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corinne vons

corinne.vons@abc.aphp.fr

Journal articles

2007
 
PMID 
Jan Martin Proske, Ibrahim Dagher, Claudiu Revitea, Alessio Carloni, Violaine Beauthier, Thierry Labaille, Corinne Vons, Dominique Franco (2007)  Day-case laparoscopic cholecystectomy: results of 211 consecutive patients.   Gastroenterol Clin Biol 31: 4. 421-424 Apr  
Abstract: OBJECTIVES: The purpose of this work was to evaluate the feasibility and outcome of elective laparoscopic cholecystectomy as a day-case procedure in a French university hospital. METHODS: Since the creation of a surgical day-care centre in 1999, patients without severe chronic disease and anticoagulant therapy were selected for elective laparoscopic cholecystectomy. They were admitted and operated on in the morning hours and discharged after a double check by the surgeon and an anaesthetist 4 to 6 hours later. They were contacted by telephone the day subsequent to surgery and were seen in the outpatient unit 8 to 10 days after. RESULTS: Two hundred eleven laparoscopic cholecystectomies were performed in day-care surgery from January 1999 to December 2005. The proportion of day-case management increased during the six-year period from 32% to 53%. Eighteen percent of patients had an overnight admission. The overall complication rate was 1.8%. None of the patients had an emergency readmission. Incapacity duration went from 1 to 15 days. CONCLUSION: These results suggest that laparoscopic cholecystectomy can be routinely performed as a day-case procedure.
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PMID 
J G Tralhão, S Kayal, I Dagher, M Sanhueza, C Vons, D Franco (2007)  Resection of hepatocellular carcinoma: the effect of surgical margin and blood transfusion on long-term survival. Analysis of 209 consecutive patients.   Hepatogastroenterology 54: 76. 1200-1206 Jun  
Abstract: BACKGROUND/AIMS: Certain prognostic factors affect the postoperative mortality and long-term survival of patients following hepatic resection for hepatocellular carcinoma (HCC) and may change the surgical strategy. METHODOLOGY: 209 consecutive patients underwent hepatic resection for HCC in our hospital. Seventy-three patients underwent major resection and 136 underwent minor resections. We looked for correlations between clinical, biological, surgical and pathological factors and postoperative mortality, disease-free survival and overall survival. RESULTS: The postoperative mortality rate was 7.7% (it fell to 0% in the last two years). The cumulative overall five-year survival rate was 27% and the overall disease-free survival rate was 7.3%. Multivariate analysis identified: (1) two independent prognostic factors for postoperative mortality: age and tumor size; (2) one risk factor for tumor recurrence: intraoperative blood transfusion, and (3) three independent prognostic factors for overall survival: infiltrative tumor type, surgical margin <10 mm and intraoperative blood transfusion. CONCLUSIONS: In addition to routine staging of the tumor, the preoperative evaluation of HCC patients should include tests to determine whether the tumor is infiltrative or expansive and whether it will be possible to obtain a surgical margin (>10 mm). This procedure should make it possible to propose an appropriate neoadjuvant treatment only to these patients. The prevention of intraoperative bleeding or blood transfusion should improve the disease-free and overall survival rates in HCC patients.
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2006
 
DOI   
PMID 
Ibrahim Dagher, Lyes Boudechiche, Julie Branger, Aurore Coulomb-Lhermine, Alexandre Parouchev, Loïc Sentilhes, Tao Lin, Marie-Thérèse Groyer-Picard, Corinne Vons, Michelle Hadchouel, Danièle Pariente, Marion Andreoletti, Dominique Franco, Anne Weber (2006)  Efficient hepatocyte engraftment in a nonhuman primate model after partial portal vein embolization.   Transplantation 82: 8. 1067-1073 Oct  
Abstract: BACKGROUND: Hepatocyte transplantation could be an alternative to whole liver transplantation for the treatment of metabolic liver diseases. However, the results of clinical investigations suggest that the number of engrafted hepatocytes was insufficient to correct metabolic disorders. This may partly result from a lack of proliferation of transplanted hepatocytes. In rodents, portal ligation enhances hepatocyte engraftment after transplantation. We investigated the effects of partial portal ligation and embolization on engraftment and proliferation of transplanted hepatocytes in primates. METHODS: Hepatocyte autotransplantation was performed in Macaca monkeys. The left lateral lobe was resected for hepatocyte isolation. The first group of monkeys underwent surgical ligation of the left and right anterior portal branches; in the second group, the same portal territories were obstructed by embolization with biological glue. To evaluate the proportion of cell engraftment hepatocytes were Hoechst-labeled and transplanted via the portal vein. Cell proliferation was measured by BrdU incorporation. RESULTS: Hepatocyte proliferation was induced by both procedures but it was significantly higher after partial portal embolization (23.5% and 11.2% of dividing hepatocytes on days 3 and 7) than after ligation (3% and 0.8%). Hepatocytes engrafted more efficiently after embolization than after ligation. They proliferated and participated to liver regeneration representing 10% of the liver mass on day seven and their number remained constant on day 15. CONCLUSIONS: These data suggest that partial portal embolization of the recipient liver improves engraftment of transplanted hepatocytes in a primate preclinical model providing a new strategy for hepatocyte transplantation.
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2005
 
DOI   
PMID 
François Gilles Brivet, Claude Smadja, Ulrich Hilbert, Corinne Vons, Frederic Jacobs, Haleh Gordji-Therani, Dominique Musset (2005)  Usefulness of abdominal CT scan in severe peritoneal sepsis linked to primary peritonitis.   Scand J Infect Dis 37: 1. 76-78  
Abstract: We report 2 cases of primary group A streptococcal peritonitis in which emergency abdominal CT scan ruled out a hollow viscus perforation, or necrosis, avoiding unnecessary laparotomy. These cases highlight the usefulness of abdominal CT scan and suggest that blind surgical exploration has no advantages.
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PMID 
Axèle Champault, Ibrahim Dagher, Corinne Vons, Dominique Franco (2005)  Laparoscopic hepatic resection for hepatocellular carcinoma. Retrospective study of 12 patients.   Gastroenterol Clin Biol 29: 10. 969-973 Oct  
Abstract: AIMS: To assess the results of laparoscopic liver resection for hepatocellular carcinoma. PATIENTS AND METHODS: From 1998 to 2003, 12 laparoscopic liver resections for hepatocellular carcinoma were performed. RESULTS: There were no operative complications and no deaths. Conversion to laparotomy was required in one patient (8%) and transfusion in three patients (25%). One patient died of liver failure. Postoperative complications occurred in three patients (25%): trocar site bleeding, cardiac failure and biliary collection. The mean hospital stay was 5 days. No ascites and no transient liver failure occurred. During the mean follow up of 15 months the recurrence rate was 45.5%. No port site or peritoneal metastases were observed. Treatment of recurrence was second resection in two patients and microwave coagulation therapy in two other patients. Mean survival was 24 months. CONCLUSION: Laparoscopic liver resection is feasible in hepatocellular carcinoma if the tumor is unique, smaller than 5 centimeters and located in the left lateral segments or in the anterior or inferior segments of the right liver. Postoperative morbidity is low and long-term results seem to be similar to laparotomy.
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2004
 
