Influence of change in surgical practice for benign thyroid disease on postsurgical outcome-Single-center experience in 1400 patients.

PURPOSE: To evaluate the rate of surgical complications during the change from subtotal resection to hemithyroidectomy or thyroidectomy over a period of 17 years. METHODS: All operations for benign goiter at our hospital were analyzed for the periods 1996-2002 (Group 1) and 2003-2012 (Group 2). The groups were compared for recurrent laryngeal nerve damage, hypocalcemia, and other surgical complications directly postoperatively. RESULTS: In total, 1462 patients were operated on for goiter between 1996 and 2012. There were 1219 patients who underwent a primary thyroid operation, whereas 50 patients had surgery for recurrence. Postoperative histology revealed thyroid cancer in 193 patients (13.2%). In Group 1, 42.7% of all operated lobes were performed as lobectomies and 57.3% as subtotal resections; in Group 2, 74.4% were performed as lobectomies and 25.6% as subtotal resections. No differences were found for reduced vocal cord function (2.4% vs. 1.9%, p = 0.746) and recurrent laryngeal nerve paralysis in the postoperative laryngoscopy (2.9% vs. 1.8%, p = 0.675). Postoperative hypoparathyroidism was detected in 13.66% in Group 1 and in 19.80% in Group 2 after bilateral resections (p = 0.037). There was no difference in the rate of reoperations for cancer between both groups (43.4% vs. 52.1%, p = 0.182). CONCLUSION: Surgical practice changed from subtotal to lobectomies for benign goiter over a period of 17 years without change in laryngeal nerve damage but with increasing rates of postoperative hypocalcemia.

Determination of the electrical conductivity of human liver metastases: impact on therapy planning in the radiofrequency ablation of liver tumors.

Background Radiofrequency ablation is used to induce thermal necrosis in the treatment of liver metastases. The specific electrical conductivity of a liver metastasis has a distinct influence on the heat formation and resulting tumor ablation within the tissue. Purpose To examine the electrical conductivity σ of human colorectal liver metastases and of tumor-free liver tissue in surgical specimens. Material and Methods Surgical specimens from patients with resectable colorectal liver metastases were used for measurements (size of metastases <30 mm). A four-needle measuring probe was used to determine the electrical conductivity σ of human colorectal liver metastasis (n = 8) and tumor-free liver tissue (n = 5) in a total of five patients. All measurements were performed at 470 kHz, which is the relevant frequency for radiofrequency ablation. The tissue temperature was also measured. Hepatic resections were performed in accordance with common surgical standards. Measurements were performed in the operating theater immediately after resection. Results The median electrical conductivity σ was 0.57 S/m in human colorectal liver metastases at a median temperature of 35.1℃ and 0.35 S/m in tumor-free liver tissue at a median temperature of 34.9℃. The electrical conductivity was significantly higher in tumor tissue than in tumor-free liver tissue ( P = 0.005). There were no differences in tissue temperature between the two groups ( P = 0.883). Conclusion The electrical conductivity is significantly higher in human colorectal liver metastases than in tumor-free liver tissue at a frequency of 470 kHz.

Comparison of bipolar radiofrequency ablation zones in an in vivo porcine model: Correlation of histology and gross pathological findings.

BACKGROUND: Continuing research ex vivo and in vivo with animal models is performed to advance the oncological safety of radiofrequency ablation (RFA) of liver tumors. In these experiments, frequently imaging modalities (e.g. MRI or CT) or macro-morphological measurements are used to determine the full extent of the different ablation zones inside of RFA lesions. However, no systematic study has been performed so far, which verified the accuracy of the macro-morphological findings. Therefore, the present study aimed to correlate histological and gross pathological findings of bipolar radiofrequency ablation zones of porcine livers with regard to cell viability in vivo. METHODS: Bipolar RFA was performed in the liver of anaesthetized female domestic pigs under CT-guidance using an internally cooled 20 mm RFA applicator. Afterwards RFA cross sections of the liver were made in a perpendicular orientation to the applicator. Ablation zones were initially documented by photography and thereafter prepared for histological analysis. Latter was based on HE-staining and NADH-diaphorase cell viability staining. Micro- and macro-morphological sections were digitally analyzed along the cross-section area for statistical correlation. RESULTS: Three different RF ablation zones could be differentiated. A central zone showing no cell viability (white zone) was surrounded by a red zone. The red zone could be divided into an inner zone of viable and non-viable cells (red zone 1), followed by a zone of edema with mostly viable cells (red zone 2).Micro- and macro-morphological data showed a strong correlation for the white zone (r = 0.95, p < 0.01), the red zone 1 (r = 0.85, p < 0.01), and the red zone 2 (r = 0.89, p < 0.01). CONCLUSION: White zone and red zone could clearly be distinguished in gross pathology and histology after bipolar RFA of porcine liver tissue in vivo. The red zone could be differentiated into an inner zone of viable and non-viable cells and an outer zone with high cell viability and intercellular edema. A strong correlation of micro- and macro-morphology could be shown for all three ablation zones. With this knowledge, gross pathological examination can be used as a reliable indicator of lethally damaged tissue in bipolar RFA of in vivo porcine liver.

