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C Sempoux

Publications and source records attributed to C Sempoux.

At least 19 recordsLinked to original sources
PubMed2003

[Multidetector CT and MRI of benign liver tumors].

With multidetector helical CT, the entire liver can be imaged rapidly with thin slices. High temporal and spatial resolution is important to improve multiphase examinations of the liver. The need to perform multiphase examinations to diagnose benign liver tumors should, however, be assessed by keeping in mind the risk of radiation and contrast-induced adverse events. MRI offers several advantages relative to CT. Excellent contrast resolution is obtained. Multiphase examinations can be performed in all patients. Reticuloendothelial contrast agents may be useful to characterize benign tumors. Several benign liver tumors, particularly hemangiomas and lesions of focal nodular hyperplasia, can be characterized with CT and MRI. Histologic examination is still needed to characterize some benign liver tumors.

Adenoma↗
PubMed2001

Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine.

BACKGROUND: Cases of so-called autoimmune hepatitis (AH) have been reported after liver transplantation. Our aim was to evaluate the incidence in a series of 471 pediatric liver transplant recipients. METHODS: Between 1984 and 1998, 471 children had orthotopic liver transplantation (OLT). Children are followed up on a regular basis, with full clinical, biochemical, and histologic evaluation at 6 months, 1, 2, 5, 7, and 10 years after OLT. Children with unexplained abnormal liver tests were screened for autoimmune markers (total gamma-globulins, smooth muscle antibodies [SMA], liver kidney microsome antibodies [LKM], antinuclear factor [ANA]). From January of 1998 until December of 1998, autoimmune markers were prospectively searched in all children admitted for regular posttransplant follow-up (n = 118). RESULTS: Eleven of 471 children (2.35%) were found with autoimmune hepatitis, 9 retrospectively and 2 prospectively. None had previous autoimmune liver disease. Patients had a history of steroid-dependent hepatitis. Histology showed variable degree of portal and lobular inflammation, piecemeal necrosis, and bridging collapse. Mean (+/-SDS) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities at diagnosis were 173+/-145 and 196+/-157 IU/L, respectively (nl<32). Median gamma-globulin levels reached 1365 mg/dl versus 931 mg/dl in controls (P<0.05). Nine had ANA (titer 1/80 up to 1/10,000), 1 SMA (1/320), and 2 LKM1 antibodies (1/1280). Patients did not respond to increasing charge of cyclosporine (n=10) or tacrolimus (n=1). Eleven received steroids (prednisolone: 2 mg/kg per day, then tapered) and azathioprine (1.5 to 2.5 mg/kg per day). All patients normalized within 3 months (mean AST/ALT levels of 26+/-8 and 30+/-9 IU/L). Three had mild to moderate relapse with increase of ALT thereafter. Gamma-globulins decreased to 1190 mg/dl (ns). Amongst the 116 remaining prospectively evaluated patients, 85 had normal evaluation, despite low titers of autoantibodies in 15 (SMA< or =1/40, ANA 1/80). Thirty-one patients had graft dysfunction, related to well-explained posttransplant causes, among which 7 had similar low levels of autoantibodies. CONCLUSIONS: A total of 2.35% of our transplant children present evidence of immune hepatitis after transplantation. Patients do not respond to increasing cyclosporine or tacrolimus levels and require steroid and azathioprine. In view of this specific treatment, systematic screening for "autoimmune" markers is advised in children with liver transplant.

