Search PubMed⌕ Search

Biomedical subjects

L Hannoun

Publications and source records attributed to L Hannoun.

At least 19 recordsLinked to original sources
PubMed2001

Functional metabolic characteristics of intact pig livers during prolonged extracorporeal perfusion: potential for a unique biological liver-assist device.

BACKGROUND: The clinical development of liver-support devices based on perfusion of either pig hepatocytes cartridges or whole pig livers has been hampered by the ability to use sufficient liver cell mass to provide adequate metabolic support, limited perfusion times, and the potential for patient exposure to pig zoonotic diseases. METHODS: We designed an original system in which an isolated intact pig liver was perfused extracorporeally under physiological conditions in a closed loop circuit with allogeneic pig blood and constant monitoring of major physiological and functional parameters. The perfusion circuit further included an interface membrane to provide for separation of patient and liver perfusion circulation. RESULTS: Prolonged (6-21 hr) liver perfusion did not produce significant liver damage as reflected by modest rises in the levels of the serum transaminases, stability of main biochemical parameters (including potassium), and the maintenance of normal cellular morphology. Optimal liver function was documented as measured by lactate consumption, control of glycemia, and the results of clotting studies and functional assays. The perfused liver cleared 82% and 79% of peak bilirubin and ammonia concentrations with clearing kinetics identical throughout perfusion. Indocyanine green clearance was identical to that observed in the living donor before explant surgery. CONCLUSIONS: In conclusion, the extracorporeal pig liver perfusion apparatus described here allows optimal pig liver function for prolonged periods of time. The microporous membrane to provide separation of donor organ and recipient and the high level of functional activity suggest that this form of liver metabolic support may have important clinical applications.

Ammonia↗
PubMed2000

Combined radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) as palliative treatment for localized unresectable or adjuvant treatment for resected pancreatic adenocarcinoma: results of a feasibility study.

PURPOSE: To evaluate a cisplatin-containing chemoradiotherapy (CRT) regimen followed by chemotherapy for unresectable (locally advanced group, n = 32) and resected (adjuvant group, n = 10) pancreatic adenocarcinoma. The quality of palliation and percentage of secondary resections were also studied for unresectable disease. METHODS AND MATERIALS: The protocol comprised CRT (45 Gy over 5 weeks), combined with 5-fluorouracil and cisplatin during the first and fifth weeks, followed, 3 weeks later, by 4 cycles of the same chemotherapy plus leucovorin. RESULTS: All patients completed CRT but only 50% of each group finished the entire protocol. Gastrointestinal toxicity and weight loss were the major side effects during CRT. Enhanced hematological toxicity limited the post-CRT chemotherapy. For the locally advanced group, median survival was 9 months; 1- and 2-year survival rates were 31 and 12. 5%, respectively. The overall response rate was 16% and 50% had stable disease. A lasting palliative effect defined as improved performance status and decreased analgesic consumption, was recorded for 43% of the patients. Only three secondary resections have been performed. For the adjuvant group, median survival was 17 months. CONCLUSIONS: Although toxic in advanced disease, this regimen significantly lowered pain and analgesic consumption, but had poor impact on secondary resectability. In an adjuvant setting, although equally toxic, this series was too small to allow conclusions to be drawn.

Adenocarcinoma↗
PubMed2000

Cold preservation injury in rat liver: effect of liposomally-entrapped adenosine triphosphate.

