Bimodal electric tissue ablation (BETA) - in-vivo evaluation of the effect of applying direct current before and during radiofrequency ablation of porcine liver.

AIM: To examine the effect of applying increasing amounts of direct current (DC) before and during alternating current radiofrequency ablation of porcine liver. MATERIALS AND METHODS: Using a Radiotherapeutics RF3000 generator, a 9 V AC/DC transformer and a 16 G plain aluminium tube as an electrode, a control group of 24 porcine hepatic radiofrequency ablation zones was compared with 24 zones created using a bimodal electric tissue ablation (BETA) technique in three pigs. All ablations were terminated when tissue impedance rose to greater than 999 Omega or radiofrequency energy input fell below 5 W on three successive measurements taken at 1 min intervals. BETA ablations were performed in two phases: an initial phase of variable duration DC followed by a second phase during which standard radiofrequency ablation was applied simultaneously with DC. During this second phase, radiofrequency power input was regulated by the feedback circuitry of the RF3000 generator according to changes in tissue impedance. The diameters (mm) of each ablation zone were measured by two observers in two planes perpendicular to the plane of needle insertion. The mean short axis diameter of each ablation zone was subjected to statistical analysis. RESULTS: With increased duration of prior application of DC, there was a progressive increase in the diameter of the ablation zone (p<0.001). This effect increased sharply up to 300 s of pre-treatment after which a further increase in diameter occurred, but at a much lesser rate. A maximum ablation zone diameter of 32 mm was produced (control diameters 10-13 mm). CONCLUSION: Applying a 9 V DC to porcine liver in vivo, and continuing this DC application during subsequent radiofrequency ablation, results in larger ablation zone diameters compared with radiofrequency ablation alone.

Postoperative death in sows as a result of gastric mucosal de-gloving at the pars oesophagea.

It is well documented that pigs frequently die from postoperative acute gastric dilatation, and proximal gastric 'stress' ulceration. Three cases of gastric mucosal 'de-gloving' are reported. This was secondary to acute gastric dilatation and resulted in death from acute haemorrhage. All animals had undergone major abdominal surgery. Histology confirmed that the proximal gastric mucosa had been 'de-gloved', or torn from the gastro-oesophageal junction, leaving exposed muscle fibres. This syndrome has not been reported previously. The postmortem appearances of this mechanical injury could easily be mistaken for extensive oesophago-gastric peptic ulceration. This has major implications for prevention.

Endoscopic perductal electrolytic ablation of the pancreas: experimental studies of morbidity and mortality.

BACKGROUND: Palliation of pancreatic cancer remains the only option for the majority of patients. Palliative techniques such as surgical bypass and endoscopic retrograde cholangiopancreatography (ERCP) with stenting are not ideal. The 'ideal' palliative technique would combine the efficacy of surgery with the minimal complications of an endoscopic procedure. Endoscopically delivered perductal electrolytic ablation of pancreatic lesions has the potential to meet these criteria. METHODS: Fifteen pigs were used. The pancreatic duct was cannulated with an electrolysis catheter. Animals were randomised to either: controls, treatment 2-week survivor or treatment 8-week survivor. An electrolytic dose was administered to the treatment animals. Post-operatively, serum amylase and leucocyte count were assessed. Pancreata were histologically examined to detect evidence of acute pancreatitis. RESULTS: Electrolysis was well tolerated. There was no difference in post-operative hyperamylasaemia and leucocyte count between the groups. Histological examination showed inflammation at the ablation site at 2 weeks, by 8 weeks this was replaced by scarring. CONCLUSION: The results of this study suggest that endoscopic perductal electrolytic ablation of the pancreas is feasible and safe. Biochemical and histological findings indicate self-limiting localised inflammation of the pancreas. This technique may have a role in the palliation of pancreatic cancer and warrants further investigation.

Electrolytic liver ablation is not associated with evidence of a systemic inflammatory response syndrome.