DOI   
PMID 
J M Proske, C Vons (2004)  Transgastric laparoscopic approach for resection of hemorrhagic Dieulafoy's vascular malformation.   Surg Endosc 18: 3. 554-556 Mar  
Abstract: We report the case of a successfully resected hemorrhagic Dieulafoy's vascular malformation using a transgastric laparoscopic approach. A 37-year-old man was admitted for hematemesis and anemia. Emergency endoscopy revealed active hemorrhage from a submucosal vascular malformation in the posterior gastric wall. Dieulafoy's disease was suspected. It was initially treated by repeated endoscopy. Due to recurrent bleeding, on day 3 the patient was scheduled for surgery. The laparoscopic treatment consisted of an anterior gastrotomy, followed by extirpation and resection of the lesion after evaluation of the gastro-esophageal junction. There was no need for intraoperative endoscopy. To our knowledge, this is the first description of the application of a transgastric laparoscopic approach for the management of a hemorrhagic Dieulafoy's vascular malformation.
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DOI   
PMID 
Isabelle Lorand, Corinne Vons, Tuan Nguyen, Virginie Di Rico, Aurore Coulomb, Dominique Franco, Frédérique Capron, Anne Weber (2004)  Portal branch ligation induces efficient retrovirus-mediated gene delivery in rat liver.   J Gene Med 6: 5. 507-513 May  
Abstract: BACKGROUND: The in vivo transduction of hepatocytes with conventional retrovirus vectors requires the induction of cell division and this can currently only be achieved by invasive surgery or by inducing severe liver damage. We hypothesised that partial portal branch ligation (PBL) could induce hepatocyte proliferation and efficient gene transfer in the rat. METHODS: We ligated the portal branch serving 70% of the liver and measured the kinetics of liver mass restoration and cell proliferation and the distribution of dividing hepatocytes after administration of 5-bromo-2'-deoxyuridine. The efficiency of retrovirus-mediated gene transfer after PBL was tested by use of beta-galactosidase-expressing recombinant retroviruses. The viruses were administered in a single injection via the portal vein at different times after PBL and the livers of transduced animals were analysed 4 days later. RESULTS: We found that the number of cycling hepatocytes remained stable between 24 and 44 h after PBL (approximately 12.5%). Although there was a high level of inter-animal variability, hepatocyte proliferation was always initiated in the same lobe of the liver. In animals that had undergone PBL, 19% of hepatocytes were transduced 28 h after the administration of a single high-titre injection of retroviruses, mainly around the portal spaces. CONCLUSIONS: PBL can mediate the efficient transduction of hepatocytes in vivo after a single intravenous injection of recombinant retroviruses. This approach is feasible in humans.
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PMID 
J M Proske, C Vons (2004)  Laparoscopic treatment of ventral hernias.   J Chir (Paris) 141: 6. 360-364 Nov  
Abstract: The use of mesh in incisional hernia repair has reduced the rate of hernia recurrence. Laparoscopic placement of mesh is a promising alternative to the classical open approach. Recent studies involving large numbers of patients have shown the laparoscopic approach to be feasible in 95% of cases; the incidence of postoperative complications was low and hernia recurrence occurred in 3-5% at three years. Several retrospective studies and one randomized study comparing open versus laparascopic ventral hernia repair suggest that the laparoscopic repair yields better results (fewer postoperative complications and lower recurrence rate) than the classical open approach.
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2003
 
DOI   
PMID 
Tuan Huy Nguyen, Nathalie Loux, Ibrahim Dagher, Corinne Vons, Ken Carey, Pascale Briand, Michelle Hadchouel, Dominique Franco, Jacqueline Jouanneau, Ralph Schwall, Anne Weber (2003)  Improved gene transfer selectivity to hepatocarcinoma cells by retrovirus vector displaying single-chain variable fragment antibody against c-Met.   Cancer Gene Ther 10: 11. 840-849 Nov  
Abstract: Engineered retroviruses are widely used vectors for cancer gene therapy approaches. However, the ability to target cells of therapeutic interest while controlling the expression of the transferred genes would improve both the efficiency and the safety of viral vectors. In this study, we investigated the ability of a retroviral amphotropic envelope displaying single-chain variable-fragment (scFv) directed against the c-Met receptor, to target the entry of recombinant retroviruses to human hepatocarcinoma cells. Four single-chain antibody fragments directed against the c-Met receptor were generated and inserted into the viral envelope protein as an N-terminal fusion. The modified envelopes were incorporated into virus particles and one of the chimeric viruses, 3D6-Env, transduced preferentially human hepatoma cells rather than proliferating human hepatocytes. In another construct, the urokinase cleavage site was inserted between the scFv moiety and the envelope. Chimeric scFv-urokinase-Env viruses transduced hepatoma cells with a similar efficiency to that of the control virus and their infectivity in human hepatocytes remained low. These results indicate that amphotropic retroviruses with engineered envelopes to display scFv directed against the c-Met receptor can efficiently and selectively deliver genes into hepatoma cells.
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PMID 
R Fior, C Vons (2003)  When should peripheral lymphadenopathy be biopsied?   J Chir (Paris) 140: 5. 291-294 Oct  
Abstract: Excisional biopsy for lymphadenopathy is sometimes necessary to confirm the diagnosis of lymphoma or metastatic disease from an unknown primary site. Lymph node excision should be preceded by less invasive approaches which may confirm a benign pathology. Collaboration with medical and hematologic specialists will allow a well-reasoned diagnostic approach with complementary studies; excisional biopsy, if necessary, will then be done under the best conditions and in the most cost-efficient manner.
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2002
 
PMID 
Vincent Gajdos, Francis Perreaux, François Brivet, Corinne Vons, Philippe Labrune (2002)  Abdominal pain and ketonuria in an 11-year-old girl five months after abdominal trauma.   J Pediatr Surg 37: 9. 1361-1362 Sep  
Abstract: Five months after an abdominal trauma, a 11-year-old girl was admitted for abdominal pain, hyperglycemia, and ketonuria, which led to the diagnosis of left diaphragmatic rupture with gastric necrosis and perforation. The girl died soon after operation.
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DOI   
PMID 
A Champault, C Vons, I Dagher, S Amerlinck, D Franco (2002)  Low-cost laparoscopic cholecystectomy.   Br J Surg 89: 12. 1602-1607 Dec  
Abstract: BACKGROUND: Hospital managers are continually trying to decrease the cost of patient care. The aim of this prospective study was to propose changes that would decrease the operating room costs of laparoscopic cholecystectomy without affecting clinical results. METHODS: The study included 112 consecutive patients who underwent an elective cholecystectomy between January 1997 and December 2000. The procedure was changed in eight ways: the American position, open laparoscopy, reusable trocars, reusable instruments, bipolar coagulation of the cystic artery, intracorporeal ligature of the cystic duct, no use of suction lavage apparatus, and use of a surgical glove as a bag to extract the gallbladder. Complete compliance with the procedure, whether any abnormal operative events or complications occurred, the duration of hospitalization, and the material and labour costs of the procedure were recorded. RESULTS: There were no abnormal operative events. Only two patients suffered from postoperative complications. The mean duration of hospitalization was 55.8 h. Fifteen patients (13.4 per cent) were not hospitalized overnight. The operating costs fell from 560 euros before the study to 330 euros in 2000. CONCLUSION: By applying simple measures, it is possible to decrease the operating room cost of laparoscopic cholecystectomy whilst maintaining good results. Such measures should be applied to other laparoscopic procedures.
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2001
 
DOI   
PMID 
M Andreoletti, N Loux, C Vons, T H Nguyen, I Lorand, D Mahieu, L Simon, V Di Rico, B Vingert, J Chapman, P Briand, R Schwall, J Hamza, F Capron, F Bargy, D Franco, A Weber (2001)  Engraftment of autologous retrovirally transduced hepatocytes after intraportal transplantation into nonhuman primates: implication for ex vivo gene therapy.   Hum Gene Ther 12: 2. 169-179 Jan  
Abstract: The main impediment to effective ex vivo liver gene therapy of metabolic diseases is the lack of experimental work on large animals to resolve such important issues as effective gene delivery, cell-processing techniques, and the development of appropriate vectors. We have used a nonhuman primate, as a preclinical model, to analyze the limiting steps of this approach using recombinant retroviruses. Seven monkeys (Macaca fascicularis) underwent the complete protocol: their left liver lobe was resected, a catheter was placed in the inferior mesenteric vein and connected to an infusion chamber, and the hepatocytes were isolated, cultured, and transduced with a retroviral vector containing the beta-galactosidase gene. The hepatocytes were harvested and returned to the host via the infusion chamber. Biopsies were taken 4-40 days later. No animal was killed in the course of the experiments. They all tolerated the procedure well. We have developed and defined conditions that permit the proliferation and transduction of up to 90% of the plated hepatocytes. A significant proportion of genetically modified cells, representing up to 3% of the liver mass, were safely delivered to the liver via the chamber. Polymerase chain reaction analysis detected integrated viral DNA sequences and quantitative analysis of the in situ beta-Gal-expressing hepatocytes indicated that a significant amount of transduced hepatocytes, up to 2%, had become integrated into the liver and were functional. These results represent substantial advances in the development of the ex vivo approach and suggest that this approach is of clinical relevance for liver-directed gene therapy.
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PMID 
C Vons (2001)  Diagnosis of appendicular syndromes: for a rational approach   J Chir (Paris) 138: 3. 143-145 Jun  
Abstract: Diagnosis of acute appendicitis is made in 80% of cases by analysis of symptoms and physical examination. Epigastric pain, secondary located in the lower quadrant, along with tenderness is the most specific sign of acute appendicitis. In 20% of cases, diagnosis is difficult. High level of leucocytosis is not of great value. Laparoscopy has been proposed to visualize the appendix. Echotomography and tomodensitometry are less invasive and less costly procedures, that let surgeons identify the appendix and confirm or reject the diagnosis of acute appendicitis. Thus, surgical acts should be restricted to necessary appendicectomies.
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PMID 
C Vons (2001)  Transplantation of isolated hepatocytes, is it an alternative for total liver transplantation? On the treatment of hereditary hepatic metabolic diseases   J Chir (Paris) 138: 6. 342-346 Dec  
Abstract: Since 1976, it has been demonstrated in the small animal that isolated hepatocytes transferred into the liver can integrate into the recipient organ, survive and perform differentiated functions. This cell therapy technique can be used to partially correct for hereditary metabolic disorders in animal models of human hereditary metabolic diseases. The first methods used for hepatocytes transplantation involved a mass of hepatocytes that was clearly to limited (about 0.5% and never more than 2%). Integration fo the hepathocytes was limited by poorly understood factors. The vary variable clinicial results in the eight trials performed in the 90s is a clear demonstration. Recent work has helped understand the mechanisms limiting the integration of transplanted hepatocytes in the recipient liver. This led to the concept of repopulation, increasing the percentage of the hepatocyte mass reconstituted during the transplantation. The goal is to give the transplanted hepatocytes a proliferation advantage over he native hepatocytes. Several models have been designed and are currently being evaluated for application in humans. We are not far from new clinical trials with hepatocyte transplantation in humans for the treatment hereditary metabolic diseases. For certain disease, 3 to 5% normally functioning hepatocytes in the recipient liver would be sufficient to achieve a clinically significant effect for the patient.
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PMID 
C Vons, N Loux, L Simon, D Mahieu-Caputo, I Dagher, M Andreoletti, J Borgnon, V Di Rico, F Bargy, F Capron, A Weber, D Franco (2001)  Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.   Transplantation 72: 5. 811-818 Sep  
Abstract: BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.
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2000
 
