[Rupture of a jejunal artery pseudo-aneurysm after a cephalic duodenopancreatectomy]. / Rupture d'un pseudo-anévrisme d'une artère jéjunale après duodénopancréatectomie céphalique.

Arterial pseudo-aneurysms complicating pancreaticoduodenectomy are rare but have a poor prognosis. They usually result from arterial erosion due to pancreatic fistula. The authors report a pseudo-aneurysm with an uncommon localization (first jejunal artery), diagnosed after a negative first arteriography, and successfully treated by radiological embolization. Special features of pseudo-aneurysms complicating pancreaticoduodenectomy are reviewed.

Hypodermin A, a new inhibitor of human complement for the prevention of xenogeneic hyperacute rejection.

BACKGROUND: Hyperacute rejection (HAR) of discordant xenografts in the pig-to-human combination can be prevented using tranplants expressing transgenic molecules that inhibit human complement. Hypodermin A (HA), a serine esterase that degrades C3, was tested in the guinea-pig-to-rat and in the pig-to-human combinations. METHODS: Hypodermin A was tested in vitro, ex vivo, and in vivo models of HAR in the guinea-pig-to-rat combination. Hamster ovary cells (CHO) and a line of porcine aortic endothelial cells (PAEC11) were transfected with HA complementary DNA (cDNA). RESULTS: The pattern of degradation of rat and human C3 by HA was different (multiple bands lower than 40 kDa) from the physiologic pattern observed after spontaneous degradation of rat C3 or physiologic activation of human C3. The CH50 activity in serum was significantly lower in rats treated with 3.2 mg HA/kg than in untreated rats (45 +/- 16 U/ml vs. 700 +/- 63 U/ml, P < 0.05). Sera from rats injected with 3.2 mg/kg of HA were less effective in lysing guinea-pig endothelial cells (12 +/- 7%) than normal rat sera (79 +/- 3%; P < 0.001). Ex vivo, guinea-pig hearts perfused by rat serum supplemented with HA survived longer than those perfused by non-treated serum (210 +/- 34 and 154 +/- 71 min, respectively; P < 0.05). In vivo, guinea-pig hearts transplanted into HA treated rats survived longer than in non-treated rats (27 +/- 5 min vs. 13 +/- 4 min; P < 0.001). In the presence of human serum, smaller amounts of C6 and C5b-9 were deposited onto HA-transfected CHO cells than onto control cells. The mHA-PAEC11 cells were significantly more resistant to lysis by human C than control PAEC11 cells. CONCLUSIONS: These data suggest that transgenic HA could be used to prevent hyperacute xenogeneic rejection.

The superoxide dismutase mimetic MnTBAP prevents Fas-induced acute liver failure in the mouse.

BACKGROUND & AIMS: Acute liver failure (ALF) of viral origin results from massive hepatocyte apoptosis induced by the interaction between Fas expressed on hepatocytes and Fas ligand on activated T lymphocytes. Because Fas-induced apoptosis of hepatocytes involves mitochondrial damages and potential reactive oxygen species (ROS) overproduction, we investigated whether manganese III tetrakis (5,10,15,20 benzoic acid) (MnTBAP), a nonpeptidyl mimic of superoxide dismutase (SOD), can inhibit Fas-induced ALF. METHODS: An agonist anti-Fas monoclonal antibody was used to induce hepatocyte apoptosis in vitro and ALF in vivo. RESULTS: Preventive and curative treatments by MnTBAP significantly increased survival rates and significantly reduced aspartate aminotransferase levels and parenchymal lesions. ROS generation was suggested by those beneficial effects and significant increases in SOD and Gpx activities after anti-Fas injection. Flow cytometry of isolated hepatocytes incubated with anti-Fas monoclonal antibody showed that ROS production was associated with the collapse of transmembrane potential and loss of cardiolipin content. After injection of anti-Fas monoclonal antibody, mitochondrial Bcl-2 was decreased, cytochrome c released, and caspase-3 activated. Mitochondrial alterations and their consequences were abrogated by MnTBAP. CONCLUSIONS: ROS are key executioners in Fas-induced hepatocyte apoptosis. This finding explains why a nonpeptidyl mimic of SOD can cure ALF in a model of viral hepatitis, pointing out the potential interest of this molecule in humans.

