Evaluation of Electrochemotherapy with Bleomycin in the Treatment of Colorectal Hepatic Metastases in a Rat Model.

BACKGROUND: The available ablative procedures for the treatment of hepatic cancer have contraindications due to the heat-sink effect and the risk of thermal injuries. Electrochemotherapy (ECT) as a nonthermal approach may be utilized for the treatment of tumors adjacent to high-risk regions. We evaluated the effectiveness of ECT in a rat model. METHODS: WAG/Rij rats were randomized to four groups and underwent ECT, reversible electroporation (rEP), or intravenous injection of bleomycin (BLM) eight days after subcapsular hepatic tumor implantation. The fourth group served as Sham. Tumor volume and oxygenation were measured before and five days after the treatment using ultrasound and photoacoustic imaging; thereafter, liver and tumor tissue were additionally analysed by histology and immunohistochemistry. RESULTS: The ECT group showed a stronger reduction in tumor oxygenation compared to the rEP and BLM groups; moreover, ECT-treated tumors exhibited the lowest levels of hemoglobin concentration compared to the other groups. Histological analyses further revealed a significantly increased tumor necrosis of >85% and a reduced tumor vascularization in the ECT group compared to the rEP, BLM, and Sham groups. CONCLUSION: ECT is an effective approach for the treatment of hepatic tumors with necrosis rates >85% five days following treatment.

Thermoablation of thyroid nodules reveals excellent results with low morbidity.

BACKGROUND: Thermoablation is an attractive treatment of thyroid nodules for its minimal-invasiveness. It remains unclear whether results and morbidity meet the patients' expectations. OBJECTIVE: The aim of the presented study is to show data obtained after microwave thyroid ablation from a patients' perspective. METHODS: Indications and preoperative diagnosis were chosen according to international guidelines. Thermoablation was achieved using a CE certified microwave system. The procedures heeded the published recommendations of the European Federation of Societies for Ultrasound in Medicine and Biology. Follow-up included ultrasound, laboratory parameters and a standardized questionnaire. RESULTS: Thirty patients were enrolled into the study. All patients reported an improvement of complaints following the procedure. Scar formation occurred in 3 cases (10%) with 0.5 ± 1.3 mm length and 0.4 ± 1.0 mm width. No cosmetic, neurological, vocal or pharyngeal complication occurred. Energy required for non-functioning nodules (n= 15, 50%) was 2.56 ± 3.41 kJ/mL, for autonomous adenoma (n= 8, 27%) 0.96 kJ/mL (p< 0.05, t-test). CONCLUSION: The presented data summarize an initial experience in selected patients and resemble excellent patient reported outcome with minimal morbidity. These preliminary data indicate the majority of patients satisfied with the procedure. Further trials will be required to endorse these findings.

Advances in local ablation of malignant liver lesions.

Local ablation of liver tumors matured during the recent years and is now proven to be an effective tool in the treatment of malignant liver lesions. Advances focus on the improvement of local tumor control by technical innovations, individual selection of imaging modalities, more accurate needle placement and the free choice of access to the liver. Considering data found in the current literature for conventional local ablative treatment strategies, virtually no single technology is able to demonstrate an unequivocal superiority. Hints at better performance of microwave compared to radiofrequency ablation regarding local tumor control, duration of the procedure and potentially achievable larger size of ablation areas favour the comparably more recent treatment modality; image fusion enables more patients to undergo ultrasound guided local ablation; magnetic resonance guidance may improve primary success rates in selected patients; navigation and robotics accelerate the needle placement and reduces deviation of needle positions; laparoscopic thermoablation results in larger ablation areas and therefore hypothetically better local tumor control under acceptable complication rates, but seems to be limited to patients with no, mild or moderate adhesions following earlier surgical procedures. Apart from that, most techniques appear technically feasible, albeit demanding. Which technology will in the long run become accepted, is subject to future work.

Clinical application of modern ultrasound techniques after liver transplantation.