PMID 
L Lorand, N Loux, J E Allain, V Di Rico, A Weber, D Franco, F Capron, C Vons (2000)  Effect of portal branch ligation on liver regeneration in the rat   Ann Chir 125: 2. 144-148 Feb  
Abstract: GOAL: The aim of this study was to assess liver regeneration after partial portal ligation. METHODS: 70% partial portal occlusion was obtained by ligation of the left portal vein branch. Total liver weight ratio were measured 96 hours after partial portal occlusion and in sham operated animals. The kinetics of hepatocytes division was evaluated by measuring the incorporation of 5-bromo-21-deoxyuridine into replicating cells at various time points by immunohistochemistry. RESULTS: Partial portal occlusion did not alter the total liver weight 96 hours after surgery. It resulted in atrophy of the ligated lobes and hypertrophy of the lobes with preserved portal flow. Hypertrophy was associated to an increase of the percentage of replicating hepatocytes. The replication rate was maximum at 28 hours with a peak at 12.5% and was prolonged beyond the 48th hour. CONCLUSIONS: Partial portal occlusion results in major and prolonged regeneration process in the liver lobes with preserved portal flow.
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PMID 
M Lungo, F Tenenbaum, P Chaumerliac, C Vons, A Mirat, F Beuzen, J P Luton, B Richard (2000)  Ovarian endometriosis cyst with iodine 131 uptake : first case of false positive in the follow up for differentiated thyroid carcinoma   Ann Endocrinol (Paris) 61: 2. 147-150 May  
Abstract: A whole body scan is performed after a radioiodine treatment in patients with differentiated thyroid carcinoma. This scan is useful coupled with thyroglobulin level for the patient's management. When unusual uptake is found, investigations have to be done to eliminate thyroid metastasis. A 28-year old woman underwent a total thyroidectomy for micro papillary carcinoma. Two years and a half after, ultrasonography of the neck showed a small lymph node in homolateral side of carcinoma. It was decided to begin treatment with iodine 131. The post-therapeutic scan showed an abnormal pelvic uptake. IRM found no osseous abnormality but an ovarian lesion. After surgery, histological diagnosis was an endometriosis cyst without thyroid or tumoral cells. Abdominal ou pelvic iodine false positive are rare. Ovarian cysts may be the cause of false positive radioiodine uptake. Endometriosis cyst was not previously described and the mecanism of iodine uptake is not clear.
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1999
 
DOI   
PMID 
M A Loriot, J P Bronowicki, D Lagorce, F Lakehal, T Persico, G Barba, M Mergey, C Vons, D Franco, J Belghiti, M Giacca, C Housset, C Bréchot (1999)  Permissiveness of human biliary epithelial cells to infection by hepatitis C virus.   Hepatology 29: 5. 1587-1595 May  
Abstract: The cellular tropism of hepatitis C virus (HCV) is an important but much debated issue. Permissivity to HCV of biliary cells has never been demonstrated. In this context, we used gallbladder epithelial cells (GBEC) as a model of the more proximal biliary epithelium. These cells were isolated from HCV-positive and -negative individuals and cultured for up to 40 days. Biliary cells from HCV-negative subjects were infected in vitro with various inocula. The retention of GBEC functional characteristics was assessed by the expression of cystic fibrosis transmembrane conductance regulator (CFTR). All 12 GBEC tested from HCV-negative patients were successfully infected by HCV. This was assessed by: 1) the detection of HCV-RNA positive and negative strands; 2) the detection of the viral capsid by immunofluorescence; and 3) the combination of single-strand conformation polymorphism (SSCP) and HVR1 sequence analysis demonstrating the distinct majoritary HCV genomes in serum and in GBEC. The level of HCV RNA in cell extracts and supernatants was low, but HCV infection was highly reproducible. Our results expand those showing the cellular tropism of HCV, and demonstrate the sensitivity of biliary cells to HCV infection. This might have an important impact in terms of pathogenesis and pathological features of HCV infection. In addition, given the easy access to these cells and the high reproducibility of in vitro infection, they should constitute an important tool for studies aimed at analyzing the issue of HCV penetration and neutralizing antibodies.
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DOI   
PMID 
M Louha, J Nicolet, H Zylberberg, A Sabile, C Vons, G Vona, K Poussin, M Tournebize, F Capron, S Pol, D Franco, B Lacour, C Bréchot, P Paterlini-Bréchot (1999)  Liver resection and needle liver biopsy cause hematogenous dissemination of liver cells.   Hepatology 29: 3. 879-882 Mar  
Abstract: We have investigated whether liver resection and needle liver biopsy cause dissemination of liver cells into peripheral blood circulation, using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay targeted against alpha-fetoprotein (AFP) mRNA. Twelve patients with and 16 without primary liver cancer (PLC) undergoing liver resection were tested before skin incision, after liver mobilization, after hepatic parenchyma transection, after abdominal wall suture, and 4 days after surgery. Two patients with and 20 without PLC were tested before, 20 minutes after, and 24 hours after needle liver biopsy. Six of 14 patients with and 0 of 36 patients without PLC scored positive before intervention (P <.001). Liver cell spreading was induced at different times after surgery and liver biopsy in 14 of 14 patients with but also 23 of 36 without PLC (P <.05). We conclude that liver resection and needle liver biopsy induce release of cells from the liver, which are not necessarily liver tumor cells, into the peripheral blood circulation. This may be, however, an important mechanism of liver cancer cell dissemination deserving further investigations.
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PMID 
V Vilgrain, M Lewin, C Vons, A Denys, D Valla, J F Flejou, J Belghiti, Y Menu (1999)  Hepatic nodules in Budd-Chiari syndrome: imaging features.   Radiology 210: 2. 443-450 Feb  
Abstract: PURPOSE: To analyze the imaging features of nodules associated with Budd-Chiari syndrome. MATERIALS AND METHODS: The authors retrospectively studied images obtained in 23 patients with liver nodules who were being followed up for Budd-Chiari syndrome. Doppler ultrasonography was performed in all patients, computed tomography in 16, and magnetic resonance (MR) imaging in 20. The following lesion features were evaluated: location, number, size, vascularization, qualitative signal intensity at MR imaging, and homogeneity. Nodules were diagnosed on the basis of histopathologic findings or clinical and biologic data with no change at imaging during 2-year follow-up. RESULTS: All patients had histopathologic features of chronic Budd-Chiari syndrome. Four patients had hepatocellular carcinoma (HCC), with one to three lesions. The mean diameter of the largest HCC lesion in each patient was 7.3 cm. All HCC lesions were heterogeneous and had high signal intensity on T2-weighted MR images. Nineteen patients had multiple benign regenerative nodules, most of which were smaller than 4 cm. Most nodules were homogeneous and hyperintense on T1- and T2-weighted images. In 15 patients, nodules were hypervascular in the arterial phase. CONCLUSION: In patients with chronic Budd-Chiari syndrome, multiple (> 10) small (< 4-cm) lesions are suggestive of benignity.
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PMID 
A el Madani, A Badawy, C Henry, J Nicolet, C Vons, C Smadja, D Franco (1999)  Laparoscopic cholecystectomy in acute cholecystitis   Chirurgie 124: 2. 171-5; discussion 175-6 Apr  
Abstract: PURPOSE: To determine the feasibility, operative risk and patients' benefit of laparoscopy in emergency cholecystectomy for acute calculous cholecystitis. PATIENTS AND METHODS: From January 1991 to December 1998, 234 patients with acute calculous cholecystitis were operated on by emergency laparoscopic cholecystectomy. There were 131 women and 103 men (mean age: 57 years), (Asa 2: 48%, Asa 3: 10%). In seven patients, choledocolithiasis was detected by endoscopic ultrasonography and preoperatively treated by endoscopic sphincterotomy. The mean delay between in-hospital admission and cholecystectomy was 20 hours (2-160). Cholecystectomy was performed with primary approach of Calot's triangle. Intraoperative cholangiography, selectively performed (n = 70), detected choledocolithiasis in three patients. RESULTS: The mean duration of surgery was 149 minutes (62-313). The conversion rate was 13% and decreased through the years. The postoperative complication rate was 18%. Eight patients (3.4%) had an abdominal complication. One patient (0.4%) died of bile peritonitis after intraoperative undetected main bile duct injury. The mean postoperative hospital stay was 6.04 days. It was 3.5 days only, very old patients and those with severe associated disease being excluded. CONCLUSION: Laparoscopy appears to be a good approach for emergency cholecystectomy in patients with acute calculous cholecystitis.
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PMID 
C Vons (1999)  Laparoscopy with a diagnostic aim in abdominal emergencies   Chirurgie 124: 2. 182-186 Apr  
Abstract: In acute abdominal syndromes when a surgical exploration is required by the presence of peritoneal symptoms, laparoscopy allows to recognize the lesions and to perform simultaneously the appropriate treatment in most cases. When the surgical indication is doubtful, mainly in case of acute appendicitis, sonography or scanography may confirm the diagnosis. In case of persisting doubt, diagnostic laparoscopy is justified and laparoscopic appendicectomy seems to be the best method when another pathology is not detected by laparoscopy. In abdominal wounds, laparoscopy is useful to confirm their intraperitoneal penetration, mainly in gunshot wounds, and to recognize a diaphragmatic wound which is often isolated and unknown. Laparoscopy often fails to detect all abdominal injuries. In blunt abdominal traumas, laparoscopy is not recommended at the first step. In conclusion, laparoscopy with diagnostic intent only is rarely indicated in abdominal emergencies and its use is not worth being extended. Diagnostic value of laparoscopy is closely linked to its therapeutic interest. Laparoscopy with both diagnostic and therapeutic intent has to be developed in most abdominal emergencies.
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PMID 
C Smadja, A Badawy, C Vons, V Giraud, D Franco (1999)  Laparoscopic cystogastrostomy for pancreatic pseudocyst is safe and effective.   J Laparoendosc Adv Surg Tech A 9: 5. 401-403 Oct  
Abstract: Between March 1997 and March 1998, three consecutive patients underwent laparoscopic cystogastrostomy for persistent giant retrogastric pancreatic pseudocyst complicating an attack of acute pancreatitis. The mean cyst diameter was 15 +/- 1 cm (range 14-16). The procedure was performed with four trocars. The anterior wall of the stomach was opened longitudinally. The pseudocyst was entered through the posterior wall of the stomach. A cystogastrostomy was created by suturing the margins of the communication by interrupted nonabsorbable sutures. The mean operative time was 123 +/- 15 min, and there were no postoperative complications. The mean postoperative hospital stay was 4 +/- 1 days. Computed tomography demonstrated complete resolution of the pseudocyst. Laparoscopic cystogastrostomy represents a good therapeutic option for persistent retrogastric pancreatic pseudocyst.
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PMID 
C Smadja, M Sbai Idrissi, M Tahrat, C Vons, E Bobocescu, P Baillet, D Franco (1999)  Elective laparoscopic sigmoid colectomy for diverticulitis. Results of a prospective study.   Surg Endosc 13: 7. 645-648 Jul  
Abstract: BACKGROUND: We undertook a prospective evaluation of elective laparoscopic sigmoid colectomy for diverticulitis in order to assess the risks and benefits of this approach. METHODS: Between November 1992 and November 1996, 54 consecutive patients were included in this study. Their mean age was 59 +/- 13 years (range, 36-81). The number of attacks of diverticulitis before colectomy ranged from one to four (mean, 2.2 +/- 0.7). The operative technique consisted of elective division of the inferior mesenteric vessels, left colonic flexure mobilization, and colorectal anastomosis using the cross-stapling technique. RESULTS: Five procedures (9.2%) were converted. The primary cause for conversion was obesity. These patients had a simple postoperative course. There were no postoperative deaths. Three patients (6.1%) developed abdominal complications, and four patients (8.2%) had abdominal wall complications. Postoperative paralytic ileus lasted only 2.3 +/- 0.7 days (range, 1-6), allowing for a rapid reintroduction of regular diet. The mean postoperative hospital stay was 6.4 +/- 2.7 days (range, 4-15). CONCLUSIONS: Elective laparoscopic colectomy for diverticulitis is feasible in most cases. In most cases, the operative risk is low and the postoperative course is uneventful. Elective sigmoid laparoscopic colectomy should be considered a good therapeutic option for symptomatic diverticulitis.
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1998
 