Minimal vascular flows cause strong heat sink effects in hepatic radiofrequency ablation ex vivo.

BACKGROUND: The present paper aims to assess the lower threshold of vascular flow rate on the heat sink effect in bipolar radiofrequency ablation (RFA) ex vivo. METHODS: Glass tubes (vessels) of 3.4 mm inner diameter were introduced in parallel to bipolar RFA applicators into porcine liver ex vivo. Vessels were perfused with flow rates of 0 to 1,500 ml/min. RFA (30 W power, 15 kJ energy input) was carried out at room temperature and 37°C. Heat sink effects were assessed in RFA cross sections by the decrease in ablation radius, area and by a high-resolution sector planimetry. RESULTS: Flow rates of 1 ml/min already caused a significant cooling effect (P ≤ 0.001). The heat sink effect reached a maximum at 10 ml/min (18.4 mm/s) and remained stable for flow rates up to 1,500 ml/min. CONCLUSIONS: Minimal vascular flows of ≥1 ml/min cause a significant heat sink effect in hepatic RFA ex vivo. A lower limit for volumetric flow rate was not found. The maximum of the heat sink effect was reached at a flow rate of 10 ml/min and remained stable for flow rates up to 1,500 ml/min. Hepatic inflow occlusion should be considered in RFA close to hepatic vessels.

Measuring and optimizing results in multipolar RFA: Techniques and early findings in an experimental setting.

Radiofrequency ablation (RFA) has shown to be a reasonable alternative for the treatment of hepatic tumors and metastases although multiple limitations remain. Cooling effects due to larger vessels can prevent complete coverage and may lead to early tumor relapse. This preliminary in vivo pig study combines the use of multipolar RFA with three applicators (six electrodes) and interrupted liver perfusion using Pringle's maneuver to overcome the most serious limitations. Furthermore, immediate detection of incomplete RFA is important to revise ablation. We used contrast enhanced computed tomography (CECT) to evaluate post ablation results in comparison to macroscopic images in healthy pig liver. We found significantly (p = 0.001) larger ablation zones and no affection by larger vessels with interrupted liver perfusion. This allows effective RFA for larger tumors. Immediate postinterventional CECT provided comparable results (r = 0.985) to macroscopic evaluation.

Vagus-preserving technique during minimally invasive esophagectomy: the effects on cardiac parameters in a swine model.

BACKGROUND: Cardiac complications are an important cause of morbidity and mortality observed after esophageal resections. We examined whether an high intrathoracic vagotomy during abdominothoracic esophagectomy would have an effect on intraoperative and early postoperative cardiac function in the setting of a minimally invasive resection. Two hypotheses were generated for this study: (1) Vagotomy would cause cardiac changes, and (2) vagus-preserving esophagectomy would prevent cardiac problems during resection and in the early postoperative phase. METHODS AND RESULTS: Thirty male pigs were operated on while cardiac parameters (heart rate [HR], cardiac index [CI], preload recruitable stroke work [PRSW], contractility speed [dp/dtmax], relaxation speed [dp/dtmin], and relaxation time [tau]) were monitored using a conductance catheter and the thermodilution method. Animals were randomized into 4 groups (each n = 7): (1) control, thoracoscopy only, (2) thoracoscopy with vagotomy, (3) esophageal resection with vagotomy, and (4) esophageal resection with vagus nerve preservation. To evaluate the first hypothesis, we compared groups 1 and 2; to evaluate the second hypothesis, we compared groups 3 and 4. HR, CI, PRSW, dp/dtmax, and tau were different in the 2 groups without resection (area under the curve; each P < .05). Vagotomy with esophagectomy resulted in nonsignificant differences between groups 3 and 4. The requirement for metoprolol administration to avoid severe tachycardia was greater in the groups that underwent vagotomy (P < .05; Fisher's exact test). CONCLUSION: An high intrathoracic vagotomy results in loss of vagal tone and a greater rate of tachycardia during thoracoscopy and esophagectomy. There were no differences, however, in cardiac dynamics between the esophagectomy groups. Thus, vagal injury is not the sole reason for cardiac dysfunction after esophagectomy.

