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Biomedical subjects

L Hannoun

Publications and source records attributed to L Hannoun.

At least 55 records · Page 3Linked to original sources
PubMed1994

Treatment of unresectable hepatocellular carcinoma with a combination of human recombinant alpha-2b interferon and doxorubicin: results of a pilot study.

Based on the in vitro and in vivo potentiation of the cytotoxic activity of chemotherapeutic agents by the interferons, a pilot study combining human recombinant alpha-2b interferon (IFN) and doxorubicin was conducted for the treatment of unresectable, histologically proven hepatocellular carcinoma. Between March 1988 and May 1990, 21 patients (median age: 60 years, range: 29-76) entered the study. The dose of doxorubicin was fixed at 35 mg/m2, every 3 weeks. The dose of alpha-2b IFN was 6 million U/m2 per day, 5 days a week. 3 patients (14%) obtained a partial response lasting 11, 16 and 30 months, and 1 had a stable disease during 8 months. The other 17 patients died within a median survival time of 4 months. All patients experienced flu-like symptoms. 7 patients experienced WHO grade III-IV haematological toxicity. We conclude that the association of alpha-2b IFN and doxorubicin is feasible, with respect to the use of doxorubicin at an inferior dose level than the same agent used without IFN. The response rate is comparable to that observed with doxorubicin used alone. Further phase I studies and randomised trials are required to confirm the role of this regimen in the treatment of unresectable hepatocellular carcinoma.

Adult↗
PubMed1994

Effect of liver transplantation on sex-hormone disorders in male patients with alcohol-induced or post-viral hepatitis advanced liver disease.

The effects of liver transplantation on the pituitary-gonadal axis and sex-hormone metabolism were evaluated by studying hormonal status (androgens, oestrogens, and gonadotropins) and sex-hormone-binding globulin levels in men with advanced liver disease of both alcoholic and viral origins. Comparison of the results prior to and 6 months after liver transplantation showed that successful liver transplantation in men induced significant differences in sex-hormone levels and in pituitary-gonadal function in both alcoholic and post-hepatitis patients. Plasma testosterone and dihydrotestosterone levels increased, oestrogen (oestrone and oestradiol) and androstenedione levels fell while gonadotropin (FSH and LH) levels increased. There was also a fall in plasma prolactin levels. Sex-hormone binding globulin plasma levels were elevated prior to transplantation and decreased thereafter. These data show that male patients with advanced liver disease have biological hypogonadism and feminization, irrespective of the aetiology, and that these abnormalities rapidly improve after successful liver transplantation. Therefore in men with advanced liver disease the biochemical signs of sex hormone disturbance are reversible and may be largely related to the liver disease.

Adult↗
PubMed1994

Topical metronidazole as an adjunct to subgingival debridement in the treatment of chronic periodontitis.

The purpose of this study was to evaluate the clinical effects of a single application of a 5% metronidazole collagen device in periodontal pockets deeper than 5 mm, in association with debridement and without reinforcement of home care and hygiene as practiced by the patient at any time. Pocket depth, attachment level, bleeding on probing, gingival index and plaque index were assessed at baseline, and on days 15, 30 and 90. Analysis of data from 28 patients indicated that both debridement and metronidazole therapy decreased pocket depth, bleeding on probing and gingival index, but results were significantly better with metronidazole. These results indicate that topical metronidazole provides an effective adjunctive treatment of advanced periodontitis.

Adult↗
PubMed1994

[Results of ileoanal anastomosis with mucosectomy and "J" pouch in hemorrhagic rectocolitis].

The aim of this study was to assess the results of ileal "J" pouch-anal anastomosis in ulcerative colitis. One hundred and fifty six patients operated on between 1983 and 1991 for ulcerative colitis were followed-up prospectively since the surgical procedure with a mean of 29 +/- 16 months (range: 6 to 92 months). There was no postoperative death. Forty-four patients (28%) presented 48 post-operative complications and 14 (9%) were reoperated. Twenty-five patients (16%) were reoperated because of a late complication. Three pouches had to be removed for untreatable fistulas which appeared to be related to a Crohn's disease in 2 cases; the reestablishment of a diverting loop ileostomy was mandatory in 2 further patients for anoperineal sepsis. The mean stool frequency at 1 year was 4.5 +/- 1.9; 40% of patients did not have nocturnal stooling. Daytime and nighttime continence were normal in 90.7% and 77.5% of cases respectively, 87% of patients considered their social life improved by the surgical cure of the disease. The results observed 5 years after the surgical procedure in 37 patients were similar to those observed at 1 year. Twenty-five patients (16%) presented one or several episodes of pouchitis, including 5 cases of chronic pouchitis. It is concluded that the treatment of ulcrerative colitis, ileal "J" pouch-anal anastomosis, is a safe and effective procedure which provides good functional results.