Adolescent↗
PubMed2001

Posttransplant lymphoproliferative disorder after liver transplantation in miniature swine.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a well-known, life-threatening complication of immunosuppressive therapy, occurring in both adult and pediatric transplant recipients. METHODS: To study the effect of major histocompatibility complex on tolerance induction to primarily vascularized liver allograft, a semi-identical miniature swine model was developed to mimic the clinical situation of parent-into-infant liver transplantation. Long-term acceptance of semi-identical liver allograft was obtained by a transient course of FK506. In a subgroup of six animals, three developed a lethal PTLD. These animals were studied by histology and immunohistochemistry and the anti-donor cellular immune response was assessed. In addition, the possible viral origin of the proliferative process was evoked. RESULTS: Histology and immunohistochemistry revealed an abnormal B-cell proliferation in many organs of swine suffering from PTLD. Evidence of human Epstein-Barr virus, cytomegalovirus, and adenovirus was not evidenced, but a porcine virus responsible for a respiratory and reproductive syndrome (PRRS) was identified in the lymphoid tissue of these animals. In mixed lymphocyte reaction, a significant antiself immune response confirmed an infection by a virus. CONCLUSIONS: This is the first report suggesting that PRRS virus might provoke PTLD in immunosuppressed miniature swine after orthotopic liver transplantation. Whether PTLD could be induced by injection of the PRRS virus in immunosuppressed animals, a pig model of PTLD might be developed and would represent an interesting preclinical model for testing anti-PTLD therapies.

Animals↗
PubMed2001

The surgical management of congenital liver cysts.

BACKGROUND: Most series that report the results of surgical treatment for congenital liver cysts focus more on the technical aspects of the operation than on the late outcome of these patients. In this paper, we emphasize the importance of appropriate patient selection and adequate surgical technique for successful long-term outcome. METHODS: Twenty-four consecutive patients with congenital liver cysts were selected for surgical treatment. According to our own classification, 13 patients had simple liver cysts, nine had multicystic liver disease, and two had type I polycystic liver disease. All of these patients were treated by the fenestration technique. An open approach was used for five patients (group 1) treated between 1984 and 1990. In 19 patients (group 2) treated since 1991, a laparoscopic approach was used. The incidence of complicated liver cysts was 40% in group 1 and 68% in group 2. RESULTS: There were no treatment-related deaths in this series. The mean postoperative hospital stay was significantly shorter for patients who underwent successful laparoscopic fenestration (p < 0.05). In the open group (group 1), there were no postoperative complications, and all patients were alive and free of symptoms during a mean follow-up of 130 months, without any sign of cyst recurrence. In the laparoscopic group (group 2), four patients were converted to open surgery. One of these patients had an inaccessible posterior cyst; another had bile within the cystic cavity. A further two cases had complicated liver cysts with an uncertain diagnosis between congenital and neoplastic cysts. Four patients (21%) developed peri- or postoperative complications. During a mean follow-up time of 38.5 months, none of the patients with simple liver cysts incurred late symptoms or signs of cyst recurrence. In the six patients with multicystic liver disease, one developed disease-related cyst progression (17%) and required reoperation. One of the two patients with type I polycystic liver disease (50%) developed asymptomatic disease-related cyst progression. CONCLUSIONS: When patients are carefully selected and a proper surgical technique is employed, excellent long-term results with a low morbidity rate can be achieved in patients with congenital liver cysts. Patients with multicystic liver disease or type I polycystic liver disease are more prone to late cyst recurrence. A tailored approach is thus indicated for patients with congenital liver cystic disease. However, the laparoscopic approach appears to be the gold standard for the treatment of highly symptomatic or complicated simple liver cysts.

Adult↗
PubMed2001

Surgical management of intraductal papillary mucinous tumors of the pancreas: the role of routine frozen section of the surgical margin, intraoperative endoscopic staged biopsies of the Wirsung duct, and pancreaticogastric anastomosis.