PMID 
C Henry, C Smadja, C Vons, E Bobocescu, D Mariette, M Tahrat, D Franco (1998)  Results of laparoscopic treatment of abdominal emergencies   Ann Chir 52: 3. 223-228  
Abstract: The purpose of this retrospective study was to evaluate the results of the laparoscopic surgical treatment of abdominal emergencies. From May 1991 to September 1995, 200 patients operated by laparoscopy for an acute abdomen were included in this study. The decision to treat the patient by laparoscopy was taken by the surgeon on duty. There were 101 males and 99 females with a mean age of 41 +/- 20 years (range 11-90 years). The main indications for operation were: acute appendicitis (109 patients), acute cholecystitis (52 patients), small bowel obstruction (14 patients) and perforated duodenal ulcer (14 patients). There was no hospital mortality. One per cent of patients experienced an operative complication which was treated by laparotomy. Conversion to laparotomy was needed in 13% of cases. The morbidity rate was 9% and reoperation by laparotomy for acute generalized peritonitis secondary to small bowel perforation was necessary in two cases. Mean postoperative hospital stay ranged from 4 to 7 days. The authors conclude that surgical laparoscopic treatment of the common abdominal emergencies is safe. The conversion rate is low as is the complication rate. These conclusions should be confirmed by a prospective study.
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PMID 
F Petit, C Vons, M Tahrat, A Coulomb-L'Hermine, F Capron, D Franco (1998)  Jaundice following laparoscopic cholecystectomy. An unusual complication of spilled stones.   Surg Endosc 12: 5. 450-451 May  
Abstract: We report the first case of obstructive cholangitis after laparoscopic cholecystectomy, related to intraperitoneal retained gallstones.
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PMID 
M S Sbaï Idrissi, C Vons, G Borgonovo, D Mariette, C Smadja, D Franco (1998)  Treatment of hepatic recurrence after resection of hepatocellular carcinomas   Ann Chir 52: 6. 543-546  
Abstract: Between October 1990 and December 1995, 86 patients underwent hepatic resection for hepatocellular carcinoma (HCC). All resections were carried out with the aim of achieving complete cure. Fifty one (60%) of these patients subsequently developed recurrent HCC. Only twenty patients could be treated in our hospital. There were 18 men and 2 women, with a mean age of 61 years at the time of recurrence. Six patients had a normal liver. Fourteen patients had associated liver cirrhosis. using Pugh's classification, 7 patients were Pugh A, 6 Pugh B and 1 Pugh C. The initial hepatic resection had consisted of major hepatectomy in 9 cases and segmentectomy in the remaining 11 patients. The mean time to recurrence was 17 months. There were 3 recurrences on the resection margin and 17 recurrences away from the hepatic stump. The therapeutic choice after hepatic recurrence was based on the number of tumors, hepatic function and the size of the liver remnant. Six patients were treated by tamoxifen due to poor hepatic function; median survival after recurrence was 6 months. Four patients with a single recurrent tumor on an atrophied liver remnant were treated by percutaneous ethanol injection with a median survival after recurrence of 15 months. Five patients with multiple diffuse lesions and good hepatic function were treated by transarterial chemoembolisation with a median survival after recurrence of 30 months. Five patients with a solitary tumor and good hepatic function underwent a second hepatic resection with a median survival after recurrence of 35 months. The overall median survival after diagnosis of recurrence was 20 months. These results suggest that an active treatment should be carried out in cases of recurrence of HCC. A second resection, if technically possible, offers the best chance of survival.
Notes:
 