Adolescent↗
PubMed1993

[Biliary scintigraphy. Application to the study of chronic cholestasis].

In a sample population of 49 subjects (7 normal, 42 with various liver diseases), the parameters of the activity/time curve of trimethylbromo-iminodicetic acid (TBIDA) biliary scintigraphy were compared with the clearances of bromosulfophthalein (BSP) and indocyanine green (ICG). Correlation between T1/2 and P2 BSP slope was r = 0.50 (n = 33; P < 0.01). Correlation between Tmax TBIDA and fractional ICG clearance (P ICG) was r = 0.65 (n = 44; P < 0.001). In 23 cases of chronic cholestasis correlations remained significant (T1/2-P2 BSP: r = 0.53; n = 17; P = 0.02; Tmax-P ICG: r = 0.59; n = 17; P < 0.01). A prospective study of 11 cases of chronic intrahepatic cholestasis (primary biliary cirrhosis 8, primary sclerosing cirrhosis 3) showed that these two types of tests varied concordantly. Biliary scintigraphy, therefore, seems to be an accurate method to explore hepatocellular mass (degree of hepatic insufficiency) and cholestasis. The validation of biliary TBIDA scintigraphy as hepatobiliary functional exploration method and the possibility to study intrahepatic "regions of interest" defined a priori would make it possible to obtain a functional estimate of hepatic segments or lobes, for example before wide liver excision.

Aged↗
PubMed1993

Repeat liver resection for recurrent colorectal metastases.

Sixteen patients underwent 18 repeat liver resections for recurrence of colorectal hepatic metastases that had been previously resected. Only minor liver resection had been undertaken at the first operation; three were palliative. The second operation was major hepatectomy in ten patients, minor resection in five and orthotopic liver transplantation in one. In one patient, lung metastases were resected before the second operation. One repeat hepatectomy was palliative. After partial liver resection, there were no deaths and complications were observed in six of 15 patients. One patient died 2 weeks after liver transplantation. After the second resection, 2-, 3- and 5-year survival rates were 67, 57 and 30 per cent; the mean survival time was 33 (range 8-93) months. Tumour recurrence was observed in 11 of 14 patients 4-32 (mean 13) months after a second curative liver resection; two patients received a third curative operation for recurrent liver metastases. After the second curative hepatectomy, seven patients died from disease after a mean of 36 (range 14-61) months and seven are currently alive at a mean of 33 (range 8-93) months. Four of these patients are free from disease 26-93 months after resection and three are alive with recurrence. Repeat hepatectomy for recurrent colorectal metastases can prolong survival in selected patients and has low operative risk.

Adult↗
PubMed1993

Function of ileal J pouch-anal anastomosis in patients with familial adenomatous polyposis.

Pouch function after proctocolectomy and ileal J pouch-anal anastomosis was assessed at 1 and 5 years in 41 patients with familial adenomatous polyposis. The mean(s.d.) stool frequency per 24 h decreased from 4.4(1.7) to 3.9(1.8) (P < 0.05), the mean(s.d.) nocturnal stool frequency fell from 0.6(1.0) to 0.3(0.6) (P < 0.05), and the number of patients having nocturnal bowel movements decreased from 16 to seven (P < 0.05). At 5 years, only one patient still followed a strict diet (versus ten at 1 year, P < 0.05) and only two needed antidiarrhoeal medication (versus ten at 1 year, P < 0.05). There were no episodes of pouchitis or late reservoir-related complications. The function of ileal pouch-anal anastomosis improves over time in patients with familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1993

Liver resection with normothermic ischaemia exceeding 1 h.

