Donor and recipient treatment with the Lazaroid U-74006F do not improve post-transplant lung function in swine.

OBJECTIVE: U-74006F is the only Lazaroid which is currently in clinical use. A number of experimental studies demonstrate that Lazaroids reduce ischemia/reperfusion injury in various organ systems. We evaluated the effect of U-74006F on reperfusion injury in a large animal model of lung allo-transplantation. METHODS: Two different treatment modalities were evaluated and compared with corresponding control groups. Unilateral left lung transplantation was performed in 21 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.51 cold (1 degrees C) LPD solution and preserved for 20 h. In group I (n = 5), donor animals were pretreated with U-74006F (10 mg/ kg i.v.) 20 min before harvest. In addition U-74006F was added to the flush solution (10 mg/l). In group III (n = 6), the Lazaroid was given to the donor before flush and to the recipient before reperfusion (3 mg/kg i.v.). Group II and IV (n = 5) served as control. One hour after reperfusion, the recipient contralateral right pulmonary artery and bronchus were ligated to assess graft function only. Extravascular lung water index (EVLWI), mean pulmonary artery pressure, cardiac output, and gas exchange were assessed during a 5 h observation period. Lipid peroxidation (TBARS) and neutrophil migration (MPO activity) were measured at the end of the assessment in lung allograft tissue. RESULTS: A significant change of TBARS concentration was shown in group III (group III 78.7+/-4.6 pmol/g vs. group IV 120.8+/-7.2 pmol/g (P = 0.0065) normal lung tissue 41.3+/-4.2 pmol/g). MPO activity was reduced in group III 3.74+/-0.25 deltaOD/mg per min vs. group IV 4.97+/-0.26 deltaOD/mg per min (P = 0.027), normal lung tissue 1.04+/-0.27 deltaOD/mg per min). Pulmonary hemodynamics and gas exchange after reperfusion did not differ between groups. In group I and III, a tendency towards a reduced EVLWI was noted. CONCLUSION: We conclude that combined treatment of donor and recipient with U-74006F reduces free radical mediated injury in the allograft. However, this intervention did not result in a significant reduction of post-transplant lung edema or improvement of pulmonary hemodynamics. Donor pretreatment alone did not improve lung allograft reperfusion injury. These results indicate that the benefit of U-74006F is too small to consider clinical application in lung transplantation.

Is growth influencing diameter and function of laparoscopic TESA hepaticojejunostomy? A comparison of adult minipigs and juvenile domestic swine.

Current treatment of obstructive jaundice includes endoscopic stenting and open surgical bypass. To combine the advantages of surgical bypass with the minimal invasive approach of endoscopic stenting we developed a laparoscopic technique, transient endoluminally stented anastomosis (TESA). As shown previously, small-diameter anastomoses (e.g., hepaticojejunostomy) by TESA technique can be performed reliably in growing domestic swine. This further preclinical trial was designed to exclude growth of the animals as the main reason for these excellent results. After ligation of the common bile duct, a laparoscopic Roux-en-y hepaticojejunostomy was performed 7 days later by TESA with a reabsorbable radiopaque polyglycolic acid stent. In group A (n = 7) growing domestic pigs and in group B (n = 5) adult minipigs were operated on. Laboratory parameters were controlled weekly. Stent degradation was followed by weekly abdominal x-ray. At necropsy 6 months after surgery, cholangiography was performed and the anastomoses were measured. Mean weight gain was 140.7 +/- 10.9 kg in domestic pigs versus 5.8 +/- 1.6 kg in minipigs. Cholestasis normalized within 7 days postoperatively. Duration of stenting was not significantly different between groups. Cholangiography at necropsy showed immediate runoff through the anastomoses in both groups. The diameter of the anastomosis was 4.7 +/- 0.5 mm in group A versus 3.0 +/- 0.4 mm in group B (p = 0.03). In conclusion, functionality of the small-diameter TESA hepaticojejunostomy is not related to age and growing factors in pigs, justifying its application in human as the next step of investigation.

