals, bilateral renal artery embolization was performed with small and narrowly calibrated microparticles. Upper and lower kidney poles were ablated with identical system parameters. Applying three-dimensional segmentation software, RFAs were segmented on registered 2 mm-thin macroscopic slices. Length, depth, width, volume_segmented, and volume_calculated were determined to describe the size of the RFAs. To evaluate the shape of the RFAs, depth-to-width ratio (perfect symmetry-to-lesion length was indicated by a ratio of 1), sphericity ratio (perfect sphere was indicated by a sphericity ratio of 1), eccentricity (perfect sphere was indicated by an eccentricity of 0), and circularity (perfect circle was indicated by a circularity of 1) were determined. Embolized compared with nonembolized RFAs showed significantly greater depth (23.4 ± 3.6 vs. 17.2 ± 1.8 mm; p < 0.001) and width (20.1 ± 2.9 vs. 12.6 ± 3.7 mm; p < 0.001); significantly larger volume_segmented (8.6 ± 3.2 vs. 3.0 ± 0.7 ml; p < 0.001) and volume_calculated (8.4 ± 3.0 ml vs. 3.3 ± 1.1 ml; p < 0.001); significantly lower depth-to-width (1.17 ± 0.10 vs. 1.48 ± 0.44; p < 0.05), sphericity (1.55 ± 0.44 vs. 1.96 ± 0.43; p < 0.01), and eccentricity (0.84 ± 0.61 vs. 1.73 ± 0.91; p < 0.01) ratios; and significantly greater circularity (0.62 ± 0.14 vs. 0.45 ± 0.16; p < 0.01). Renal artery embolization with small and narrowly calibrated microparticles affected the coagulation diameter, volume, and shape of RFAs in porcine kidneys. Embolized RFAs were significantly larger and more spherical compared with nonembolized RFAs.

Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse.

BACKGROUND: ALCAM (activated leucocyte cell adhesion molecule, synonym CD166) is a cell adhesion molecule, which belongs to the Ig superfamily. Disruption of the ALCAM-mediated adhesiveness by proteolytic sheddases such as ADAM17 has been suggested to have a relevant impact on tumour invasion. Although the expression of ALCAM is a valuable prognostic and predictive marker in several types of epithelial tumours, its role as a prognostic marker in pancreatic cancer has not yet been reported. METHODS: In this study, paraffin-embedded samples of 97 patients with pancreatic cancer undergoing potentially curative resection were immunostained against ALCAM, ADAM17 and CK19. Expression of ALCAM and ADAM17 was semiquantitatively evaluated and correlated to clinical and histopathological parameters. RESULTS: We could show that in normal pancreatic tissue, ALCAM is predominantly expressed at the cellular membrane, whereas in pancreatic tumour cells, it is mainly localised in the cytoplasm. In addition, univariate and multivariate analyses show that increased expression of ALCAM is an adverse prognostic factor for recurrence-free and overall survival. Overexpression of ADAM17 in pancreatic cancer, however, failed to be a significant prognostic marker and was not coexpressed with ALCAM. CONCLUSIONS: Our findings support the hypothesis that the disruption of ALCAM-mediated adhesiveness is a relevant step in pancreatic cancer progression. Moreover, ALCAM overexpression is a relevant independent prognostic marker for poor survival and early tumour relapse in pancreatic cancer.

[Virtual microscopy in pathology teaching and postgraduate training (continuing education)]. / Virtuelle Mikroskopie in Lehre und Ausbildung in der Pathologie.

As with conventional microscopy, virtual microscopy permits histological tissue sections to be viewed on a computer screen with a free choice of viewing areas and a wide range of magnifications. This, combined with the possibility of linking virtual microscopy to E-Learning courses, make virtual microscopy an ideal tool for teaching and postgraduate training in pathology. Uses of virtual microscopy in pathology teaching include blended learning with the presentation of digital teaching slides in the internet parallel to presentation in the histology lab, extending student access to histology slides beyond the lab. Other uses are student self-learning in the Internet, as well as the presentation of virtual slides in the classroom with or without replacing real microscopes. Successful integration of virtual microscopy depends on its embedding in the virtual classroom and the creation of interactive E-learning content. Applications derived from this include the use of virtual microscopy in video clips, podcasts, SCORM modules and the presentation of virtual microscopy using interactive whiteboards in the classroom.