Prospective controlled animal study on biopsy sampling with new flexible cryoprobes versus forceps: evaluation of biopsy size, histological quality and bleeding risk.

BACKGROUND: Cryoextraction is a procedure used for the recanalization of obstructed airways caused by visible exophytic endobronchial tumor. Biopsy samples obtained by this technique have been shown to be useful for histological assessment. OBJECTIVES: The aim of the present animal study was to systematically evaluate biopsy size, histological quality and bleeding risk after cryobiopsy with new, flexible cryoprobes in comparison with forceps biopsy, serving as the gold standard. METHODS: Biopsies were obtained from anesthetized pigs with the flexible bronchoscopy technique, and evaluated histologically with respect to their size and quality. Bleeding frequency, bleeding duration and histological changes in the biopsy bed were also recorded. RESULTS: Cryobiopsies were significantly larger than forceps biopsies. The size of cryobiopsies was dependent on the freezing time. The histological quality of the cryobiopsy specimenswas not impaired by the freezing process, whereas forceps biopsies showed typical crush artifacts. Despite the larger defects left in the tracheobronchial system after cryobiopsy, bleeding frequency and duration were not higher compared to forceps biopsy. CONCLUSIONS: Since cryobiopsy sampling is not associated with a higher bleeding risk compared with forceps biopsy, this new biopsy technique offers--in addition to a good specimen quality--a safe and valuable tool with the potential of improving the outcome of diagnostic endoscopy.

Evaluation of the hemostatic and coagulation effects of AUTO CUT and DRY CUT using a computer-controlled cutting system.

OBJECTIVES: To evaluate a newly developed computer-controlled cutting system for the generation of standardized resections and to systematically compare the hemostatic properties and tissue effect of 2 cutting modes, namely, AUTO CUT and DRY CUT used in urologic procedures. METHODS: An isolated perfused kidney model was used to assess blood loss and coagulation depth after resection of tissue specimens of standardized geometry, size, and cutting velocity with a resection loop. Three different effect settings (E1, E3, and E6; 200 W) of the electrosurgical modes AUTO CUT and DRY CUT were compared. Blood loss was determined semiquantitatively by weighing a swab before and after placing it onto the resection area. The coagulation depth was estimated microscopically on cross sections. RESULTS: The computer-controlled cutting system creates resections of standardized geometry and size with a high reproducibility. An effect level-dependent increase in hemostasis and coagulation depth could be demonstrated with the cutting modes DRY CUT and AUTO CUT using this computer-controlled cutting system. The hemostatic effect with DRY CUT is significantly more pronounced than with AUTO CUT (E1, E3: P < .0001, E6: P = .004), and the coagulation is significantly deeper (E1, E3, E6: P < .0001). CONCLUSIONS: The computer-controlled cutting system creating reproducible resections in combination with the isolated perfused kidney model offers the possibility to systematically investigate bleeding rate and coagulation depth. The stronger hemostatic properties of the DRY CUT mode are more favorable for urologic interventions requiring a higher hemostatic effect than the AUTO CUT mode.

Investigation of the thermal tissue effects of the argon plasma coagulation modes "pulsed" and "precise" on the porcine esophagus, ex vivo and in vivo.

BACKGROUND: Argon plasma coagulation (APC) is a monopolar, noncontact, thermal procedure that is widely used in therapeutic endoscopy. Systematic investigations of the tissue damage ex vivo and in vivo with the new, second-generation APC modes are lacking. OBJECTIVE: The aim of this study is to compare the tissue effects of the pulsed effect 2 and precise APC modes. DESIGN AND SETTING: Ex vivo and in vivo animal model. SUBJECTS: This study involved 3 explanted porcine esophagi and 8 pigs under general anesthesia. INTERVENTION: APC application on 3 explanted esophagi and during esophagoscopy. MAIN OUTCOME MEASUREMENTS: The tissue effect was subjected to histological and statistical investigation. RESULTS: In vivo, a well known type of superficial tissue damage (type A) of the tunica mucosa and a new injury pattern (type B) limited to the tunica muscularis, were found. Ex vivo, only type A injuries were seen. Thermal injury of the tunica muscularis was significantly lower with precise APC compared with pulsed APC in vivo. The pulsed effect 2 shows a positive correlation between the penetration depth and the power (r = 0.38, P < .0002) or application time for the highest power setting used (40 W, r = 0.77, P < .0001). This correlation could not be detected with precise APC because of its very superficial tissue effect. LIMITATIONS: This was an animal study. The distance of the APC probe to the esophagus may have varied between applications in vivo. CONCLUSION: Thermal damage by APC of the esophageal tunica muscularis seems to be underestimated ex vivo. The extent of tissue injury was significantly lower with precise APC than with pulsed APC, indicating that precise APC may be suitable for the treatment of particularly thermosensitive, thin-wall anatomy.

Intracerebral and intrathecal infusion of the TGF-beta 2-specific antisense phosphorothioate oligonucleotide AP 12009 in rabbits and primates: toxicology and safety.

Here, we provide first evidence that long-term continuous infusion of highly purified antisense phosphorothioate oligodeoxynucleotides (S-ODN) into brain parenchyma is well tolerated and thus highly suitable for in vivo application. AP 12009 is an S-ODN for the therapy of malignant glioma. It is directed against human transforming growth factor-beta (TGF-beta2) mRNA. In the clinical setting, AP 12009 is administered intratumorally by continuous infusion directly into the brain tumor. In view of this clinical application, the focus of our data is on local toxicology studies in rabbits and monkeys to evaluate the safety of AP 12009. AP 12009 was administered either by intrathecal bolus injection into the subarachnoidal space of the lumbar region of both cynomolgus monkeys and rabbits or by continuous intraparenchymatous infusion directly into the brain tissue of rabbits. Intrathecal bolus administration of 0.1 ml of 500 microM AP 12009 showed neither clinical signs of toxicity nor macroscopically visible or histomorphologic changes. After a 7-day intraparenchymatous continuous infusion of 500 microM AP 12009 at 1 microl/h in rabbits, there was no evidence of toxicity except for local mild to moderate lymphocytic leptomeningoencephalitis. Additionally, AP 12009 showed good tolerability in safety pharmacology as well as in acute toxicity studies and 4-week subchronic toxicity studies in mice, rats, and monkeys. This favorable safety profile proves the suitability of AP 12009 for local administration in brain tumor patients from the point of view of toxicology.