Effect of soluble complement receptor type 1 on reperfusion edema and neutrophil migration after lung allotransplantation in swine.

OBJECTIVE: Soluble complement receptor type 1 inhibits complement activation by blocking C3 and C5 convertases of the classical and alternative pathways. We evaluated the effect of soluble complement receptor type 1 on lung allograft reperfusion injury. METHODS: Left lung transplantation was performed in 13 weight-matched pigs (25 to 31 kg) after prolonged preservation (20 hours at 1 degree C). One hour after reperfusion the recipient contralateral right lung was excluded to assess graft function only. Complement activity and C3a levels were measured after reperfusion and at the end of the assessment. Extravascular lung water index, intrathoracic blood volume, and cardiac output were assessed during a 5-hour observation period. Gas exchange and hemodynamics were monitored. At the end of the 5-hour assessment period, myeloperoxidase assay and bronchoalveolar lavage were performed to assess neutrophil migration, and C5b-9 (membrane attack complex) deposits in the allograft were detected by immunohistochemistry. Two groups were studied. In group II (n = 6) recipient animals were treated with soluble complement receptor type 1 (15 mg/kg) 15 minutes before reperfusion. Group I (n = 7) served as the control group. RESULTS: Serum complement activity was completely inhibited in group II. In contrast to group I, C5b-9 complexes were not detected in group II allograft tissue samples. C3a was reduced to normal levels in group II (p = 0.00005). Extravascular lung water index was higher in group I animals throughout the assessment period (p = 0.035). No significant difference in allograft myeloperoxidase activity (p = 0.10) and polymorphonuclear leukocyte count of the bronchoalveolar lavage fluid (p = 0.057) was detected. CONCLUSION: Inhibition of the complement system by soluble complement receptor type 1 blocks local complement activation in the allograft and reduces posttransplantation reperfusion edema but does not improve hemodynamic parameters.

Effect of a short period of warm ischemia after cold preservation on reperfusion injury in lung allotransplantation.

OBJECTIVE: A short period of warm ischemia during lung allograft implantation is inevitable. We studied the effect of 2 h of warm ischemia before implantation after 18 h of cold preservation on reperfusion edema and pulmonary hemodynamics in a large animal model. METHODS: Left lung transplantation was performed in ten weight-matched pigs (25-31 kg). Donor lungs were flushed with 1.5 l cold (1 degree C) LPD solution and preserved for 20 h. In Group I (n = 5) the grafts were preserved for 20 h at 1 degree C and topically cooled with ice slush during implantation until reperfusion. In Group II (n = 5) lungs were stored at 1 degree C for 18 h followed by 2 h preservation at room temperature (20 degrees C). Topical cooling was not used during implantation. At 1 h after reperfusion the recipient contralateral right pulmonary artery and bronchus were ligated to assess graft function only. Extravascular lung water index (EVLWI), intrathoracic blood volume (ITBV), mean pulmonary artery pressure (PAP) and cardiac output (CO) were assessed during a 4 h observation period. Quantitative myeloperoxidase (MPO) activity and thiobarbituric acid-reactive substance (TBARS) levels as an indicator for lipid peroxidation were determined in allograft tissue samples taken 5 h after reperfusion. RESULTS: In Group II a tendency to improved pulmonary vascular resistance and cardiac output was noted. Surprisingly, lung edema, assessed by EVLWI, did not increase in animals with warm ischemia. Even a tendency to a reduced EVLWI was noted. However, differences between groups did not reach statistical significance. Gas exchange did not differ statistically significant between groups. CONCLUSION: Our results indicate that a short period of warm ischemia before reperfusion does not lead to increased pulmonary edema. In animals with a short period of warm ischemia before reperfusion, even a tendency to reduced posttransplant lung reperfusion injury was noted. In this model, topical graft cooling during lung implantation did not improve posttransplant graft function.

VATS resection of an oesophageal leiomyoma in a patient with neurofibromatosis Recklinghausen.