PMID 
C Vons, D Chauveau, E Martinod, C Smadja, F Capron, J P Grunfeld, D Franco (1998)  Liver resection in patients with polycystic liver disease   Gastroenterol Clin Biol 22: 1. 50-54 Jan  
Abstract: OBJECTIVES: Polycystic liver disease is sometimes responsible for chronic symptoms linked to hepatomegaly which can result in acute complications such hemorrhage or infection of cysts. The aim of this retrospective study was to evaluate the results of partial hepatic resection in patients with symptomatic or complicated polycystic liver disease. METHODS: Twelve patients (11 women and one man, mean age 49) with diffuse polycystic liver disease were treated by partial liver resection (left lateral lobectomy in 7, left hepatectomy in 4, and extended right hepatectomy in 1). Four patients had terminal renal failures and three had chronic haemodialysis. Median follow-up was 34 months. RESULTS: Ascites occurred postoperatively in 10 patients (83%) and was long-lasting (> 2 weeks) in 5; all patients with end-stage renal failure had long-lasting ascites. One of them died on the 40th postoperative day of ascites infection. Another patient with end-stage renal failure died two years postoperatively from chronic disabling ascites and malnutrition while awaiting kidney transplantation. The 10 other patients were markedly improved after partial liver resection, including a marked decrease in hepatomegaly, and the disappearance of chronic symptoms and cystic complications. This beneficial effect was incomplete in the two surviving patients with end-stage renal failure until kidney transplantation was performed. CONCLUSION: These results suggest that partial liver resection is a highly effective treatment in patients with symptomatic polycystic liver disease, preferably before the onset of end-stage renal failure.
Notes:
1997
 
DOI   
PMID 
D Mariette, C Smadja, S Naveau, G Borgonovo, C Vons, D Franco (1997)  Preoperative predictors of blood transfusion in liver resection for tumor.   Am J Surg 173: 4. 275-279 Apr  
Abstract: BACKGROUND: Hepatic resection remains a hemorrhagic procedure. The purpose of this study was to investigate the preoperative predictive factors of intraoperative blood transfusion. METHODS: One hundred consecutive patients who underwent hepatic resection for tumor were included in this retrospective study. Resection was performed for primary malignancies (n = 52), metastases (n = 18), and benign tumors (n = 30). Liver resection was performed under intermittent clamping of the portal triad. Seventeen variables were analyzed. RESULTS: The operative blood loss was 1,872 mL (mean 1,104; range 650 to 4500) for the 22 transfused patients. The mean blood transfusion was 5.5 units (mean 3.2; range 2 to 12) of packed red cells. Multivariate analysis demonstrated that the size of liver resection (P <0.001) and the prothrombin rate (P <0.001) were independently correlated with blood transfusion. CONCLUSIONS: Patients undergoing extended resection or with abnormal coagulation could be considered for autologous blood transfusion.
Notes:
 
DOI   
PMID 
M Louha, K Poussin, N Ganne, H Zylberberg, B Nalpas, J Nicolet, F Capron, O Soubrane, C Vons, S Pol, M Beaugrand, P Berthelot, D Franco, J C Trinchet, C Bréchot, P Paterlini (1997)  Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer.   Hepatology 26: 4. 998-1005 Oct  
Abstract: The prognosis for patients with primary liver cancer (PLC) often depends on tumor recurrence and the development of extrahepatic metastases, particularly after liver transplantation. We have developed a sensitive test to detect both spontaneous circulation of tumor cells and the spread of liver cells due to chemoembolization and alcoholization. Reverse-transcription polymerase chain reaction was used to search for cells expressing alpha-fetoprotein (AFP) messenger RNA in the peripheral blood of 84 patients with PLC and 102 controls (55 patients with chronic hepatitis and/or cirrhosis, 10 patients with benign liver tumors or liver metastases from intestinal cancers, and 37 healthy individuals). By spiking the blood of healthy volunteers with HepG2 cells, we assessed the sensitivity limit: one HepG2 cell mixed with 10(7) leukocytes. All 102 controls tested negative. In contrast, 28 patients (33.3%) with PLC tested positive. Positivity for the test was significantly associated with portal thrombosis, tumor size, intravascular tumor emboli, serum AFP level, and extrahepatic metastases. Patients were followed up for a mean period of 39 +/- 51 weeks: the probability of developing extrahepatic metastases was significantly higher in positive than in negative patients. Eighteen negative patients with PLC were tested before, 1 hour after, and 24 hours after locoregional therapy: 9 tested positive either 1 or 24 hours after alcoholization or chemoembolization. In conclusion, we have developed a highly specific and sensitive test to detect circulating tumor cells in patients with PLC. This test is likely to be clinically useful in evaluating the risk of developing extrahepatic metastases and the possibility of iatrogenic spreading of liver-derived, possibly tumorous, cells.
Notes:
1996
 
PMID 
J C Pagès, M Andreoletti, N Loux, C Vons, D Mahieu, F Bargy, J Chapman, P Briand, D Franco, A Weber (1996)  Towards gene therapy in familial hypercholesterolemia   C R Seances Soc Biol Fil 190: 1. 53-65  
Abstract: Familial hypercholesterolemia (FH) is an inherited disease caused by a defect in the gene encoding the Low Density Lipoprotein receptor (LDL-R). The ex vivo hepatic gene therapy which restore the expression of the normal protein in hepatocytes should correct the disease. Improved transduction efficiency and long lasting expression of the transduced gene remain the main goals of gene therapy research. We developed an efficient and reliable method for in vivo transduction of human, mouse and primate primary hepatocytes. A retroviral vector bearing the LDL-R cDNA driven by the liver-type pyruvate kinase promoter allows high and tissue specific expression of the gene in primary hepatocytes. A second vector with a housekeeping promoter corrects the LDL-R deficiency in fibroblasts from a FH patient. Ex vivo preclinical studies in non-human primates will provide new insight in transduced cells biology after reimplantation.
Notes:
 
PMID 
D Mariette, S Sbai-Idrissi, E Bobocescu, C Vons, D Franco, C Smadja (1996)  Laparoscopic colectomy: technique and results   J Chir (Paris) 133: 1. 3-5 Jan  
Abstract: Laparoscopic preparation before colectomy consists of freeing the colon laparoscopically followed by a small elective laparotomy for resection and anastomosis. From January 1993 to October 1994, we performed 86 consecutive planned colectomies including 16 (19%) which had laparoscopic preparation. In 3 of these cases (19%) the procedure was converted to laparotomy due to difficult dissection. The 13 patients with complete laparoscopically prepared colectomy were retained for this study. There were 9 men and 4 women, mean age 54 +/- 14 years (range 34-79). Indications for surgery were benign tumor (n = 4), metastatic cancer (n = 3), diverticulosis (n = 3), volvulus of the pelvic colon (n = 2), and endometriosis involving the sigmoid (n = 1). Operative procedures were: short segmentary colectomy (n = 6), sigmoidectomy (n = 5), right colectomy (n = 2). Surgery duration was 280 +/- 75 minutes (range 150-390). The post-operative period was uneventful in all patients. Bowel activity resumed on the second day after surgery in most patients. Mean hospitalization time was 7.4 +/- 1.4 days (range 5-10 days). Laparoscopically prepared colectomy is a reliable simple method providing good patient comfort post-operatively. This technique should find its place in surgery of the colon.
Notes:
 
PMID 
C Vons, A Hadengue, C Smadja, D Franco, D Lebrec (1996)  Long-term hemodynamic effects of portocaval shunt and Sugiura procedure in patients with cirrhosis.   HPB Surg 9: 4. 209-213  
Abstract: Systemic and splanchnic hemodynamics were studied before and six months after a portal systemic shunt (n = 6) or a Sugiura procedure (n = 9) in 15 patients with cirrhosis and a past history of variceal bleeding. Hepatic blood flow was estimated by hepatic extraction and clearance of continuous indocyanine green infusion. Azygos blood flow was measured with a continuous thermodilution catheter. After portocaval shunt, the cardiac index increased significantly from 4.0 +/- .4 to 5.4 +/- 0.8 l/min m2 (p < 0.05), the hepatic venous pressure gradient and hepatic blood flow were significantly decreased from 21 +/- 3 to 13 +/- 5 mm Hg (p < 0.05) and from 1.20 +/- 0.35 to 0.37 +/- 0.16 l/min (p < 0.05) respectively. The decrease in azygos blood flow was not significant (0.51 +/- 0.31 vs 0.25 +/- 0.33 l/min; p = 0.1). After Sugiura procedure, there was no significant change in cardiac index, hepatic venous pressure gradient, hepatic blood flow or azygos blood flow. This is the first study to show the long-term maintenance of splanchnic and systemic hemodynamics in patients with cirrhosis after Sugiura procedure. The absence of long-term hemodynamic alterations could explain the absence of encephalopathy after this procedure.
Notes:
 
