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This prospective, randomized, controlled, single-blinded study investigates the peritoneal adhesion formation of HybridAPC (waterjet elevation of the peritoneum with subsequent argon plasma coagulation) versus only waterjet (elevation with the same instrument, but without subsequent argon plasma coagulation) in a rat model (24 female Wistar rats). Bilateral lesions were created on the abdominal wall with HybridAPC on one sidewall and waterjet elevation on the other sidewall of the peritoneum in a standard fashion. After 10 days, the rats were euthanized to evaluate the peritoneal trauma sites. Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. Incidence of adhesion formation was 2.3% for HybridAPC; no adhesions occurred for peritoneal elevation with saline (p = 1.00). Histologic evaluation revealed no acute inflammation in both groups. An overall moderate degree of granulation tissue formation and myonecrosis was observed in the HybridAPC group, whereas no chronic inflammation and myonecrosis occurred after elevation without thermal ablation (p

Objective To investigate peritoneal adhesion formation of monopolar contact coagulation (MCC) versus noncontact argon plasma coagulation (APC) in a rat model. Design Randomized, controlled, single-blinded animal study. Setting University laboratory. Animal(s) Sixteen female Wistar rats. Intervention(s) Bilateral lesions were created on the abdominal wall with MCC and APC in a standard fashion. After 10 days, the rats were euthanized to evaluate the peritoneal trauma sites. Main Outcome Measure(s) Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. Result(s) Average energy intake was 99.5 ± 7.39 J for APC and 95.7 ± 9.62 J for monopolar contact coagulation. Incidence of adhesion formation was 50.0% for noncontact APC and 85.4% for MCC. MCC induced significantly more vascular adhesions. Histological evaluation revealed no significant differences regarding average depth of lesions induced by APC and MCC. Both groups showed almost identical morphology of necrosis and granulation tissue formation. Conclusion(s) This study compares for the first time adhesion formation of MCC versus noncontact APC in a rat model. With a similar energy intake, contact coagulation induced a significantly higher rate of adhesion formation. APC-induced adhesions were significantly less vascularized compared with MCC adhesions. Besides the thermal effects of both coagulation methods, the direct mechanical contact of the MCC electrode with the highly sensitive peritoneum is thus determined to be a pivotal additional stimulus for adhesion formation.

The aim of this study is to systematically investigate under standardized experimental conditions the effects of instrument contamination and wear on the quality of bipolar vessel sealing (BVS) achieved using a reusable instrument.The study was designed as a prospective, randomized, and controlled in vitro study and conducted in an academic research environment. Reusable bipolar coagulation forceps (BiClamp® 200 C, ERBE Elektromedizin) were used to apply sealing pressures of 300-1,100 mN/mm(2) to 239 renal arteries from commercially slaughtered female pigs (Swabian-Hall Swine). Forceps jaws were coated with porcine blood, blood and collagen, or blood, collagen, and fat to simulate instrument contamination with biological material during surgery. Clinical wear was mimicked by sandpaper abrasion. The main outcome measures were seal success (resistance to 250 mmHg intraluminal pressure for 2 min) and seal stability (burst pressure).Sealing pressure had a significant impact, with 800 mN/mm(2) producing the best sealing results. Seal success increased with total energy applied to the tissue, a higher maximum temperature, and longer coagulation as indicated by desiccation time. Experimental contamination had no significant impact on seal success and only a limited effect on seal stability. Similarly, abrasive wear also had no significant effect on either seal quality or seal strength.The impact of bipolar forceps contamination and wear on seal success and quality was negligible in our in vitro model. To achieve high-quality seals, it is essential to use adequate sealing pressures. Our findings could have direct implications for the design and clinical handling of BVS instruments.

Electrosurgical vessel sealing produces seals that can withstand intraluminal pressures well above the physiological range. In many cases it is more efficient than other methods, such as sutures, hemoclips, and ultrasonic coagulation devices, but bears lateral thermal damage as a side effect. The overall aim of this study was to compare the thermal lateral damage (TL) in vivo versus ex vivo using two different bipolar vessel sealing instruments in an epigastric vein animal model.A total of 96 thermofusions of bilateral epigastric veins were carried out in a prospective, randomized and controlled study design. The laparoscopic BiClamp (type Maryland) and the bipolar clamp Kelly model Clermont-Ferrand were used for ex vivo versus in vivo investigation. After exposure of the two bilateral epigastric veins the proximal sections were bilaterally coagulated in vivo with the two different instruments. For ex vivo coagulation, the uncoagulated section of the vein was removed and coagulated ex vivo. The TL was investigated by infrared measurement, light microscope and histological analysis.The comparison of the extent of coagulation damage between ex vivo and in vivo coagulation did not differ significantly: no differences between in vivo and ex vivo measurements were found for the Kelly clamp. In the case of the Maryland clamp only a significant greater TL in vivo was shown for stereomicroscopic measurements.Ex vivo TL results are comparable with in vivo results. This might prospectively spare in vivo studies with respect to TL and might facilitate the design of future experiments for the development of bipolar electrocoagulation devices.

