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Christoph E Broelsch

Publications and source records attributed to Christoph E Broelsch.

At least 19 recordsLinked to original sources
PubMed2006

Increased frequencies of CD8+ T lymphocytes recognizing wild-type p53-derived epitopes in peripheral blood correlate with presence of epitope loss tumor variants in patients with hepatocellular carcinoma.

Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.

Aged↗
PubMed2006

[Recurrent disease after liver transplantation. A therapeutic dilemma or treatable?].

BACKGROUND: Side effects of immunosuppressive drugs, the development of de novo malignancies and disease relapse determine the prognosis of liver transplant patients in the long-term course. RECURRENT DISEASE AFTER LIVER TRANSPLANTATION: Treatment of carefully selected and monitored hepatitis C liver transplant patients with interferon-alpha and ribavirin is safe but less efficacious as compared to the non-transplant setting. Postoperative hepatitis B hyperimmune globulin and nucleoside analog combination therapy has resulted in a decrease of reinfection rates to < 10%. New molecular techniques as well as genotyping of hepatocellular carcinoma gain increasing importance for estimation of recurrence-free survival. Diagnosis of disease relapse in cholestatic and autoimmune liver disease is more challenging than in the non-transplant setting and therapeutic options are limited. Psychiatric evaluation and careful validation of compliance are important issues for estimation of the risk of disease recurrence in patients with alcohol-related liver disease. During long-term course, up to one half of patients die of transplant-related causes; 30-70% of these cases are attributed to relapse of primary disease. CONCLUSION: Further improvement of strategies for prevention and treatment of recurrent disease after liver transplantation is warranted in order to increase long-term survival.

Age Factors↗
PubMed2006

Severe neurological events following liver transplantation.

BACKGROUND: Problems related to the central nervous system may have major impact on morbidity and mortality. The aim of this retrospective study was to evaluate the nature and incidence of serious neurologic events in patients following liver transplantation. METHODS: Between January 2001 and May 2004, 168 patients (105 female, 63 male) requiring transplantation for alcoholic cirrhosis, hepatitis B and C, and acute liver failure were admitted to the Intensive Care Unit (ICU) of University Hospital Essen after liver transplantation. We identified the reason for the neurologic events, the underlying disease, type of immunosuppression, and the survival rate. RESULTS: Severe neurologic events occurred in 46 (27.3%) of the patients. The length of stay of these patients in the ICU (18.4 +/- 19.7 days) was longer in comparison to the total patients (8.3 +/- 9.5 days, p < 0.05). The most common neurological complications were encephalopathy (18.5%) and seizures (5.4%). The survival rate after liver transplantation with neurological events was lower compared to patients without, but not significantly different (73.9 vs. 79.5%). The calcineurin inhibitor used had no impact on neurological events [cyclosporine (25.5%); tacrolimus (32.5%)]. CONCLUSIONS: There was a high incidence of serious neurologic events after liver transplantation. The major neurologic manifestation in our patients was encephalopathy followed by seizures.

Adult↗
PubMed2006

Portopulmonary hypertension in the early phase following liver transplantation.

BACKGROUND: Portopulmonary hypertension (PPH) is a severe complication of liver cirrhosis, which poses a high risk for postliver transplantation (LT) mortality. In most liver transplant centers, severe PPH is viewed as an absolute contraindication for LT, but recent reports challenge this. The purpose of our study was to determine the incidence of PPH, its influence on the 30-day mortality rate following LT and to determine the sensitivity and specificity of Doppler echocardiography and electrocardiography as noninvasive tools to determine PPH. METHODS: We studied 74 consecutive patients that underwent LT between February 2004 and November 2005. Pulmonary arterial pressure and cardiac index were repeatedly determined during surgery and postoperatively. PPH was defined as mild (mean pulmonary arterial pressure (MPAP) 25-35 mm Hg), moderate (MPAP of 35-45 mm Hg) and as severe (MPAP >45 mm Hg). RESULTS: The total incidence of PPH was 31% (16 mild, 5 moderate, and 2 severe). There was a tendency towards increased 30-day mortality rate in patients with PPH compared to controls (22% vs. 12%, P=0.1). However, the two patients with the most severe PPH survived. The duration of ventilation and total stay at the intensive care unit did not differ significantly between groups. The positive predictive value of Doppler echocardiography for PPH was 39% and the negative predictive value 90%. CONCLUSIONS: Mild pulmonary hypertension is common in patients with liver failure, whereas moderate and severe hypertension is not. Severe PPH should not be considered as absolute contraindication for LT.

Blood Pressure↗
PubMed2006

Does PEEP impair the hepatic outflow in patients following liver transplantation?