DOI   
PMID 
J C Pagès, N Loux, S Bellusci, D Farge, M Bennoun, C Vons, J Jouanneau, D Franco, P Briand, A Weber (1996)  Hepatocyte growth factor expressed by a retrovirus-producing cell line enhances retroviral transduction of primary hepatocytes: implications for in vivo gene transfer.   Biochem Biophys Res Commun 222: 3. 726-731 May  
Abstract: Hepatocyte Growth Factor (HGF) is the more potent mitogen of mature hepatocytes. We have examined the effect of human HGF expression by a recombinant retroviral cell line (MFG-LacZ) on retroviral transduction of primary mouse and human hepatocytes. The HGF in the supernatant of MFG-LacZ cell line was correctly processed and biologically active. Transduction of mouse and human hepatocytes with the supernatant of transfected cells was increased 5-fold, as determined by beta-galactosidase activity. The production of HGF was stable and did not interfere with the viral titers of the producer cells. This study provides evidence that expression of HGF within a retrovirus-producer cell line increases the transduction rate of primary hepatocytes. Since the number of corrected cells is a limiting step for phenotypic correction of liver deficiencies, our approach should improve hepatic gene therapy efficiency. Furthermore this cell line should be useful for in vivo liver gene therapy.
Notes:
 
PMID 
H Mabit, C Vons, S Dubanchet, F Capel, D Franco, M A Petit (1996)  Primary cultured normal human hepatocytes for hepatitis B virus receptor studies.   J Hepatol 24: 4. 403-412 Apr  
Abstract: BACKGROUND/AIMS: We analyzed the hepatitis B virus envelope specificities (HBs, preS2 and preS1) involved in virus attachment to normal human hepatocytes, and we performed in vitro hepatitis B virus infection experiments without addition of dimethyl sulfoxide and polyethylene glycol, which may affect cell membrane integrity, in order to study further the early steps of the life cycle of the hepatitis B virus. METHODS: Primary normal human hepatocytes were prepared from surgical biopsies by the two-step collagenase perfusion technique, and cultured in a fetal calf serum-free medium supplemented with 10(-6) M dexamethasone. Cell-binding assays, ligand blotting and immunohistochemistry experiments were carried out using our anti-idiotypic (Ab2) antibodies (Ab2s/preS1, Ab2s/preS2 and Ab2s/HBs). RESULTS: Probing primary normal human hepatocytes, the 35-kDa major preS1-binding protein (preS1-BP35) we have previously identified in human hepatoma HepG2 cells was recognized in blotting, whereas both HBs- and preS1-specificities of the hepatitis B virus envelope interacted strongly with normal human hepatocyte cell membrane in cell-binding assays and immunohistochemistry experiments. Hepatitis B virus infectivity studies confirmed a great inter-experimental variability depending on donors and liver perfusion, and demonstrated a great intra-experimental variability depending on the serum-derived hepatitis B virus isolate used for the inoculation. In our culture conditions, only increased detection of the RC and CCC DNA forms of hepatitis B virus in cells and of hepatitis B virus surface antigens in medium was observed 4 to 8 days after exposure of cells to hepatitis B virus. CONCLUSION: These findings support a potential role for preS1-BP35 as a receptor protein for hepatitis B virus. In our hands, limitation(s) in the hepatitis B virus life cycle may occur at some step after virion binding, and likely result from complex regulation of reverse transcription of the RNA and translation of core protein by extrahepatic host factors or/and by the virus itself. However, the normal human hepatocyte model developed here is available for studying the initial steps in hepatitis B virus entry into cells.
Notes:
 
PMID 
G Borgonovo, M Costantini, D Grange, C Vons, C Smadja, D Franco (1996)  Comparison of a modified Sugiura procedure with portal systemic shunt for prevention of recurrent variceal bleeding in cirrhosis.   Surgery 119: 2. 214-221 Feb  
Abstract: BACKGROUND. There is no agreement on the management of patients with cirrhosis and recurrent variceal bleeding after failure of medical or endoscopic treatments or both. Portal systemic shunts are highly effective in preventing rebleeding but are associated with a high incidence of chronic encephalopathy. This study compared the results of a slightly modified Sugiura procedure (esophageal transection plus esophagogastric devascularization plus splenectomy) with those of nonselective portal systemic shunts in patients with previous variceal bleeding. METHODS. Fifty-four patients were included in this randomized controlled study between January 1984 and April 1989. The major end point was chronic encephalopathy. Secondary end points were recurrent variceal bleeding, survival, ascites, and hepatocellular carcinoma. RESULTS. Twenty-seven patients were assigned to each group. The rate of chronic encephalopathy was significantly (p = 0.002) lower after modified Sugiura procedure than after portal systemic shunt. Recurrent variceal bleeding was more frequent after modified Sugiura procedure than after portal systemic shunt, but the difference is not significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%, respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively, in the portal systemic shunt group (p = 0.044). CONCLUSIONS. These results suggest that the modified Sugiura procedure is better overall than the nonselective portal systemic shunt in the management of patients with cirrhosis and recurrent variceal bleeding. Although the rebleeding rate is higher after the modified Sugiura procedure, this does not seem to affect mortality in these patients.
Notes:
1995
 
PMID 
J C Pages, M Andreoletti, M Bennoun, C Vons, J Elcheroth, P Lehn, D Houssin, J Chapman, P Briand, R Benarous (1995)  Efficient retroviral-mediated gene transfer into primary culture of murine and human hepatocytes: expression of the LDL receptor.   Hum Gene Ther 6: 1. 21-30 Jan  
Abstract: The ex vivo approach to hepatic gene therapy involves several steps, which include the isolation and culture of hepatocytes, followed by their transduction with a retrovirus. Subsequently, autologous hepatocytes are transplanted. The number of hepatocytes that can be transduced by retroviruses bearing the therapeutic gene is one of the limiting steps that can impair the success of this strategy. We presently describe an experimental approach that leads to improved transduction efficiency in mouse and human hepatocytes in vitro. By using a recombinant retrovirus bearing the Escherichia coli beta-galactosidase gene, we show that addition of growth factors to the cells, namely human hepatocyte growth factor (HGF), allows marked increase in the transduction efficiency in mouse (up to 80%) and human (40%) hepatocytes. Familial hypercholesterolemia (FH) is due to mutation in the low-density lipoprotein (LDL) receptor gene and results in a deficiency in LDL receptors. Transduction of the human LDL receptor cDNA under the transcriptional control of the L-type pyruvate kinase promoter-activator into mouse hepatocytes led to an elevated tissue-specific expression of the human protein. These results suggest that the ex vivo approach remains a promising alternative for hepatic gene therapy.
Notes:
 
PMID 
T Tordjmann, L Combettes, B Berthon, C Vons, D Franco, M Claret (1995)  Hormone-mediated calcium responses of rat and human hepatocytes. Study of multicellular systems by videomicroscopy   Gastroenterol Clin Biol 19: 12. 980-990 Dec  
Abstract: OBJECTIVES AND METHODS: Activation of hepatocyte hormonal receptors leads to the mobilization of intracellular Ca2+ which is thought to be an elaborate system for encoding hormonal messages. We studied hormone-induced calcium signals in freshly isolated multicellular systems of normal rat and human hepatocytes. Calcium signals were recorded by videomicroscopy after stimulation with noradrenaline, angiotensin II, and vasopressin. RESULTS: Calcium signals were highly organized in multiplets: the different hepatocytes responded to Ca(2+)-mobilizing hormones in a sequentially ordered manner, with a first, a second (doublets) and a third (triplets) responding cells. This pattern was an intrinsic feature of the multicellular systems, and seemed to be a result of a gradual heterogeneity of the sensitivity of the different cells, to the hormones. The stimulation of the same multiplet with two different agonists and the removal of the hormone during cell responses provides some evidence for the major role of hormonal receptors in this heterogeneity. CONCLUSIONS: Hormone responses in multicellular systems of rat and human hepatocytes are highly elaborate. The density of hormonal receptors could be the major determinant of the sequential pattern of Ca2+ responses. Hormonal receptors may be gradually distributed among the different cells of the multiplets in vitro and along the porto-centrilobular axis in situ.
Notes:
1994
 
PMID 
J Elcheroth, C Vons, D Franco (1994)  Role of surgical therapy in management of intractable ascites.   World J Surg 18: 2. 240-245 Mar/Apr  
Abstract: Almost 10% of patients with cirrhosis and ascites develop intractable ascites. When large-volume paracentesis fails to relieve ascites, patients may be submitted to one of the three following surgical options: portosystemic shunting, peritoneovenous shunting, or liver transplantation. Portosystemic shunting is efficient in clearing ascites, but it is associated with a high rate of encephalopathy and liver failure. The indications for portosystemic shunting are therefore limited for treatment of intractable ascites and should be performed only in patients with good liver function in whom all other treatments failed. Peritoneovenous shunting has been associated with a high rate of early complications and valve obstruction. Improvements in perioperative care and in the material used have greatly reduced the operative risks and increased the patency rate. Mortality remains high in patients with severe liver failure or with a history of spontaneous bacterial peritonitis or variceal bleeding. Peritoneovenous shunting should not be done when these risk factors are present. In the absence of such risk factors, peritoneovenous shunting is a good procedure and may provide definitive relief of ascites and long-term survival in more than 50% of the operated patients. In patients with poor risk factors liver transplantation may be preferable, and the onset of intractable ascites in a patient with a severely compromised liver should trigger the indication of liver replacement.
Notes:
1992
 