BACKGROUND/AIMS: Energy charge and capacity for adenosine triphosphate (ATP) synthesis have been demonstrated to play a major role in the maintenance of organ function after liver preservation for transplantation. The aim of this study was to evaluate whether a supply of liposomally-entrapped ATP during preservation could improve the energy state and metabolism of cold-stored rat liver. METHODS: In the first set of experiments, the uptake of ATP-containing liposomes and their effects on hepatic viability were determined in isolated perfused unstored rat liver. In the second set of experiments, rat livers were preserved for 18 h at 4 degrees C in UW solution in the presence of these liposomes, and effects on energy state, cell volume and metabolism were evaluated. In each part, data were compared with adequate control, unloaded liposome-treated, and free ATP-treated groups (n=6 in each group). RESULTS: In non-stored livers, ATP-containing liposomes were taken up by the liver; they did not alter hepatic viability and induced a decrease in energy substrate consumption (glucose and amino acids), and an improvement in intrahepatic ATP content (+23% vs. Control). Addition of liposomally-entrapped ATP during cold storage produced a significant attenuation of the decrease in hepatic ATP content (Lip ATP 2: 524+/-45 vs. Control 2: 364+/-106 nmol/g; p<0.05), and induced, during reperfusion, a decrease in proteolysis associated with an increase in cell volume compared with the other groups (Lip ATP 2: 633+/-63 vs. Control 2: 532+/-38, Unloaded Lip 2: 483+/-55 and Free ATP 2: 500+/-29 microl/g; p<0.01). CONCLUSIONS: These data indicate that liposomally-entrapped ATP represents an effective means to improve liver graft energy state and function. The decrease in protein degradation may be related to the modification of cell volume.

Adenosine Triphosphate↗
PubMed2000

Surgical treatment of hepatocellular carcinoma in cirrhosis.

Hepatocellular carcinoma is one of the most frequent forms of cancer worldwide and its diagnosis and treatment have changed substantially during the last few years. Recent advances in ultrasonography, spiral computed tomography scan and nuclear magnetic resonance have further simplified the diagnostic approach to hepatocellular carcinoma. Ultrasonography is the reference examination, giving a wide variety of information on tumour size, location, relationship with portal and hepatic veins and splanchnic haemodynamics. Surgical resection and liver transplantation can both be defined as curative treatment while other techniques such as percutaneous ethanol injection and chemoembolization must be considered as palliative. Therapeutic strategies for hepatocellular carcinoma are based upon data concerning the characteristics of the tumour the functional status of non-tumoural liver parenchyma and patients' general conditions. Surgery of hepatocellular carcinoma in cirrhotic liver is mainly restricted by lack of functional hepatic reserve and by the limited capacity of hepatic regeneration. The best surgical results are obtained in early tumoural stages which generally need limited resection. Nevertheless, major liver resections have a specific role in selected cases. Recurrence rate after surgical resection is high and is related to a large number of factors. For this reason, liver transplantation, removing at the same time, the tumour and the underlying disease, is considered, theoretically, the best treatment for hepatocellular carcinoma, but its role is still debated and limited by difficult organ sharing. Integration of present therapeutic schemes are under evaluation with promising preliminary results.

Carcinoma, Hepatocellular↗
PubMed2000

Prevention of proteolysis in cold-stored rat liver by addition of amino acids to the preservation solution.

BACKGROUND: One process identified as detrimental in liver preservation is proteolysis. METHODS: We tested the effects of adding antiproteolytic amino acids (L-alanine, L-glutamine, L-histidine, L-leucine, L-methionine, L-phenylalanine, L-proline, L-tryptophan) to the preservation medium, in a model of reperfusion of 24 h cold-stored rat livers. RESULTS: During the preservation period, antiproteolytic amino acids inhibited the proteolysis observed in stored livers as shown by branched-chain amino acid fluxes, which switched from release to uptake. During reperfusion, cold storage of lives without the addition of antiproteolytic amino acids resulted in a decrease in the total amino acid and branched-chain amino acid uptake and a lower perfusion flow rate. The addition of antiproteolytic amino acids during liver storage resulted in the maintenance of total amino acid and branched-chain amino acid uptake and a significant improvement in the perfusion flow rate during reperfusion. CONCLUSIONS: The presence of antiproteolytic amino acids in the preservation medium might be of interest in improving hepatic graft viability in transplantation.

Amino Acids↗
PubMed1999

Phase I and phase II drug-metabolizing enzymes are expressed and heterogeneously distributed in the biliary epithelium.

