Markus Enderle

Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: A preliminary study

BACKGROUND AND STUDY AIMS Open, laparoscopic, or percutaneous radiofrequency (RF) ablation of the pancreas is still dangerous, whereas endoscopic ultrasound (EUS)-guided ablation might reduce risk because it is less invasive and provides real-time monitoring. We aimed to demonstrate the feasibility of transluminal RF ablation and to evaluate the efficacy and safety of a new flexible bipolar ablation probe combining RF and cryotechnology. METHODS 14 ablations were performed in 14 pigs. Energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) were standardized. Application time range was 120 - 900 seconds. Ablation area was measured by EUS immediately after ablation (area T0), and before euthanasia (area T1). Macroscopic findings (area T2) and histological findings after necropsy served as gold standard. The interval from application to euthanasia was either 1 or 2 weeks. RESULTS The correlation between EUS findings (area T1) and macroscopic appearance (area T2) was good ( R = 0.89). The correlation between the T2 ablation area and the application time showed a fitted ratio of 2.3 ( P < 0.0001) with a 1-week interval and 0.2 ( P = 0.01) with a 2-week interval. No pig died because of the procedure. Two pigs showed histochemical pancreatitis, which was clinically overt in one. Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. CONCLUSIONS Selective transluminal RF ablation of the pancreas under EUS control in a living pig model is feasible. The new flexible bipolar probe creates an ablation area with extent related to the duration of application, and with fewer complications than conventional RF ablation techniques.

A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia

Background For endoscopic resection of early GI neoplasia, endoscopic submucosal dissection (ESD) achieves higher rates of complete resection (R0) than endoscopic mucosal resection (EMR). However, ESD is technically more difficult and evidence from randomised trial is missing. Objective We compared the efficacy and safety of ESD and EMR in patients with neoplastic Barretts oesophagus (BO). Design BO patients with a focal lesion of high-grade intraepithelial neoplasia (HGIN) or early adenocarcinoma (EAC) ≤3 cm were randomised to either ESD or EMR. Primary outcome was R0 resection; secondary outcomes were complete remission from neoplasia, recurrences and adverse events (AEs). Results There were no significant differences in patient and lesion characteristics between the groups randomised to ESD (n=20) or EMR (n=20). Histology of the resected specimen showed HGIN or EAC in all but six cases. Although R0 resection defined as margins free of HGIN/EAC was achieved more frequently with ESD (10/17 vs 2/17, p=0.01), there was no difference in complete remission from neoplasia at 3 months (ESD 15/16 vs EMR 16/17, p=1.0). During a mean follow-up period of 23.1±6.4 months, recurrent EAC was observed in one case in the ESD group. Elective surgery was performed in four and three cases after ESD and EMR, respectively (p=1.0). Two severe AEs were recorded for ESD and none for EMR (p=0.49). Conclusions In terms of need for surgery, neoplasia remission and recurrence, ESD and EMR are both highly effective for endoscopic resection of early BO neoplasia. ESD achieves a higher R0 resection rate, but for most BO patients this bears little clinical relevance. ESD is, however, more time consuming and may cause severe AE. Trial registration number NCT1871636

Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer

BACKGROUND New therapies are needed for pancreatic cancer. OBJECTIVE To determine the feasibility and safety of a new endoscopic treatment. Secondary endpoints were to determine effects on tumor growth measured with CT scan and to find the overall survival. DESIGN A cohort study of patients with local progression of advanced pancreatic adenocarcinoma after neoadjuvant therapy. The cryotherm probe (CTP), a flexible bipolar device that combines radiofrequency with cryogenic cooling, was used under EUS guidance. SETTING San Raffaele Hospital, Milan, Italy; University Medical Center, Hamburg-Eppendorf, Germany. PATIENTS A total of 22 patients (male/female 11/11; mean age 61.9 years) were enrolled from September 2009 to May 2011. INTERVENTION Radiofrequency heating: 18 W; pressure for cooling: 650 psi (Pounds per Square Inch); application time: depending on tumor size. MAIN OUTCOME MEASUREMENTS Feasibility was evaluated during the procedure. A clinical and radiologic follow-up was planned. RESULTS The CTP was successfully applied in 16 patients (72.8%); in 6 it was not possible because of stiffness of the GI wall and of the tumor. Amylase arose in 3 of 16 patients; none had clinical signs of pancreatitis. Late complications arose in 4 cases: 3 were mostly related to tumor progression. Median postablation survival time was 6 months. A CT scan was performed in all patients, but only in 6 of 16 was it possible to clearly define the tumor margins after ablation. In these patients, the tumor appeared smaller compared with the initial mass (P = .07). LIMITATIONS Small sample of patients, difficulty of objectifying the size of the ablated zone by CT scan. CONCLUSION EUS-guided CTP ablation is feasible and safe. Further investigations are needed to demonstrate progression-free survival and local control.

Comparison of standard endoscopic submucosal dissection (ESD) versus an optimized ESD technique for the colon: an animal study.

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.

Endoscopic submucosal dissection of early gastric neoplasia with a water jet–assisted knife: a Western, single-center experience

BACKGROUND Endoscopic submucosal dissection (ESD) of early gastric neoplasia has not yet been established in Western countries because of a lack of data and the difficult, time-consuming, and hazardous nature of the method. Some of the technical limitations may be overcome by use of a water jet-assisted knife, which allows a combination of a high-pressure water jet and electrosurgical interventions. OBJECTIVE To evaluate the efficacy and safety of water jet-assisted ESD (WESD) with a water jet-assisted knife in selected patients with early gastric neoplasia. DESIGN Single-center, prospective study. PATIENTS This study involved 29 consecutive patients (13 female; median age 61 years; age range 35-93 years) with early gastric neoplasia that met the expanded criteria of the Japanese Gastric Cancer Association. Histology of biopsies had shown gastric adenocarcinoma in 21 cases, adenoma in 8 case, and suspicion of a GI stromal tumor in 1 case. The median maximal diameter of the lesions was 20 mm (range 10-40 mm). INTERVENTION All procedures were done with patients under sedation with propofol. The water jet-assisted knife was used for setting coagulation markers around the neoplastic lesions, then for circumferential incision and dissection in combination with repeated submucosal injection of saline solution with a water jet system. Bleeding was treated with diathermia by use of the water jet-assisted knife or hemostatic forceps in case of failure or larger vessels. Clips were used for closure of perforations. MAIN OUTCOME MEASUREMENTS Complete resection of neoplasia, procedure time, complication and recurrence rates. RESULTS According to endoscopic criteria, complete resection of the targeted area could be achieved in all cases, with an en bloc resection rate of 90%. The median procedure duration was 74 minutes (range 15-402 minutes). Exchange of the device was needed in only 10 cases because of severe bleeding from larger vessels, which could be managed by use of hemostatic forceps. The 30-day morbidity rate was 4 of 30 (13.8%) because of postprocedure pain in 3 cases and delayed bleeding in 1 case. A 93-year-old patient died the night after WESD without evidence of a procedure-related complication. Histology of the resected specimens showed adenocarcinoma in 20 cases, adenoma in 7, no neoplasia in 2, and a plasmacytoma in 1. Complete resection (R0) was histologically confirmed in 18 of 28 patients (64.3%) with resected neoplastic specimens. A horizontal or vertical neoplasia-free margin could not be confirmed in 9 cases and 1 case, respectively. Complete local remission of neoplasia was achieved in 25 of 28 patients (89.3%) who were followed over a median period of 22 months (range 6-44 months). In 1 patient, a metachronous gastric adenocarcinoma was identified 54 weeks after initial WESD. LIMITATIONS Noncontrolled study with a limited number of patients. CONCLUSION The use of a water jet-assisted knife simplifies ESD because exchange of devices is rarely needed. WESD promises to be effective and safe. The study demonstrates that the high rates of en bloc resection of early gastric neoplasia reported in Asia can be reproduced in Western referral centers. However, histology may not always confirm complete resection of horizontal tumor margins. In spite of the unfavorable histology results, the high rate of complete local remission of neoplasia promises that surgical treatment of early gastric neoplasia can be avoided in the majority of cases.