A retrospective study was made of 34 patients who underwent major liver resection with a single period of vascular occlusion exceeding 60 min. The liver remnant was normal in all cases. Vascular occlusion was achieved by continuous portal triad clamping (15 patients), hepatic vascular exclusion (15) or a sequential combination of both procedures (four). Liver cooling was not used. The mean (s.e.m.) duration of continuous normothermic liver ischaemia was 73.6 (2.5) (range 60-127) min. The mean (s.e.m.) amount of blood transfused during operation was 5.3(0.8) units packed red cells. There were no deaths after surgery and the postoperative course was uneventful, or limited to asymptomatic pleural effusion, in 18 patients. Three patients suffered postoperative bleeding necessitating further surgery and one of these required reintervention for a prolonged bile leak. Four patients had transient liver failure that resolved spontaneously within 15 days. There was a 13-fold increase in serum transaminase activities and the proaccelerin level was 45 per cent that of normal on day 1 after operation. These changes were returning to normal levels within 15 days. Continuous vascular occlusion during major liver resection is a useful manoeuvre that may be performed safely on normal hepatic parenchyma for up to 90 min.

Adult↗
PubMed1993

Secondary proctectomy and ileal pouch-anal anastomosis after ileorectal anastomosis for familial adenomatous polyposis.

Conversion of ileorectal anastomosis to ileal pouch-anal anastomosis (IPAA) was indicated in 29 patients with familial adenomatous polyposis but technically impossible in three because of unsuspected pelvic desmoid tumours. There was no operative mortality and overall postoperative morbidity and late complication rates were no different from those in a group of 120 patients who underwent IPAA as a first operative procedure. Unsuspected adenocarcinoma (one invasive, three in situ) was found in four patients. The functional results in patients with IPAA did not differ from those of ileorectal anastomosis before conversion or from those obtained after IPAA as a first-choice procedure. Secondary proctectomy and IPAA can be safely offered to patients with ileorectal anastomosis and a high risk of rectal cancer.

Adenomatous Polyposis Coli↗
PubMed1993

Previous subtotal colectomy with ileostomy and sigmoidostomy improves the morbidity and early functional results after ileal pouch-anal anastomosis in ulcerative colitis.

The aim of this work was to study the effects of previous subtotal colectomy (STC) with ileostomy and sigmoidostomy on the outcome of ileal J-pouch-anal anastomosis (IPAA) in patients with acute ulcerative colitis. Between 1983 and 1991, we conducted a prospective, nonrandomized study of 156 patients who underwent IPAA in our center. Fifty-five patients (34.3 percent) had undergone STC with ileostomy and sigmoidostomy for either severe acute colitis (36.5 percent of cases) or nonresolving acute colitis (63.5 percent) up to six months before IPAA with covering ileostomy. There were no perioperative deaths; six patients (11 percent) developed complications requiring reoperation (three cases of pelvic sepsis, two occlusions, and one stenosis of the ileostomy). IPAA was successfully carried out at a later stage in all cases. The results of IPAA in these patients were compared with those in 78 patients who underwent the classical two-stage IPAA procedure. The rates of pelvic sepsis and postoperative occlusion were lower in the subgroup of patients who underwent the three-step procedure. Three months after closure of the ileostomy, the mean number of daily stools was significantly lower in the patients who had undergone prior STC (5.09 vs. 5.9), but there was no significant difference between the two groups with regard to diurnal and nocturnal continence, the need to wear a pad, discrimination between gas and stools, or the use of antidiarrheal medication. In addition, there was no significant difference at one year in terms of functional parameters. We conclude that STC is a simple and safe procedure for the treatment of a severe attack of colitis and that it does not compromise the results of later IPAA. Because it does not increase the morbidity of subsequent IPAA and is associated with more rapid functional recovery, STC appears to be suitable for the treatment of patients with nonresolving acute colitis before the onset of malnutrition or steroid dependency.

Adolescent↗
PubMed1993

5-Fluorouracil combined with the [6S]-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma. A phase I-II study of two consecutive regimens.