HYPOTHESIS: Resection of intraductal papillary mucinous tumors of the pancreas (IPMTP) should be tailored to longitudinal spreading into the pancreatic ductal system and the presence of malignant transformation. OBJECTIVE: To review a single institutional experience with IPMTP, focusing on the operative strategy of tailoring resection to the extent of disease. DESIGN: Retrospective study. SETTING: Academic tertiary referral center. PATIENTS: Thirteen patients with IPMTP were referred for resection during the past 10 years. Malignant growth was present in 7 patients (54%). According to the determination of tumor extent, distal pancreatic resection was performed in 3 patients, pancreatoduodenectomy was done in 9 patients, and total pancreatectomy was performed in 1 patient. The median follow-up time in this series was 46 months (range, 3-104 months). MAIN OUTCOME MEASURES: Preoperative and perioperative diagnosis, final pathologic results, and long-term outcome. RESULTS: A correct preoperative or perioperative diagnosis of IPMTP was achieved in 9 patients (69%). Routine frozen section of the surgical margin was used in all patients, changing the operative strategy in 3 (23%) of 13 patients by extending resection or leading to total pancreatectomy in 2 patients and 1 patient, respectively. A perioperative endoscopic examination of the Wirsung duct was performed in 3 patients with a correct preoperative or perioperative diagnosis of IPMTP and a dilated pancreatic duct. This allowed the examination of the entire pancreatic ductal system and staged intraductal biopsies, changing the operative strategy in 1 of these patients. Finally, after pancreatoduodenectomy, pancreaticogastric anastomosis was constructed in 5 patients, allowing endoscopic assessment of the pancreatic stump during long-term follow-up. The 5-year actuarial survival rate was 56.8% in the whole series. All patients with benign or microinvasive malignant disease remained disease-free, whereas all patients with invasive malignant disease died of tumor recurrence. CONCLUSIONS: Accurate determination of the extent of ductal disease and residual malignant growth, when present, is critical during surgical exploration to achieve radical resection and cure. Operative strategy should be based on routine frozen section of the surgical margin and perioperative endoscopic examination of the Wirsung duct with staged intraductal biopsies when technically feasible. The routine use of pancreaticogastric anastomosis after pancreatoduodenectomy allows easy, safe, and efficient long-term endoscopic assessment of the pancreatic stump.

Aged↗
PubMed2001

Biodistribution of ultrasmall iron oxide particles in the rat liver.

Ferumoxtran, an ultrasmall superparamagnetic iron oxide particle, can be located in several tissue compartments in the liver, namely the extracellular space (blood and interstitium), reticuloendothelial cells, and possibly hepatocytes. To better understand the compartmental distribution of ferumoxtran in the liver, we performed a longitudinal study in the rat using microscopy and magnetic resonance imaging. At light microscopy, no substantial cellular uptake of ferumoxtran was observed before one hour after injection. With a dose of 15 micromol Fe/kg, the number of ferumoxtran particles in the reticuloendothelial cells peaked between one and four hours and with a 150 micromol Fe/kg dose, it peaked between eight and 24 hours. Within hepatocytes, only sparse particles were observed with electron microscopy, at a dose of 150 micromol Fe/kg. Imaging performed up until one hour after ferumoxtran injection showed a significant increase in liver signal intensity on T1-weighted images. These results suggest that ferumoxtran mainly acts as an extracellular agent for at least one hour in the rat and that reticuloendothelial accumulation peaks at later time points. Substantial uptake within hepatocytes did not occur.

Animals↗
PubMed2001

Adult liver transplantation and steroid-azathioprine withdrawal in cyclosporine (Sandimmun)-based immunosuppression - 5 year results of a prospective study.