Fully automatic anatomical, pathological, and functional segmentation from CT scans for hepatic surgery.

OBJECTIVE: To improve the planning of hepatic surgery, we have developed a fully automatic anatomical, pathological, and functional segmentation of the liver derived from a spiral CT scan. MATERIALS AND METHODS: From a 2 mm-thick enhanced spiral CT scan, the first stage automatically delineates skin, bones, lungs, kidneys, and spleen by combining the use of thresholding, mathematical morphology, and distance maps. Next, a reference 3D model is immersed in the image and automatically deformed to the liver contours. Then an automatic Gaussian fitting on the imaging histogram estimates the intensities of parenchyma, vessels, and lesions. This first result is next improved through an original topological and geometrical analysis, providing an automatic delineation of lesions and veins. Finally, a topological and geometrical analysis based on medical knowledge provides hepatic functional information that is invisible in medical imaging: portal vein labeling and hepatic anatomical segmentation according to the Couinaud classification. RESULTS: Clinical validation performed on more than 30 patients shows that delineation of anatomical structures by this method is often more sensitive and more specific than manual delineation by a radiologist. CONCLUSION: This study describes the methodology used to create the automatic segmentation of the liver with delineation of important anatomical, pathological, and functional structures from a routine CT scan. Using the methods proposed in this study, we have confirmed the accuracy and utility of the creation of a 3D liver model compared with the conventional reading of the CT scan by a radiologist. This work may allow improved preoperative planning of hepatic surgery by more precisely delineating liver pathology and its relationship to normal hepatic structures. In the future, this data may be integrated with computer-assisted surgery and thus represents a first step towards the development of an augmented-reality surgical system.

Transgenic expression of CD95 ligand on thyroid follicular cells confers immune privilege upon thyroid allografts.

Constitutive Fas ligand (FasL) expression by specialized cells in the body participates in the immune privilege status of tissues containing these cells. This property has been used to prevent rejection of allogeneic grafts. Nevertheless, the mechanism responsible for such protection has not been fully elucidated. Unfortunately, grafting of FasL transgenic (TG) tissues has been unsuccessful. We have generated TG mice expressing FasL (soluble + membrane bound) on thyroid follicular cells (TFC), and used them to show that ectopic FasL expression prevents thyroid allograft rejection. FasL expression on TFC led to markedly decreased anti-allogeneic, cytotoxic, and helper T lymphocyte activities. The alloantibody response in TG thyroid recipients was either completely inhibited or switched toward a T2-Ab response. Surprisingly, the beneficial effect of FasL on TG thyroid grafts was abolished by host CD4(+) T cell depletion. Host CD8(+) T cell depletion improved nontransgenic (NTG), but not TG graft survival. Altogether, our results suggest that FasL-induced tolerance is concomitant with a move away from a T1 type response, and a CD4 T cell-mediated regulation of the allocytotoxic T cell response. These results were dependent upon the level of FasL expression on TFC, in that low expression of FasL led to a less marked effect compared with the effect observed with high expression of FasL. These results provide some insight into the role of FasL in regulating destructive alloimmune responses in the case of whole organ grafting, and they have important implications for the development of FasL-based immunotherapy in organ transplantation.

Telerobotic laparoscopic cholecystectomy: initial clinical experience with 25 patients.