BACKGROUND: Potentiation of the antitumor activity of 5-fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase (TS), fluorodeoxyuridylate (FdUMP), and methylene tetrahydrofolate (5,10-CH2-FH4), which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C6 carbon of the pteridine ring. Only the levorotatory [6S]-folinic acid is transformed into active folate cofactors. However, the [6R]-stereoisomer is not inert; it was shown to interfere with the [6S] form at the cellular level. The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out 2 consecutive phase I-II studies of 5-FU combined with the [6S]-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. PATIENTS AND METHODS: Treatment comprised 5-FU by i.v. infusion for 2 hours (the initial dose was 350 mg/m2/d; it was incremented by 25 mg/m2/d until a maximal dose of 550 mg/m2/d) and [6S]-folinic acid (100 mg/m2/d by rapid i.v. injection in Regimen 1, and 100 mg/m2 by rapid i.v. injection followed by a 2-hour infusion of 250 mg/m2 in Regimen 2) for 5 days, every 21 days. Twenty-five pts and 27 pts were assessed in Regimen 1 and in Regimen 2, respectively. They had had no prior chemotherapy. The median follow-up time was 9 months and 15.5 months for patients treated with Regimen 1 and Regimen 2, respectively. For pts treated with Regimen 1, the response rate was 52% (CR, 12%; PR, 40%). The median time to disease progression was 9.2 months. The probability of survival at 12 months was 73%. For pts treated with Regimen 2, the response rate was 37% (CR, 7%; PR, 30%). The median time to disease progression was 8.9 months. The probability of survival at 12 months was 67%. Improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects (WHO grades > or = 3) were diarrhea, dermatitis, and mucositis. One single episode of grade 4 diarrhea occurred. After injection according to the schema in Regimen 1, [6S]-folinic acid was rapidly cleared from plasma (mean t 1/2 alpha and t 1/2 beta of 7.2 and 126 minutes, respectively). The mean concentration of the [6S]-stereoisomer two hours after injection was 5.8 mmol/L. After a rapid i.v. injection of 100 mg/m2 followed by a 2-hour infusion of 250 mg/m2, the mean concentration of [6S]-folinic acid two hours after the injection was 57.5 mmol/L. Pharmacokinetic data suggests saturation of the metabolic conversion of [6S]-folinic acid when large doses are administered. CONCLUSION: The [6S]-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. However, increase of the daily dose of the folate did not result in a therapeutic improvement. The present results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines.

Adenocarcinoma↗
PubMed1993

A report of forty-four instances of pancreaticoduodenal resection in patients more than seventy years of age.

Between January 1970 and December 1990, 223 patients underwent pancreaticoduodenal resection for pancreatic or periampullary tumors. Forty-four of these patients were 70 years of age or older and 179 patients were less than 70 years of age. In the older group, 27 patients were operated upon after 1986. The overall operative mortality rate was 9.0 percent and 2.5 percent during the last five years. The overall operative mortality rate was 4.5 percent in patients more than 70 years of age and 10 percent in those less than 70 years of age. The overall operative morbidity rate was 35 percent; 36 percent in patients more than 70 years of age and 35 percent in those less than 70 years of age. Survival was related to tumor histologic factors. For carcinoma of the pancreas, the survival rate at five years was 17 percent in patients more than 70 years of age and 19 percent in patients less than 70 years of age. For the ampullary carcinoma, the survival rate at five years was 38 percent in patients more than 70 years of age and 45 percent in patients less than 70 years of age. It can be concluded that, in a selected group, age is not a limiting factor for pancreaticoduodenal resection.

Adult↗
PubMed1993

Endothelin-1 secretion by human gallbladder epithelial cells in primary culture.

BACKGROUND: The three isoforms of endothelin (ET), ET-1, ET-2, and ET-3 are potent contractile agonists for smooth muscle in a wide variety of tissues including the gallbladder. There is increasing evidence that endothelin acts in a paracrine fashion, however, its cell source in the gallbladder is unclear. EXPERIMENTAL DESIGN: To examine the production of ET by gallbladder and bile duct epithelium. RESULTS: We show that human gallbladder epithelial cells in primary culture secrete endothelin. ET release was time-dependent, and intracellular ET was negligible, indicating de novo synthesis. Secretion was increased by physiologic concentrations of cholecystokinin. Epithelial cells lining hepatic cysts in primary culture also released ET, suggesting that the intrahepatic, as well as the extrahepatic biliary epithelium is a source of this cytokine. High performance liquid chromatography separation of the conditioned medium from both cell types showed a single peak corresponding to that of ET-1. In vivo, ET-1 was present in hepatic cyst fluid, but was not detectable in gallbladder or choledochal bile. On tissue sections, both intrahepatic and extrahepatic bile duct epithelial cells were labeled with an anti-"big" ET-1 polyclonal antibody. CONCLUSIONS: These results suggest that ET-1 is locally produced in the biliary tract and by a paracrine route, could play a role in choledochal motility and gallbladder contraction.

Bile Ducts↗
PubMed1993

Operation and abdominal desmoid tumors in familial adenomatous polyposis.