BACKGROUND: Local ablation has been proposed for treatment of liver tumours. Cryoshock, a variant of the systemic inflammatory response syndrome (SIRS), is a potentially fatal complication of cryoablation caused by systemic release of necrotic breakdown products from ablated liver. The proinflammatory cytokines tissue necrosis factor (TNF) alpha and interleukin (IL) 1 are important mediators of this response. This study assessed the risk of SIRS complicating electrolytic liver ablation by measuring circulating levels of inflammatory cytokines, other inflammatory markers and clinical markers of organ function. METHODS: Electrolytic liver ablation was performed in 16 pigs and four pigs served as controls. Platelet count, and serum levels of urea, creatinine, liver enzymes, C-reactive protein (CRP), TNF-alpha and IL-1beta were measured before treatment and for 72 h after the procedure. RESULTS: There were significant dose-related increases in CRP and alanine aminotransferase levels with liver electrolysis. There was no significant derangement in renal function or platelet count following ablation. A rise in serum TNF-alpha and IL-1beta levels was not associated with liver electrolysis. CONCLUSION: There was no evidence of organ failure or significantly raised levels of proinflammatory cytokines as a result of liver electrolysis, suggesting that this is a safe procedure for liver ablation.

Perductal electrolytic ablation of the porcine pancreas: a minimally invasive option-studies of morbidity and mortality.

BACKGROUND: Pancreatic cancer has a dismal prognosis. Few patients are suitable for surgical resection, leaving the majority requiring symptom palliation. Current palliative techniques such as surgical bypass and endoscopic retrograde cholangiopancreatography (ERCP) are imperfect. A novel palliative therapy combining the symptom control of surgical bypass with the minimally invasive nature of ERCP is required. METHODS: Perductal electrolytic ablation of pancreatic tissue, in a porcine model, was performed. There were two survival groups of 2 weeks (n = 4) and 8 weeks (n = 4). Postoperatively, serum biochemistry, amylase and C-reactive protein (CRP) were assessed. Histological examination of the pancreas, lungs, and kidneys was performed to determine the presence of acute pancreatitis or systemic inflammatory response. RESULTS: An immediate transient increase in both amylase and CRP was seen. Although pancreatic histology demonstrated localised necrosis at the electrolytic site at 2 weeks, there was no evidence of generalized pancreatitis or a systemic inflammatory response at either 2 or 8 weeks. CONCLUSIONS: This study suggests that, although there is localized pancreatic necrosis and transient hyperamylasemia, perductal pancreatic electrolytic ablation is safe, with neither generalized pancreatitis nor a systemic inflammatory response, in the medium and long term. Although performed in normal porcine pancreas, because of the absence of a large-animal model of pancreatic cancer, this study suggests that electrolytic pancreatic ablation is safe. This technique may have a role in the palliation of pancreatic cancer, especially if delivered via a minimally, invasive approach, and warrants further investigation.

Segmental nature of the porcine liver and its potential as a model for experimental partial hepatectomy.

BACKGROUND: In-depth knowledge of pig liver anatomy allows potential research into segmental liver resections and hepatic regeneration, as well as liver transplantation techniques. The segmental anatomy, however, remains largely unknown. This study aimed to delineate the segmental anatomy of the porcine liver in comparison with that of the human. METHODS: The segmental anatomy of the porcine liver was determined using acrylic injection casting of ex vivo pig livers, allowing the arterial, venous and biliary supply to be visualized directly. This was correlated using multi-slice computed tomography (CT) and three-dimensional reconstructions. RESULTS: Although the external morphology of the porcine liver differs from that of the human, the segmental anatomy is remarkably similar in term of its vascularity and biliary tree. CONCLUSION: Acrylic casting of the porcine liver accurately delineates the vascular and biliary anatomy, and is a useful tool for performing experimental liver surgery. The similarities between porcine and human segmental anatomy allow domestic swine to be used as a comparable model. Three-dimensional CT reconstructions can also accurately visualize the anatomy and may be used to perform virtual surgery, or to assess segmental volumes.

Palliation of pancreatic cancer using electrolytic ablation.

BACKGROUND: Inoperable pancreatic cancer has a dismal prognosis. Palliation involves either stenting or surgical bypass. Stenting does not relieve gastric outlet obstruction, and surgical bypass is a major procedure. A minimally invasive procedure is needed that relieves both gastric outlet and biliary obstruction, with the potential for relieving pain. METHODS: In an experimental model, pancreatic electrolysis was investigated. The pancreatic duct was cannulated via a transduodenal approach with an electrode catheter. In 6 animals an electrolytic "lesion" was created using a direct current generator. Six animals were controls. The local and systemic effects of electrolysis were assessed using histological and biochemical parameters. RESULTS: The pancreatic duct was cannulated in all animals and treatment was uneventful. Electrolytic lesions comprised a central area of necrosis with a sharp demarcation between necrotic and viable pancreas. All animals developed transient hyperamylasemia after electrolysis. There was no significant difference between treatment and controls. Importantly, no animal had clinical, biochemical, or histological evidence of pancreatitis. CONCLUSIONS: This experimental study suggested that electrolytic palliation of inoperable pancreatic cancer via the gastrointestinal tract is potentially safe. In patients, this treatment could be performed during endoscopic retrograde cholangiopancreatography and may have therapeutic advantages when compared to stenting or biliary bypass.