OBJECTIVE: To determine the safety and feasibility of performing telerobotic laparoscopic cholecystectomies. This will serve as a preliminary step toward the integration of computer-rendered three-dimensional preoperative imaging studies of anatomy and pathology onto the patient's own anatomy during surgery. SUMMARY BACKGROUND DATA: Computer-assisted surgery (CAS) increases the surgeon's dexterity and precision during minimally invasive surgery, especially when using microinstruments. Clinical trials have shown the improved microsurgical precision afforded by CAS in the minimally invasive setting in cardiac and gynecologic surgery. Future applications would allow integration of preoperative data and augmented-reality simulation onto the actual procedure. METHODS: Beginning in September 1999, CAS was used to perform cholecystectomies on 25 patients at a single medical center in this nonrandomized, prospective study. The operations were performed by one of two surgeons who had previous laboratory experience using the computer interface. The entire dissection was performed by the surgeon, who remained at a distance from the patient but in the same operating room. The operation was evaluated according to time of dissection, time of assembly/disassembly of robot, complications, immediate postoperative course, and short-term follow-up. RESULTS: Twenty of the 25 patients had symptomatic cholelithiasis, 1 had a gallbladder polyp, and 4 had acute cholecystitis. Twenty-four of the 25 laparoscopic cholecystectomies were successfully completed by CAS. There was one conversion to conventional laparoscopic cholecystectomy. Set-up and takedown of the robotic arms took a median of 18 minutes. The median operative time for dissection and the overall operative time were 25 and 108 minutes, respectively. There were no intraoperative complications. There was one postoperative complication of a suspected pulmonary embolus, which was treated with anticoagulation. All patients were tolerating diet at discharge. CONCLUSIONS: Laparoscopic cholecystectomy performed by CAS is safe and feasible, with operative times and patient recovery similar to those of conventional laparoscopy. At present, CAS cholecystectomy offers no obvious advantages to patients, but the potential advantages of CAS lie in its ability to convert the surgical act into digitized data. This digitized format can then interface with other forms of digitized data, such as pre- or intraoperative imaging studies, or be transmitted over a distance. This has the potential to revolutionize the way surgery is performed.

Detoxification of reactive oxygen species by a nonpeptidyl mimic of superoxide dismutase cures acetaminophen-induced acute liver failure in the mouse.

Drug-induced acute liver failure (ALF) is a devastating and often fatal disease mainly caused by poisoning by acetaminophen (APAP). The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), that leads to gluthatione depletion has been suspected to be the main effector of hepatocyte apoptosis during APAP-induced ALF. We have investigated whether reactive oxygen species (ROS) also play a role in APAP-induced ALF, and whether manganese III tetrakis (5,10,15,20 benzoic acid) (MnTBAP), a mimic of superoxide dismutase (SOD) with catalase-like activity, can treat the disease in mice. The effects of MnTBAP were tested on APAP-intoxicated mice and on isolated hepatocytes incubated with APAP. MnTBAP preventively and curatively administered significantly improved survival times, and dramatically reduced serum transaminase activity levels and parenchymal lesions in APAP-intoxicated mice. Whereas pretreatment with N-acetyl-L-cysteine (NAC) prevented ALF in a dose-dependent manner, the molecule was ineffective when curatively administered. The significant increase in glutathione peroxidase (Gpx) activity following APAP administration, and the beneficial effects of MnTBAP suggested that ROS were produced during APAP-induced ALF. A direct evidence of ROS generation was provided by flow cytometry of isolated hepatocytes incubated with APAP. In vitro, ROS production was associated with mitochondrial damage characterized by the collapse of transmembrane potential and the loss of cardiolipin content. In livers of intoxicated mice, ALF was associated with cytochrome c release that led to the activation of caspases-9 and -3. The capacity of MnTBAP to abrogate all those alterations suggests that ROS play a role in APAP-induced apoptosis of hepatocytes, and explains the beneficial effects of MnTBAP, which could be of interest in APAP-induced ALF in humans.

Teleeducation in surgery: European Institute for Telesurgery experience.

The information age is revolutionizing the practice and education of surgery. The use of video-conference systems through Integrated Service Digital Network (ISDN) teletransmission connects surgeons around the world without the limits of distance. Teleeducation, teleteaching, teletraining, telementoring, and teleaccreditation have been clearly demonstrated and are now common practice. Pre- and perioperative surgical advice may be obtained from expert networks. Patient data can be reconstructed as virtual tridimensional images analyzed by computers, and the surgical procedure can be simulated to obtain an optimal surgical decision. Finally, the use of the Internet will provide access to this information, whenever and wherever necessary, through dedicated websites. It remains to be adequately demonstrated that these means will allow improvement in patient care.

