[Immunobiology of tolerance of hepatic allografts: to what degree can the immunosuppressive treatment be avoided?].
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Biomedical subjects
Publications and source records attributed to L Hannoun.
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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.
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.
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.
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.
Endothelial damage within the sinusoids of the liver probably plays a key role in primary liver dysfunction following transplantation. The aim of this work was to study the serum levels of two potential markers of endothelial damage, creatine kinase-BB and soluble thrombomodulin, during human graft revascularization. Thirteen human liver grafts were preserved in UW solution (mean time: 13.8 h). Creatine kinase-BB and transaminase activities and soluble thrombomodulin levels were measured: 1) in effluent and 2) in serum samples sequentially collected before revascularization, then during the first 120 min of revascularization and first post-operative week. No correlation was observed between serum values (peak) and effluent values. In serum, pre-operative creatine kinase-BB activities were correlated with soluble thrombomodulin levels (p = 0.01). Both increased significantly during the first minutes of the revascularization, then decreased markedly. In contrast, AST activity was maximal at day 1. This detectable and early release of creatine kinase-BB and soluble thrombomodulin in blood is in keeping with the early occurence of endothelial damage. Together with previous data, these findings suggest that serum determination of these two markers may be a useful tool in the assessment of endothelial injury in liver transplantation.
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The authors report the case of a 16-year-old man with recurrent abdominal pain. Ultrasonography showed two gallbladder polyps, one of them larger than 10 mm. Laparoscopic cholecystectomy was performed. Histologic examination revealed gastric heterotopia. The authors discuss the clinical, pathophysiologic and histologic features of the present case and those reported in the literature.
BACKGROUND: Hepatic vascular exclusion allows the performance of major hepatic resections with minimal intraoperative blood loss. We have previously shown that normothermic ischemia can be tolerated by a healthy liver for up to 90 minutes, and this period is increased to 4 hours if the liver is cooled to 4 degrees C using University of Wisconsin solution. STUDY DESIGN: This study assessed whether these techniques could be successfully applied for patients requiring resection of a diseased liver, which is more sensitive to ischemic damage. Between July 1990 and May 1994, 12 patients (6 men, 6 women; mean age, 57.8 years) in whom the planned hepatic resection was believed to require hepatic vascular exclusion for more than 1 hour were treated with perfusion with the University of Wisconsin solution. The surgical procedures were right hepatectomy (one patient), extended right hepatectomy (seven patients), and extended left hepatectomy (four patients). The underlying hepatic disease was cirrhosis or severe fibrosis with hepatocellular carcinoma (four patients), cholestasis (due to cholangiocarcinoma and biliary stricture, one patient each), and more than 30 percent steatosis after treatment of hepatic metastases with chemotherapy (six patients). The University of Wisconsin solution that had been cooled to 4 degrees C was perfused through a cannula placed in the portal vein or the hepatic arterial branch of the segment to be resected, but with flow directed toward the liver that should be retained and effluent fluid drained through a cavotomy. Before reperfusion, the liver was rinsed with Ringer's lactate solution, which was also 4 degrees C. RESULTS: The mean duration of hepatic ischemia was 121 minutes (range, 65 to 250 minutes), and venovenous bypass was used in three cases. The mean amount of blood transfused intraoperatively was 4.3 +/- 4 U; four cases required no transfusion. One patient died on postoperative day seven of portal vein thrombosis. The median hospital stay was 21 days (range, 12 to 56 days). Postoperative complications consisted of pneumonia (one patient), liver insufficiency (one patient, who recovered spontaneously), and subphrenic abscess (one patient). The postoperative tests of hepatic function were altered to the same degree as that seen after hepatic vascular exclusion of less than 1-hour duration in healthy livers. All patients who left the hospital were alive at 1 year. CONCLUSIONS: Cooling of the hepatic parenchyma allowed us to perform major hepatic resection in patients with diseased livers using hepatic vascular exclusion for longer than 1 hour without increased morbidity or mortality. However, because of particular difficulties due to the size or location of the lesions, the application of these new techniques should only be considered for the largest and most complex hepatic resections for which hepatic vascular exclusions longer than 1 hour are foreseen.
The early phases of the rejection of xenografts exchanged between closely-related species are dominated by a vigorous humoral immune response. We have recently used a linkermediated polymerase chain reaction to generate Ig heavy and light chain specific cDNA libraries to examine the Ig gene control of a prototypic IgM monoclonal antibody, HAR-1, that causes the hyperacute rejection of hamster xenografts. Recombinant clones from the library were screened directly from bacterial colonies by PCR and the nucleic acid sequences of the clones established. Our results demonstrate that the HAR-1 hybridoma is encoded by Ig VH and JH genes in a germline configuration. Comparison of the cDNA sequence for HAR1-VH with the germline equivalent of the gene isolated from newborn LEW liver (provisionally designated VH1.1) showed that the two VH sequences share a nucleic acid identity of 99,3%. Similarly, the HAR-1 monoclonal uses a Ig JH gene that is 98,2% identical with the JH1 nucleic acid sequence available in the GenBank. The use of Ig VH and JH genes in a germline configuration is similar to that seen with polyreactive natural antibodies to infectious agents and autoantibodies. These humoral responses are thought to be the results of the stimulation of a T cell-independent subset of B cells, the B-1a/B-1b subset, that are responsible for producing antibodies that serve as a primitive humoral (natural antibody) defense mechanism against infectious diseases. Our results suggest that the humoral component of the rejection of xenografts in the hamster-to-rat model may represent the stimulation of this type of B cell antibody response by xenogeneic target antigens that share antigenic epitopes with bacteria and other infectious agents.
A case of symptomatic giant hemangioma of the liver with fever, anemia, and increased erythrocyte sedimentation rate is reported. Spontaneous hyperdense areas at CT, and high signal-intensity areas at T1-weighted MR images were demonstrated within the hemangioma. Marked hemorrhagic zones demonstrated at pathologic examination may explain these uncommon clinical and imaging features.
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Varus deformity of the knee is common in young children who have suffered from fulminating purpura. This study was directed at the anatomic features of the vascularisation of the upper end of the tibia that might account for such deformation. It was based on the dissection of 28 anatomic specimens prepared by injection of Indian ink into the vascular trunk. 16 specimens were diaphanised for better analysis of the intracartilaginous distribution of the vessels. The study showed that the vascularisation of the medial condyle of the tibia is poor and of terminal nature, which may explain the occurrence of ischemic growth disorders following fulminating purpura.
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We describe a case of localized macronodular tuberculosis of the liver, the so-called hepatic tuberculoma. Liver US scan demonstrated an hypoechoic well-delineated lesion of the left liver lobe. Liver CT scan demonstrated a hypodense lesion before and after contrast enhancement. Liver MR scan demonstrated a lesion hypointense to liver on T1-weighted images and isointense to liver on T2-weighted images.
PURPOSE: Gracilis muscle transposition for treatment of fecal incontinence gives variable results. Electric stimulation of transposed muscle recently brought this technique to the surface. METHODS: We reviewed patients who had gracilis muscle transposition for fecal incontinence to determine who might benefit from electrostimulation. RESULTS: Between 1979 and 1991, 22 patients underwent gracilis muscle transposition. At six months, 18 patients had improved continence, but 12 of the 18 were stable with time, and only 1 was fully continent. Six patients were candidates for electrostimulation; four had a contractile but fatigable transposed muscle, and two had ineffective transposed muscle with a gaping nonfibrotic anus. CONCLUSION: Gracilis muscle transposition should be used first for severe incontinent patients, and electrostimulation should be used if there are unsatisfactory results.