A series of reports in the literature suggest an association of neurofibromatosis Recklinghausen with intestinal tumors as carcinoids, leiomyomas and leiomyosarcomas. We present a case of a 23-year-old man with severe cutaneous manifestation of neurofibromatosis. Dysphagia was the main symptom. CT scan suggested the diagnosis of an oesophageal leiomyoma. The oesophageal muscle layers were split and the tumor was enucleated by video assisted thoracoscopic surgery (VATS). The postoperative course was uneventful. The patient was drinking liquids from day 1 and was eating a normal diet from day 3 postoperatively. He was dismissed from the hospital on the 4th postoperative day. We conclude that in patients with neurofibromatosis and oesophageal symptoms an intestinal manifestation of the disease in the oesophagus has to be considered and that VATS resection of intramural and extrinsic oesophageal leiomyomas is the treatment of choice.

Laparoscopic Roux-en-Y choledochojejunostomy.

OBJECTIVE: Although surgical biliary bypass for nonresectable periampullary tumors is superior to endoscopic stent placement, the latter has become popular because of the "minimally invasive" approach. Laparoscopic biliary bypass would appear to offer the advantages of both. However, this technique remains technically difficult using existing instrumentation. This study investigates the efficacy of a new endoscopic device designed for rapidly completing a small-diameter intestinal anastomosis under laparoscopic guidance. METHODS: Eighteen female pigs (mean weight 35 kg, range 31 to 44) were randomly divided into three groups: animals undergoing handsewn (group H) or instrumental transient endoluminally stented anastomosis (TESA; groups P and D) laparoscopic Roux-en-Y choledochojejunostomy. For TESA two different reabsorbable stents were used, polyglycolic acid (PGA; group P) and polyurethane ester (Degrapol; group D). Blood chemistry, weight gain, and abdominal X-rays were taken weekly to document any possible migration or reabsorption of the radio-opaque stents. After 3 months, necropsy was performed. Patency of the biliary bypass and choledochojejunostomy were examined using fluoroscopy and measured by introducing graduated dilators into the anastomosis. RESULTS: Fluoroscopy revealed immediate passage of contrast through the anastomosis in all animals. Weight gain, bilirubin, and alkaline phosphatase were within normal range in all groups. Diameter of the bile duct (group H 10.7 +/- 2.9 mm/group P 9.5 +/- 3.6 mm/group D 11.0 +/- 4.6 mm) and choledochojejunostomy (group H 4.5 +/- 1.1 mm/group P 4.7 +/- 1.8 mm/group D 3.6 +/- 1.9 mm) did not differ. The time required to complete the biliary bypass was significantly decreased when TESA was applied (group H 152 +/- 13 min/group P 86 +/- 14 min, P <0.001/group D 110 +/- 20 min, P <0.002). CONCLUSIONS: Applying TESA, laparoscopic choledochojejunostomy can be performed rapidly and safely, revealing good bypass function over a period of 3 months. With regard to treatment for nonresectable periampullary tumors, TESA may offer a new therapeutic approach combining the benefits of minimally invasive endoscopic stent placement with the functional results and lower readmission of conventional Roux-en-Y choledochojejunostomy.

An experimental teaching model for laparoscopic choledochojejunostomy.

For advanced laparoscopic procedures, team collaboration and good suturing skills are only two of many requirements to achieve success. Teaching opportunities are mandatory to allow general surgeons to become acquainted with advanced procedures and to gain confidence in new laparoscopic procedures. In this teaching model presented herein, the technical difficulties and operative steps of a laparoscopic choledochojejunostomy and drainage via Roux-en-Y-loop are outlined as performed on eight pigs weighing about 35 kg each (range, 31.2-41.2) with nondistended common bile ducts (5.6 mm; range, 4.2-6.3). Functionality of the bypass was assessed by a weekly monitoring of bilirubin levels and a contrast material injection into the gallbladder after a 4-month follow-up with measurements of the common bile duct (9.8 mm; range, 7.2-15.2) and the diameter of the choledochojejunostomy (5.0 mm; range, 3.6-6.2) at necropsy. This model provides outstanding conditions for teaching laparoscopic suture techniques to be applied in advanced laparoscopy and demonstrates the feasibility of laparoscopic choledochojejunostomy within a reasonable operation time (122 min; range, 105-155).