Tissue expression of drug-metabolizing enzymes influences susceptibility to drugs and carcinogens. Because the biliary epithelium, exposed to bile-borne chemicals, may give rise to drug-induced cholangiopathies and to cholangiocarcinomas, we determined the pattern of expression of drug-metabolizing enzymes in this epithelium. We first demonstrated by blot analyses that biliary epithelial cells (BEC) isolated from human gallbladders display cytochrome P450 (CYP) 1A, 2E1, and 3A, microsomal epoxide hydrolase (mEH), alpha, mu, and pi glutathione S-transferase (GST), transcripts and proteins. We also identified CYP-associated steroid 6beta-hydroxylase activity in BEC. CYP and mEH expression was 5- to 20-fold lower in BEC than in autologous hepatocytes, and further differed by a higher ratio of CYP3A5/CYP3A4, and by CYP1A1 predominance over CYP1A2. alphaGST was highly expressed in both hepatocytes and BEC, while piGST was restricted to BEC. In approximately 50% of individuals, muGST was expressed in hepatocytes and at lower levels in BEC. By using the same antibodies as those used in immunoblots, we could show by immunohistochemistry that CYP2E1, CYP3A, mEH, alpha, mu, and piGST immunoreactivities are expressed and display a heterogeneous distribution in the epithelium lining the entire biliary tract except for small intrahepatic bile ducts that were devoid of CYP3A and alphaGST immunoreactivities. In conclusion, BEC contribute to phase II, and although to a lesser extent than hepatocytes, to phase I biotransformation. The distribution of drug-metabolizing enzymes in BEC suggest that they are heterogeneous in their ability to generate and detoxicate reactive metabolites, which may contribute to specific distributions of cholangiopathies.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

[Role of surgery in the treatment of refractory ascites in cirrhotic patients].

Ascites, generally directly reflecting portal hypertension, is the commonest cause of hospitalisation in patients with cirrhosis. In almost 10% of patients with ascites, optimal medical treatment combining bed rest, salt and water restriction, and diuretic treatment, is unable to induce sodium excretion and decrease the volume of the ascites, corresponding to the definition of refractory ascites. In other cases, it is the treatment of ascites itself (salt and water restriction and diuretics) which induce complications: water and electrolyte disturbances, functional renal failure, encephalopathy, the development of which also corresponds to refractory ascites. The therapeutic armamentarium for the management of refractory ascites remains varied, with the use of aspiration of ascites with compensation, peritoneovenous shunts, transhepatic or surgical porto-systemic anastomoses, and finally, liver transplantation. At the present time, each therapeutic measure must be taken while keeping in mind the possibility of subsequent liver transplantation and the potential risk of compromising liver transplantation by inappropriate treatments. In this context, the authors review and analyse the respective places of the various therapeutic modalities in the management of refractory ascites in cirrhotic patients.

Ascites↗
PubMed1998

Microbiological hazards related to xenotransplantation of porcine organs into man.

Pigs are emerging as the most likely providers of genetically engineered organs and cells for the purpose of clinical xenotransplantation. Introduction of clinical trials has been delayed primarily by uncertainties regarding the risk of swine pathogen transmission that could harm the recipient. The concern that xenotransplantation carries the potential for a new epidemic has been highlighted by recent experiences with both bovine spongiform encephalopathy and human immunodeficiency diseases. As clinical trials have been postponed and xenotransplantation teams are working actively to gather data for an estimation of the risk, this review provides the reader with a state-of-the-art estimation of the microbiological hazards related to xenotransplantation of porcine organs to man. Particular emphasis is put on viral and retroviral hazards. Both current diagnostic tools and those under development are described, along with breeding strategies to provide donor animals that would not put the recipient or the general population at risk.

Animals↗
PubMed1997

Deletion of hydroxyethylstarch from University of Wisconsin solution induces cell shrinkage and proteolysis during and after cold storage of rat liver.