The mystery of liver regeneration.

BACKGROUND: Partial hepatectomy is the strongest stimulator of hepatic regeneration. The process of initiation and the control of the final size of the regenerated liver have been the subject of research for many years. A better understanding of this process and the effect of disease may allow better selection of patients for partial hepatectomy. It may also allow an insight into the possible application of clinical stimulation of regeneration. METHODS: Data were reviewed from the published literature using the Medline database. RESULTS: Most knowledge comes from in vitro studies and the study of resection in the rat model. A variety of cytokines, hormones and growth factors are involved in regeneration but very few have been found capable of stimulating regeneration in vitro. The exact interactions are not known, but there is probably a cascade involving different factors at differing stages of regeneration. CONCLUSION: Further in vivo research should allow greater understanding of liver regeneration, thereby providing a potential therapeutic tool in patients for whom regeneration has failed, or is likely to fail. Such research is also important in respect of liver support devices, which may inhibit liver regeneration by filtration of many of the factors involved.

Lateral laparoscopic port sites should all be closed: the incisional "spigelian" hernia.

Incisional hernias are a recognized complication of all abdominal surgery, including laparoscopic surgery. Although most cases of laparoscopic port incisional hernias are seen in the midline, particularly around the umbilicus, there are several reports of herniation at laterally placed ports. Accepted surgical practice is to close the deep fascial layers at midline laparoscopic ports. However, the deep layers at the lateral ports are not usually closed. Two near-identical cases are reported in which incisional hernias have developed at the site where laterally placed 10-mm ports have pierced the spigelian fascia. Hernia development at an iatrogenic defect in an area that is already potentially weak, and therefore prone to herniation, has implications for lateral 10-mm port site closure. The closure of the deep layers of all lateral laparoscopic ports is advocated, especially if the spigelian fascia is pierced.

A novel technique for the laparoscopic resection of mesenteric cysts.

Mesenteric cysts are rare, invariably benign intraabdominal tumors. Optimal surgical management requires complete excision of these lesions. The advent of laparoscopic surgery has allowed resection of these cysts to be achieved without full laparotomy. However, laparoscopic resection necessitates drainage of the cyst within the abdomen to facilitate extraction of the cyst through the laparoscopic ports. This article describes a novel technique in which the cyst was partially aspirated as the initial surgical maneuver. This in turn allowed traction to be applied to the cyst wall, such that it could be drawn up into the epigastric port, to aid the further dissection and removal of the cyst from the peritoneal cavity.

Electrolytic ablation as an adjunct to liver resection: experimental studies of predictability and safety.

BACKGROUND: Combined liver resection and local ablation may offer the only chance of cure to patients with liver metastases who are presently deemed unresectable because of a single awkwardly placed metastasis. By definition, such a metastasis is often close to a major vein. An ablative technique is needed that is both predictable and safe in such a circumstance. METHODS: Electrolytic liver lesions were created in 21 pigs using platinum electrodes, connected to a direct current generator. Both electrolytic 'dose' and electrode separation were varied to produce different sized lesions. The 'dose' was correlated with the volume of necrosis and any vascular damage was determined histologically. RESULTS: There was a significant (P < 0.001) correlation between the electrolytic 'dose' and the volume of liver necrosis. For a given 'dose' the volume of necrosis was less when the electrodes were together, rather than separated. Liver enzymes were only transiently deranged. There were no significant vascular injuries. CONCLUSION: Predictable and reproducible necrosis is produced by electrolysis in the pig liver. The treatment appears to cause little or no damage to immediately adjacent liver or major vascular structures and, when combined with resection, may offer the chance of a cure to many patients who are currently unresectable.

Management of thoracic duct injuries after oesophagectomy.

BACKGROUND: Thoracic duct laceration is a rare but potentially life-threatening complication of oesophagectomy. The management of such an injury is uncertain in respect of the relative merits of conservative and surgical treatment. METHODS: The literature was reviewed by searching Medline databases from 1966 to the present time. The majority of the evidence presented is level 3, as no randomized or controlled data are available. RESULTS: Prolonged conservative treatment of thoracic duct injury is associated with a mortality rate of 50-82 per cent. The results of early surgical ligation of the duct are more encouraging, with a mortality rate of 10-16 per cent. Elective ligation of the duct reduces the incidence of postoperative chylothorax. CONCLUSION: The thoracic duct should be ligated during oesophagectomy. A high index of suspicion for duct injury must be maintained in all patients after operation. A policy of very early thoracic duct ligation at 48 h from diagnosis is proposed for duct injury if aggressive conservative management fails.

