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Daniel Jaeck

Publications and source records attributed to Daniel Jaeck.

At least 19 recordsLinked to original sources
PubMed2007

Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes.

In colorectal cancer, the molecular alterations that lead to metastasis are not clearly established, probably because of their high genetic complexity. To identify combinations of genetic changes involved in tumor progression and metastasis, we focused on chromosome instable (CIN) colon cancers. We compared by allelotyping of 33 microsatellites, the genomic alterations of 38 primary colon tumors with the synchronously resected matched liver metastases (CLM). We observed that (i) the number of patients with alterations at certain loci did not differ significantly between the whole primary tumor and the paired CLM, (ii) a group of patients had fewer alterations in the metastasis when compared with the matched primary tumor. A 2-way hierarchical unsupervised clustering of the allelotyping data revealed 2 tumor subtypes that have different levels of CIN (CIN-High, CIN-Low). Both subtypes have a minimal common set of alterations at chromosomes 8p, 17p and 18q, but does not include alteration at 5q or mutation at K-Ras. These 2 subtypes were also observed using a collection of 104 independent primary CIN colon tumors. In addition, we found a third subtype, consisting of tumors with a very low number of alterations not associated with specific loci (CIN-Very Low). We found that colon carcinogenesis may require a minimal set of alterations and that, in contrast to the current hypothesis, the level of CIN does not correlate with tumor progression. Therefore, our results suggest that metastasis potential could be present at very early stages of tumor development.

Alleles↗
PubMed2006

Cryopreserved human hepatocytes in suspension are a convenient high throughput tool for the prediction of metabolic clearance.

Hepatocyte assays, routinely used to assess the metabolic stability of new chemical entities, were recently improved by using hepatocytes in suspension instead of primary cultures [N. Blanchard, L. Richert, B. Notter, F. Delobel, P. David, P. Coassolo, T. Lavé, Impact of serum on clearance predictions obtained from suspensions and primary cultures of rat hepatocytes, Eur. J. Pharm. Sci. 23 (2004) 189-199]. The aim of the present study was to investigate miniaturising the suspension assay by using cryopreserved human hepatocytes, i.e., 150,000 cells/well in 96-well plates, to predict hepatic clearance (CLH) in order to increase compound throughput and decrease cost and tissue requirements. For this, an evaluation was first carried out with rat hepatocytes. Then, human hepatocytes from various donors were used under these predetermined conditions, either immediately after isolation, either after a 20-h-cold storage period in UW or after cryopreservation. The values of CLint and CLH determined using human hepatocytes in suspension in 96-well plates, immediately after isolation, after cold storage or after cryopreservation, were comparable to those obtained with hepatocytes in primary culture. In particular, the use of cryopreserved human hepatocytes in suspension in a 96-well format appeared to be largely satisfactory as a tool for screening and ranking of compounds in the early phase of the drug discovery process.

Aged↗
PubMed2006

3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome.

BACKGROUND: Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation. METHODS: We analysed data from 34,664 first adult liver transplants from the European Liver Transplant Registry to identify factors associated with mortality at 3-months (n=21,605 in training dataset) and 12-months (n=18,852 in training dataset) after transplantation. We used multivariable logistic regression models to generate mortality scores for each individual, and assessed model discrimination and calibration on an independent validation dataset (n=9489 for 3-month model and n=8313 for 12-month model). FINDINGS: 2540 of 21,605 (12%) individuals in the 3-month training sample had died by 3 months. Compared with those transplanted in 2000-03, those transplanted earlier had a higher risk of death. Increased mortality at 3-months post-transplantation was associated with acute liver failure (adjusted odds ratio 1.61), donor age older than 60 years (1.16), compatible (1.22) or incompatible (2.07) donor-recipient blood group, older recipient age (1.12 per 5 years), split or reduced graft (1.96), total ischaemia time of longer than 13 h (1.38), and low United Network for Organ Sharing score (score 1: 2.43; score 2: 1.67). However, cirrhosis with hepatocellular carcinoma, alcohol cirrhosis, hepatitis C or primary biliary cirrhosis, donor age 40 years or younger, or less, hepatitis B, and larger size of transplant centre (> or = 70 transplants per year) were associated with improved early outcomes. The 3-month mortality score discriminated well between those who did and did not die in the validation sample (C statistic=0.688). We noted similar findings for 12-month mortality, although deaths were generally underestimated at this timepoint. INTERPRETATION: The 3-month and 12-month mortality models can be effectively used to assess outcomes both within and between centres. Furthermore, the models provide a means of assessing the risk of post-transplantation mortality, giving clinicians important data on which to base strategic decisions about transplant policy in particular individuals or groups.

