Biomedical subjects

Rolf Schauer

Publications and source records attributed to Rolf Schauer.

11 recordsLinked to original sources

PubMed2005

Beneficial effects of ischemic preconditioning in patients undergoing hepatectomy: the role of neutrophils.

HYPOTHESES: Temporary vascular clampage (Pringle maneuver) during liver surgery can cause ischemia-reperfusion injury. In this process, activation of polymorphonuclear leukocytes (PMNLs) might play a major role. Thus, we investigated the effects of hepatic ischemic preconditioning on PMNL functions. DESIGN: Prospective randomized study. Patients who underwent partial liver resection were randomly assigned to 3 groups: group 1 without Pringle maneuver; group 2 with Pringle maneuver, and group 3 with ischemic preconditioning using 10 minutes of ischemia and 10 minutes of reperfusion prior to Pringle maneuver for resection. SETTING: University hospital, Munich, Germany. PATIENTS: Seventy-five patients underwent hepatic surgery mostly owing to metastasis. MAIN OUTCOME MEASURES: Perioperative factors for PMNL activation, inflammation, and postoperative hepatocellular integrity. RESULTS: Ischemia-reperfusion of the human liver (mean +/- SD time to perform the Pringle maneuver, 35.5 +/- 2.6 minutes) caused (1) a decrease in the number of circulating PMNLs, (2) their intrahepatic sequestration, (3) their systemic activation, and (4) a significant correlation between the degree of their postischemic activation and the postoperative rise in liver enzyme serum levels. In parallel, cytokines with proinflammatory and chemotactic properties were released reaching the highest values when stimulation of PMNLs was most pronounced. When ischemic preconditioning preceded the Pringle maneuver, activation of PMNLs and cytokine plasma levels was reduced as evidenced by the attenuation of superoxide anion production, beta(2)-integrin up-regulation, and interleukin 8 serum concentrations, followed by a significant reduction in serum alanine aminotransferase levels on the first and second postoperative days. CONCLUSIONS: These results demonstrate in humans that ischemic preconditioning reduces activation of PMNLs elicited by the Pringle maneuver. The down-regulation of potentially cytotoxic functions of PMNLs might be one of yet unknown important pathways that altogether mediate protection by ischemic preconditioning.

CD18 Antigens↗

PubMed2005

Analysis of promoter methylation in stool: a novel method for the detection of colorectal cancer.

BACKGROUND & AIMS: Detection of tumor-derived DNA alterations in stool is an intriguing new approach with high potential for the noninvasive detection of colorectal cancer (CRC). Because of heterogeneity of tumors, usually multiple markers distributed throughout the human genome need to be analyzed. This is labor intensive and does not allow for high through-put screening. Therefore, markers with high sensitivity and good specificity are needed. We explored the potential of a single epigenetic marker in comparison with fecal occult blood testing (FOBT) for the discrimination of patients with CRCs and adenomas from those without. METHODS: Methylation-specific polymerase chain reaction (PCR) was performed to analyze hypermethylated in cancer 1 (HIC1) promoter methylation status in a blinded fashion in stool samples from 26 patients with CRC, 13 with adenoma > or =1 cm, 9 with hyperplastic polyps, 9 with chronic inflammatory bowel disease, and 32 with endoscopically normal colon. RESULTS: Ninety-seven percent of the stool samples contained amplifiable DNA. Forty-two percent of the samples from patients with CRC and 31% of the samples from patients with colorectal adenoma > or =1 cm were positive for HIC1 promoter methylation. No methylated HIC1 promoter DNA was detected in the fecal DNA from patients with endoscopically normal colon or hyperplastic polyps. CONCLUSIONS: The epigenetic marker HIC1 promoter methylation carries high potential for the remote detection of CRCs. We postulate that a panel of merely a few genetic and epigenetic markers will be required for the highly sensitive and specific detection of CRCs and adenomas in fecal samples from affected patients.

Age Distribution↗

PubMed2004

Effect of chemoradiotherapy with gemcitabine and cisplatin on locoregional control in patients with primary inoperable pancreatic cancer.