Electrolytic treatment of colorectal liver tumour deposits in a rat model: a technique with potential for patients with unresectable liver tumours.

BACKGROUND/AIMS: Patients with unresectable malignant liver tumours have a poor prognosis. A technique is needed which improves long-term survival. Previous studies in the rat have shown that electrolysis is a safe, predictable and reproducible method for creating areas of necrosis in the normal rat liver. This study examined the effects of electrolysis on colorectal liver 'metastases' in the rat. METHODS: Tumours of colorectal origin were implanted into the livers of Wistar-WAG rats. Two weeks after implantation the tumours were treated with electrolysis. A direct current generator, connected to 2 platinum intrahepatic electrodes was used to examine the effects of various electrode configurations on the extent of tumour necrosis. RESULTS: Significant (p<0.001) tumour ablation was achieved with all electrode configurations. Tumour necrosis was more complete (p<0.05) with the electrodes positioned on either side of the tumour than with both electrodes placed in the centre of the tumour. Liver enzymes (AST and ALT) were significantly (p<0.001) elevated after treatment, but returned towards normal by 2 days. CONCLUSIONS: This study has shown that colorectal liver 'metastasis' can be ablated by electrolysis in a rat model. Two separate mechanisms of tumour ablation were observed: With the electrodes directly in or adjacent to the tumour, necrosis resulted from the action of cytotoxic electrode products, whereas by positioning the electrodes proximal to the tumour, necrosis was induced by a 'secondary' ischaemic effect. The findings confirm the view that electrolysis has great potential for treating patients with unresectable malignant liver tumours.

The safety of electrolytically induced hepatic necrosis in a pig model.

BACKGROUND: Electrolysis fulfils the criteria for an ideal treatment of patients with unresectable liver tumours. Previous studies in the rat and pig have shown that controlled necrosis can be safely produced by inserting platinum electrodes into normal liver' parenchyma and liver tumours. As with any new treatment it is mandatory to investigate the 'worst-case scenario' of inadvertent intravascular electrode placement in a large animal model before progressing to clinical trials. METHODS: Under ultrasound control in six pigs, electrodes were inserted into, or immediately adjacent to, an hepatic vein. An electrolytic 'dose' of 100 C was then administered and the evolution of the lesion was monitored using ultrasound. Venous blood was collected before and during the electrolysis to evaluate potential acid/base disturbances and animals were closely monitored during electrolysis and during their recovery until a full autopsy was performed 4-7 days after treatment. RESULTS: Gas bubbles were seen to enter the hepatic veins or interior vena cava during treatment in five of the six animals. There were no major complications as a consequence and all animals recovered and remained in a healthy state until they were killed. At autopsy one animal had complete thrombotic occlusion of the left hepatic vein. Otherwise, findings were normal. CONCLUSION: In the clinical setting, due to the use of ultrasound to guide electrode placement into the centre of a tumour, the electrodes should rarely juxtapose an hepatic vein. Nevertheless, in this extreme situation, electrolysis is surprisingly safe with only one major vascular occlusion and no morbidity or mortality.

Electrochemical lesions in the rat liver support its potential for treatment of liver tumors.

BACKGROUND: An effective therapy is needed for patients with surgically unresectable liver tumors who have very limited life expectancy. One possible treatment is electrochemical tumor necrosis. This study investigated the natural history of electrochemical lesions in the normal rat liver. MATERIALS AND METHODS: A direct current generator, connected to platinum electrodes, was used to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2 weeks, 2 months, and 6 months after treatment and the macroscopic and histological appearance of the necrotic lesions was followed. RESULTS: No animal died as a result of electrolysis; postoperatively, all gained weight normally. Liver enzymes were significantly (P < 0.001) elevated after treatment, but returned to normal after a week. Two days after electrolysis, histology confirmed an ellipsoidal area of coagulative necrosis at the site of the electrode tip and commonly a segment of peripheral necrosis. After 2 weeks there was histological evidence of healing. By 6 months, very little necrotic tissue remained within a small fibrous scar. CONCLUSIONS: Electrolysis is a safe method for creating defined areas of liver necrosis that heal well with no associated mortality. This study supports the potential of electrolysis for treating patients with unresectable liver tumors.