Liver transplantation has been established as a first-line therapy for a number of indications. Conventional ultrasound and contrast-enhanced ultrasound (CEUS) are methods of choice during the postoperative period as a safe and fast tool to detect potential complications and to enable early intervention if necessary. CEUS increases diagnostic quality and is an appropriate procedure for the examination of vessels and possibly bile ducts. This article presents the state of the art of ultrasound application during the early period after liver transplantation. It addresses common vascular complications and describes the identification of postoperative abnormal findings using ultrasound and CEUS.

Comprehensive complication index for NOTES procedures: results from a randomized controlled trial and comparison to published NOTES complication data.

OBJECTIVE: This investigation uses the comprehensive complication index (CCI) to compare complications after natural orifice transluminal endoscopic surgery (NOTES) procedures. BACKGROUND: NOTES procedures are developed to miniaturize surgical trauma. NOTES publications inconsistently report complications. The CCI improves reporting of complications. METHODS: The CCI is calculated using complication data from a single center, double blind, randomized controlled trial comparing transvaginal [transvaginal cholecystectomy (TVC), N = 41] and conventional laparoscopic cholecystectomy (CLC, N = 51). Complications are assessed using the classification of surgical complications (CSC). Two different scenarios are applied to the CSC for definition of complications with an emphasis on minor complications. CSC data are fed into the free online CCI-calculator. The CCIs from complication data from other NOTES reports are calculated accordingly and compared to our results. RESULTS: The CCI allows easy indexing of complications with or without a CSC table. For scenario I, the mean CCI of CLC versus TVC is 3.3 (± 6.3; SD) versus 3.5 (± 6.4; n.s.) and for scenario II it is 7.6 (± 6.4) versus 6.5 (± 7.0; n.s.). The difference of the mean between the two scenarios is highly significant (p < 0.000). The mean CCIs of both groups and scenarios are below the CCI of 8.7 for a grade I CSC complication. Similar calculation of CCIs from other NOTES publications yields mean CCIs below 8.7 for the surgical procedures reported. CONCLUSION: The CCI results in a single, easily comparable complication index for surgical procedures whereas the CSC yields tabular results. A significant difference in interpretation occurs with variation in definition of complications. Average CCIs below a value of 10 describe low complication rates. Authors need to describe their definition of complications if using the CSC and the CCI. More emphasis should be given to reporting of minor complications. The use of the CCI for NOTES procedures will enable international comparison.

Risk of local failure after ultrasound guided irreversible electroporation of malignant liver tumors.

INTRODUCTION: Irreversible electroporation (IRE) is considered superior to thermoablations for tumors in the vicinity of larger vessels and the liver hilum. We report on an initial clinical experience of IRE. MATERIALS AND METHODS: Indications included focal liver lesions <3 cm, irresectability due to contraindications and expected complications and/or irradicality following radiofrequency ablation (RFA). Ultrasound was chosen for guidance and needle placement. RESULTS: IRE was intended to perform in 14 patients with 1 procedure aborted due to technical failure. Among the 13 successfully treated were 7 percutaneous, 4 laparoscopic, and 2 open surgical procedures. The average age was 63 ± 10 years. Twelve solitary nodules and one bifocal disease were treated with an average size of 1.5 cm ± 0.5 cm. Median follow-up was 6 months. Three incomplete ablations account for 21% (3/14), 2 of them occurring in 2 metastases larger than 2 cm percutaneously treated with 5 needles instead of 4 used for smaller tumor sizes. CONCLUSION: IRE was introduced without difficulties into clinical practice. As a main obstacle emerged in visualization of the needles, computed tomography may offer advantages in the guidance of percutaneous IRE of liver metastases larger than 2 cm. Local failure occurred in 21%.

Contrast enhanced ultrasound cholangiography via T-tube following liver transplantation.