Complications after end-to-end vs. side-to-side anastomosis in ileocecal Crohn's disease--early postoperative results from a randomized controlled multi-center trial (ISRCTN-45665492).

BACKGROUND: Recurrent Crohn's disease activity at the site of anastomosis after ileocecal resection is of great surgical importance. This prospective randomized multi-center trial with an estimated case number of 224 patients was initially planned to investigate whether stapled side-to-side anastomosis, compared to hand-sewn end-to-end anastomosis, results in a decreased recurrence of Crohn's disease following ileocolic resection (primary endpoint). The secondary endpoint was to focus on the early postoperative results comparing both surgical methods. The study was terminated early due to insufficient patient recruitment and because another large study investigated the same question, while our trial was ongoing. METHODS AND STUDY DESIGN: Patients with stenosing ileitis terminalis in Crohn's disease who underwent an ileocolic resection were randomized to side-to-side or end-to-end anastomosis. Due to its early discontinuation, our study only investigated the secondary endpoints, the early postoperative results (complications: bleeding, wound infection, anastomotic leakage, first postoperative stool, duration of hospital stay). RESULTS: From February 2006 until June 2010, 67 patients were enrolled in nine participating centers. The two treatment groups were comparable to their demographic and pre-operative data. BMI and Crohn's Disease Activity Index were 22.2 (± 4.47) and 200.5 (± 73.66), respectively, in the side-to-side group compared with 23.3 (± 4.99) and 219.6 (± 89.03) in the end-to-end group. The duration of surgery was 126.7 (± 42.8) min in the side-to-side anastomosis group and 137.4 (± 51.9) min in the end-to-end anastomosis group. Two patients in the end-to-end anastomosis group developed an anastomotic leakage (6.5%). Impaired wound healing was found in 13.9% of the side-to-side anastomosis group, while 6.5% of the end-to-end anastomosis group developed this complication. The duration of hospital stay was comparable in both groups with 9.9 (± 3.93) and 10.4 (± 3.26) days, respectively. CONCLUSIONS: Because of the early discontinuation of the study, it is not possible to provide a statement about the perianastomotic recurrence rates regarding the primary endpoint. With regard to the early postoperative outcome, we observed no difference between the two types of anastomosis.

Effectiveness of various thermal ablation techniques for the treatment of nodular thyroid disease--comparison of laser-induced thermotherapy and bipolar radiofrequency ablation.

Alternative minimally invasive treatment options such as radiofrequency ablation (RFA) or laser-induced thermotherapy (LITT) are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. So far, studies have not been able to show a secure advantage for neither LITT nor RFA. The aim of this study was to compare the two ablation procedures in terms of their effectiveness. Thermal lesions were induced in porcine thyroid glands either by LITT or bipolar RFA ex vivo (n = 110 each) and in vivo (n = 10 each) using power settings between 10 and 20 W. Temperature spread during application was documented in 5- and 10-mm distance of the applicator. Postinterventional lesion diameters were measured and lesion size was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed in vivo. Lesion volumes induced by LITT ranged between 0.74 ± 0.18 cm(3) (10 W) and 3.80 ± 0.41 cm(3) (20 W) with a maximum of 5.13 ± 0.16 cm(3) at 18 W. The inducible lesion volumes by RFA were between 2.43 ± 0.68 cm(3) (10 W) and 0.91 ± 0.71 cm(3) (20 W) with a maximum of 2.80 ± 0.85 cm(3) at 14 W. The maximum temperatures were 112.9 ± 9.2°C (LITT) and 61.6 ± 13.9°C (RFA) at a distance of 5 mm and 73.2 ± 6.7°C (LITT) and 53.5 ± 8.6°C (RFA) at a distance of 10 mm. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage both for LITT and RFA. This study is the first to compare the effectiveness of laser-induced thermotherapy and radiofrequency ablation of thyroid tissue. LITT as well as RFA are suitable for singular thyroid nodules and induces reproducible clinically relevant lesions in an appropriate application time. The maximum inducible lesion volumes by LITT are significantly larger than by RFA with the devices used herein.

In vivo validation of a therapy planning system for laser-induced thermotherapy (LITT) of liver malignancies.