Adult↗
PubMed2006

Early decrease in circulating dendritic cells number after liver transplantation could favor hepatitis C virus recurrence.

Cirrhosis and hepatocarcinoma related to hepatitis C virus (HCV) lead to more than 30% of liver transplantations. Host- and virus-related mechanisms, involved in the recurrence of HCV infection of the liver graft, are not yet well known. A weak CD4+ T-cell response was shown to be involved in the outcome of re-infection but whether dendritic cell numbers are modified in patients transplanted for HCV-related disease has never been evaluated. Eight transplanted patients for HCV-related disease and eight non-HCV-infected transplanted controls were included. Blood plasmacytoid dendritic cells and myeloid dendritic cells were quantified before transplantation, at day 7 and 1 month after transplantation. Plasma interferon (IFN)-alpha and interleukin (IL)-12 were concomitantly measured. The results showed a significant decrease in the relative (P < 0.0001) and absolute (P = 0.0002) values of blood plasmacytoid dendritic cells at day 7 after transplantation when compared to the values obtained before transplantation, increasing again 1 month later, in both HCV-infected patients and controls. The same tendency was observed for myeloid dendritic cell relative values (P = 0.0004) and plasma IL-12 (P < 0.05). IFN-alpha appeared to be less often detectable for HCV-infected patients. These results obtained on dendritic cell numbers could explain partially the early and systematic recurrence of HCV infection on the liver graft and contribute to better adapted therapeutic strategies.

Cell Count↗
PubMed2006

Toward zero pancreatic fistula after pancreaticoduodenectomy with pancreaticogastrostomy.

BACKGROUND: Postoperative morbidity after pancreaticoduodenectomy has been associated mainly with the development of pancreatic fistula. However, postoperative complications unrelated to pancreatic fistula cannot be disregarded after pancreaticoduodenectomy. The aim of the present study was to investigate the postoperative morbidity in a large series of pancreaticoduodenectomies with pancreaticogastrostomies without pancreatic fistula. METHODS: The present study analyzed the data from 194 consecutive patients undergoing a pancreaticoduodenectomy with a pancreaticogastrostomy between July 1997 and June 2003 in whom no postoperative pancreatic fistula occurred. RESULTS: The overall rate of postoperative morbidity was 33.5%. Specific and general complications occurred in 16% and 17.5% of the patients, respectively. An American Society of Anesthesiologists (ASA) score of 3 and blood transfusion were the only independent factors associated with postoperative morbidity. CONCLUSIONS: Our study found that the overall morbidity after a pancreaticoduodenectomy with a pancreaticogastrostomy still remains high even in the absence of pancreatic fistula and is associated with the preoperative medical condition (ASA score) of the patients and with blood transfusion.

Anastomosis, Surgical↗
PubMed2006

Outcome after pancreaticoduodenectomy for cancer in elderly patients.

During the last decade, the outcome after pancreaticoduodenectomy (PD) for cancer showed a continuous improvement. Therefore, an increasing number of patients, especially elderly patients, have been considered for this procedure. However, the debate on the possible deleterious influence of patients' advanced age on their postoperative outcome after pancreaticoduodenectomy still continues. From June 1995 to October 2003, 70 elderly patients (range, 70-84 years) underwent pancreaticoduodenectomy with pancreato-gastrostomy for cancer. Among them, 38 patients were 70-75 years old and 32 were > or =75 years. Patients were identified from a prospective database of a single institution, and their records were reviewed retrospectively. Patient and tumor characteristics, postoperative morbidity and mortality, length of hospital stay, readmission rate, and overall survival were compared between the two groups. There were no statistical differences regarding the postoperative mortality (P = 0.205), overall morbidity (P = 0.267), mean length of hospital stay (P = 0.345), and readmission rate (P = 1) between both groups. Only delayed gastric emptying was significantly more frequent in patients > or =75 years (P = 0.039). The median overall survival was 20 months. Survival was significantly influenced by the pathological type of the tumor, with worse results for patients with ductal pancreatic adenocarcinoma. In elderly patients, age does not seem to influence the postoperative outcome after pancreaticoduodenectomy with pancreato-gastrostomy.