BACKGROUND: The objective was to evaluate contrast enhanced ultrasound (CEUS) based cholangiography compared to conventional radiography as a reference method in patients after liver transplantation. MATERIAL/METHODS: Contrast agents were administered through T-tubes, which were placed during the operation. Twelve patients with side-to-side choledocho-choledochostomy and standardized intraoperative T-tube placement were investigated on the 5th postoperative day (POD 5) with both techniques. All images were digitally acquired and assessed in consensus by two investigators regarding complete anatomic visualization, depiction of pathology (e.g. delayed contrast outflow, stenosis and leakage) and general image quality. RESULTS: CEUS cholangiography showed comparable results in the detection of biliary pathology and overall image quality. Regarding the visualization of the extrahepatic bile duct CEUS produced limited results in 6 patients. CONCLUSIONS: In conclusion, CEUS cholangiography via T-tube represents a potential bedside test for visualization of intrahepatic bile ducts of transplanted livers; its diagnostic value remains to be determined in further studies.

Laparoscopic radiofrequency ablation of liver tumors: comparison of MR guidance versus conventional laparoscopic ultrasound for needle positioning in a phantom model.

Laparoscopic radiofrequency ablation (LapRFA) is an established procedure for liver tumors in patients who are unsuitable for resection. A novel technique of magnetic resonance (MR) guided needle positioning during LapRFA was developed and compared to conventional ultrasound (US) guidance in a phantom model. MR-guided procedures were conducted in a 1.0 tesla high field open MR using an MR compatible endoscope and camera. The ultrasound-guided procedure was performed with a clinically established laparoscopy setup and a 2D laparoscopic US probe. During both techniques an identical monopolar non-ferromagnetic RFA needle and a silicon-based phantom model were applied. Finally needle positioning was performed by two surgeons and one interventionalist. Time to needle placement and number of trials were recorded and statistically analyzed. MR-guided needle positioning under laparoscopic control was technically feasible. Average time to correct needle placement was 2' 6″ in the LapUS group and 1' 54″ in the MR group. The number of trials was 3.2 in the LapUS group and 2.6 in the MR group. Image quality was assessed by all participants. MR images showed a better tissue to tumor contrast and allowed an improved orientation due to multiplanar visualization. MR-guided laparoscopic RFA is a promising technique offering multiplanar needle positioning with high soft tissue contrast with immediate therapy control. In a phantom model it showed comparable results regarding needle positioning to the established technique of laparoscopic US guidance.

Initial results of MR-guided liver resection in a high-field open MRI.

BACKGROUND: The goal of this study was to evaluate high-field open magnetic resonance imaging (MRI) for intraoperative real-time imaging during hand-assisted laparoscopic liver resection. MR guidance has several advantages compared to ultrasound and may represent a future technique for abdominal surgery. Various MRI-safe and -compatible instruments were developed, tested, and applied to realize minimally invasive liver surgery under MR guidance. As proof of the concept, liver resection was performed in a porcine model. METHODS: All procedures were conducted in a 1.0-T open MRI unit. Imaging quality and surgical results were documented during three cadaveric and two live animal procedures. A nonferromagnetic hand port was used for manual access and the liver tissue was dissected using a Nd:YAG laser. RESULTS: The intervention time ranged from 126 to 145 min, with a dissection time from 11 to 15 min. Both live animals survived the intervention with a blood loss of 250 and 170 ml and a specimen weight of 138 and 177 g. A dynamic T2W fast spin-echo sequence allowed real-time imaging (1.5 s/image) with good delineation of major and small hepatic vessels. The newly developed MR-compatible instruments and camera system caused only minor interferences and artifacts of the MR image. CONCLUSION: MR-guided liver resection is feasible and provides additional image information to the surgeon. We conclude that MR-guided laparoscopic liver resection improves the anatomical orientation and may increase the safety of future minimally invasive liver surgery.

Open surgical is superior to percutaneous access for radiofrequency ablation of hepatic metastases.