PURPOSE: In situ ablation is increasingly being used for the treatment of liver malignancies. The application of these techniques is limited by the lack of a precise prediction of the destruction volume. This holds especially true in anatomically difficult situations, such as metastases in the vicinity of larger liver vessels. We developed a three-dimensional (3D) planning system for laser-induced thermotherapy (LITT) of liver tumors. The aim of the study was to validate the system for calculation of the destruction volume. METHODS: LITT (28 W, 20 min) was performed in close contact to major hepatic vessels in six pigs. After explantation of the liver, the coagulation area was documented. The liver and its vascular structures were segmented from a pre-interventional CT scan. Therapy planning was carried out including the cooling effect of adjacent liver vessels. The lesions in vivo and the simulated lesions were compared with a morphometric analysis. RESULTS: The volume of lesions in vivo was 6,568.3 ± 3,245.9 mm(3), which was not different to the simulation result of 6,935.2 ± 2,538.5 mm(3) (P = 0.937). The morphometric analysis showed a sensitivity of the system of 0.896 ± 0.093 (correct prediction of destructed tissue). The specificity was 0.858 ± 0.090 (correct prediction of vital tissue). CONCLUSIONS: A 3D computer planning system for the prediction of thermal lesions in LITT was developed. The calculation of the directional cooling effect of intrahepatic vessels is possible for the first time. The morphometric analysis showed a good correlation under clinical conditions. The pre-therapeutic calculation of the ablation zone might be a valuable tool for procedure planning.

Bipolar radiofrequency ablation for nodular thyroid disease--ex vivo and in vivo evaluation of a dose-response relationship.

BACKGROUND: The prevalence of thyroid nodules ranges between 2% and 60% depending on the population studied. However, minimally invasive procedures like radiofrequency ablation (rfA) are increasingly used to treat tumors of parenchymatous organs, and seem to be suitable for singular thyroid nodules as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose-response relationship for rfA of thyroid nodules. MATERIAL AND METHODS: Thermal lesions were induced in healthy porcine thyroid glands ex vivo (n=110) and in vivo (n=10) using a bipolar radiofrequency system; rf was applied in a power range of 10-20 watts. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The transversal and axial lesion diameters were measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. RESULTS: The inducible lesion volumes were between 0.91±0.71 cm(3) at 20W and 2.80±0.85 cm(3) at 14W. The maximum temperatures after rf ablation were between 44.0±9.7°C and 61.6±13.9°C at a distance of 5 mm and between 30.0±8.6°C and 53.5±8.6°C at a distance of 10 mm from the applicator. The histochemical analysis demonstrates a complete loss of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. CONCLUSION: This study is the first to demonstrate a dose-response relationship for rfA of thyroid tissue. rfA is suitable for singular thyroid nodules and induces reproducible, clinically relevant lesions with irreversible cell damage in an appropriate application time.

Impact of sleep deprivation on medium-term psychomotor and cognitive performance of surgeons: prospective cross-over study with a virtual surgery simulator and psychometric tests.

BACKGROUND: Despite recent work hour restrictions, 24-hour calls remain an important part of patient care. The aim of this study was to assess the impact of 24-hour night calls on the psychomotor and cognitive skills of surgeons with a virtual surgery simulator (VSS) and psychometric tests. We hypothesized that sleep loss impairs surgical skills and concentration performance. METHODS: Seventeen surgery residents (test group) and 13 medical students (reference group) performed a 5-day training program on the VSS. The test group was then assessed during a night call on 4 test points (8 am and 4 pm on the on-call day, 8 am on the postcall day, and 8 am on the recovery day) to assess the effects of sleep loss on these surgery residents. The reference group performed the same tests but without a night call. RESULTS: The training resulted in a homogenous performance level for both groups. The average time for the test group was 26 minutes. The analysis between rested and sleep-deprived participants (6.5 +/- 0.9 vs 2.9 +/- 1.4 hours of night sleep) in the on-call part showed no performance differences. No impairment was found for the VSS and the cognitive tests within the test group between the start of the working day and the start of the postcall day after the night of relative sleep loss. The subgroup analysis showed no significant differences regarding the amount of night sleep and laparoscopic experience. CONCLUSION: No performance impairment was found for surgeons with a VSS and standardized cognitive tests after a night of relative sleep loss. Although there is no doubt that sleep deprivation ultimately impairs human functioning, typical surgical skills do not necessarily deteriorate with a limited amount of sleep loss under clinical conditions.

