Benoit Malassagne

Laparoscopic Liver Resections: A Feasibility Study in 30 Patients

ObjectiveTo assess the feasibility and safety of laparoscopic liver resections. Summary Background DataThe 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. MethodsA 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. ResultsFrom 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. ConclusionLaparoscopic 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.

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

OBJECTIVEnTo 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.nnnSUMMARY BACKGROUND DATAnMajor 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.nnnMETHODSnThe 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.nnnRESULTSnSerum 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.nnnCONCLUSIONnA 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.

Telerobotic laparoscopic cholecystectomy : Initial clinical experience with 25 patients

ObjectiveTo 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 DataComputer-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. MethodsBeginning 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. ResultsTwenty 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. ConclusionsLaparoscopic 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.

Hepatic Vascular Exclusion With Preservation of the Caval Flow for Liver Resections

OBJECTIVEnTo report the technique and results of an alternative method of vascular clamping during liver resections.nnnBACKGROUNDnMost 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.nnnMETHODSnHepatic 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.nnnRESULTSnHemodynamic 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.nnnCONCLUSIONnHVEPC 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.

Association of the 5′ HS4 sequence of the chicken β‐globin locus control region with human EF1α 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 β‐globin locus and the promoter and the first intron from the human EF1α 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 β‐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.

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.

Biliary Administration of Naked DNA Encoding Fas–Fc Protein Prevents Acute Liver Failure in Mice

Acute liver failure (ALF) of infectious origin results from massive Fas-mediated hepatocyte apoptosis. To cure Fas-induced ALF in mice, we have designed a noninvasive procedure for intrahepatic transfer of a plasmid that encodes a molecule inhibiting Fas-Fas ligand interaction. For that purpose, naked pDNA encoding green fluorescent protein (GFP) or the Fas-Fc chimeric protein was transferred into mice by the biliary route. Ten percent of hepatocytes expressed GFP. After pFas-Fc transfer, about 40 ng of Fas-Fc protein per milliliter could be detected in sera from day 4 to day 28. Serum recombinant Fas-Fc could neutralize Fas-induced cell death in vitro. Furthermore, pFas-Fc biliary transfer efficiently protected mice against Fas-mediated ALF, because survival rates (p < 0.01), serum transaminase activities (p < 0.05), and histological data (p < 0.02) were improved versus control pTNFR-Fc-transfected mice. In conclusion, naked pDNA encoding Fas-Fc is efficiently expressed by hepatocytes after biliary gene transfer in mice. This method, devoid of virus-related risks, could be considered for the treatment of Fas-mediated ALF in humans.