Background and study aims Endoscopic submucosal dissection (ESD) is a promising therapeutic technique for en bloc resection of large gastrointestinal tumors. However, this technique has disadvantages such as a long intervention time, complexity of the procedure, and a higher rate of complications. The primary aims of the study were to show the feasibility of ESD in the pig colon and to evaluate a new ESD technique comprising the use of a newly developed hybrid knife for colon procedures combining RF (radiofrequency) application and a distance-dependent water-jet application. Materials and methods ESD was conducted at three different locations in the colon according to the computer-generated randomization list, using either the standard technique (injection needle, flex knife, and hook knife as therapeutic instruments and DRY CUT and SWIFT COAG as RF currents), or the new ESD technique (hybrid knife as the therapeutic instrument combined with the new cutting mode ENDO CUT D) in 12 healthy pigs. The perforation and bleeding rates were documented and statistically analyzed. Intervention time, resected specimen size, thermal and mechanical damage of the resection bed, and number of instrument changes required were also recorded. Results A total of 16 and 18 ESD procedures were performed by the standard and new techniques, respectively. Complete en bloc resection was achieved in all cases. The standard ESD technique showed a perforation rate of 25 % (4/16) whereas the new ESD technique resulted in a 5.5 % perforation rate (1/18) ( P = 0.035); bleeding rates were similar. The new ESD technique was significantly safer compared with the standard ESD technique. Conclusions A new ESD technique for the successful en bloc resection in thin-walled regions such as pig colon has been described. This procedure is as effective as the standard procedure but is easier to handle and significantly safer.

BACKGROUND AND STUDY AIMS: In a previous study, a new flexible bipolar hybrid cryotherm probe was applied with success to the pancreas of a living pig. Here we evaluated feasibility, efficacy, and safety of its application to the porcine liver and spleen. MATERIAL AND METHODS: Ten applications to the liver and nine to the spleen were performed in 19 pigs. Power input (16 - 18 W) and simultaneous cooling with CO 2 (standardized pressure: 675psi) as the cryogenic agent were investigated. Application time varied from 120 seconds to 900 seconds. The ablation area was measured by endoscopic ultrasound (EUS) after ablation (T0), and before euthanasia (T1). Gross pathology (T2) and histology after necropsy represented the gold standard. The interval from treatment to euthanasia was 1 or 2 weeks. RESULTS: For both organs the correlation between EUS and gross pathology was good (correlation coefficient R liver = 0.71; R spleen = 0.73). EUS tended to overestimate the area of the ablated zone. EUS observed a time-dependent ablation area: we demonstrated a positive trend of lesion size (T1) over time in liver tissue (R = 0.51 ( P = 0.1)). In the spleen we found a clear correlation of lesion area T2 and application time (R = 0.75, P = 0.01). There were no complications. CONCLUSIONS: Selective EUS-guided transgastric cryotherm ablation of the liver and spleen in a pig model is feasible and safe. The new bipolar probe creates a time-dependent ablation area without any complications, and opens a field of new potential indications of RF-ablative therapies.

Background. This is a prospective, randomized, controlled, single-blinded study to investigate peritoneal adhesion formation of standard argon plasma coagulation (APC) versus aerosol plasma coagulation in a rat model. Methods. Bilateral lesions were created on the abdominal wall of 16 female Wistar rats with standard and aerosol plasma coagulation APC energy in a standard fashion. After 10 days, the rats were killed humanely to evaluate the peritoneal trauma sites. Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. Results. Average energy intake was 97.7 ± 3.1 J for APC and 93.8 ± 4.2 J for aerosol plasma coagulation. Incidence of adhesion formation was 74.2% for standard APC and 16.1% for aerosol plasma coagulation ( P < .0001). Standard APC mainly results in dense adhesions. Histological evaluation revealed no significant difference with regard to the average depth of lesions created by APC and aerosol plasma coagulation ( P = 0.21) at day 10; both groups showed an identical morphology of necrosis and granulation tissue formation. Conclusions. This study compares adhesion formation of standard APC versus aerosol plasma coagulation in a rat model. Standard APC produced significantly more adhesions. Aerosol plasma coagulation creates fewer adhesions, which are of lower grade, which seems to be achieved mainly by improved peritoneal conditioning in this animal model.