Determination of the temperature-dependent electric conductivity of liver tissue ex vivo and in vivo: Importance for therapy planning for the radiofrequency ablation of liver tumours.

INTRODUCTION: Knowledge about the changes in the electric conductivity during the coagulation process of radiofrequency ablation of the liver is a prerequisite for the predictability of produceable thermonecrosis in the liver. MATERIALS AND METHODS: Continuous measurements of the electric conductivity sigma in ex vivo porcine liver (n = 25) were done during the coagulation and cooling process at the temperature range of the radiofrequency ablation at a frequency of 470 kHz relevant for the radiofrequency ablation. Measurements of the electric conductivity were performed in both perfused porcine liver (n = 3) and a human surgical specimen from a colorectal liver metastasis. RESULTS: At a body temperature of 37 degrees C, conductance sigma was 0.41 siemens per metre (0.32 S/m; 0.52 S/m). Conductance sigma increased continuously and uniformly at a temperature of 77 degrees C. Maximum conductance sigma with 0.79 S/m (0.7 S/m; 0.87 S/m) was reached at 80 degrees C. A continuous reduction of conductance was observed during the cooling phase. At 37 degrees C, the specific conductance sigma in the healthy perfused porcine liver was 0.52 S/m, 0.55 S/m and 0.57 S/m (mean 0.55 S/m). The electric conductivity of the human colorectal liver metastasis was clearly higher. CONCLUSION: Changes in the specific conductivity during the coagulation and the cooling phase play an important role for the produceable size of a coagulation necrosis and necessitates an adaptation of the therapy parameters during radiofrequency ablation.

Ex vivo and in vivo evaluation of laser-induced thermotherapy for nodular thyroid disease.

BACKGROUND AND OBJECTIVE: The prevalence of thyroid nodules ranges between 2% and 60% depending on the population studied. However, minimally invasive procedures like laser-induced thermotherapy (LITT) are increasingly used to treat tumors of parenchymatous organs and seem to be suitable for singular thyroid nodules as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose-response relationship for LITT of thyroid nodules. MATERIALS AND METHODS: Thermal lesions were induced in healthy porcine thyroid glands ex vivo (n = 110) and in vivo (n = 10) using an Nd:YAG laser (1,064 nm). Laser energy was applied for 300 seconds in a power range of 10-20 W. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The lesions were longitudinally and transversally measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. RESULTS: The maximum inducible lesion volumes were between 0.74 +/- 0.18 cm(3) at a laser power of 10 W and 3.80 +/- 0.41 cm(3) at 20 W. The maximum temperatures after ablation were between 72.9 +/- 2.9 degrees C (10 W) and 112.9 +/- 9.2 degrees C (20 W) at a distance of 5 mm and between 49.5 +/- 2.2 degrees C (10 W) and 73.2 +/- 6.7 degrees C (20 W) at a distance of 10 mm from the applicator. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. CONCLUSIONS: This study is the first to demonstrate a dose-response relationship for LITT of thyroid tissue. LITT is suitable for singular thyroid nodules and induces reproducible clinically relevant lesions with irreversible cell damage in an appropriate application time.

Ex vivo evaluation of a bipolar application concept for radiofrequency ablation.

BACKGROUND: Bipolar radiofrequency ablation (RFA) can avoid complications such as thermal tissue damage, a possible consequence of monopolar RFA. However, basic studies about the dosage/effect relationship of bipolar systems are missing. This is systematic research on ex vivo beef livers to find which capacity parameters produce high energy in the tissue and achieve large lesion volumes. MATERIALS AND METHODS: The active lengths 20, 30 and 40 mm of a bipolar, internally cooled applicator were studied. The tissue was fresh ex vivo beef liver. Five measurements each for each active applicator with a power between 10 and 50 W were conducted. RESULTS: The best power for the 20 mm applicator was 15 W, since the highest achieved volume was 5,599+/-1,760 mm(3) and the highest amount of energy introduced to the tissue was 15+/-3 kJ. The best power for the 30 mm applicator was 20 W (volume 14,538+/-1,220 mm(3), energy 24+/-1 kJ). For the 40 mm applicator, the best power was 20 W, (volume 20,562+/-896 mm(3), energy 24+/-0 kJ). CONCLUSION: The results of this study help clinicians determine which active length is required for the applicator and which presetting should be selected to achieve a defined coagulation volume size.

Oral vs intravenous antibiotic prophylaxis in elective laparoscopic cholecystectomy: an exploratory trial.

