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Alexis Laurent

Publications and source records attributed to Alexis Laurent.

12 recordsLinked to original sources
PubMed2006

Successful reuse of liver graft 13 years after initial transplantation.

The shortage of organ donors and the increased demand for liver transplantation has led to new strategies to increase the availability of liver grafts for transplantation. Occasionally, previous liver transplant recipients may experience brain death and become organ donors. Although this is a very rare situation, we and others have showed that reuse of liver grafts could be performed successfully within one week after transplantation. Late reuse has, however, not been reported to date. We report the first case in which a liver graft was successfully reused 13 years after the first transplantation.

Brain Death↗
PubMed2006

Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo.

Intracellular events following paclitaxel binding to microtubules that lead to cell death remain poorly understood. Because reactive oxygen species (ROS) are involved in the cytotoxicity of anticancer agents acting through independent molecular targets, we explored the role of ROS in paclitaxel cytotoxicity. Within 15 min after in vitro exposure of A549 human lung cancer cells to paclitaxel, a concentration-dependent intracellular increase in O(o)(2)(-) and H(2)O(2) levels was detected by spectrofluorometry. Addition of N-acetylcysteine (NAC) or glutathione, two H(2)O(2) scavenger, induced a 4-fold increase in paclitaxel IC(50). Delaying NAC co-incubation by 4 hr, resulted in a 3-fold reduction in cell protection. The glutathione synthesis inhibitor, buthionine sulfoximine significantly increased paclitaxel cytotoxicity and H(2)O(2) accumulation, but did not modify O(o)(2)(-) levels. Co-incubation with diphenylene iodonium suggested that paclitaxel induced-O(o)(2)(-) production was in part associated with increased activity of cytoplasmic NADPH oxidase. Concomitant treatment with inhibitors of caspases 3 and 8 increased cell survival but did not prevent the early accumulation of H(2)O(2.) To evaluate the role of ROS in paclitaxel antitumoral activity, mice were injected with LLC1 lung cancer cells and treated with paclitaxel i.p. and/or NAC. The antitumoral activity of paclitaxel in mice was abolished by NAC. In conclusion, the accumulation of H(2)O(2) is an early and crucial step for paclitaxel-induced cancer cell death before the commitment of the cells into apoptosis. These results suggest that ROS participate in vitro and in vivo to paclitaxel cytotoxicity.

Acetylcysteine↗
PubMed2006

Improvement of the therapeutic index of anticancer drugs by the superoxide dismutase mimic mangafodipir.

BACKGROUND: Anticancer drugs act by increasing intracellular hydrogen peroxide levels. Mangafodipir, a superoxide dismutase (SOD) mimic with catalase and glutathione reductase activities, protects normal cells from apoptosis induced by H2O2. We investigated its and other oxidative stress modulators' effects on anticancer drug activity in vitro and in vivo. METHODS: Cell lysis and intracellular reactive oxygen species levels were assessed in vitro in human leukocytes from healthy subjects and in murine CT26 colon cancer cells. Cells were exposed to the chemotherapeutic agents paclitaxel, oxaliplatin, or 5-fluorouracil, either in the presence or absence of mangafodipir and other oxidative stress modulators. Cell viability was evaluated by the methylthiazoletetrazolium assay. The effects of mangafodipir and other oxidative stress modulators on peripheral blood counts and on tumor growth were studied in BALB/c mice that were implanted with CT26 tumors and treated with 20 mg/kg paclitaxel. Survival of BALB/c mice infected with Staphylococcus aureus was also examined by treatment group. Statistical tests were two-sided. RESULTS: In vitro lysis of leukocytes exposed to paclitaxel, oxaliplatin, or 5-fluorouracil in combination with mangafodipir was decreased by 46% (95% confidence interval [CI] = 44% to 48%), 30.5% (95% CI = 29% to 32%), and 15% (95% CI = 10% to 20%), compared with lysis of cells treated with anticancer agent alone. Mangafodipir also statistically significantly enhanced in vitro anticancer drug cytotoxicity toward CT26 cancer cells. In vivo, mangafodipir protected mice against paclitaxel-induced leukopenia. Moreover, the survival rate of mice infected with S. aureus and treated with paclitaxel was higher when mangafodipir was also administered (survival: 3 of 17 versus 14 of 17, P < .001). In addition, mangafodipir amplified the inhibitory effect of paclitaxel on CT26 tumor growth in mice. CONCLUSIONS: Mangafodipir decreased hematotoxicity and enhanced cytotoxicity of anticancer agents.