Purpose To test the efficacy of internally CO 2 -cooled radiofrequency (RF) ablation in vivo and to compare its effectiveness to a standard water-cooled RF probe and to a gas-cooled microwave (MW) device. Method and materials 49 ablations were performed on 15 pigs under general anesthesia using 15G monopolar CO 2 -cooled RF applicators, 17G monopolar water-cooled RF applicators and 15G internally CO 2 -cooled microwave devices. The power of the MW device was 45 W, the current of the gas-cooled RF device was 1200–1600 mA. At the water-cooled RF probe, maximum power of 200 W was set. Ablation time was 15 min. The short and long axes of the ablation zone were measured. Histological analyses and NADH-staining were performed. The diameters and the ablation volumes were compared using an analysis of variance. Results No spots of untreated tissue were observed close to the cooled needle track in any of the ablation zones. The largest short axis diameter was 3.4 ± 0.5 cm achieved with the gas-cooled monopolar applicator. With the water-cooled applicators, short axis diameter was significantly smaller, reaching 2.5 ± 0.4 cm. Gas-cooled MW probes achieved 2.9 ± 1.0 cm. The largest ablation volume was 31.5 ± 12 ml (gas-cooled RF), and the smallest was 12.7 ± 4 ml (water-cooled RF). Short/long axis ratio was largest for gas-cooled RF probes with 0.73 ± 0.08 versus 0.64 ± 0.04 for the water-cooled probes and 0.49 ± 0.25 for the microwave applicator. Conclusion Gas-cooled RF applicators may have a higher potential for effective destruction of liver lesions than comparable water-cooled RF systems, and may be an alternative to standard RF and MW ablation devices.

17beta-Estradiol (E2) is implicated in the genesis and the development of estrogen-dependent diseases. Its concentration is mainly regulated by 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which catalyzes the reduction of the weak estrogen estrone (E1) to the highly potent E2. This enzyme is thus an important target for the treatment of hormone-dependent diseases. Thirty-seven novel substituted 6-phenyl-2-naphthols were synthesized and evaluated for 17beta-HSD1 inhibition, selectivity toward 17beta-HSD2 and the estrogen receptors (ERs) alpha and beta, and pharmacokinetic properties. SAR studies revealed that the compounds most likely bind according to binding mode B to the active site, i.e., the 6-phenyl moiety mimicking the steroidal A-ring. While substitution at the phenyl ring decreased activity, introduction of substituents at the naphthol moiety led to highly active compounds, especially in position 1. The 1-phenyl compound 32 showed a very high inhibitory activity for 17beta-HSD1 (IC50 = 20 nM) and good selectivity (17beta-HSD2 and ERs) and pharmacokinetic properties after peroral application.

Human 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyzes the reduction of the weak estrogen estrone (E1) to the highly potent estradiol (E2). This reaction takes place in the target cell where the estrogenic effect is exerted via the estrogen receptor (ER). Estrogens, especially E2, are known to stimulate the proliferation of hormone-dependent diseases. 17beta-HSD1 is overexpressed in many breast tumors. Thus, it is an attractive target for the treatment of these diseases. Ligand- and structure-based drug design led to the discovery of novel, selective, and potent inhibitors of 17beta-HSD1. Phenyl-substituted bicyclic moieties were synthesized as mimics of the steroidal substrate. Computational methods were used to obtain insight into their interactions with the protein. Compound 5 turned out to be a highly potent inhibitor of 17beta-HSD1 showing good selectivity (17beta-HSD2, ERalpha and beta), medium cell permeation, reasonable metabolic stability (rat hepatic microsomes), and little inhibition of hepatic CYP enzymes.

Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5alpha-reductase isozymes 1 and 2. The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC(50) values in the nanomolar range. The phenylacetic acid derivatives were more potent than the analogous benzoic acids. Bromination in the 4-position of the phenoxy moiety led to the strongest inhibitor in this class (12; IC(50) = 5 nM), which was equipotent to finasteride. Since oral absorption is essential for a potential drug, 12 was further examined. In the parallel artificial membrane permeation assay (PAMPA) it turned out to be a good permeator, whereas it was a medium permeator in Caco2 cells. After oral administration (40 mg/kg) to rats a high bioavailability and a biological half-life of 5.5 h were observed, making it a promising candidate for clinical evaluation.