Adenocarcinoma↗
PubMed2006

Right portal vein embolization before right hepatectomy for unilobar colorectal liver metastases reduces the intrahepatic recurrence rate.

AIM: To assess the effect of portal vein embolization (PVE) on intrahepatic recurrence rate after right hepatectomy for unilobar colorectal liver metastases (CLM). SUMMARY AND BACKGROUND: Recent research suggests that CLM could spread retrogradely through the portal vein. PVE may reduce tumor shedding by the occlusion of distal portal branches. However, no study reported the clinical effect of PVE on intrahepatic recurrence after CLM resection. PATIENTS AND METHODS: Between 1995 and 2003, 44 patients requiring a right hepatectomy for unilobar CLM were operated in our institution. Right hepatectomy was performed after PVE in 23 patients (group A) and without PVE in 21 (group B). Surgical outcome and site of recurrence were analyzed. RESULTS: The postoperative mortality was nil. Overall morbidity and transitory liver failure rates were similar in groups A and B (43.4% and 17.3% vs. 33.3% and 14.2%, respectively). The 3- and 5-year overall survival rates did not differ in group A and B patients (61.2% and 43.7% vs. 49.7% and 35.5%, respectively; P = 0.862). The disease-free survival rate was similar in both groups. Thirty patients (68.2%) developed recurrences. Recurrences were intrahepatic in 22 patients (50%) and extrahepatic in 27 (61.3%). Intrahepatic recurrence rate was significantly lower in group A compared with group B (26.0% vs. 76.1% respectively; P < 0.001). PVE, number of CLM, and administration of neoadjuvant chemotherapy were independent prognostic factors for intrahepatic recurrences. CONCLUSION: This study showed that PVE reduces intrahepatic recurrence rate after right hepatectomy for unilobar CLM.

Adult↗
PubMed2006

Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1,452 patients and development of a prognostic model.

OBJECTIVE: To determine the utility of hepatic resection (HR) in the treatment of patients with noncolorectal nonendocrine liver metastases (NCNELM). SUMMARY BACKGROUND DATA: The place of HR in the treatment of NCNELM remains controversial, primarily due to the limitations of previously published reports and the heterogeneity of primary tumor sites and histologies. METHODS: A multivariate risk model was developed by analyzing prognostic factors and long-term outcomes in 1452 patients with NCNELM treated with HR at 41 centers from 1983 to 2004. RESULTS: Hepatic metastases were solitary in 56% and unilateral in 71% (mean diameter, 50.5 mm). Extrahepatic metastases were present in 22%. The most common primary sites were breast (32%), gastrointestinal (16%), and urologic (14%). The most common histologies were adenocarcinoma (60%), GIST/sarcoma (13.5%), and melanoma (13%). R0 resection was achieved in 83% of patients with a 60-day mortality rate of 2.3% and a major complication rate of 21.5%. Tumor recurred in 67% of patients (liver, 24%; extrahepatic, 18%; both, 25%). Overall and disease-free survivals at 5 years were 36% and 21% and at 10 years were 23% and 15%, respectively. In multivariate analysis, factors associated with poor prognosis were patient age >60 years, nonbreast origin, melanoma or squamous histology, disease-free interval <12 months, extrahepatic metastases, R2 resection, and major hepatectomy (all P < or = 0.02). A prognostic model based on these factors effectively stratified patients into low-risk (0-3 points, 46% 5-year survival), mid-risk (4-6 points, 33% 5-year survival), and high-risk (>6 points, <10% 5-year survival) groups (P = 0.0001). DISCUSSION: HR for NCNELM is safe and effective, with outcomes mainly dependent on primary tumor site and histology. For individual patients, a statistical model based on key prognostic factors could validate the indication for hepatic resection by predicting long-term survivals.

Adolescent↗
PubMed2006

Entry of hepatitis C virus pseudotypes into primary human hepatocytes by clathrin-dependent endocytosis.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Studies of the early steps of HCV infection have been hampered by the lack of convenient in vitro or in vivo models. Although several cell-surface molecules that mediate the binding of HCV envelope proteins to target cells have been identified, mechanisms of viral entry into human hepatocytes are still poorly understood. Vesicular stomatitis virus/HCV pseudotyped viruses expressing the HCV envelope glycoproteins on the viral envelope were generated and it was found that their entry into human hepatocytes required co-expression of E1 and E2 on the pseudotype surface. Neutralization of pseudotype infection by anti-HCV antibodies suggested that cellular entry was mediated by HCV envelope glycoproteins and by previously characterized cell-surface molecules, including CD81. An entry assay based on the release of a fluorochrome from labelled HCV pseudotypes provided evidence for a pH-dependent fusion of the pseudotype envelope with a cellular compartment. By using a panel of endocytosis inhibitors, it is postulated that penetration of HCV into primary cultures of hepatocytes takes place by clathrin-mediated endocytosis.