OBJECTIVE: Evaluation of the impact of end-expiratory pressure (PEEP) ventilation on venous liver outflow, portal vein, and hepatic artery flows as well as systemic hemodynamics in patients following liver transplantation (LT). DESIGN: Prospective, interventional patient study. SETTING: University hospital intensive care unit. PATIENTS: 65 consecutive patients after LT. INTERVENTIONS: All patients were intubated and mechanically ventilated with biphasic positive airway pressure (BIPAP). The effects of three levels of PEEP (0, 5, and 10 mbar) applied at random order on hepatic inflow and outflow were studied in the immediate postoperative period. MEASUREMENT AND RESULTS: Central venous-, arterial pressure, and cardiac index was recorded from every patient at three different PEEP levels (0, 5, and 10 mbar). Simultaneously, flow velocities in the hepatic-, portal vein, and hepatic artery were determined by Doppler ultrasound. PEEP of 10 mbar significantly increased central venous pressure in comparison with zero PEEP. Mean arterial pressure and cardiac index was not influenced. Hepatic inflow and outflow of the transplanted livers were not impaired by any of the used PEEP levels. CONCLUSIONS: BIPAP ventilation with PEEP levels up to 10 mbar does not affect systemic hemodynamics. Furthermore, neither venous outflow nor portal venous or hepatic artery inflow of the liver are impaired at PEEP levels up to 10 mbar immediately following liver transplantation. Although these results suggest that PEEP ventilation up to 10 mbar does not affect liver hemodynamics, further studies are needed to determine whether these findings could be confirmed for a longer ventilation period with PEEP.

Analysis of Variance↗
PubMed2006

Administration of granulocyte colony stimulating factor after liver transplantation leads to an increased incidence and severity of ischemic biliary lesions in the rat model.

AIM: Recently it has been reported that granulocyte colony stimulating factor (G-CSF) can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model. METHODS: A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk. RESULTS: Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals. CONCLUSION: G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications.

Animals↗
PubMed2006

Liver transplantation with "rescue organ offers" within the eurotransplant area: a 2-year report from the University Hospital Essen.

Liver transplantation (LTx) is the only treatment for patients with end-stage liver failure. This report focuses on 45 deceased donor liver allografts allocated through Eurotransplant as "rescue offers," which were accepted and subsequently transplanted at our center over a two-year period. These organs had been officially offered to and rejected by other transplant centers a total of 162 times prior to our acceptance. Primary nonfunction was observed in six patients. Two of them died and four were retransplanted. Overall patient survival was 84.4%. LTx with such "rescue organs" constitutes an additional transplant option and a safe mechanism to "rescue" organs within Eurotransplant.

Adult↗
PubMed2006

Left hepatic trisectionectomy for hepatobiliary malignancies.

BACKGROUND: Left hepatic trisectionectomy is the most extended hepatic resection. To date, few data are available on longterm outcomes after this operation. STUDY DESIGN: Between June 1998 and July 2004, a total of 52 patients underwent left trisectionectomy for primary or secondary hepatobiliary tumors at our institution. Data were analyzed with regard to patient characteristics, intraoperative details, pathologic findings, perioperative morbidity and mortality, and outcomes as determined by survival. RESULTS: Left trisectionectomy was combined with caudate lobectomy and hilar lymph node dissection in 29 and 35 patients, respectively. In addition, 43 procedures were performed in 31 patients: resection of hilar bifurcation (n = 15), bile-duct revision (n = 5), wedge resection of segment VI/VII (n = 10), gastrectomy (n = 1), and resection or reconstruction of hepatic vessels or the inferior vena cava (n = 12). Operative morbidity and mortality were 50% and 11.9%, respectively. By multivariate analysis, additional operative procedures constituted the only positive predictor of postoperative morbidity. One-, 3-, and 5-year survival rates were 65%, 52%, and 33%, respectively. After R0 resection (n = 37), 1-, 3-, and 5-year survival rates were 78%, 68%, and 44% compared with 38%, 15%, and 7% after R1 resection (p = 0.0004). Survival corresponding to the four most frequent tumor types (hepatocellular carcinoma, cholangiocellular carcinoma, hilar cholangiocarcinoma, and colorectal metastases) was comparable with survival data reported in the literature after less-extensive resections. CONCLUSIONS: Left trisectionectomy provides acceptable survival rates in both locally advanced primary hepatobiliary malignancies and large metastatic liver tumors. Despite major progress in surgical technique and perioperative management, left trisectionectomy is still associated with higher operative mortality and morbidity than less-extensive resections. Because selection criteria for this type of procedure are not clearly defined, particular attention should be focused on the oncologic benefits when considering this operation.