PURPOSE: This study was designed to determine the best approach to radiofrequency ablation (RFA) in the liver. METHODS: From a total of 41 procedures, 37 patients with 47 tumors were treated with RFA for metastatic disease. Indications included colorectal cancer (n=28, 68%), neuroendocrine tumors (n=2, 5%), gynecological primaries (n=4, 10%), pancreatic/duodenal cancer (n=2, 5%), and miscellaneous entities (n=5, 12%). Mean follow-up period was 18 (median, 18) months. All ways of approach to RFA were applied: percutaneous was chosen in 17 (41.5%), laparoscopic and hand-assisted laparoscopic in 5 (12.2%), and open surgical in 19 cases (46.3%), and in 10 cases, RFA was combined with hepatic resection. The average maximum tumor size was 2.3 (range, 0.8-6) cm, and the mean number of nodules treated per patient in a single session was 1.3 (range, 1-3). RESULTS: Overall survival was 59.5% at 2 years, recurrence-free 2-year survival was 12.6%, local tumor recurrence rate was 34%, and overall recurrence was 75.6%. Local tumor recurrence and disease-free survival were significantly improved in the open surgically treated patients compared with the percutaneous treatment group (15.8% [n=3] vs. 58.8% [n=10] and 11.5 vs. 7.9 months, p<0.01 [chi2 test] and p<0.05 [log-rank test], respectively). CONCLUSIONS: Open surgical approach is superior to percutaneous access for RFA in metastatic hepatic disease.

Radiofrequency ablation of liver tumors using a novel bipolar device.

PURPOSE: Radiofrequency ablation (RFA) is now an established tool for treating unresectable liver tumors. Monopolar RFA is currently the accepted standard. However, the variability of the ablation shape and size impedes their further advancement. For this study, we were interested in the evaluation of a new bipolar device for technical feasibility. PATIENTS AND METHODS: We have treated 6 patients [5 with hepatocellular carcinoma (HCC) one with metastatic disease] with a total of 7 tumors (6 HCCs, a solitary metastasis), using a new bipolar RFA device consisting of two separate needles, each with deployable electrodes. The treatment approaches included two percutaneous, three laparoscopic, and one open surgical. Average tumor size was 2.5 cm. Follow-up examinations were performed at intervals of 3 months and included computed tomography, (18)fluorodeoxyglucose positron emission tomography, magnetic resonance imaging and B-mode ultrasound. RESULTS: All tumors could be ablated successfully. Electrode placement was accurate and visualization in transabdominal, laparoscopic, or intraoperative ultrasound was excellent. Because of the requirement of positioning two needles simultaneously, particularly in the laparoscopic RFA, the procedures were more time-consuming (average, 104 minutes) than placing a single needle. Local tumor control after a follow-up of 6 months was 100%. No major complication occurred. CONCLUSIONS: Successful ablation of liver tumors, using the new bipolar device, is feasible and without complications. The procedure is technically demanding; however, local tumor control seems to be superior, as compared to other RFA devices. The long-term success of the procedure has yet to be evaluated.

[Local recurrence following hepatic radiofrequency ablation: diagnosis and treatment]. / Diagnostik und Therapie von Lokalrezidiven nach Radiofrequenzablation an der Leber.