New immunosuppressants are said to be superior to cyclosporine due to their higher incidence of steroid sparing and to the reduced incidence of side-effects. From May 1992 to February 1995, 79 adults underwent primary liver transplantation using cyclosporine A (Sandimmun)-based triple drug immunosuppression. Nine patients who died early after liver transplantation due to reasons unrelated to immunological problems were excluded from this analysis. The long-term outcome of the remaining 70 patients was prospectively studied in relation to steroid and azathioprine withdrawal. They were re-evaluated 6-monthly in relation to liver and kidney function; cholesterolemia, infection, de novo diabetes mellitus and arterial hypertension, malignancy, ophthalmological and osteomuscular diseases. In case of rejection occurring during or after steroid tapering, patients were switched, by protocol, to tacrolimus therapy. Median follow-up was 81 months (range 60-96). Forty-four patients (62.8 %) were biopsied 5 years after transplant; 20 patients (28.6 %) were biopsied at a median follow-up of 32 months (range 7.8-47). Six patients (8.6 %) who refused biopsies more than 1 year after liver transplantation had normal liver values throughout the whole follow-up period. Five-year actual patient and graft survivals were 75 % and 65.8 %, respectively, for the whole group (n = 79) and 85.7 % and 74.3 % for the studied group (n = 70). Steroids could be withdrawn in all but two patients (97.1 %) at a median time of 7 months (range 3-42). Steroids were restarted in six patients (8.6 %) for extrahepatic reasons. Freedom from steroids was thus observed in 62 patients (88.6 %). Seven patients (10 %) had rejection after steroid tapering; six were switched to tacrolimus. Two patients (2.9 %) needed retransplantation because of acute and chronic rejection whilst still being on full immunosuppression. In total, three patients (4.3 %) had histological signs of chronic rejection during follow-up. At 5 years post-transplant, 66.6 % and 13.3 % of the 60 patients at risk were on cyclosporine and tacrolimus monotherapy, respectively; 93.3 % were steroid-free. Mean creatinine and cholesterol levels were 1.56 +/- 1.3 mg/dl and 193.5 +/- 56.6 mg/dl; incidences of de novo arterial hypertension, insulin dependent diabetes mellitus were 26.6 % and 13.3 %. Two patients (2.8 %) developed post-transplant lymphoproliferative disease, two (2.8 %) had skin cancer. Cyclosporine-based immunosuppression allows safe steroid withdrawal in most patients and cyclosporine monotherapy can be achieved in two-thirds without compromising graft and patient survival. Results of new immunosuppressive strategies should be approached with caution, especially when considering steroid sparing and the incidence of side-effects.

Adolescent↗
PubMed2001

Investigations on the liver toxicity of a blend of HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane) and HCFC-124 (2-chloro-1,1,1,2-tetrafluoroethane) in guinea-pigs.

2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) has been developed as a substitute for ozone-depleting chlorofluorocarbons (CFCs). It is a structural analogue of halothane and similarities in the metabolic pathways and liver toxicity of both compounds have been described. The present study was initiated after an accidental outbreak of hepatitis in an industrial setting to examine whether concomitant exposure to 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), which is not hepatotoxic, could enhance the liver toxicity of HCFC-123. Male Hartley guinea-pigs were exposed for 4 h to 5,000 ppm HCFC-123 alone or blended with 5,000 ppm HCFC-124, either once (single exposure) or on 5 consecutive days (repeated exposure). The animals were killed either 24 or 48 h after the last exposure. A transient cytolytic action of HCFC-123 was evident by increased mean serum levels of alanine aminotransferase at 24 h and isocitrate dehydrogenase at 24 and 48 h, both after a single or repeated exposure. The liver toxicity of HCFC-123 was confirmed by pathological examination of liver tissue, which showed mild (foci of necrotic hepatocytes) to moderate (multifocal random degeneration and necrosis) damage. Steatosis was also observed and was more pronounced after repeated exposure than after single. One animal out of 6 that were repeatedly exposed to the blend and sacrificed at 24 h showed liver lesions similar to halothane hepatitis. Although a few other animals responded markedly in the blend-treated group, on average, no significant difference in the biochemical or pathological lesions was found between the groups treated with HCFC-123 alone or with the blend. Urinary excretion of trifluoroacetic acid and chlorodifluoroacetic acid increased dose-dependently upon exposure to HCFC-123 and indicated accumulation after repeated exposure. No difference in metabolite excretion was found between animals treated with HCFC-123 alone or blended with HCFC-124. Treatment with HCFC-123 depleted hepatic glutathione levels by about 40 and 25% after single and repeated exposure, respectively; the amplitude of this reduction was not modified by co-exposure to HCFC-124. In conclusion, this study confirmed the hepatotoxicity of HCFC-123, based on biochemical, histopathological and metabolite studies, and found only very limited indication of a potentiation by HCFC-124 of this hepatotoxic effect.

Administration, Inhalation↗
PubMed2001

After portal branch ligation in the rat, cellular proliferation is associated with selective induction of c-Ha-ras, p53, cyclin E, and Cdk2.