Animals↗
PubMed2006

Laparoscopic liver resection for peripheral hepatocellular carcinoma in patients with chronic liver disease: midterm results and perspectives.

OBJECTIVE: Report the midterm results of laparoscopic resection for hepatocellular in chronic liver disease (CLD). SUMMARY BACKGROUND DATA: Surgical resection for hepatocellular carcinoma (HCC) in chronic liver disease (CLD) remains controversial because of high morbidity and recurrence rates. Laparoscopic resection of liver tumors has recently been developed and could reduce morbidity. METHODS: From 1998 to 2003, patients with HCC and CLD were considered for laparoscopic liver resection. Inclusion criteria were chronic hepatitis or Child's A cirrhosis, solitary tumor < or =5 cm in size, and location in peripheral segments of the liver. Mortality, morbidity, recurrence rates, and survival were analyzed. RESULTS: A total of 27 patients were included. Liver resections included anatomic resection in 17 cases and non anatomic resection in 10. Seven conversions to laparotomy (26%) occurred for moderate hemorrhage in 5 cases and technical difficulties in 2 cases. Mortality and morbidity rates were 0% and 33%, respectively. Postoperative ascites and encephalopathy occurred in 2 patients (7%) who both had undergone conversion to laparotomy. Mean surgical margin was 11 mm (range, 1-47 mm). After a mean follow-up of 2 years (range, 1.1-4.7), 8 patients (30%) developed intrahepatic tumor recurrence of which one died. Treatment of recurrence was possible in 4 patients (50%), including orthotopic liver transplantation, right hepatectomy, radiofrequency ablation, and chemoembolization in 1 case each. There were no adhesions in the 2 reoperated patients. Overall and disease-free 3-year survival rates were 93% and 64%, respectively. CONCLUSION: Our study shows that laparoscopic liver resection for HCC in selected patients is a safe procedure with very good midterm results. This approach could have an impact on the therapeutic strategy of HCC complicating CLD as a treatment with curative intent or as a bridge to liver transplantation.

Adult↗
PubMed2005

Controlling tumor growth by modulating endogenous production of reactive oxygen species.

Paradoxically, reactive oxygen species (ROS) can promote normal cellular proliferation and carcinogenesis, and can also induce apoptosis of tumor cells. In this report, we study the contribution of ROS to various cellular signals depending on the nature and the level of ROS produced. In nontransformed NIH 3T3 cells, ROS are at low levels and originate from NADPH oxidase. Hydrogen peroxide (H(2)O(2)), controlled by the glutathione system, is pivotal for the modulation of normal cell proliferation. In CT26 (colon) and Hepa 1-6 (liver) tumor cells, high levels of ROS, close to the threshold of cytotoxicity, are produced by mitochondria and H(2)O(2) is controlled by catalase. N-acetylcysteine, which decreases H(2)O(2) levels, inhibits mitogen-activated protein kinase and normal cell proliferation but increases tumor cell proliferation as H(2)O(2) concentration drops from the toxicity threshold. In contrast, antioxidant molecules, such as mimics of superoxide dismutase (SOD), increase H(2)O(2) levels through superoxide anion dismutation, as well as in vitro proliferation of normal cells, but kill tumor cells. CT26 tumors were implanted in mice and treated by oxaliplatin in association with one of the three SOD mimics manganese(III)tetrakis(4-benzoic acid) porphyrin, copper(II)(3,5-diisopropylsalicylate)2, or manganese dipyridoxyl diphosphate. After 1 month, the volumes of tumors were respectively 35%, 31%, and 63% smaller than with oxaliplatin alone (P < 0.001). Similar data were gained with Hepa 1-6 tumors. In conclusion, antioxidant molecules may have opposite effects on tumor growth. SOD mimics can act in synergy with cytotoxic drugs to treat colon and liver cancers.

Animals↗
PubMed2005

Colonic J-pouch-anal anastomosis for rectal cancer: a prospective, randomized study comparing handsewn vs. stapled anastomosis.