Abdominal desmoid tumors (ADT) have become an important problem because of the increased survival of patients with familial adenomatous polyposis (FAP). Of 240 patients operated upon for FAP between 1978 and 1991, 29 (16 men and 13 women) had ADT. Diagnosis was made at laparotomy in 19 patients, while an abdominal mass or intestinal obstruction was the principal cause of discovery in the ten remaining patients. Twenty ADT were discovered after a previous laparotomy performed an average of three years earlier. Nine ADT occurred in 146 patients who had previously undergone a coloproctectomy and ileal pouch-anal anastomosis and eight occurred in 74 patients who had abdominal colectomy and ileorectal anastomosis. Desmoid tumors were responsible for eight instances of intestinal obstruction and one instance of small intestinal perforation. One death was directly related to ADT. In four of nine patients, ADT was responsible for a deterioration of the functional results of ileoanal anastomosis, but pouch removal was not necessary. Conversion of ileorectal anastomosis to ileoanal anastomosis and excision of carcinomas that occur in the residual rectum after ileorectal anastomosis were impossible because of ADT in three and two patients, respectively. Complete surgical removal of the tumor was possible in seven patients only and four patients had a recurrence. None of the medical therapies used (sulindac, tamoxifen and chemotherapy) were effective. The results of this study confirm the high incidence, severity and absence of effective treatment of ADT in FAP. Desmoid tumors occurring after ileorectal anastomosis seem to be more severe than after ileoanal anastomosis because, in the former instance, they may interfere with the further management of the rectal stump.

Abdominal Muscles↗
PubMed1992

[Colonic complications of acute necrotizing pancreatitis].

Among 126 patients operated upon for acute necrotizing pancreatitis in our department over a 10-year period starting in November 1979, 17 had a colonic resection. Colectomy was made mandatory by a necrotic or ischaemic appearance (12 cases, including 3 bowel perforations), an isolated perforation (2 cases) or extensive fat necrosis of the pericolonic atmosphere (3 cases). The hospital mortality was 5 out of the 17 cases. In 6 patients, the pathological results suggested that colonic resection was unnecessary. Since May 1988, a diverting loop ileostomy has been performed whenever colonic viability was found to be dubious at laparotomy. After this policy was introduced no case of secondary colonic complication was encountered. Nevertheless, there still are "abusive" colectomies unjustified by the pathology. Their number should be reduced by a more cautious indication of colonic resection in acute necrotizing pancreatitis.

Acute Disease↗
PubMed1992

Fluorouracil combined with the pure (6S)-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma: a phase I-II study.

BACKGROUND: Potentiation of the antitumor activity of fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase, fluorodeoxyuridine monophosphate, and methylene tetrahydrofolate, which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C-6 carbon of the pteridine ring. Only the levorotatory (6S)-stereoisomer of folinic acid is transformed into active folate cofactors. However, the (6R)-stereoisomer of folinic acid is not inert; it was shown to interfere with the (6S) form at the cellular level. PURPOSE: The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out a phase I-II study of 5-FU combined with the (6S)-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. We also determined the plasma pharmacokinetics of folates after intravenous (IV) injection of (6S)-folinic acid at the dose used in this study. METHODS: Treatment consisted of 5-FU (350-550 mg/m2 per day by IV infusion for 2 hours) and (6S)-folinic acid (100 mg/m2 per day by IV bolus injection) given for 5 consecutive days; the treatment was repeated every 21 days. Twenty-five patients with advanced colorectal carcinoma, who had had no prior chemotherapy, were evaluated for antitumor activity. The quantity of folates in plasma was measured using a microbiological assay. RESULTS: The median follow-up time was 9 months (range, 3.5-15.2 months). The response rate was 52% (complete response, 12%; partial response, 40%). The median time to disease progression for responding patients was 9.2 months (range, 5.9-15+ months). The estimated probability of survival at 12 months was 73%. Palliative improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects were grade 3 diarrhea, dermatitis, and oral mucositis. Grade 4 toxicity did not occur. Myeloid toxicity was minor. After IV injection, (6S)-folinic acid was rapidly cleared from plasma (mean half-lives: alpha = 7.2 minutes and beta = 126 minutes). The mean concentration of the unchanged compound 2 hours after injection was 5.8 mumol/L. CONCLUSION: The (6S)-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. IMPLICATION: Our results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines.

Adult↗