BACKGROUND: Radiofrequency ablation (RFA) is an established treatment in irresectable malignant liver disease. The most severe constraint is re-occurrence at site of ablation. Whereas factors influencing local recurrence rates have been determined, little is known about the timespan within local recurrence (LR) is to be expected, and further treatment options. PATIENTS AND METHODS: In the presented trial, RFA was performed using two different types of monopolar devices. All procedures were conducted under general anesthesia. Follow-up examinations took part after 3, 6, 12 months and annually. RESULTS: 149 RFAs in 125 patients were enrolled. Percutaneous access was chosen in 74 cases (50%), laparoscopic in 15 (10%) and open surgical in 60 cases (40%). Indications were primary liver tumors in 99 (67%) and metastases in 50 cases (33%). Overall LR rate was 29.5% on a per-patient- and 19.7% on a per-tumor-basis. The majority of LRs (71%) occurred within 9 months after the RFA despite observations beyond 2 years following the treatment (Figure 1). 75% of LR could be treated by targeted interventions (RFA, n = 18, 53%, laser-induced thermo therapy (LITT), n = 2.6%, brachytherapy, n = 2.6% or transarterial chemoembolisation (TACE), n = 2.6%) or resection (n = 6.18%); 4 patients underwent liver transplantation (12%) (Figure 2). CONCLUSION: Local recurrence can be considered rather common after RFA. It is observed during the first 3 years of the follow-up period, and schedules have to be designed according to this finding. Follow-on treatment is feasible in approximately 75% of LR. Factors influencing the secondary success of repeated procedures have yet to be determined.

Radiofrequency ablation prior to liver transplantation: focus on complications and on a rare but severe case.

BACKGROUND: Radiofrequency ablation (RFA) is an established treatment for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation, due to its comparably low rate of complication and high effectiveness. Complications are thought to be rare and mostly self-limiting. By contrast, we report on a life-threatening complication and discuss it in the context of other complications. PATIENTS AND METHODS: Out of a total of 149 RFA procedures, the incidence of major complications was 4% on a per-procedure basis. Mortality was 0.67%. Major complications included intractable pain, intrahepatic hematoma, skinburn at the site of patch electrode, and sectorial bile duct stricture. All complications occurred after percutaneous RFA. Highlighted is a young patient listed for liver transplantation because of HCC recurrence following hepatic resection, who was treated by percutaneous RFA as a bridging therapy until a suitable graft became available. Post-operatively, gastric perforation occurred due to heat injury of the gastric wall. CONCLUSIONS: The percutaneous RFA approach can occasionally lead to detrimental complications, particularly in patients with intra-abdominal adhesions, due to previous surgery if new intrahepatic malignant lesions accrue near the resection margin. Even widespread HCC disease can be treated effectively with orthotopic liver transplantation if the tumor growth is limited to the liver.

Role of B-mode ultrasound screening in detection of local tumor recurrence in the first year after radiofrequency ablation in the liver.

BACKGROUND: Ultrasound is known to be useful in imaging radiofrequency ablation (RFA) lesions intra- and postoperatively. The presented study intends to prove the value of ultrasound examination as a means of screening RFA-treated patients for local tumor recurrence. PATIENTS AND METHODS: During a period of 47 months, 91 RFA treatments were performed in 61 patients in a single institution. Indications for RFA were hepatocellular carcinoma (74%), colorectal metastases (18%), recurrent cholangiocellular carcinoma (5%) and one neuroendocrine tumor metastasis as well as one metastasis of pancreatic cancer (1.5% each). RFA was only considered in non-resectable liver cancer. All applications were conducted under sonographic guidance following preoperative evaluation. Postoperative screening included sonographic examinations at intervals of 3, 6 and 12 months postoperatively, and further annual follow-up examinations. Mean follow-up period was 11.8 months. RESULTS: Within the first 12 months after treatment, the lesions become more and more inhomogenous with mixed echogeneity. Occasionally, this evolves as a misleading finding, mimicking early tumor recurrence. To clarify suspicious cases (31%), magnetic resonance imaging (20%) or computed tomography (10%) was engaged. Ultrasound led to the detection of local tumor recurrence in 78% of recurrent HCC (13 patients), but only in 67% of metastatic diseases (3 patients). Overall local recurrence rate was 18%. CONCLUSION: Ultrasound screening as a follow-up of primary hepatic malignancies is, due to its sensitivity, capable of detecting early local recurrence despite its low specifity. Appropriate application of particular criteria of local recurrence allows B-mode ultrasound to play a major role in screening RFA-treated patients.

Indications for hand-assisted laparoscopic radiofrequency ablation for liver tumors.