Prospective evaluation of a new high-power argon plasma coagulation system (hp-APC) in therapeutic gastrointestinal endoscopy

Objective. The aim of this study was to prospectively evaluate a new high-power argon plasma coagulation system (hp-APC) in therapeutic gastrointestinal (GI) endoscopy. Material and methods. From February to June 2005, 216 patients (167 M (77.3%), mean age 66 years) underwent treatment with hp-APC in a total of 275 sessions. Main indications were additive ablation therapy in Barretts esophagus, palliative treatment of esophageal cancer, gastric polyps/carcinomas, angiodysplasias, Zenkers diverticula, and duodenal adenomas. The new hp-APC device (VIO 300 D with APC 2) was used (15–120 W) in upper GI endoscopy, push-enteroscopy, and double-balloon enteroscopy. Results. The mean number of treatment sessions required was 1.7 (1–5). For palliative tumor ablation in the esophagus, the number of sessions was 2.3 (1–5). Minor complications (pain, dysphagia, neuromuscular irritation, asymptomatic gas accumulation in the intestinal wall) were observed in 29/216 patients (13.4%). Major complications (perforation, stenosis occured) in 2 patients (0.9%). Conclusions. Hp-APC appears to be safe and effective in the treatment of various GI condition using different types of endoscopes including double-balloon enteroscopy. Because of the low number of treatment sessions required, hp-APC could be used as an alternative to Nd:YAG laser treatment in tumor debulking.

Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study

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: 675 psi) 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.

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.

Second-generation argon plasma coagulation : Two-center experience with 600 patients

Background and Aim:  Second‐generation argon plasma coagulation (APC; APC 2/VIO APC) with its modes ‘forced’, ‘pulsed’, and ‘precise’ is a further development of the ICC/APC 300 system (first‐generation APC). Until now, only limited data has existed on the use of APC 2.

Submucosal cushioning with water jet before endoscopic mucosal resection : Which fluids are effective?

BackgroundSeveral new techniques have recently been described that allow the endoscopic mucosal resection even of broad-based flat lesions in the gastrointestinal tract. The technique recently described by us of using a water jet dissector (Helix HydroJet®) for a selective deposition of liquid in the submucosal lamina has now been combined with different substances, and their effects have been compared.Material and MethodsGastroscopies were carried out in 8 pigs under intubation anesthesia, and 2 submucosal cushions each were created in the stomach using one out of 4 test substances (gelatin, glucose 50, hydroxyethyl starch [HES] 10%, dextran 40), as well as one cushion of isotonic saline solution placed in each area via the Helix HydroJet®. The height of the submucosal cushions was intermittently measured over a period of 40 or 20 min, respectively, by miniprobe endosonography. In 7 of the animals the stomach was subsequently subjected to mucosal resection. The specimens and the gastric wall were histologically assessed to evaluate the localization of the liquid cushion and the effect on adjacent layers of the gastric wall.ResultsAll test substances produced strictly selective liquid cushions in the submucosa. With HES 10% and dextran the maximum height of the cushions initially increased and then decreased during the further course to an average of 90% of the initial height within 40 min. Isotonic saline solution showed the most rapid decrease in height (72% after 20 min). The histological assessment confirmed the selective nature of the liquid deposit in the submucosa.DiscussionPlasma expanders produced cushions that initially increased in height but then remained constant for a longer period than cushions produced using glucose 50, gelatin, or isotonic saline solution. The combination of transmucosal jet application for elevation of the mucosa with plasma expanders is therefore an interesting approach to optimize endoscopic mucosal resections.