Adult↗
PubMed2006

Surgery for hepatocellular carcinoma arising in hereditary hemochromatosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a well-known complication of hereditary hemochromatosis. The benefit of surgical therapy in this clinical entity is not well documented. The purpose of this study was to evaluate the outcome of such patients both in our own experience as well as in the published literature. METHODS: 320 patients with a diagnosis of HCC were evaluated at our institution to undergo either surgical resection (n = 262) or liver transplantation (n = 58) during the 4- year period from January 2001 to December 2004. We identified 5 patients with HCC arising in the setting of hemochromatosis. A literature search was performed to estimate resectability rates as well as outcomes after liver transplantation for HCC arising in hemochromatosis. RESULTS: HCC was multifocal in 4 instances and solitary in 1 case. The liver was cirrhotic in all but 1 case. Three patients underwent an exploratory laparotomy, 1 an exploratory laparoscopy, and 1 underwent transplantation. HCC was unresectable in all cases. The patient with a solitary tumor and cirrhosis underwent 5 sessions of transarterial chemoembolization and is alive 37 months after surgical exploration. The 3 patients with multifocal tumors who underwent exploratory laparotomies died within 6 months after the intervention. The fifth patient who underwent a deceased donor split liver transplantation for multifocal tumor is alive without recurrence 3 years after transplantation. These results are similar to those in the literature that concur with the low resectability rate and the favorable outcome after liver transplantation. CONCLUSION: Resectability rates of HCCs arising in hemochromatosis are extremely low, given that tumors are usually multifocal and the livers cirrhotic in the majority of the instances. Early detection of hemochromatosis as well as intensive tumor screening of cirrhotic patients with hemochromatosis could possibly optimize the role of surgery or accelerate the decision to proceed with liver transplantation.

Aged↗
PubMed2006

A limited set of human MicroRNA is deregulated in follicular thyroid carcinoma.

CONTEXT: Although the pathogenesis of follicular thyroid carcinoma (FTC) and its relation to follicular adenoma (FA) remains unclear, detailed understanding of FTC carcinogenesis would facilitate addressing the scientific and clinical challenges, given that there are morphological and molecular similarities between FTC and the frequently occurring FA. Micro-RNAs (miRNAs) are a new class of small, noncoding RNAs implicated in development and cancer and may lend novel clues to FTC genesis. For the latter process, a deregulated miRNA can orchestrate the aberrant expression of several hundred target genes. OBJECTIVE: The objective of the study was to identify deregulated miRNAs in FTC. DESIGN: We used two high-density expression arrays to identify miRNAs and their target genes that are differentially expressed between FTC and FA. Validation was done by quantitative RT-PCR. We further functionally characterized the effect of deregulated miRNAs in vitro using HEK293T, FTC133, and K5 cell lines. PATIENTS: In total, 45 primary thyroid samples (23 FTC, 20 FA, four normal control thyroid) were analyzed. RESULTS: Two specific miRNAs, miR-197 and miR-346, were significantly overexpressed in FTC. In vitro overexpression of either miRNA induced proliferation, whereas inhibition led to growth arrest. Overexpression of miR-197 and miR-346 repressed the expression of their predicted target genes in vitro and in vivo. CONCLUSIONS: Our observations show that miR-197 and miR-346 contribute to FTC carcinogenesis. Both miRNAs and their target genes might potentially provide for novel molecular markers and act as novel targets for treatment by interference, which could potentially normalize the deregulated profile of many downstream target genes.

Adenocarcinoma, Follicular↗
PubMed2006

The role of surgery in Caroli's disease.

BACKGROUND: Caroli's disease is a rare congenital disorder characterized by multifocal segmental dilation of the intrahepatic bile ducts. Whether conservative or surgical strategies should be preferred is still a matter of debate. The aim of this study was to evaluate the role of surgery in the management of Caroli's disease. STUDY DESIGN: From April 1998 until August 2005, 12 consecutive patients with Caroli's disease were treated in the Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Germany. All patients were intended to receive liver resections or liver transplantations. RESULTS: There were seven men and five women, with a median age of 39 years (range 7 months to 70 years). Eight patients had monolobar and four patients had bilobar liver involvement. All patients had a history of recurrent cholangitis, with up to 16 unsuccessful conservative treatment attempts. Nine patients (75%) underwent liver resection and two (17%) had liver transplantation. Intraoperatively, three patients (25%) were found to have cholangiocarcinoma, of which one was unresectable. There was no mortality and only low morbidity (16%) postoperatively. After a median followup of 31 months, 11 patients are well with no recurrent symptoms. CONCLUSIONS: Surgery can offer a definite therapy, with an acceptable morbidity and virtually no mortality in localized Caroli's disease. In diffuse disease, the use of extended resections or liver transplantation can provide good longterm results.