Among the numerous components of the University of Wisconsin (UW) solution used for organ preservation, the usefulness of hydroxyethylstarch (HES), the colloido-osmotic support of this solution, is controversial. The aim of our study was to determine the influence of HES on hepatic metabolism and intracellular hydration state during hypothermic preservation and after reperfusion in a model of isolated perfused rat liver. Three groups of eight livers were perfused either immediately or after 18 hours of cold storage in a UW-based preservation solution with or without HES. Omission of HES results in 1) a stimulation of protein degradation shown by the marked increase in branched-chain amino acid (BCAA) release (211 +/- 55 vs. 87 +/- 28 nmol/min/g; P < .05, modified UW group vs. UW group), 2) an increase in oxygen consumption (81.7 +/- 4.8 vs. 61.5 +/- 5.0 micromol/h/g; P < .05), 3) a decrease in glucose production (2.3 +/- 0.6 vs. 5.0 +/- 0.6 micromol/min/g; P < .05), and 4) a reduction in intracellular volume (414 +/- 36 vs. 557 +/- 41 microL/g; P < .05). We conclude that HES plays an important role in liver preservation by limiting proteolysis, possibly through the observed preservation of cell volume.

Animals↗
PubMed1997

Results of liver transplantation in the treatment of metastatic neuroendocrine tumors. A 31-case French multicentric report.

OBJECTIVE: The purpose of this study was to assess the value and timing of orthotopic liver transplantation (OLT) in the treatment of metastatic neuroendocrine tumors (NET). SUMMARY BACKGROUND DATA: Liver metastasis from NET seems less invasive than other secondary tumors. This observation suggests that OLT may be indicated when other therapies become ineffective. However, the potential benefit of this highly aggressive procedure is difficult to assess due to the scarcity and heterogeneity of NET. METHODS: A retrospective multicentric study was carried out, including all cases of OLT for NET performed in France between 1989 and 1994. There were 15 cases of metastatic carcinoid tumor and 16 cases of islet cell carcinomas. Hormone-related symptoms were present in 16 cases (55%). Only 5 patients (16%) had no previous surgical or medical therapy before OLT. Median delay from diagnosis of liver metastasis and OLT was 19 months (range, 2 to 120). RESULTS: The primary tumor was removed at the time of OLT in 11 cases, by upper abdominal exenteration in 7 cases and the Whipple resection in 3. Actuarial survival rate after OLT was 59% at 1 year, 47% at 3 years, and 36% at 5 years. Survival rates were significantly higher for metastatic carcinoid tumors (69% at 5 years) than for noncarcinoid apudomas (8% at 4 years), because of higher tumor- and non-tumor-related mortality rates for the latter. CONCLUSION: OLT can achieve control of hormonal symptoms and prolong survival in selected patients with liver metastasis of carcinoid tumors. It does not seem indicated for other NET.

Adult↗
PubMed1997

Effects of combined topical metronidazole and mechanical treatment on the subgingival flora in deep periodontal pockets in cuspids and bicuspids.

The Effect on the subgingival microflora of a single topical administration of a 95% collagen and 5% metronidazole device in combination with debridement was investigated in 30 adult periodontitis patients in comparison with mechanical treatment alone. For each patient, plaque samples from test and control sites in cuspids and bicuspids were collected for culture and enumeration of total anaerobically cultivable bacteria (TA), black-pigmented anaerobes (BPA), and Actinobacillus actinomycetemcomitans (Aa). Spirochetes and fusiforms were quantified by direct microscopic examination after Giemsa staining. A decrease was observed for all parameters, and a significant difference in comparison with the control group was found for fusiforms. After treatment, a lower number of Aa positive sites were observed in the test group (13/25). These results show that a single application of topical metronidazole seems to be effective as adjunctive antimicrobial treatment in adult periodontitis.

Administration, Oral↗
PubMed1997

[Non-surgical treatment of biliary stenoses after hepatic transplantation].

We report the initial and long-term results of non surgical procedures performed for the treatment of biliary strictures in liver transplant patients. Twelve liver transplant patients with biliary strictures underwent 16 interventional radiological procedures. Initial technical success was achieved in 11 of 12 patients (91%). Within long-term, with a follow-up of 27 months, primary success rate (only one procedure) was 58% (7 of 12 patients). Three restenoses occurred. They were all treated by interventional radiological procedures. The secondary success rate (one or more procedures) was 83% (10 of 12 patients). Two complications occurred including one pancreatitis and one cholangitis. Non surgical management may be performed for patients with biliary strictures after liver transplantation.