[A new model of isolated perfused heart. Study of hypodermin A in hyperacute xenograft rejection]. / Mise au point d'un modèle de coeur isolé perfusé. Application à l'étude de l'hypodermine A dans la prévention du rejet suraigu xénogénique.

AIMS OF THE STUDY: Isolated perfused heart (IPH) system and heart transplantation in the guinea-pig/rat combination represent a good model for the study of hyperacute xenograft rejection (HAR) in which the component plays a central role. Hypodermin A (HA), a protease cleaving the component, could be used to delay the HAR. METHODS: Creation of an original IPH working with rat serum (30 mL) and ex vivo study of HAR and I'HA. RESULTS: Study of HAR is possible with this IPH system. The mean guinea-pig heart survival after perfusion by normal rat serum was 38 +/- 7 min and was lower than survival observed after perfusion by guinea-pig serum (210 +/- 34 min) (p < 0.001), by decomplemented rat serum (177 +/- 45 min) (p < 0.001), and by rat serum with 20 micrograms/mL of HA (154 +/- 71 min) (p < 0.001). CONCLUSION: We developed an original system of isolated perfused heart allowing ex vivo study of HAR. HA delayed the occurrence of the HAR and confirmed the central role of the component in the HAR.

Laparoscopic liver resections: a feasibility study in 30 patients.

OBJECTIVE: To assess the feasibility and safety of laparoscopic liver resections. SUMMARY BACKGROUND DATA: The use of the laparoscopic approach for liver resections has remained limited for technical reasons. Progress in laparoscopic procedures and the development of dedicated technology have made it possible to consider laparoscopic resection in selected patients. METHODS: A prospective study of laparoscopic liver resections was undertaken in patients with preoperative diagnoses including benign lesion, hepatocellular carcinoma with compensated cirrhosis, and metastasis of noncolorectal origin. Hepatic involvement had to be limited and located in the left or peripheral right segments (segments 2-6), and the tumor had to be 5 cm or smaller. Surgical technique included CO2 pneumoperitoneum and liver transection with a harmonic scalpel, with or without portal triad clamping or hepatic vein control. Portal pedicles and large hepatic veins were stapled. Resected specimens were placed in a bag and removed through a separate incision, without fragmentation. RESULTS: From May 1996 to December 1999, 30 of 159 (19%) liver resections were included. There were 18 benign lesions and 12 malignant tumors, including 8 hepatocellular carcinomas in cirrhotic patients. Mean tumor size was 4.25 cm. There were two conversions to laparotomy (6.6%). The resections included 1 left hepatectomy, 8 bisegmentectomies (2 and 3), 9 segmentectomies, and 11 atypical resections. Mean blood loss was 300 mL. Mean surgical time was 214 minutes. There were no deaths. Complications occurred in six patients (20%). Only one cirrhotic patient developed postoperative ascites. No port-site metastases were observed in patients with malignant disease. CONCLUSION: Laparoscopic resections are feasible and safe in selected patients with left-sided and right-peripheral lesions requiring limited resection. Young patients with benign disease clearly benefit from avoiding a major abdominal incision, and cirrhotic patients may have a reduced complication rate.

[Xenotransplantation: physiopathology of hyperacute and differentiated rejection, and therapeutic perspectives]. / La x¿enotransplantation, physiopathologie du rejet suraigu et diff¿er¿e, et perspectives th¿erapeutiques.