PURPOSE: Colonic J-pouch-anal anastomosis performed after complete proctectomy and total mesorectal excision for adenocarcinoma of the rectum can be handsewn or stapled. Stapling the coloanal anastomosis is believed to shorten operating time and reduce morbidity, but there are no randomized trials comparing the techniques. METHODS: Between January 1999 and May 2001, all patients with rectal adenocarcinoma requiring total mesorectal excision were randomized intraoperatively to handsewn or stapled anastomosis. Mortality, intraoperative, and postoperative findings and functional results at 3, 6, and 12 months were analyzed. RESULTS: Thirty-seven patients (12 females; mean age, 60 +/- 10 years) were randomized (stapled group: n = 20; handsewn group: n = 17). The two groups were comparable for age, gender, distance between the tumor and the levator ani, tumor volume, and use of preoperative radiotherapy (3 in each group). Morbidity did not differ between stapled group (3/20) and handsewn group (4/17; P > 0.05). Mean +/- standard deviation operative time was shorter in stapled group (261 +/- 40 minutes) than in handsewn group (314 +/- 46 minutes; P = 0.0008), and median distance between the anastomosis and the anal verge was shorter in handsewn group (19 +/- 9 mm) than in stapled group (27 +/- 8 mm; P = 0.01). Three patients of handsewn group and none of stapled group developed an anastomotic stricture requiring a single digital dilation (not significant). Number of stools per 24 hours, urgency, incidence of fragmented stools, degree of continence, requirement for protective pad, and/or need to take medication at 3, 6, and 12 months were similar in both groups. CONCLUSIONS: Stapled co-loanal anastomosis is significantly faster than handsewn CAA and has similar functional results. It should be the preferred technique when it is feasible.

Adenocarcinoma↗
PubMed2004

Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis.

Nonalcoholic fatty liver disease, frequently associated with obesity, can lead to nonalcoholic steatohepatitis (NASH) and cirrhosis. The pathophysiology of NASH is poorly understood, and no effective treatment is available. In view of a potential deleterious role for reactive oxygen species (ROS), we investigated the origin of ROS overproduction in NASH. Mitochondrial production of ROS and its alterations in the presence of antioxidant molecules were studied in livers from ob/ob mice that bear a mutation of the leptin gene and develop experimental NASH. N-acetyl-cysteine and the superoxide dismutase (SOD) mimics ambroxol, manganese [III] tetrakis (5,10,15,20 benzoic acid) (MnTBAP), and copper [II] diisopropyl salicylate (CuDIPS) were used to target different checkpoints of the oxidative cascade to determine the pathways involved in ROS production. Liver mitochondria from ob/ob mice generated more O(2)*- than those of lean littermates (P <.01). Ex vivo, all three SOD mimics decreased O(2)*- generation (P <.001) and totally inhibited lipid peroxidation (P <.001) versus untreated ob/ob mice. Those modifications were associated with in vivo improvements: MnTBAP and CuDIPS reduced weight (P <.02) and limited the extension of histological liver steatosis by 30% and 52%, respectively, versus untreated ob/ob mice. In conclusion, these data demonstrate deleterious effects of superoxide anions in NASH and point at the potential interest of nonpeptidyl mimics of SOD in the treatment of NASH in humans.

Animals↗
PubMed2003

Laparoscopic liver resection for subcapsular hepatocellular carcinoma complicating chronic liver disease.

HYPOTHESIS: Laparoscopic liver resection for subcapsular hepatocellular carcinoma in patients with chronic liver disease is associated with lower morbidity than open resections. DESIGN: A case-comparison study. SETTING: A tertiary referral center. PATIENTS AND INTERVENTION: From December 1, 1998, to November 30, 2000, 13 patients with chronic liver disease who underwent laparoscopic resection of hepatocellular carcinoma formed the laparoscopic group (LG). Tumors were 5 cm or smaller, subcapsular, and located in anterolateral segments (segments II-VI). A control group was created by matching each laparoscopic case with patients identical for liver disease, tumor size, and location and type of hepatectomy who underwent open liver resection. Fourteen patients fulfilled the criteria and formed the open group (OG). MAIN OUTCOME MEASURES: Postoperative mortality and morbidity. RESULTS: One segment or less was resected in 21 patients and 2 in 6 patients. Operative duration and cumulative portal triad clamping times were longer in the LG (267 +/- 79 minutes vs 182 +/- 57 minutes, P =.006; 68 +/- 24 minutes vs 25 +/- 19 minutes, P =.006, respectively). Mortality rates were 0% in the LG and 14% (2/14) in the OG (P =.2). Postoperative liver failure and ascites occurred in 8% (1/13) in the LG and 36% (5/14) in the OG (P =.15). Surgical margin was not different in the 2 groups. Three-year survival was significantly higher in the LG (89% vs 55%; P =.04), but 3-year recurrence rates were similar (46% vs 44%). CONCLUSION: Our study suggests that, despite longer operative and clamping times without clinical consequences, the rate of decompensation of liver disease could be lower after laparoscopy.