PURPOSE: Radiofrequency ablation has established itself as the preferred treatment for irresectable liver tumors. It can be performed either percutaneously, laparoscopically, or by open surgery. The choice of approach depends on the patient and tumor-related variables. The laparoscopic approach appears to be the safest and most effective method for small tumors on the liver surface. It also provides additional information on the intrahepatic tumor burden with the use of intraoperative ultrasound and staging laparoscopy. Furthermore, the pneumoperitoneum reduces the flow of the portal vein and increases the efficacy of the ablation. Depending on the location of the tumor, mobilization of the liver or lysis of adhesions from previous surgery can require open surgery. Our aim was to study the combined use of laparoscopy and laparotomy by using hand-assisted laparoscopic radiofrequency ablation. MATERIALS AND METHODS: We performed hand-assisted laparoscopy to ablate nine tumors in seven patients, enabling us to combine most of the advantages of laparoscopy and open surgery. The radiofrequency ablation was technically simple to perform. A laparoscopy of the entire abdominal cavity and a thorough examination of the entire liver via ultrasound was also performed. RESULTS: The electrode was accurately placed in all patients. In four patients, a complete mobilization of the right lobe was performed to obtain the easiest possible access to the tumor. In three patients, severe adhesions from previous surgeries were removed prior to insertion of the laparoscopic tools. The ablation was completed safely and successfully in all patients. CONCLUSION: Our overall impression of the hand-assisted laparoscopic approach is that it seems to have a major advantage in comparison with simple laparoscopy, specifically for adhesions from previous surgeries and when the right liver lobe requires mobilization. Also, needle placement seems to be far more accurate than with simple laparoscopy.

The surgical approach for radiofrequency ablation of liver tumors.

Radiofrequency ablation for the treatment of liver tumors is one of the best alternative treatment modalities when surgical resection is not possible. To find the right indication for the treatment, every patient should be treated in a high-volume center for the treatment of liver tumors in an interdisciplinary conference consisting of liver surgeons, interventional radiologists, medical oncologists, and gastroenterologists. With a multimodal approach including anatomic segmental and wedge resection of the liver, RFA, and chemotherapy, a median survival of 36 months was achieved in technically unresectable patients with colorectal liver metastases (Elias et al. 2005). This survival doubles the survival rate of any other treatment modality in this group of patients. These interdisciplinary conferences also serve to determine the approach for RFA, whether it should be percutaneous, laparoscopic, or open surgery. The safest ablation with the fewest adverse events from RFA is the open surgical approach, followed by the laparoscopic approach. The approach with the highest risk of injury to organs in proximity to the liver is the percutaneous approach. Therefore, many variables must be evaluated before making definite decisions. After choosing RFA as the best alternative treatment option after evaluation of all variables for a particular patient, it offers a treatment option with a potential cure. A major advantage is the possible combination with liver resection, which extends the indication for surgical or ablative therapy.

Complex vascular reconstructions in living donor liver transplantation.

We describe here the indications for and our experience with complex vascular reconstructions in living donor liver transplantation. From December 1999 to June 2002, 59 patients underwent liver transplantation, 51 receiving the right lobe, and 8 the left lateral lobe, as a graft from a living donor. The indication for interpositional grafts on the arterial side (6/59, 10%) were stenoses of the celiac trunk and after resection of the hepatic artery for oncological reasons in adults. In children, arterial interpositional grafts were performed in situations of long distances between the donor and recipient artery, or in cases of inflow release from the aorta in patients with small hepatic arteries. On the portal-venous side, one interpositional graft was performed after an oncological resection. Once the portal vein was partially arterialized because of insufficient inflow. We used veins from the recipient, and native or cryopreserved arterial homografts for these grafts. All patients were treated during the first 6 months after transplantation with aspirin only. During the follow-up we did not observe vascular complications. If required, vascular interpositional grafts in the arterial and portal-venous position can be performed without adding postoperative complications.