Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

Selective tissue elevation by pressure for endoscopic mucosal resection of colorectal adenoma: first clinical trial.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection of large lateral spreading tumors currently are technically limited by complications such as bleeding, perforation, and disturbed large procedural sites, leading to incomplete resection and secondary surgery. Further technical improvements are necessary. The authors previously demonstrated the effectiveness of a focused water jet for elevation of the lamina submucosa in animal studies. For the first time, the clinical application of selective tissue elevation by pressure (STEP) for the treatment of colorectal adenomas as a prospective single-arm human trial is presented. METHODS: This trial evaluated 59 patients who had primary colorectal adenomas with diameters exceeding 12 mm classified as 0-IIa or 0-IIb according to Paris classification. A submucosal cushion was created with a flexible water jet applicator using the Helix HydroJet. The adenoma was subsequently resected with a mucosal resection snare. All results were recorded. The resected specimens were assessed histologically. RESULTS: A total of 59 patients underwent resection of 70 lesions with a maximum diameter of 80 mm (mean, 27 mm). Submucosal elevation with the water jet dissector was possible in all cases and locations from the pectinate line to the ileocecal valve. Of the 70 lesions, 64 (91%) were resected completely in one session. Histologically, the resected specimens were found to be adenocarcinomas (n = 2, 3%), adenomas with high-grade intraepithelial neoplasia (n = 24, 34%), adenomas with low-grade intraepithelial neoplasia (n = 38, 54%), and hyperplastic polyps (n = 6, 9%). Hemostasis during the resection was necessary in 24 cases (34%). No perforation required surgical intervention. CONCLUSION: This first clinical trial to analyze STEP technique demonstrated that STEP used to elevate large mucosal lesions in any location is feasible and facilitates EMR for colorectal adenoma.

Resuscitation of warm ischaemia predamaged porcine kidneys by fibrinolytic preflush with streptokinase: reduction of animal experiments.

In order to reduce the number of animal experiments, the use of non-heart-beating donors (NHBDs) from a commercial abattoir has been proposed. Since the use of slaughterhouse organs is legally not defined as animal experiment, this would fulfil international standards as an alternative to animal experiments. The development of intravascular thrombosis after cardiac arrest negatively impacts organ preservation and thus viability during ischaemic storage and reperfusion. A fibrinolytic preflush with streptokinase might overcome these limitations. Therefore, the functional and histomorphological integrity of kidneys preserved immediately with intact circulation (control group A) and kidneys preserved after cardiac arrest with a 30 min period of warm ischaemia (WI) (group B) was compared with kidneys preflushed with 12.5 kU/L (group C) or 50 kU/L streptokinase (group D) after 30 min WI prior to preservation. We could demonstrate that kidneys preflushed with 12.5 kU/L streptokinase (group C) performed better than those without streptokinase pretreatment after WI (group B). Parameters like oxygen consumption, perfusion pressure, laboratory values, lactate dehydrogenase level and lipidperoxidation were closer to that of the control (group A) than in groups B and D. The higher streptokinase concentration of 50 kU/L (group D) resulted histologically in a more pronounced tissue damage and an attenuated renal function, indicating toxic effects. On the basis of our results we believe streptokinase preflushed slaughterhouse kidneys to be an adequate alternative to organs from laboratory animals with the potential to further reduce the number of animal experiments.

Cleavage of AML1/MTG8 by asymmetric hammerhead ribozymes.

The chromosomal translocation t(8;21) is one of the most frequent aberrations associated with acute myeloid leukaemia. It joins the 5' section of the AML1 gene with the almost complete open reading frame of MTG8 (ETO). The resulting fusion RNA represents a leukaemia-specific target for antisense/ribozyme inhibition. We tested several asymmetric hammerhead ribozymes targeted against the fusion site for their ability to cleave the AML1/MTG8 RNA at low magnesium concentrations. One ribozyme cleaves AML1/MTG8 RNA with high catalytic efficiency without binding or cleaving the wild-type AML1 transcript. The presence of cellular RNA does not affect the cleavage. Injection of AML1/MTG8 RNA and ribozyme RNA into Xenopus eggs or oocytes causes a specific reduction of AML1/MTG8 protein expression. Asymmetric anti-AML1/MTG8 ribozymes may be valuable modulators of AML1/MTG8 expression in leukaemic cells.