A novel flexible cryoprobe for EUS-guided pancreatic biopsies.

BACKGROUND: EUS-guided FNA (EUS-FNA) is an established technique for the cytologic diagnosis of pancreatic disease. Attempts to obtain adequate histologic specimens have yielded variable and mostly insufficient results. OBJECTIVE: To evaluate the safety, feasibility, and quality of histologic biopsy specimens obtained by using a new cryobiopsy probe and to compare them with standard EUS-FNA and (laparoscopic) trucut biopsy specimens of pancreatic tissue. DESIGN: Animal non-survival study. INTERVENTION: Eighty-four pancreatic biopsy specimens (12 per group) were obtained in 4 anesthetized pigs by using one of the following the 18-gauge flexible cryoprobe; a conventional, 19-gauge, EUS-FNA needle; or a rigid, trucut biopsy device (18 gauge). The latter, used in laparoscopic surgery, was considered as the criterion standard for obtaining histology specimens. MAIN OUTCOME MEASUREMENTS: Specimens were evaluated for artifacts and specimen quality by a blinded pathologist who used a 7-point Likert scale to assess histologic adequacy. Biopsy size and bleeding time after biopsy also were recorded. RESULTS: The new cryoprobe was equivalent to the rigid, trucut needle and superior (P < .001) to the conventional 19-gauge FNA needles with respect to artifacts, quality of the specimen, biopsy specimen size, and bleeding. LIMITATIONS: Animal model. CONCLUSION: EUS-guided cryobiopsy was associated with better specimen quality for histologic analysis and a shorter bleeding time compared with a conventional 19-gauge FNA needle in the animal model. It is a promising new technique for histologic examination of pancreatic tissue.

A prospective, randomized clinical comparison between UltraCision and the novel sealing and cutting device BiCision in patients with laparoscopic supracervical hysterectomy.

BACKGROUND: Various surgical procedures for hysterectomy exist; with laparoscopic supracervical hysterectomy (LASH) becoming an established option in recent years. Therefore, energy-based technologies for rapid tissue sealing and cutting are in the focus of surgeons. The aim of this trial was to prove or disprove investigated noninferiority of the novel device BiCision in comparison to the widely used UltraCision in a routine procedure ( www.clinicaltrials.gov ; study identifier NCT01806012). METHODS: Thirty LASH procedures were performed with UltraCision and BiCision after randomization of the preparation sides. The primary end point was the resection time per side and instrument. The instruments were also compared concerning blood loss and coagulation and cutting qualities as well as postoperative complications. The patients were followed for 3 months. RESULTS: Mean preparation time per side was 8.8 ± 1.8 min for BiCision and 8.3 ± 1.9 min for UltraCision (p = 0.31), which was not significantly different. Both instruments achieved complete transection without the need of additional cutting attempts. BiCision was significantly superior regarding the number of coagulations for complete hemostasis before and after the removal of the uterine corpus (before: 6.9 ± 4.8 for BiCision and 8.6 ± 4.1 for UltraCision, p = 0.047; after: 5.4 ± 1.2 for BiCision and 8.6 ± 3.2 for UltraCision, p < 0.0001) and intraoperative blood loss (score 1.07 ± 0.25 for BiCision vs. 1.63 ± 0.49 for UltraCision, p < 0.0001). Tissue sticking to the instrument occurred less often on the BiCision side (score 0.14 ± 0.35 for BiCision vs. 0.60 ± 0.81 for UltraCision, p = 0.015). BiCision showed a significantly better fixation of the tissue (grip score 0.23 ± 0.43 for BiCision vs. 1.00 ± 0.74 for UltraCision, p < 0.0001). No intraoperative or postoperative complications were seen for both instruments. CONCLUSIONS: The efficacy and quality of vessel sealing and cutting with BiCision is not inferior to the UltraCision device. Resection time was comparable, and complete hemostasis could be achieved faster in a clinical setting. Therefore, BiCision is at least as reliable as UltraCision for laparoscopic indications.

Efficacy and safety of the novel electrosurgical vessel sealing and cutting instrument BiCision®.