The mechanisms of xenograft rejection involved in closely related species of donors and recipients are not the same as in disparate combinations. When the donor and the recipient are phylogenetically close, such as the monkey and the human being, the rejection of xenografts is essentially mediated by a cellular immune response, and is clinically similar to a strong allograft rejection. When the donor and the recipient belong to widely disparate species, such as in the pig-to-human combination, the graft is destroyed by a hyperacute rejection before a cellular rejection has started. Hyperacute rejection is triggered by the fixation of the recipient's preformed antibodies on the graft endothelium, and subsequent activation of the recipient's complement. The activation of endothelial cells that ensues leads to the formation of an extensive thrombosis within the graft and to its necrosis within minutes or hours after grafting. When hyperacute rejection is overcome by means of complement inhibitors, a delayed vascular rejection occurs within 36 to 48 hours, mainly involving antibody-dependent cellular cytotoxicity and contributing to the extension of the thrombosis. Both hyperacute and delayed vascular rejections can be prevented by depletion of preformed antibodies, inhibition of complement activation, or by masking the dominant xeno-epitope Gal alpha 1,3 Gal. Transgenic pigs expressing molecules that inhibit xenogeneic rejection are being produced. However, prior to any clinical use, the infectious risks, and particularly the viral risk must be evaluated.

Major liver resection for carcinoma in jaundiced patients without preoperative biliary drainage.

BACKGROUND: The role of preoperative biliary drainage (PBD) before liver resection in the presence of obstructive jaundice remains controversial. Our patients with proximal duct carcinoma undergo noninvasive assessment followed by rapid laparotomy without PBD if the lesion is deemed resectable. HYPOTHESIS: Our aim was to report operative outcome of these patients and to analyze their specific features by comparison with patients without biliary obstruction who underwent major liver resection. DESIGN: A case-comparison study. SETTING: A tertiary care university hospital in a metropolitan area. PATIENTS: Twenty consecutive jaundiced patients underwent major liver resection without PBD. The jaundiced patients were matched with 27 nonjaundiced patients with normal underlying liver selected from a computer bank of 261 patients undergoing liver resections and identical for age, tumor size, type of liver resection, and vascular occlusion. MAIN OUTCOME MEASURE: Postoperative course including mortality, morbidity, transfusion rates, and results of liver function tests. RESULTS: Seventeen jaundiced patients (85%) and 13 nonjaundiced patients (48%) received blood transfusions (P = .03). Morbidity was 50% in jaundiced and 15% in nonjaundiced patients (P = .006), mainly resulting from subphrenic collections and bile leaks occurring only in jaundiced patients. In contrast, there were no significant differences for mortality (5% vs 0%) and liver failure (5% vs 0%). Postoperative changes in liver function test results were comparable between groups. CONCLUSIONS: Major liver resections without PBD are safe in most patients with obstructive jaundice. Recovery of hepatic synthetic function is identical to that of nonjaundiced patients. Transfusion requirements and incidence of postoperative complications, especially bile leaks and subphrenic collections, are higher in jaundiced patients. Whether PBD could improve these results remains to be determined.

Association of the 5'HS4 sequence of the chicken beta-globin locus control region with human EF1 alpha gene promoter induces ubiquitous and high expression of human CD55 and CD59 cDNAs in transgenic rabbits.

Whatever its field of application, animal transgenesis aims at a high level of reproducible and stable transgene expression. In the case of xenotransplantation, prevention of hyperacute rejection of grafts of animal origin requires the use of organs expressing human inhibitors of complement activation such as CD55 (DAF) and CD59. Pigs transgenic for these molecules have been produced, but with low and variable levels of expression. In order to improve cDNA expression, a vector containing the 5'HS4 region from the LCR of the chicken beta-globin locus and the promoter and the first intron from the human EF1 alpha gene, was used to co-express human CD55 and CD59 cDNAs in transgenic rabbits. The transgenic lines with the 5'HS4 region displayed dramatically enhanced CD55 and CD59 mRNA concentrations in brain, heart, kidney, liver, lung, muscle, spleen and aortic endothelial cells in comparison with the transgenic lines without the 5'HS4 region. In the absence of the 5'HS4 region, only some of the transgenic lines displayed specific mRNAs and at low levels. Human CD55 and CD59 proteins were detectable in mononuclear cells from transgenic rabbits although at a lower level than in human mononuclear cells. On the other hand, primary aortic endothelial cells from a bi-transgenic line were very efficiently protected in vitro against human complement-dependent lysis. Transgenic rabbits harbouring the two human inhibitors of complement activation, CD55 and CD59, can therefore be used as new models in xenotransplantation. Moreover, the vector containing the 5'HS4 region from the LCR of the chicken beta-globin locus seems appropriate not only for xenotransplantation but also for any other studies involving transgenic animals in which cDNAs have to be expressed at a high level in all cell types.