Animals↗
PubMed2005

Catalytic subunit of human telomerase reverse transcriptase is an independent predictor of survival in patients undergoing curative resection of hepatic colorectal metastases: a multicenter analysis.

PURPOSE: To determine the role of the catalytic subunit of human telomerase reverse transcriptase (hTERT) in predicting survival after resection of hepatic colorectal metastases (CRM). PATIENTS AND METHODS: Two hundred one patients who underwent curative resection of hepatic CRM between 1990 and 2000 were identified from a multicenter database. The CRM were analyzed for hTERT nucleolar expression by standard immunohistochemical techniques. hTERT expression and known clinicopathologic factors of survival were examined. RESULTS: With a median follow-up of 80 months, 152 patients (75.6%) had died; the 5-year overall survival was 30.7%. On univariate analysis, number of metastases greater than two (P = .0005), extrahepatic disease (P = .0054), disease-free interval less than 12 months (P = .006), carcinoembryonic antigen level greater than 200 ng/mL (P = .0071), and positive hTERT nucleolar staining (P < .0001) were associated with decreased survival. On multivariate analysis, three factors independently predicted survival: number of metastases (relative risk [RR] = 1.74; P = .0011); disease-free interval (RR = 1.70; P = .0035); and positive hTERT nucleolar staining (RR = 2.03; P < .0001). Patients with none or one of these factors had a 5-year survival rate of 48%, whereas those with two or three of these factors had a 5-year survival of 15% (P < .0001). CONCLUSION: hTERT nucleolar expression is associated with worse survival after resection of hepatic CRM. hTERT expression in conjunction with number of hepatic metastases and disease-free interval may permit more accurate prediction of survival after resection of hepatic CRM.

Adult↗
PubMed2005

Experimental models of acute and chronic liver failure in nude mice to study hepatocyte transplantation.

Although hepatocyte transplantation is a promising therapy for acute liver failure in human, there is still a lack of animal models suffering from hepatic injury in which the benefits of hepatocyte transplantation could be evaluated solely, without the bias caused by immunosuppression. As a consequence, the aim of the study was first to develop reproducible models of partial hepatectomy and of thioacetamide (TA)- or Jo2-induced acute liver failure in nude mice. Chronic liver disease was also investigated by repeated injections of sublethal doses of thioacetamide. Survival rates, routine histologic observations, alanin aminotransferase sera content, Ki67, and caspase 3 immunodetection were investigated both after 40% partial hepatectomy and after toxic-induced damages. Liver injuries were more severe and/or precocious in nude mice than in Balb/c mice for a given treatment with a maximum of acute injury obtained 24 h after single toxic injection, and were found to be transitory and reversible within 10 days. Toxics induced apoptosis followed by necrosis, confirming recent published data. Onset of fibrosis leading to reproducible chronic cirrhosis in nude mice correlated with increasing number of Ki67-positive cells, indicating that high levels of cell proliferation occurred. Chronic cirrhosis progressively reversed to fibrosis when the treatment ceased. Preliminary results demonstrated that engrafted xenogeneic hepatocytes could be detected in the host liver by anti-MHC class I immunohistochemistry. Fractions enriched in 2n or 4n hepatocytes by cell sorting using a flow cytometer were equivalent to the unpurified fraction in terms of engraftment in control nude mice or in nude mice subjected to PH. However, in mice suffering from liver injury 24 h after Jo2 or TA treatment, the engraftment of 2n hepatocytes was about twice that of an unpurified hepatocyte population or of a population enriched in 4n hepatocytes.

Animals↗
PubMed2004

Pancreaticogastrostomy decreased relaparotomy caused by pancreatic fistula after pancreaticoduodenectomy compared with pancreaticojejunostomy.