PMID 
H Mosnier, O Farges, C Vons, J Belghiti, F Fékété (1992)  Gastroduodenal ulcer perforation in the patient with cirrhosis.   Surg Gynecol Obstet 174: 4. 297-301 Apr  
Abstract: This retrospective study was done to stress the particular features of perforation of the gastroduodenal ulcer in patients with cirrhosis. From 1979 to 1987, 135 patients were operated upon for perforation of the gastroduodenal ulcer: clinical, biologic and roentgenographic data of 22 patients with cirrhosis were compared with 112 patients without cirrhosis. In the 22 patients with cirrhosis, three gastrectomies and 19 simple closures with omental patch were performed. Clinical ascites was present in 16 of 22 patients with cirrhosis. Acute abdominal pain and leukocytosis were less frequent in patients with cirrhosis (p less than 0.05), whereas associated bleeding in the upper part of the gastrointestinal (GI) tract was more frequent (p less than 0.05). In patients with cirrhosis, abnormal plasma creatinine level and associated upper GI bleeding were more frequent in patients with ascites (p less than 0.05); on the other hand, acute abdominal pain and rebound tenderness were less frequent (p less than 0.05). The incidence of pneumoperitoneum was higher in patients with cirrhosis. Surgical treatment was significantly delayed in patients with cirrhosis and ascites. Ulcers were larger in patients with cirrhosis and ascites than without (p less than 0.001). Over-all morbidity and mortality rates in patients with cirrhosis were 77.3 and 50.0 per cent, respectively. Mortality and morbidity were significantly higher in patients with ascites than without (62.5 versus 16.6 and 100 versus zero per cent, respectively), in patients with prothrombin times of less than 50 per cent and with plasma creatinine levels more than 110 micromolars.
Notes:
1991
 
PMID 
C Vons, A Hadengue, S S Lee, C Smadja, D Franco, D Lebrec (1991)  Splanchnic and systemic hemodynamics in cirrhotic patients with refractory ascites. Effect of peritoneovenous shunting.   HPB Surg 3: 4. 259-67; discussion 267-9 Apr  
Abstract: The splanchnic and systemic hemodynamics of 14 patients with refractory ascites were studied and were compared to those of 15 patients with ascites responding to medical treatment. Among the 14 patients, 10 were grade B and 4 C, according to the Pugh classification. Of the 15 patients, 5 were Pugh B and 10 C. In patients with refractory ascites, free hepatic venous pressure was significantly higher and hepatic venous pressure gradient was significantly lower than in patients with responsive ascites. Hepatic and azygos blood flows were not significantly different between the two groups. Cardiac output was lower in patients with refractory ascites (p less than 0.05) than in those with responsive ascites. In patients with refractory ascites, six months after peritoneovenous shunting, there was a significant reduction of wedged and free hepatic venous pressures and azygos blood flow. Cardiac output increased by 20 % (p less than 0.02). This study shows that hemodynamic alterations in patients with refractory ascites is the consequence of increased intraabdominal pressure due to chronic ascites. Six months after peritoneovenous shunting splanchnic and systemic hemodynamics became similar to those observed in patients without ascites.
Notes:
 
PMID 
C Vons, J P Pegorier, J Girard, C Kohl, M A Ivanov, D Franco (1991)  Regulation of fatty-acid metabolism by pancreatic hormones in cultured human hepatocytes.   Hepatology 13: 6. 1126-1130 Jun  
Abstract: The effects of pancreatic hormones and cyclic AMP on long-chain fatty-acid metabolism were investigated in human hepatocytes isolated from 12 liver biopsy specimens and cultured for 4 days in an insulin-free medium. Glucagon (10(-6) mol/L) increased endogenous ketone body production by 150%. This resulted from alterations in the partition of long-chain fatty acids from esterification toward oxidation. Glucagon or cyclic AMP enhanced (14C) oleate oxidation (basal = 45.8% +/- 5.0%; glucagon = 66.8% +/- 5.3%; cyclic AMP = 67.6% +/- 5.0% of metabolized oleate) at the expense of oleate esterification. Insulin (10(-7) mol/L) antagonized the glucagon-induced oleate oxidation. After 24 hr in basal culture conditions, the rate of lipogenesis decreased to the same low rate as in glucagon-treated cells. The presence of insulin did not restore a high rate of lipogenesis. These results are the first direct evidence of a control of ketone body production by glucagon in the human liver.
Notes:
 
PMID 
M Gagner, D Franco, C Vons, C Smadja, R L Rossi, J W Braasch (1991)  Analysis of morbidity and mortality rates in right hepatectomy with the preoperative APACHE II score.   Surgery 110: 3. 487-492 Sep  
Abstract: Morbidity and mortality rates in 70 patients who underwent major liver resection for liver tumors (primary and metastatic) were determined and correlated with the preoperative APACHE II score. Patients were divided into three groups according to their preoperative APACHE II score: low (0 to 3), mid (4 to 7), and high (8 and above). A higher score was closely correlated with increased postoperative morbidity and operative mortality rates. The group with low scores had a postoperative morbidity rate of 34% and a mortality rate of 0%, the group with mid scores had a postoperative morbidity rate of 54% and a mortality rate of 3%, and the group with high scores had a postoperative morbidity rate of 80% and a mortality rate of 20%. Age did not correlate with morbidity. It was therefore postulated that morbidity and mortality rates were related to the combination of points for abnormal physiologic variables and points for chronic health, or APACHE II score minus points for age. As the combination of these points increases the postoperative morbidity and operative mortality rates increase significantly (from 24% in the 0-point group to 69% in the greater than or equal to 3-point group). Also the two deaths occurred in the group with 3 or more points. The preoperative APACHE II score may be used by clinicians to evaluate before surgery the risk of postoperative morbidity and death in elective major liver surgery.
Notes:
 
PMID 
T Perniceni, C Vons, B Gayet, J Belghiti, F Fekete (1991)  Total duodenal diversion in patients with previous gastric surgery.   Hepatogastroenterology 38: 6. 528-530 Dec  
Abstract: Total duodenal diversion (TDD) was performed in 19 patients with severe post-gastric surgery symptoms. Previous operations were truncal vagotomy associated with pyloroplasty or antrectomy (n = 6), proximal esophagogastrectomy (n = 8) or total gastrectomy (n = 5). Technical adjustments to the standard procedure (truncal vagotomy, antrectomy and gastrojejunal anastomosis using a 70 cm Roux-en-Y loop) were required. There were no postoperative deaths, no anastomotic leakage or anastomotic ulceration. The main symptoms were eliminated, and endoscopic gastritis and esophagitis healed in all patients. Heartburn and bilious vomiting ceased in all patients, but in five out of 14 patients with a residual stomach some symptoms persisted. TDD proved a safe and effective treatment of disabling symptoms following gastric surgery.
Notes:
1990
 
PMID 
S Houry, C Vons, M Huguier (1990)  Treatment of local recurrence of colonic and rectal cancer initially treated by resection-anastomosis   Gastroenterol Clin Biol 14: 1. 28-32  
Abstract: Between 1970 and 1988, 32 patients underwent laparotomy for local recurrence following a curative and restorative resection for carcinoma of the colon and rectum. Histological confirmation was obtained in 30 cases. Of the 28 patients for whom the site of local recurrence could be defined, the previous anastomosis was involved in 25. At laparotomy, 12 patients had disseminated lesions: 5 of these patients had complete resection of lesions which were, however, considered as palliative. Twenty patients had a local recurrence without metastasis. Five of them had unresectable lesions and 15 were amenable to curative resection. After curative resection, the median survival time was 34 months, and 5-year actuarial survival time was 26 percent. After palliative surgery, the median survival time was 5 months, but 1 patient is still alive 12 years after radiationtherapy. These results emphasize the importance of follow-up, given the high salvage rate in patients in whom curative resection can be performed.
Notes:
 
PMID 
A Michel, C Vons, S Hillaire, P Icard, G Hazebroucq, F Kemeny, D Houssin, D Franco (1990)  Comparison of rat liver preservation with Eurocollins and a modified University of Wisconsin solution: transplantation and isolation of hepatocytes for culture.   Eur Surg Res 22: 5. 249-255  
Abstract: The efficiency of Eurocollins or modified University of Wisconsin (UW) solution (MUW) in preserving rat livers was compared. After cold storage with one of the solutions, the livers were transplanted or perfused by collagenase for isolation of hepatocytes. Five of the 6 rats receiving a graft preserved with MUW versus none of the 6 rat receiving a graft preserved with Eurocollins solution survived 24 h or more. A significantly greater number of hepatocytes were isolated from livers preserved with MUW than from livers preserved with Eurocollins solution. This suggests a better reperfusion of MUW-preserved livers by collagenase resulting from less endothelial injury. LDH release by cultured hepatocytes, ketone body production and stimulation by glucagon were not significantly different between the two groups. These results confirm the superiority of MUW solution over Eurocollins in preserving liver grafts. They suggest that the advantage of MUW solution results from better protection of vascular endothelium rather than of hepatocytes.
Notes:
 