Adult↗
PubMed1997

Surgical strategy for the management of hilar bile duct cancer.

BACKGROUND: Since the first attempts at resection of Klatskin tumours, an increasingly aggressive surgical treatment has been proposed. Results obtained after examination of the specimen have shown that a significant proportion of resections were palliative. Curative resection appears to be difficult to perform selectively. METHODS: This retrospective study evaluates the results of a surgically-oriented management of hilar bile duct cancers. Thirty-nine patients were operated on in the period 1982-1994. Eighteen resections were carried out, requiring liver resection in 13 cases. Pathology of the specimen showed that the resection had been curative in 14 cases. The remaining 21 patients had surgical palliation, i.e. bypass and/or stenting. RESULTS: In the resection group, there was no death but four patients suffered severe complications. The 1- and 5-year survival rates were 67 and 47 per cent respectively, with a median survival of 26 months. In the palliation group, the mortality rate was 14 per cent and median survival was 7 months. CONCLUSION: In the absence of evident contraindications, surgical exploration is worthwhile as it allows detection of the cases where curative resection is possible. Curative resection often requires a major hepatectomy, but mortality and morbidity may be kept low, and it offers a real hope of cure.

Adult↗
PubMed1996

[Cancer of the upper 3rd of the extra-hepatic bile ducts: surgical indication].

OBJECTIVES: Evaluate the surgical approach of curative resection in patients treated for cancer of the hepatic hilus. METHODS: We made a retrospective analysis of 50 cases collected between 1982 and 1994. Preoperative work-up was progressively centered on ultrasonography and Doppler examinations together with transhepatic cholangiography. Surgery was performed in 39 patients; surgery was not attempted in 11 patients in poor health status or with advanced stage disease. RESULTS: Curative resection was performed in 14 of the 39 operated patients. There were no hospital deaths and mean survival at 5 years was 60%. Median survival was 23 months. A palliative procedure was used in 25 patients with 3 deaths and a 7-month median survival. Transhepatic intubation of the bile ducts was performed in the 11 non-operated patients: there were 3 deaths and median survival was 3 months. CONCLUSIONS: A surgical approach, based on a simple preoperative work-up and extensive surgical exploration together with extemporaneous pathology can detect cases in which curative surgery is indicated. Care for operated patients given only palliative treatment is not compromised with this attitude and results are at least as good as those obtained with endoscopic or transhepatic intubation.

Adenocarcinoma↗
PubMed1996

Tandem high-dose chemotherapy with ifosfamide, carboplatin, and teniposide with autologous bone marrow transplantation for the treatment of poor prognosis common epithelial ovarian carcinoma.

BACKGROUND: A phase I or II trial was conducted to assess the toxicity and the efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and teniposide in patients with poor prognosis ovarian carcinoma. METHODS: Thirty-seven patients were scheduled to receive tandem high dose therapy combining ifosfamide 7500 to 11250 mg/m2, carboplatin 875 ot 1000 mg/m2 and teniposide 750 to 1000 mg/m2, followed by autologous bone marrow transplantation (ABMT). Eight patients were refractory to the platin-based regimen, 7 were treated in chemosensitive relapse, and 22 in partial or complete response (PR/CR) were treated. Sixty-six cycles were administered. Sixteen patients were evaluated for response. RESULTS: The overall response rate was 56% (CR rate: 12%). Toxic effects consisted of mainly renal toxicity, esophagitis, and enterocolitis. Three patients died of therapy-related complications. Since the time of ABMT, the median overall survival (OS) duration of the whole population was 18 months and the survival rate was 14% at 60 months. For the 22 patients treated after PR or CR, the median OS duration was 24 months and the survival rate was 32% at 60 months. Tandem high dose therapy with ABMT was unable to circumvent resistance to conventional chemotherapy or to prolong the duration of survival for patients treated in chemosensitive relapse. For patients treated after CR or PR, the survival results were similar to that achieved with conventional therapy. CONCLUSIONS: Prospective, randomized studies, including patients only after CR or with minimal residual disease, are urgently required to evaluate the activity of high dose therapy in the treatment of advanced ovarian carcinoma.