INTRODUCTION: The application of perioperative intravenous antibiotic prophylaxis is often considered a necessary routine procedure. The only way to decide whether an antibiotic prophylaxis is necessary in elective gallbladder surgery is to conduct a multicenter randomized trial. The aim of this exploratory trial was to clarify whether an oral application of an antibiotic prophylaxis is a feasible and safe procedure compared to intravenous application. This exploratory trial was conducted prospective randomized, using a double-dummy design. The main target criteria included tolerance, adverse effects, pharmacokinetics, and cost of treatment. MATERIAL AND METHODS: Patients undergoing elective laparoscopic cholecystectomy were randomized double-blinded to an oral or intravenous application group of one antibiotic (gyrase inhibitor) using a double-dummy design. Exclusion criteria were acute cholecystitis, icterus, and choledocholithiasis. In addition to a tolerance analysis, the antibiotic concentration was determined in serum and bile by high-pressure liquid chromatography (HPLC). RESULTS: One hundred fifty one patients (75 patients with oral and 76 with intravenous prophylaxis) were evaluated for the tolerance analysis. Four patients (1 p.o., 3 i.v.) had adverse reactions to the antibiotics. The antibiotic serum concentration was 0.83 mg/l (p.o.) vs 8.44 mg/l (i.v.) before surgery, 0.81 mg/l (p.o.) vs 4.43 mg/l (i.v.) during surgery, and 0.69 mg/l (p.o.) vs 2.77 mg/l (i.v.) after surgery. The bile concentration was higher after oral administration with 9.20 mg/l than after intravenous application with 5.79 mg/l. The costs of medication for intravenous application were 20 times higher than those for oral application. CONCLUSION: The oral application of an antibiotic (gyrase inhibitor) was feasible and safe for perioperative antibiotic prophylaxis in laparoscopic cholecystectomy in this exploratory trial.

Bipolar radiofrequency ablation of liver metastases during laparotomy. First clinical experiences with a new multipolar ablation concept.

BACKGROUND AND OBJECTIVE: Radiofrequency ablation (RFA) is a promising method for local treatment of liver malignancies. Currently available systems for radiofrequency ablation use monopolar current, which carries the risk of uncontrolled electrical current paths, collateral damages and limited effectiveness. To overcome this problem, we used a newly developed internally cooled bipolar application system in patients with irresectable liver metastases undergoing laparotomy. The aim of this study was to clinically evaluate the safety, feasibility and effectiveness of this new system with a novel multipolar application concept. PATIENTS AND METHODS: Patients with a maximum of five liver metastases having a maximum diameter of 5 cm underwent laparotomy and abdominal exploration to control resectability. In cases of irresectability, RFA with the newly developed bipolar application system was performed. Treatment was carried out under ultrasound guidance. Depending on tumour size, shape and location, up to three applicators were simultaneously inserted in or closely around the tumour, never exceeding a maximum probe distance of 3 cm. In the multipolar ablation concept, the current runs alternating between all possible pairs of consecutively activated electrodes with up to 15 possible electrode combinations. Post-operative follow-up was evaluated by CT or MRI controls 24-48 h after RFA and every 3 months. RESULTS: In a total of six patients (four male, two female; 61-68 years), ten metastases (1.0-5.5 cm) were treated with a total of 14 RF applications. In four metastases three probes were used, and in another four and two metastases, two and one probes were used, respectively. During a mean ablation time of 18.8 min (10-31), a mean energy of 48.8 kJ (12-116) for each metastases was applied. No procedure-related complications occurred. The patients were released from the hospital between 7 and 12 days post-intervention (median 9 days). The post-interventional control showed complete tumour ablation in all cases. CONCLUSIONS: Bipolar radiofrequency using the novel multipolar ablation concept permits a safe and effective therapy for the induction of large volumes of coagulation in the local treatment of liver metastases.

Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.

Neuronal damage mediated by the TRAIL-system might be involved in the pathogenesis of neuroinflammatory diseases of the central nervous system. Here we used an investigator-independent approach to quantify TRAIL-mediated death of total CNS cells and neurons in a living human brain slice culture system, a model which is much closer to the in vivo situation than dissociated cell culture. We observed dose-dependent TRAIL-mediated death of both total human CNS cells and neurons, which was prevented by flupirtine-maleate, a centrally acting analgesic drug with proposed neuroprotective properties. Our data suggest flupirtine-maleate as an orally available neuroprotective approach in the course of neuroinflammation.