PMID 
J Moreaux, C Vons (1990)  Elective resection for diverticular disease of the sigmoid colon.   Br J Surg 77: 9. 1036-1038 Sep  
Abstract: From 1966 to 1987, 177 consecutive patients were operated on electively for diverticular disease of the sigmoid colon. The indications for surgery were: colovesical fistula (n = 12), suspicion of residual abscess (n = 39), two or more previous attacks of acute inflammation (n = 52), chronic symptoms (n = 72) and suspicion of carcinoma (n = 2). An abscess was found at operation in 76 patients (43 per cent) and this was extracolic with local peritonitis in 52 patients (29 per cent). An unsuspected abscess was found in 25 of the 72 patients operated on for chronic symptoms. Colonic resection with primary anastomosis was performed in 95 per cent of the 177 patients and in 94 per cent of those 52 patients with an extracolic abscess. There were no postoperative deaths and no clinical anastomotic leakages. Long-term results were very good in 85 per cent of the 177 patients and in 82 per cent of the 72 patients operated on for chronic symptoms. The results of this series suggest that a one-stage procedure can be safely performed with some technical precautions in most patients operated on electively for diverticular disease, even if an extracolic abscess is found. The good long-term results in patients operated on for chronic symptoms suggest that such symptoms should be taken into account with respect to surgical indications.
Notes:
1989
 
PMID 
C Vons, C Smadja, F Kemeny, R Lejeune, D Grange, D Franco (1989)  Results of the excision of benign tumors of the liver in 22 patients   Gastroenterol Clin Biol 13: 3. 280-284 Mar  
Abstract: Between 1979 and 1987, 22 patients underwent resection for a benign liver tumor. A total of 24 tumors were resected: 8 adenomas, 8 focal nodular hyperplasias and 8 hemangiomas. In two patients, focal nodular hyperplasia was associated with hemangioma. Preoperative diagnosis of the nature of the tumor by radiologic investigations (ultrasonography, CT-scan, and selective angiography) was made in only 4 patients (18 p. 100), 3 with hemangioma and one with focal nodular hyperplasia. Ten patients underwent major hepatectomies and 12 had either a segmentectomy (8 patients) or atypical resection (4 patients). Progress in operative management significantly decreased transfusion of packed red cells (p less than 0.05) and that of fresh frozen plasma (p less than 0.02). Ten patients received no blood for fresh frozen plasma. Suppression of abdominal drainage when surgery was uneventful significantly decreased postoperative in-hospital stay (p less than 0.05) to a low 7.8 +/- 0.8 days and improved comfort of patients. These results confirm that preoperative diagnosis of a benign liver tumor is uneasy. They suggest that resection has become a benign procedure in selected surgical centers. The risk of ignoring malignant tumors or leaving a tumor with potential complications should prompt resection when the nature of a liver tumor has not been precisely determined by usual radiologic investigative procedures.
Notes:
1988
 
PMID 
D Franco, C Vons, O Traynor, C de Smadja (1988)  Should portosystemic shunt be reconsidered in the treatment of intractable ascites in cirrhosis?   Arch Surg 123: 8. 987-991 Aug  
Abstract: Fifty-seven cirrhotic patients with intractable ascites had a portosystemic shunt. In 35 patients, a peritoneovenous shunt had previously failed. Forty-six patients were in Pugh's class B and 11 were in class C. There were three operative deaths (5.3%). Fifty-three (98.2%) of the 54 survivors were cleared of ascites. In one patient, ascites persisted because of postshunt heart failure that resulted in a marked increase of caval pressure. Twenty-seven patients (50%) had late encephalopathy, which was severe and disabling in 12 (22%). One- and three-year survival rates were 72% and 36%, respectively. These results suggest that although portosystemic shunts are remarkably effective in dealing with ascites, the high rate of postoperative encephalopathy is a strong argument against their routine use in the management of intractable ascites in cirrhosis.
Notes:
1987
 
PMID 
E Attias, C Smadja, C Vons, O Traynor, D Franco (1987)  Bleeding from intestinal varices after a Warren shunt.   J Clin Gastroenterol 9: 5. 585-587 Oct  
Abstract: A 62-year-old man with alcoholic cirrhosis presented with massive gastrointestinal bleeding 4 years after a Warren operation. Angiographic examination suggested that the bleeding was due to ruptured jejunal varices. Treatment by propranolol and a side-to-side portacaval shunt failed to prevent further bleeding. An emergency laparotomy for life-threatening gastrointestinal (GI) rebleeding disclosed dense hypervascular adhesions between the second jejunal loop and the retroperitoneum, and a large submucosal varix of the jejunum that had ruptured. Development of intestinal varices after a Warren operation is facilitated by the persistence of a high pressure in the mesenteric territory and by adhesions between the initial part of the intestine and the area of dissection of the renal vein. This case illustrates one of the possible causes of rebleeding after a Warren operation.
Notes:
1986
 
PMID 
D Franco, C Vons, Y Lecompte, G Nuzzo, C Smadja (1986)  Portoatrial shunt in Budd-Chiari syndrome.   Surgery 99: 3. 378-380 Mar  
Abstract: It is now well accepted that mesoatrial bypass is an efficient treatment of Budd-Chiari syndrome and that it is indicated when the inferior vena cava is obstructed. This report presents a patient in whom the superior mesenteric vein was thrombosed after a previous mesocaval shunt. A bypass was constructed between the left side of the portal vein and the right atrium with a 16 mm diameter reinforced polytetrafluoroethylene prosthesis. The prosthesis passed between the left lobe of the liver and the caudate lobe and had a direct trajection. The procedure was simple, the postoperative course was uneventful, and the patient was well 20 months later. This observation suggests that portoatrial shunt is a good alternative to mesoatrial shunts in patients with Budd-Chiari syndrome and unavailable inferior vena cava and superior mesenteric vein.
Notes:
 
PMID 
C Vons, C Smadja, E Bourstyn, A M Szekely, P Bonnet, D Franco (1986)  Results of portal systemic shunts in Budd-Chiari syndrome.   Ann Surg 203: 4. 366-370 Apr  
Abstract: Nine patients with Budd-Chiari syndrome (BCS) were treated by a portal systemic shunt. One had thrombosis of the superior mesenteric vein (SMV) and another had complete obstruction of the retrohepatic inferior vena cava (IVC). All other patients had a marked stenosis of the retrohepatic IVC with caval pressure ranging from 12 to 24 mmHg (mean: 17 mmHg). Seven patients had an interposition mesocaval shunt using an autologous jugular vein. The patient with a thrombosed SMV had a portoatrial shunt. The patient with an obstructed IVC had a cavoatrial shunt after an erroneous portacaval shunt had failed to relieve ascites. There were no operative deaths and no major postoperative complications. One patient died 19 months after operation of acute leukemia complicating polycythemia rubra vera. All other patients were alive and well 8 months to 6 years after operation. None of them had encephalopathy. These results suggest several comments: Portal systemic shunts are a good treatment for BCS and have a low operative risk. The mesocaval shunt is an efficient procedure, even when there is stenosis of the IVC with high caval pressure; shunts to the right atrium should be performed only in the case of complete obstruction or inaccessibility of the IVC. The long-term prognosis is excellent, except in patients with potential malignancies. Therefore, portal systemic shunts should be indicated early in patients with symptomatic BCS.
Notes:
 
PMID 
C Vons, S Houry, F Lacaine, M Huguier (1986)  Treatment of local recurrence after primary restorative resection or Hartmann's operation for carcinoma of the colon and the rectum.   Int J Colorectal Dis 1: 4. 227-230 Oct  
Abstract: Between 1970 and 1985, 20 patients underwent laparotomy for local recurrence following a restorative resection or Hartmann's operation for carcinoma of the colon and rectum. Histological confirmation was made in 18 cases and in 2, recurrence not confirmed at surgery became apparent during subsequent follow-up. Of the 16 patients in whom the site of local recurrence could be defined, there was involvement of the previous anastomosis in 13. At laparotomy 7 patients had disseminated disease and in 5 patients without dissemination, local disease was unresectable. Ten recurrences were amenable to resection. Of these 8 patients had a curative operation with a median survival of 26 months and a 5-year actuarial survival rate of 50%. In 10 patients no resection was performed. Median survival in this group was 5 months but 1 patient is still alive at 10 years after radiotherapy. The results emphasise the importance of follow-up given the high salvage rate in patients in whom a curative resection was possible.
Notes:
1985
1984
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