Hepatic vascular exclusion with preservation of the caval flow for liver resections.

OBJECTIVE: To report the technique and results of an alternative method of vascular clamping during liver resections. BACKGROUND: Most liver resections require vascular clamping to avoid excessive blood loss. Portal triad clamping is often sufficient, but it does not suppress backflow bleeding, which can be prevented only by hepatic vascular exclusion. The latter method adds clamping of the inferior vena cava, which results in hypotension, requiring invasive anesthetic management. There is growing evidence that intermittent clamping is better tolerated than continuous clamping, especially in the presence of underlying liver disease. METHODS: Hepatic vascular exclusion with preservation of the caval flow (HVEPC) involved conventional inflow clamping associated with outflow control by clamping the major hepatic veins, thus avoiding caval occlusion. HVEPC was used in 40 patients undergoing major or complex liver resection, including 16 with underlying liver disease. HVEPC was total (clamping of the porta hepatis and all major hepatic veins) in 20 cases and partial (clamping of the porta hepatis and the hepatic veins of the resected territory) in 20. Clamping was continuous in 22 cases and intermittent in 18. Resections included 12 hemihepatectomies, 12 extended hepatectomies, 3 central hepatectomies, and 13 uni- or bisegmentectomies. RESULTS: Hemodynamic tolerance of clamping was excellent in all cases, without the need for therapeutic adjustment. Median red cell transfusion requirements were 0 units, and 28 patients (70%) did not receive any transfusions during the hospital stay. There were no deaths, and the morbidity rate was 17.5%. Median hospital stay was 10 days. CONCLUSION: HVEPC is a safe and effective procedure applicable to liver tumors without invasion to the inferior vena cava. It offers the advantages of conventional hepatic vascular exclusion without its hemodynamic drawbacks, and it can be applied intermittently or partially.

Risk of major liver resection in patients with underlying chronic liver disease: a reappraisal.

OBJECTIVE: To explore the relation of patient age, status of liver parenchyma, presence of markers of active hepatitis, and blood loss to subsequent death and complications in patients undergoing a similar major hepatectomy for the same disease using a standardized technique. SUMMARY BACKGROUND DATA: Major liver resection carries a high risk of postoperative liver failure in patients with chronic liver disease. However, this underlying liver disease may comprise a wide range of pathologic changes that have, in the past, not been well defined. METHODS: The nontumorous liver of 55 patients undergoing a right hepatectomy for hepatocellular carcinoma was classified according to a semiquantitative grading of fibrosis. The authors analyzed the influence of this pathologic feature and of other preoperative variables on the risk of postoperative death and complications. RESULTS: Serum bilirubin and prothrombin time increased on postoperative day 1, and their speed of recovery was influenced by the severity of fibrosis. Incidence of death from liver failure was 32% in patients with grade 4 fibrosis (cirrhosis) and 0% in patients with grade 0 to 3 fibrosis. The preoperative serum aspartate transaminase (ASAT) level ranged from 68 to 207 IU/l in patients with cirrhosis who died, compared with 20 to 62 in patients with cirrhosis who survived. CONCLUSION: A major liver resection such as a right hepatectomy may be safely performed in patients with underlying liver disease, provided no additional risk factors are present. Patients with a preoperative increase in ASAT should undergo a liver biopsy to rule out the presence of grade 4 fibrosis, which should contraindicate this resection.

[Selective use of vascular clamps in major hepatectomy]. / Utilisation sélective des clampages vasculaires au cours des hépatectomies majeures.