A new treatment for unresectable liver tumours: long-term studies of electrolytic lesions in the pig liver.

The majority of liver tumours are inoperable and an alternative treatment to surgical resection is urgently needed. Electrolysis has been investigated in a rat model and the procedure is safe, with accurate and predictable effects. The necrosis produced has also been shown to cause destruction of tumour deposits in the rat liver. A similar evaluation in a large animal model was necessary before clinical trials could commence. Using platinum electrodes connected to a d.c. generator, areas of hepatic necrosis were created in the pig liver. Animals were killed at various time points after treatment to assess the extent of healing. Treatment was uneventful and all animals made a full recovery. No animal died from the treatment or had to be killed prematurely. After 2 days of treatment, healing was minimal but at successive time points there was progressive evidence of healing, such that after 4 months, the original electrolytic lesion was greatly reduced in size and the large area of necrosis seen at the early time points was largely replaced by a fibrous scar with only small islands of necrotic tissue. In a large animal model, electrolysis is a safe method for creating areas of hepatic necrosis. The lesions heal with time and are associated with minimal morbidity. The results support a trial of electrolysis in patients with unresectable liver tumours.

Laparoscopic repair of perforated peptic ulcers. The role of laparoscopy in generalised peritonitis.

This non-randomised concurrent cohort study conducted in two teaching hospital Departments of Surgery examined the assumption that the benefits of elective laparoscopic upper gastrointestinal surgery would apply to those with generalised peritonitis due to perforated peptic ulcers. It compared 20 consecutive laparoscopic repairs of perforated peptic ulcers with a concurrent group of 16 consecutive open repairs. There were no differences pre-operatively between the two groups. The mean duration of surgery was similar (P = 0.46). There were no differences in the rate of GI tract recovery, but opiate analgesia requirement in the laparoscopic group was significantly less (P < 0.0001). Intensive care was required in three patients in the laparoscopic group (two with renal failure) and two in the open (no renal failure). Two patients in the laparoscopic and one in the open group died. The median duration of stay was five days in the laparoscopic group and six in the open. This comparison shows that the patho-physiological insult of laparoscopy in the setting of generalised peritonitis does not obviously increase the peri-operative risk of organ failure but objective benefits are small.

The laryngeal mask airway in experimental pig anaesthesia.

The pig is used as a large animal model in many research projects. Standard practice for airway maintenance under general anaesthesia is using endotracheal (ET) intubation after intravenous induction to a near surgical plane. This is a technically demanding skill, requiring the assistance of an experienced technician. A technique is required which simplifies pig anaesthesia. This study examined the feasibility and potential advantages of using the laryngeal mask airway (LMA) in 10 pigs during laparotomy under spontaneous breathing anaesthesia. The results show that the LMA can be inserted rapidly, with minimal time for airway control by researchers relatively inexperienced in anaesthesia and is associated with few complications. By removing the need for intravenous induction, an entire step in the anaesthetic process is removed. The LMA designed for humans fits well in the pig hypopharynx; all pigs could be manually ventilated with no detectable gas leak. Although the pigs in this study were spontaneously breathing it is proposed that the LMA should be further investigated in studies of artificially ventilated pigs.

Experimental study of electrolysis-induced hepatic necrosis.

BACKGROUND: One of the most promising but unexplored methods for treating patients with irresectable liver tumours is electrolysis. This study examined the effect of increasing 'current dose' on the volume of the lesion induced in normal rat liver. METHODS: A direct current generator, connected to platinum electrodes implanted in the rat liver, was used to examine the effect of (1) varying current doses from 1 to 5 coulombs and (2) electrode separation (2 or 20 mm), on the volume of liver necrosis. RESULTS: There was a significant correlation (P < 0.001) between the current dose and the volume of necrosis produced for each electrode separation. Placing the electrodes 2 mm apart resulted in smaller total volumes of necrosis than placing them 20 mm apart when anode lesions were significantly larger than cathode lesions (P< 0.05). Liver enzymes (aspartate aminotransferase, alanine aminotransferase) were significantly raised 1 day after treatment (P < 0.001) and predicted the total volume of hepatic necrosis (P < 0.001). CONCLUSION: Predictable and reproducible areas of liver necrosis are produced with electrolysis. If these results extrapolate to larger animal models, this technique has potential for patients with irresectable primary and secondary liver tumours.