HYPOTHESIS: Pancreaticogastrostomy (PG) is associated with a lower relaparotomy rate following pancreaticoduodenectomy (PD) than pancreaticojejunostomy (PJ). DESIGN: Retrospective clinical trial. SETTING: Department of digestive surgery and transplantation. PATIENTS: Between 1987 and 2001, 250 consecutive patients underwent PD in our institution. Among them, 83 patients underwent PJ and 167, PG. MAIN OUTCOME MEASURES: Preoperative clinicopathological features, intraoperative parameters, in-hospital mortality, postoperative morbidity, pancreatic fistula (PF), relaparotomy rates, and length of hospital stay were analyzed and compared between 2 reconstructive methods, PJ and PG, after PD. RESULTS: The morbidity rate, including PF, was lower in the PG group (38.3%) than in the PJ group (53.0%; P =.02). The mortality rate did not differ between the PG group (2.9%) and PJ group (2.4%). Conversely, the incidence of PF and the mean +/- SD length of hospital stay were significantly lower in the PG group (2.3% and 17.2 +/- 7.7 days) than in the PJ group (20.4% and 23.3 +/- 11.7 days; P<.001 for both variables). Moreover, the overall relaparotomy rate was significantly lower in the PG group (4.7%) than in the PJ group (18.0%; P =.001). Nine (52.9%) of 17 patients with PF in the PJ group underwent relaparotomy. These 9 patients underwent subsequent completion pancreatectomy (n = 7) or removal of peripancreatic necrotized tissue (n = 2) with a postoperative mortality rate of 22.2%. However, no patient required relaparotomy for PF in the PG group because medical therapy succeeded in all 4 patients with PF. Moreover, no mortality related to PF occurred in the PG group. CONCLUSION: The PG procedure is a safe method of reconstruction after PD, with a significantly lower rate of PF and relaparotomy.

Chi-Square Distribution↗
PubMed2004

Surgical resection of hepatocellular carcinoma. Post-operative outcome and long-term results in Europe: an overview.

A multicenter retrospective review of 1467 patients treated by liver resection (LR) for hepatocellular carcinoma (HCC) in Europe over a 13-year period showed a mean mortality rate of 10.6%, which was correlated with the extent of LR, the etiology of cirrhosis and the study period with an improvement during the last years. Improved 5-year overall survival (20-51%) and disease-free survival (20-33%) reached similar rates in cirrhotic than in non-cirrhotic patients. Overall results were similar to those reported in Asian series as far as patients and tumor characteristics were comparable.

Adult↗
PubMed2004

Chronic inflammatory demyelinating polyradiculoneuropathy in patients with liver transplantation.

We report two patients with orthotopic liver transplantation (OLT) who developed a syndrome that fulfilled criteria for definite chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One patient had OLT because of alcoholic cirrhosis and one following hepatitis C-induced hepatic failure. Both had immunosuppressive therapy, with cyclosporine and prednisolone in one case and tacrolimus in the other case. Treatment with intravenous immune globulin (IVIG) significantly improved the neuropathy in both patients. In patients with OLT developing disabling sensorimotor neuropathies, CIDP should be considered as should the use of potentially beneficial immunosuppressive treatment.

Electrodiagnosis↗
PubMed2004

Randomized trial of adjuvant chemotherapy after curative resection for gastric cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy of adjuvant chemotherapy on survival after resection for gastric cancer. METHODS: Patients were enrolled if they underwent resection of gastric cancer but had lymph node or serosal involvement or both. Surgical resection was either total or partial gastrectomy according to the site of the tumor, and surgeons were allowed to perform either D1 or D2 gastrectomy. The subjects were random assigned in two treatment groups as follows: surgery alone as the control group, or surgery and adjuvant chemotherapy. Nine cycles of 5 days protocol every 4 weeks was proposed to the patients of the chemotherapy group. The protocol included a daily administration of 200 mg/m(2) of folinic acid, 5-fluorouracil (375 mg/m(2) during the first session increasing 25 mg by session until reaching 500 mg/m(2)) and CDDP 15 mg/m(2). Two hundred patients were required. Kaplan-Meier survival curves were compared according to the log-rank and the Mantel-Haenszel methods. RESULTS: In all, 205 patients were enrolled in the study; 104 had surgery alone and 101 had surgery and adjuvant chemotherapy. The patients' characteristics were similar except for the mean age, which was 4 years less in the control group. Because of toxicity, 54% of the patients stopped the protocol before the end of the nine courses, and 46% of the patients received the nine courses including 32% with a decreased dose and 14% with a full dose. The 5-year survival rate was 39% in the control group and 39% in the chemotherapy group. CONCLUSIONS: This protocol of adjuvant chemotherapy failed to improve the 5-year survival after resection for gastric cancer.

Adult↗