OBJECTIVE: To report the results of a selective use of vascular occlusions in major hepatectomies according to the size and location of the hepatic lesion. BACKGROUND: Total vascular exclusion (TVE) and portal triad clamping (PTC) ensure efficient hemostatic effect but lead to warm ischemia of the liver. Lobar vascular occlusion (LVO) avoids warm ischemia of the remnant liver but could result in increased blood loss. PATIENTS AND METHODS: Sixty consecutive major hepatectomies were studied. TVE was applied in 22 patients with large lesions (= 10 cm) or lesions with connections to the major hepatic veins or inferior vena cava. PTC (n = 15) and LVO (n = 23) were applied in remaining cases. RESULTS: Clamping method was efficient in 87%, 93% and 100% for LVO, PTC and TVE, respectively. Median blood transfusions were 0.3 and 2 units for LVO, PTC and TVE, respectively. Postoperative aminotransferase peak value was significantly lower after LVO than after PTC or TVE, while those peaks were not statistically different with these latter two methods. Postoperative prothrombin time fall value was identical in the three groups. Mortality was 3.3% (2/60) and was not influenced by the type of clamping, but both deaths and most complications occurred in patients with abnormal underlying liver parenchyma. CONCLUSION: Provided that adequate techniques are used, the need for blood transfusions is more dependent on the characteristics of the resected tumor than on the type of clamping used. Total vascular exclusion does not create more ischemic injury to the liver than portal triad clamping and it should be recommended for the resection of large or strategically located tumors. Other tumors can be resected in more than 80% of the cases with LVO, thus avoiding ischemia to the remnant liver. With the control of hemorrhage, pathology of underlying liver parenchyma has emerged as the main prognostic factor in major liver resections.

Human preformed IgG combining with membrane-bound porcine serotransferrin lyse porcine endothelial cells through antibody-dependent cellular cytotoxicity.

Preformed antibodies are involved in xenograft rejection. The purpose of this work was to characterize porcine xenoantigens recognized by human preformed IgG (hpIgG), and to investigate the role of hpIgG in xenogeneic rejection. IgG eluted from porcine livers perfused with human plasma, human sera and total human IgG were immunoblotted on porcine aortic endothelial cell extracts. The amino acid sequence of a 76-kDa antigen constantly revealed was 100% homologous with porcine serotransferrin (psTf). hpIgG from human sera, human IgG1 and IgG2 and F(ab')2gamma specifically bound to psTf. Neutralization by psTf abolished that binding. Although alpha1,3-linked galactose residues (Gal(alpha)1,3Gal) is the dominant epitope recognized by preformed antibodies in the swine-to-human combination, the analysis of carbohydrate composition of psTf showed that the molecule was devoid of Gal(alpha)1,3Gal moieties and that preformed anti-psTf IgG bound to epitopes localized on the peptide core of the molecule. Purified human anti-psTf IgG antibodies were able to bind to psTf linked to its receptor on porcine endothelial cells, and to kill those cells through antibody-dependent cellular cytotoxicity.

Safety of selective vascular clamping for major hepatectomies.

BACKGROUND: Although hepatic vascular clampings are widely used during major hepatic resections, they may not always be necessary. Selective vascular clamping, which only controls the afferent blood flow of the resected liver, could be a valuable alternative, provided that blood loss is not increased because the opposite liver remains perfused. STUDY DESIGN: The aim of the study was to assess the safety of selective vascular clamping in 43 patients who underwent 36 right hepatectomies and 7 left hepatectomies for lesions located peripherally within the liver. Blood transfusions, hepatic tests, morbidity, mortality, and hospital stay were evaluated. RESULTS: Selective vascular clamping was efficient in 34 of the 43 attempts (79%), but bleeding from the contralateral liver required conversion to portal triad damping in 9 patients (21%). Median blood transfusions were 0 units (range 0 to 4 U), and 28 patients (65%) did not require transfusions. Postoperative laboratory tests showed that larger changes occurred at day 1 and tended to return to preoperative values at the end of the first postoperative week. Median time of hospitalization was 10 days (range 7 to 28 days). Postoperative course was uneventful in 35 patients (81%). Nonlethal complications occurred in 7 patients (16.3%). One patient (2%) with massive hepatic steatosis died of liver failure after right hepatectomy. CONCLUSIONS: Selective vascular clamping is a safe alternative to total inflow occlusion for major hepatectomies applicable in 80% of selected patients with peripheral liver tumors.