BACKGROUND: The use of energy-based tissue-sealing and cutting instruments is becoming more and more popular in visceral, urological, and gynecological surgery. For their safe and efficacious use in clinical practice, such instruments have to reliably seal vessels with a minimal sealing failure rate, cause minimal thermal damage to adjacent tissue, and have good cutting qualities. METHODS: The efficacy and safety of the novel energy-based instrument for dissection, hemostasis and cutting (BiCision(®), ERBE) was compared to a commercially available device (EnSeal(®), Ethicon Endo-Surgery). We investigated vessel-sealing reliability (success rate), sealing quality and sealing time, lateral thermal damage cutting quality, tissue sticking to the instrument, burst pressure and delayed complications in an acute and chronic pig model after splenectomy, small bowel resection, nephrectomy, salpingo-oophorectomy, and sealing of peripheral vessels. RESULTS: For all parameters investigated, BiCision(®) was at least equivalent to EnSeal(®). BiCision(®) was even superior to EnSeal(®) with respect to the burst pressure in arteries (p = 0.044) and veins (p = 0.023) and the cut quality in all locations (arteries, p = 0.0009; veins, p = 0.043). The course of the 7-day chronic study was uneventful except for one animal that developed an intestinal obstruction. None of the animals showed any signs of postoperative bleeding. On second-look laparotomy at day 7, macroscopic inspection of the sealed tissue and vessels did not show any signs of complications or evidence that bleeding had occurred. Histologically, the integrity of vessel wall fusion, thermal alterations, and inflammatory reactions were comparable, confirming substantial equivalence. CONCLUSION: We demonstrated that the efficacy and quality of vessel sealing with BiCision(®) is at least equivalent to those of EnSeal(®) for vessel diameters up to 7 mm. Since EnSeal(®) has already been shown to be safe in clinical practice, BiCision(®) should be as reliable as EnSeal(®) under clinical conditions.

The contribution of endobronchial ultrasound-guided forceps biopsy in the diagnostic workup of unexplained mediastinal and hilar lymphadenopathy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) provides material for the cytological diagnostic workup. To improve the evaluation of unexplained intrathoracic lymphadenopathy, the availability of material for histological evaluation would be desirable. For this purpose, the technique of endobronchial ultrasound-guided mediastinal forceps biopsy (EBUS-guided forceps biopsy) is a potentially good candidate. The aim of the present study was, using simple methodology, to establish the additional diagnostic yield provided by supplemental EBUS-guided forceps biopsy in comparison with EBUS-TBNA alone. METHODS: The data of 50 consecutive patients with mediastinal, lobar, and hilar space-consuming lesions were analyzed. In all patients, immediately following EBUS-TBNA with a 22-gauge needle, a 21-gauge forceps was introduced through the opening created in the bronchial wall and an EBUS-guided forceps biopsy performed. The improvement in the diagnostic yield was determined. The diagnostic yield of the EBUS-guided forceps biopsy in relation to the size of the biopsy specimen and that of the EBUS-TBNA in relation to the cell-block technique were determined. RESULTS: Combining the techniques increased the diagnostic sensitivity of the EBUS-TBNA from 50.0 to 82.0%. EBUS-guided forceps biopsies measuring ≥ 3 mm enabled a specific diagnosis to be established more often than did forceps biopsies <3 mm (90.9% vs. 57.1%). A cell block was prepared in 29 patients. In this case, EBUS-TBNA provided a higher diagnostic yield (65.5% vs. 28.6%) compared to cytology alone. CONCLUSION: EBUS-guided forceps biopsy should be employed for the bronchoscopic diagnosis of intrathoracic lymphadenopathy of unknown etiology.

Efficiency and safety of bipolar vessel and tissue sealing in visceral surgery.