Adult↗
PubMed1996

Ileal pouch-anal anastomosis as the first choice operation in patients with familial adenomatous polyposis: a ten-year experience.

BACKGROUND: The choice between ileal pouch-anal anastomosis (IPAA) and ileorectal anastomosis (IRA) in the treatment of patients with familial adenomatous polyposis remains controversial. The aims of this study were to assess our 10-year experience with proctocolectomy, endoanal mucosectomy, construction of an ileal reservoir pouch, and IPAA in a series of 171 patients with familial adenomatous polyposis and to compare the functional results after IPAA with those after IRA. METHODS: Data from patients treated by IPAA at one institution were prospectively accumulated from October 1983 to October 1993. Medical records of 171 consecutive patients were studied regarding morbidity and functional results. These functional results were compared with those of a series of 23 patients who underwent IRA at the same institution. RESULTS: One patient (0.6%) died after operation. Sixty-two patients (36%) had concomitant colorectal carcinoma, 36 of which tumors were invasive (15 stage A, 13 stage B, and 8 stage C). Forty-six patients (27%) had at least one postoperative complication, with 14 patients requiring reoperation (8%). Twenty-six patients (15%) had obstruction. Seven patients (4%) had pelvic sepsis, and one had transient impotence (0.6%). Only two patients (1%) had a typical episode of pouchitis. The mean follow-up was 29 months (range, 3 to 100 months); 101 patients were monitored for more than 1 year. Little difference was noted between bowel function after IRA and that after IPAA. The mean daytime stool frequency after IPAA was 4.2 with 26% of patients having an average of 1 bowel movement at nighttime, compared with a stool frequency of 3.0 and 13% of patients having night evacuation after IRA. Daytime continence was normal for 98% of patients after IPAA and for all the patients after IRA. Nighttime continence was normal in 96% and 98% of patients, respectively. CONCLUSIONS: Morbidity and functional results after IPAA for familial adenomatous polyposis do not differ from those reported after IRA. For this reason and because of the risk of rectal cancer after ileorectal anastomosis, IPAA with endoanal mucosectomy is our first choice in the treatment of patients with familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1996

Phase II trial of 5-fluorouracil, leucovorin and cisplatin for treatment of advanced pancreatic adenocarcinoma.

BACKGROUND: Advanced pancreatic adenocarcinoma is a rapidly fatal disease for which an active chemotherapy regimen is sought. Here we report the outcome of a phase II trial to assess the toxicity and efficacy of a combination of 5-fluorouracil (5-FU), leucovorin and cisplatin (CDDP). METHODS: A regimen combining leucovorin (200 mg/m2/d x 5d), 5-FU (375 mg/m2/d x 5d in a 2-hour infusion) and CDDP (15 mg/m2/d x 5d) was given to 52 patients with histologically-proven, previously untreated, locally advanced (n = 13) and/or metastatic (n = 39) pancreatic adenocarcinoma. RESULTS: Of 48 patients evaluable for response, 10 achieved partial responses, for an overall response rate of 21% (95% CI 9.5%-32.5%), and a palliative effect was observed in 52%. The median survival was 9.5 months (18 months for locally-advanced and 5 months for metastatic disease) with a 1-year survival of 34.6% and a median progression-free survival of 4.5 months. Chemotherapy was well tolerated with grades 3 or 4 nausea/vomiting in 12%, diarrhea in 6%, anaemia in 17%, neutropenia in 12%, and thrombocytopenia in 10%. Eleven patients (21%) had Grade 2 peripheral neuropathy. CONCLUSION: The combination of leucovorin, 5-FU and CDDP seems to be an effective palliative treatment, with moderate toxic effects, in advanced pancreatic adenocarcinoma.

Adenocarcinoma↗