BACKGROUND: In liver regeneration after portal branch ligation we previously showed that early cellular changes are observed in both the proliferating and atrophying liver lobes. They are therefore not indicative of future proliferative response. In this study we attempted to define precisely, in the same model, the time at which the cellular processes diverge between the lobes by measuring various parameters associated with cellular proliferation. We also investigated the possible role of inhibitors of cell proliferation in the absence of progression towards the S phase in the atrophying lobes. AIMS: Expression of p53, c-Ha-ras, cyclin E, cyclin dependent kinase (Cdk2), transforming growth factor (TGF)-beta, and interleukin (IL)-1alpha and IL-1beta were assessed in relation to their potential role in proliferating and atrophying cellular phenomenons. METHODS: Immunohistochemistry, northern blotting, western blotting, and reverse transcription-polymerase chain reaction were performed, mainly at time points corresponding to mid-G1/S phase progression (8-24 hours after surgery). RESULTS: The common and thus most likely non-specific response was still evident 5-8 hours after surgery and included an increase in IL-1 mRNA as well as p53 and cyclin E proteins. From 12 hours onwards, p53, c-Ha-ras, cyclin E, and Cdk2 were selectively induced in proliferating lobes whereas IL-1beta was predominantly activated in atrophying lobes. No changes in TGF-beta or IL-1alpha expression were observed at the same time points in any of the liver lobes. CONCLUSIONS: The initial response to portal branch ligation and thus probably to partial hepatectomy seems to be non-specific for at least eight hours. Thereafter, p53, c-Ha-ras, cyclin E, and Cdk2 seem to drive cellular proliferation while IL-1beta is associated with cellular atrophy. In contrast, TGF-beta and IL-1alpha do not seem to play a role in determining the commitment of cells towards atrophy or proliferation.

Animals↗
PubMed2001

Human type 2 diabetes: morphological evidence for abnormal beta-cell function.

The exact nature of the beta-cell defect in type 2 diabetic patients is still unclear. beta-Cell mass reduction has been reported but remains controversial. A preliminary study of a large series of patients has demonstrated that in most, the beta-cell defect is not related to a decreased beta-cell mass. Amyloid deposits are observed in the islets of some type 2 diabetic patients but also in normoglycemic subjects. Because it has been claimed that these deposits interfere with beta-cell function, we evaluated in situ the effect of insular amyloid deposits on beta-cell transcription and translation. Pancreases were obtained at autopsy from 28 normoglycemic patients and 41 type 2 diabetic patients. Staining with hemaluneosin and Congo red was used to analyze the general features of the islets and the presence of amyloid deposits, respectively. Immunohistochemistry for proinsulin was performed with an antibody recognizing the junction between B-chain and C-peptide, thus specifically labeling the Golgi area where proinsulin is produced. In seven patients, we evaluated insulin gene transcription by in situ hybridization of proinsulin mRNA combined with Congo red staining, and we evaluated insulin storage by double immunostaining for insulin and amylin. In many type 2 diabetic patients, the islets appeared entirely normal. Amyloid deposits were found in 57% of diabetic subjects and 33% of normoglycemic age-matched control subjects. The percentage of amyloid-infiltrated islets varied from 0.4 to 74%. beta-Cells from amyloid-containing islets still had specific Golgi proinsulin labeling. In obese type 2 diabetic patients, the number of beta-cells with abnormal expression of proinsulin in the whole cytoplasm was significantly higher than in normoglycemic control subjects. Proinsulin mRNA was significantly reduced in islets with amyloid deposits when compared with amyloid-free islets, but the mean reduction did not exceed 16%. Insulin was still present in the beta-cells of amyloid-containing islets, and its amount, estimated by measurement of the insulin-labeling optical density, was not statistically different from that in amyloid-free islets. In conclusion, even in amyloid-containing islets, beta-cells maintain active insulin transcription and translation and normal insulin storage. Taking into account that in most cases only a small proportion of islets are infiltrated by amyloid, the limited reduction in proinsulin mRNA is unlikely to play a major role in the pathogenesis of diabetes.

Amyloid↗
PubMed2000

Angiomyolipoma of the liver: ferumoxides-enhanced MR imaging.