Adolescent↗
PubMed2006

Primary organ function of warm ischaemically damaged porcine kidneys after retrograde oxygen persufflation.

BACKGROUND: As warm ischaemic damage is a major reason for the loss of donor organs, an experimental study was performed in order to evaluate retrograde oxygen persufflation (ROP) as a method to extend the warm ischaemic tolerance of kidneys. METHODS: Kidneys of 32 pigs were exposed to warm ischaemia for 60, 90 or 120 min. Then, 16 kidneys were subjected to ROP for 4 h at 4 degrees C and 16 controls were stored in cold UW-solution, followed by autotransplantation. RESULTS: Only in the group with 60 min warm ischaemic time and ROP did all animals survive the observation period of 7 days. In all other groups some animals died due to anuria. Short-term survivors in these groups had significantly higher creatinine levels. CONCLUSIONS: In this setting, ROP was superior to cold storage when applied after 60 min of warm ischaemia. Clinical evaluation of ROP in the setting of marginal donors and non-heartbeating donation is recommended.

Animals↗
PubMed2006

Neurological complications after cadaveric and living donor liver transplantation.

Problems related to the central nervous system have a major impact on survival and quality of life. The aim of this retrospective study was to evaluate the incidence of neurological complications after liver transplantation (LT), including both cadaveric and living donor liver transplantation. Between April 2001 and March 2004 174 patients (120 cadaveric liver transplantations, 54 living donor transplantations) were admitted to our intensive care after liver transplantation. Of the transplanted patients 24.7% developed neurological complications. These patients' stay in the intensive care (14.2 +/- 17.2 days) was much longer than that of all admitted patients (8.4 +/- 10.5 days, p < 0.05). The most common neurological complications were encephalopathy (72.1%) and seizures (11.6 %). The incidence of neurological complications in living donor liver transplanted patients was significantly lower than in cadaveric transplantation patients (20.4% vs 26.7 %). The cold ischemia time in living donor transplanted patients was significantly shorter in comparison with cadaveric transplanted patients (215 +/- 119.3 vs. 383.7 +/- 214.7). The survival rate after liver transplantation of patients with neurological complications was lower than that of patients without, but not significantly different (79.1 % vs. 82.4%, p > 0.05). The incidence of neurological symptoms was found to be similar between the patients treated with cyclosporine (25%) and tacrolimus (23.8 %) in this study. In conclusion, there was a high incidence of neurological complications after LT, prolonging the patients' stay in intensive care significantly. The major neurological manifestation in our patients was encephalopathy followed by seizures. Living donor liver transplantation was associated with a significantly lower incidence of neurological complications compared with patients who had received a cadaveric graft. This might be due to the good quality of the organ and the much shorter cold ischemia time of the graft when the donor was alive.

Adult↗
PubMed2006

Liver transplantation and incidentally found hepatocellular carcinoma in liver explants: need for a new definition?

BACKGROUND: "Incidentally" identified hepatocellular carcinoma (iHCC) in liver explants after liver transplantation (LTx) is a frequently reported finding, which is characterized with a good prognosis. The purpose of this study was to evaluate the outcome of patients with these tumors in our series and in literature reports, and to compare their prognosis to that of HCC diagnosed preoperatively. METHODS: From April 1998 to December 2003, 432 patients underwent deceased-donor LTx at our center for nonmalignant indications. An additional 31 patients with a preoperative known HCC (pkHCC) received deceased-donor grafts. A literature search was performed intending to estimate the incidence of iHCC in liver explants and the outcome after LTx. RESULTS: iHCC was found in 5 of the 432 patients. All five patients are currently alive without evidence of tumor recurrence after a median follow-up of 43 months. On the other hand, in the group of the 31 patients with pkHCC, 22 of them are at the moment alive in a median follow-up of 28 months. When comparing the two groups, no difference in survival could be found (P=0.1419 in log-rank test). Literature reports of 705 instances with iHCC over the past 20 years showed a statistical "better survival" in only 24 cases. CONCLUSION: Literature reports showed a remarkable "deviation" of the expected tumor characteristics for the iHCC. Obviously, this is because of a widely characterization of iHCC, including also tumors which are rather undetected HCC during the waiting time to LTx. A more precise definition for the iHCC is needed.

Carcinoma, Hepatocellular↗
PubMed2006

Cyclosporine versus tacrolimus in patients with HCV infection after liver transplantation: effects on virus replication and recurrent hepatitis.

AIM: To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus (HCV) replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS: The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS: HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant (P=0.49 at 12 mo). In addition, recurrent hepatitis as determined by serum transaminases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo (P=0.34). CONCLUSION: Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV-infected patients after liver transplantation.

Adult↗