BACKGROUND: The aim of this study was to analyze the efficiency and safety of the bipolar tissue/vessel sealing and cutting device EnSeal(™) in comparison to the conventional clamp and ligation technique in visceral surgery. MATERIAL AND METHODS: In an acute animal model, a part of the small bowel, a part of the colon and the kidneys were resected either with the conventional clamp and ligation technique or with EnSeal(™). Operation time, blood loss and blood parameters as well as the lateral thermal spread were evaluated. RESULTS: Small bowel, colon and kidney resection time with the EnSeal(™) device was shorter compared to the conventional clamp and ligation technique (small bowel: EnSeal(™): 4.7 ± 1.0 min vs. con: 35.1 ± 2.3 min; colon: EnSeal(™): 7.0 ± 1.4 min vs. con: 16.3 ± 1.5 min, kidney: EnSeal(™): 5.7 ± 1.3 min vs. con: 16.7 ± 3.7 min, p < 0.05) and blood loss was significantly lower. Blood analysis demonstrated no differences in both groups. The lateral thermal spread was not more than 1 mm with EnSeal(™). CONCLUSION: The bipolar sealing in visceral surgery with EnSeal(™) can be performed more efficiently in a shorter time, with significantly less blood loss, minimal thermal damage and without changes of blood parameters, indicating biological safety and integrity.

Evaluation of the novel bipolar vessel sealing and cutting device BiCision® in a porcine model.

BACKGROUND: Energy-based technologies for tissue sealing and cutting are increasingly supplementing current standards used for haemostasis and dissection during laparoscopic surgery. For their safe and efficacious use in clinical practice, these instruments have to guarantee sufficient burst resistance and low thermal damage to adjacent tissue in combination with good cutting characteristics. MATERIAL AND METHODS: The novel laparoscopic, bipolar electrosurgical sealing and cutting instrument BiCision® was compared to a commercially available laparoscopic device (EnSeal(™)) on visceral and peripheral arteries and veins in an animal model. RESULTS: For all parameters investigated (burst pressure, cut quality, tissue adhering to the instrument, time needed to seal and cut the vessel and thermal damage), BiCision® was at least as good as EnSeal(™). Regarding the burst pressure, BiCision® was superior over EnSeal(™) in arteries: 600 mmHg (±478) versus 241 (±269) mmHg, respectively (p < 0.0001*). In veins, almost equivalent burst pressures of 155 ± 134 mmHg (BiCision®) and 173 ± 139 mmHg (EnSeal(™)) were obtained. CONCLUSION: BiCision® appeared to be as good as or even superior to EnSeal(™). Since EnSeal(™) has already been shown to be safe and has been successfully used in clinical practice, BiCision® is assumed to be as efficient and reliable as EnSeal(™) under pre-clinical conditions.

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.

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.

Experimental study on biopsy sampling using new flexible cryoprobes: influence of activation time, probe size, tissue consistency, and contact pressure of the probe on the size of the biopsy specimen.

Cryoextraction is a procedure for recanalization of obstructed airways caused by exophytic growing tumors. Biopsy samples obtained with this method can be used for histological diagnosis. The objective of this study was to evaluate the parameters influencing the size of cryobiopsies in an in vitro animal model. New flexible cryoprobes with different diameters were used to extract biopsies from lung tissue. These biopsies were compared with forceps biopsy (gold standard) in terms of the biopsy size. Tissue dependency of the biopsy size was analyzed by comparing biopsies taken from the lung, the liver, and gastric mucosa. The effect of contact pressure exerted by the tip of the cryoprobe on the tissue was analyzed on liver tissue separately. Biopsy size was estimated by measuring the weight and the diameter. Weight and diameter of cryobiopsies correlated positively with longer activation times and larger diameters of the cryoprobe. The weight of the biopsies was tissue dependent: lung < liver < stomach. Only little tissue dependency was found for the biopsy diameter. The biopsy size increased when the probe was pressed on the tissue during cooling. Cryobiopsies can be taken from different tissue types with flexible cryoprobes. The size of the samples depends on tissue type, probe diameter, application time, and pressure exerted by the probe on the tissue. Even the cryoprobe with the smallest diameter can provide larger biopsies than a forceps biopsy in lung. It can be expected that the same parameters influence the sample size of biopsies in vivo.

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.

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.