We report a case of angiomyolipoma of the liver with emphasis on the appearance at MRI after administration of ferumoxides. Post-contrast T1- and T2-weighted images showed a frank decrease of signal intensity in a rim on the margin of the tumor. This unusual finding was related to the presence of an increased number of CD68-positive histiocytic cells in the periphery of the lesion and in the adjacent liver parenchyma.

Angiomyolipoma↗
PubMed2000

The compensatory hyperplasia (liver regeneration) following ligation of a portal branch is initiated before the atrophy of the deprived lobes.

BACKGROUND/AIMS: In rats, partial ligation of portal branches produces atrophy of the deprived lobes and hypertrophy of the intact lobes. The hepatocyte proliferation observed in the nondeprived lobes is viewed as a compensatory hyperplasia, implying that the atrophy somewhat precedes the initiation of the proliferative response. As this has not been demonstrated, the time course and magnitude of those two sequences of events were investigated and compared with the well-defined response to a partial hepatectomy. METHODS: The portal branch feeding the anterior liver lobes was ligated in male Wistar rats. One-third and two-thirds partial hepatectomies were also performed. Liver weight, the aminopyrine demethylation rate, an index of the liver mass, the DNA content and various indices of cell proliferation were measured. RESULTS: Resection of the anterior lobes (PH) or ligation of their portal blood supply (PBL) induced a marked DNA synthesis in the posterior lobes (3H-thymidine incorporation) reaching its maximum 24 h after both interventions. This response can even be accelerated by performing a sham operation 6 h before the PBL. The process leading to DNA synthesis thus seems to start as early after PBL as after a PH, although the weight of the liver or the aminopyrine demethylation rate was nearly unchanged 2 h following PBL. The initiation of the proliferative response clearly precedes and is thus independent of the reduction of the liver mass. On the other hand, the progressive reduction of the liver mass seems to determine the magnitude of the proliferative response, which is, for instance, greatly increased following the excision of the deprived lobes, as late as 10 h after ligation of their portal branches. In comparison with the results obtained after a 113 PH, the peak of DNA synthesis at the 24th hour is greater than predicted by the liver weight loss, but this parameter could underestimate the reduction of the functional liver mass. CONCLUSION: The proliferative response following a PBL can be divided into an early phase occurring independently of the reduction of the liver mass and a late phase controlled by this reduction. The paradox of the proliferative response which seems to start before the atrophy to be compensated is resolved by this hypothesis.

Animals↗
PubMed1999

Clinical features of 52 neonates with hyperinsulinism.

BACKGROUND: Neonatal hyperinsulinemic hypoglycemia is often resistant to medical therapy and is often treated with near-total pancreatectomy. However, the pancreatic lesions may be focal and treatable by partial pancreatic resection. METHODS: We studied 52 neonates with hyperinsulinism who were treated surgically. The type and location of the pancreatic lesions were determined by preoperative pancreatic catheterization and intraoperative histologic studies. Partial pancreatectomy was performed in infants with focal lesions, and near-total pancreatectomy was performed in those with diffuse lesions. The postoperative outcome was determined by measurements of plasma glucose and glycosylated hemoglobin and by oral glucose-tolerance tests. RESULTS: Thirty neonates had diffuse beta-cell hyperfunction, and 22 had focal adenomatous islet-cell hyperplasia. Among the latter, the lesions were in the head of the pancreas in nine, the isthmus in three, the body in eight, and the tail in two. The clinical manifestations were similar in both groups. The infants with focal lesions had no symptoms of hypoglycemia and had normal preprandial and postprandial plasma glucose and glycosylated hemoglobin values and normal results on oral glucose-tolerance tests after partial pancreatectomy (performed in 19 of 22 neonates). By contrast, after near-total pancreatectomy, 13 of the patients with diffuse lesions had persistent hypoglycemia, type 1 diabetes mellitus developed in 8, and hyperglycemia developed in another 7; overall, only 2 patients with diffuse lesions had normal plasma glucose concentrations in the first year after surgery. CONCLUSIONS: Among neonates with hyperinsulinism, about half may have focal islet-cell hyperplasia that can be treated with partial pancreatectomy. These neonates can be identified through pancreatic catheterization and intraoperative histologic studies.

ATP-Binding Cassette Transporters↗