Aged↗
PubMed2003

Mangafodipir prevents liver injury induced by acetaminophen in the mouse.

BACKGROUND/AIMS: Acute liver failure (ALF), characterized by massive hepatocyte necrosis, is often caused by drug poisoning, particularly with acetaminophen (APAP). Hepatocyte necrosis is consecutive to glutathione depletion by NAPQI, a metabolite of APAP, and to mitochondrial damages caused by reactive oxygen species (ROS) overproduction. Considering the structure of Mangafodipir, a contrast agent currently used in magnetic resonance imaging of the liver, we hypothesized that this molecule could exert an antioxidant activity and be possibly used as a treatment of APAP-induced ALF. METHODS/RESULTS: Mangafodipir is endowed with superoxide dismutase, catalase, and glutathione reductase activities. It can inhibit ROS production by hepatocytes in culture, and protect those cells from oxidative stresses induced by exposure to xanthine oxidase, H(2)O(2), or UV light. Moreover, preventive or curative administration of Mangafodipir to mice with APAP-induced ALF significantly increases survival rates, and abrogates aspartate aminotransferase elevation and histological damage. CONCLUSIONS: Those data point out the potential interest of Mangafodipir in the treatment of toxic ALF in humans.

Acetaminophen↗
PubMed2003

Laparoscopic versus open left lateral hepatic lobectomy: a case-control study.

BACKGROUND: After technical advances in hepatic surgery and laparoscopic surgery, some teams evaluated the possibilities of laparoscopic liver resections. The aim of our study was to assess the results of laparoscopic left lateral lobectomy (bisegmentectomy 2-3) and to perform a case-control comparison with the same operation performed by open surgery. STUDY DESIGN: From 1996 to 2002, 60 laparoscopic resections were performed in selected patients, including 18 left lateral lobectomies. The resected lesions were benign tumors, hepatocellular carcinomas with compensated cirrhosis, and metastases. Surgical procedures were performed with a harmonic scalpel, an ultrasonic dissector, linear staplers, and portal pedicule clamping when necessary. Results were compared with those of patients who underwent open left lateral lobectomies selected from our liver resection database in a case-control analysis. Both groups were similar for age, type and size of the tumor, and presence of underlying liver disease. RESULTS: Compared with laparotomy, laparoscopic left lateral lobectomies were associated with a longer surgical time (202 versus 145 minutes, p < 0.01), a longer portal triad clamping (39 versus 23 minutes, p < 0.05), and a decreased blood loss (236 versus 429 mL, p < 0.05). There were no deaths in either group, and the morbidity rates were 11% in the laparoscopic group and 15% in the open group. There were no specific complications of hepatic resection after laparoscopy (no hemorrhage, subphrenic collection, or biliary leak), but some were observed in the open group. CONCLUSIONS: This study demonstrates the safety of laparoscopic left lateral lobectomy. Despite longer operation and clamping time, without any clinical consequences, the laparoscopic approach was associated with decreased blood loss and absence of specific complications of the hepatic resection.

Adult↗
PubMed2003

Real-time quantification of AFP mRNA to assess hematogenous dissemination after transarterial chemoembolization of hepatocellular carcinoma.

OBJECTIVE: To determine whether the number of hepatocytes containing AFP mRNA shed into the bloodstream during transarterial chemoembolization (TAE) affects the incidence and pattern of recurrence of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We developed a Taqman procedure to quantify AFP mRNA prospectively in 52 consecutive patients before and after TAE. Results are expressed in hepatocytes /mL. RESULTS: Thirteen of the patients (24.5%) were positive for AFP mRNA (42 +/- 19 hepatocytes/mL) before TAE and 13 (24.5%) (80 +/- 32 hepatocytes/mL) after TAE; the difference was not significant. The presence of AFP mRNA in the bloodstream before TAE was associated with larger nodules (85.2 +/- 73.8 mm versus 34.8 +/- 26.1 mm; P = 0.006). Six of the patients were excluded from the analysis because they underwent curative surgery or were lost to follow-up. The circulating levels of AFP mRNA released in the 46 remaining patients after TAE did not affect metastasis-free survival. A significant number of extrahepatic metastases were found in patients exhibiting at least 1 AFP mRNA-positive blood sample either before or after TAE. However, the TAE procedure did not increase the risk of extrahepatic recurrences. CONCLUSION: Cells containing AFP mRNA are inconsistently released into the circulation during TAE. The amount of these cells released does not affect the recurrence of HCC.

Adult↗