A comparison of the pathophysiologic effects of carbon dioxide, nitrous oxide, and helium pneumoperitoneum on intracranial pressure.

BACKGROUND: Previous studies have suggested that diagnostic laparoscopy may be contraindicated in multiple trauma patients with closed head injuries because of the detrimental effects of carbon dioxide (CO2) pneumoperitoneum on intracranial pressure (ICP). In this study we compared the effects of two alternative inflation gases, helium (He) and nitrous oxide (N2O), against the standard agent used in most hospitals, CO2. ICP was monitored in experimental animals both with and without a space occupying intracranial lesion designed to simulate a closed head injury. METHODS: Twenty-four domestic pigs (mean, 30 kg) were divided into four groups (6 CO2, 6 He, 6 N2O, and 6 control animals without insufflation). All animals were monitored for ICP, intraabdominal pressure, mean arterial pressure, end-tidal CO2 (ETCO2), and arterial blood gases. These parameters were measured for 30 minutes prior to introducing a pneumoperitoneum and then for 80 minutes thereafter. The measurements were repeated after artificially elevating the ICP with a balloon placed in the epidural space. RESULTS: The mean ICP increased significantly in all groups during peritoneal insufflation compared with the control group (P < 0.005). The CO2-insufflated animals also showed a significant increase in PaCO2 (P < 0.05) and ETCO2 (P < 0.05), as well as a decrease in pH (P < 0.05). After inflating the epidural balloon the ICP remained significantly higher in animals inflated with CO2 as compared with the He and N2O groups (P < 0.05). CONCLUSIONS: Peritoneal insufflation with He and N2O resulted in a significantly less increase in ICP as compared with CO2. That difference was most likely due to a metabolically mediated increase in cerebral perfusion (PaCO2) in the CO2 group. Further studies need to be conducted to determine the safety and efficacy of using He and N2O as inflation agents prior to attempting diagnostic or therapeutic laparoscopy in patients with potential closed head injuries.

Laparoscopic treatment of biliary and gastric outlet obstruction.

To avoid laparotomy in patients with biliary or gastric outlet obstruction in inoperable carcinoma of the pancreas, we evaluated the feasibility of double-bypass operation in 20 pigs. In model A (n = 10), biliary bypass was a Roux-en-Y loop for cholecystojejunostomy after choledochal clip occlusion. In model B (n = 10) an additional Roux-en-Y loop was attached to the stomach after transection of the duodenum. Model A showed functioning biliary bypass with patent and leak-free anastomoses at necropsy on day 28. In model B, four pigs were sacrificed earlier, but nine had normal functioning double bypass (two intussusceptions of the ileum, one bleeding ulcer at the gastroenterostomy, one necrotic Roux-en-Y-loop). Based on the presented bypass function, we are encouraged to perform laparoscopic biliary and gastroenteral bypass in humans to treat malignant jaundice and gastric outlet obstruction.

The multimodal water jet dissector--a technology for laparoscopic liver surgery.

UNLABELLED: In order to avoid laparotomy in patients with superficially and/or anatomically favourably located liver lesions, the feasibility of laparoscopic liver resection using an aqua jet was evaluated in 6 pigs. For this purpose a commercially available water jet dissector was adapted for laparoscopic use and modified to a multifunctional device providing aqua jet, suction and cautery. To improve laparoscopic vision during jet activity a hydrolaparoscope was used. The left lateral lobe was resected using clips for haemostasis only. RESULTS: All animals (34-55 kg, average 41 kg) survived the procedure. The blood loss at operation consisted of 225 ml (50-600 ml), the haematocrit 3.3% (1-8%). No bleeding or other complications were encountered postoperatively. The average weight of the specimens was 201 g (120-289 g). CONCLUSIONS: Laparoscopic liver resection using an aqua jet is feasible. Safe haemostasis can be achieved with clips if the vessels are entirely freed with the jet before clipping.