Gemcitabine sensitizes tumor cells to radiation and cisplatin and thereby enhances the cytotoxic effect of gemcitabine. Here we report the efficacy and toxicity of concurrent chemoradiation with gemcitabine and cisplatin in the treatment of patients with locally advanced, unresectable pancreatic cancer. A total of 47 patients (29 men, 18 women; median age 61 years) with histologically proven advanced pancreatic carcinoma were included in the study. They underwent chemotherapy with gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 on days 1, 8, 22, and 29; concurrent radiation (45-50 Gy) was applied to the tumor and regional lymph nodes (1.8-2.0 Gy/fraction 5 days per week). Subsequent to chemoradiotherapy, treatment was continued with more two cycles of gemcitabine (1000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a 4-week cycle. After completion of chemoradiotherapy, 9 patients (19.1%) achieved a complete response and 23 patients (48.9%) a partial response, for an overall response rate of 68%. The lesions were considered resectable in 27 patients, and 25 of the 27 patients underwent laparotomy. The other 20 patients underwent a definitive pancreatic resection. Altogether, 13 patients had negative surgical margins. With a median follow-up of 25.7 months (range 12.7-38.7 months) after completion of chemoradiation, distant metastasis had occurred in 23 patients and local recurrence in only 4 of 44 patients (8.5%). the median progression-free survival was 7.8 months (range 6.2-9.4 months). The median survival amounted to 10.7 months (range 8.4-13.0 months) for all patients, whereas it was prolonged to 24.2 months (range 6.8-41.7 months) for those undergoing R0 resection. The main toxicities associated with chemoradiation included grade 3/4 leukopenia (68% of patients) and thrombocytopenia (61%). Episodes of cholangitis were observed in 11 patients. We concluded that gemcitabine and cisplatin can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients whose tumors are rendered completely resectable.

Adult↗

PubMed2004

Estimation of liver size for liver transplantation: the impact of age and gender.

In general, the liver is considered to be larger in males than in females. In the present study, data on liver weight from 728 legal autopsies were analyzed with respect to gender, age, body height (BH), body weight (BW), body mass index (BMI), and body surface area (BSA). Descriptive statistics revealed that liver weight increases with age, reaching maximum values between 41 and 50 years in men and between 51 and 60 years in women. Thereafter, liver weight decreases again. Because this loss in liver weight starts earlier in men while liver weight continues to rise in women, the difference in liver weight between men and women is lost above the age of 50. Thus, this age defines a threshold value below which gender is expected to be a critical factor in the calculation of liver weight. When demographic data mentioned above were subjected to multiple stepwise linear regression analysis, liver weight (LW) was best predicted in younger people (16-50 years) by body weight, age, and gender: LW (g) = 452 + 16.34 x BW + 11.85 x age - 166 x gender (r(2) = 0.381; "gender": 1 = female, 0 = male). In contrast, in elderly people (51-70 years) LW was best predicted by BW and age only. Gender was not a significant factor. LW (g) = 1390 + 15.94 x BW - 12.86 x age (r(2) = 0.35). When these formulas were applied to demographic data from 97 organ donors and compared to published formulas (which, however, do not consider the age-dependent effects of gender), the new formulas best predicted male to female liver weight ratios in younger and elderly donors. In conclusion, the new formulas might better predict liver weight in organ donors and transplant recipients to avoid liver size mismatch.

Adolescent↗

PubMed2004

Analysis of a successful HCV-specific CD8+ T cell response in patients with recurrent HCV-infection after orthotopic liver transplantation.

Virus-specific CD8+ T cells play a major role in antiviral immune defenses; their significance in the transplant setting, however, is unclear. In the present study, we asked whether hepatitis C virus (HCV)-specific CD8+ T cells were detectable in the presence of an immunosuppressive treatment and whether the HCV-specific CD8+ T cell response correlates with treatment outcome in patients who receive interferon (IFN)-alpha / ribavirin therapy after orthotopic liver transplantation (OLTx). Liver- and blood-derived T cell lines of 21 patients after OLTx were studied before, at the end of, and after antiviral treatment. Virus-specific IFN-gamma production in response to a panel of previously identified HCV-specific epitopes restricted by the human leukocyte antigen (HLA) class I molecules A2, A3, B7, B35, and B44 of structural and nonstructural HCV protein was determined by enzyme-linked immunospot (ELISPOT) assay. Before treatment, only low numbers of HCV-specific CD8+ T cells were detectable. In 6 patients with a sustained virological response, a significant, multispecific, and sustained CD8+ T cell response was detectable, which was mainly found in the peripheral blood. Nonresponders and transient responders showed undetectable, weak, or transient HCV-specific CD8+ T cell responses. (Sustained responders vs. transient and nonresponders: Wilcoxon rank-signed test; P < .01). In conclusion, our data indicate that despite immunosuppression, HCV-specific CD8+ T cells are detectable in patients with recurrent HCV infection after OLTx and that a significant, multispecific, and long-lasting HCV-specific CD8+ T cell response contributes to viral elimination.

Adult↗

PubMed2003

Rapid development of esophageal squamous cell carcinoma after liver transplantation for alcohol-induced cirrhosis.

Liver transplant recipients have an increased risk of developing de novo malignancies. It is generally accepted that chronic alcohol abuse is a contributive factor in the pathogenesis of several malignancies, in particular, of oropharyngeal squamous cell carcinoma (SCC). Thus, patients with end-stage alcohol-induced cirrhosis could be at risk of esophageal SCC following orthotopic liver transplantation (OLT). From January 1986 to December 1997 a total of 313 patients underwent OLT for various indications. Of these patients, 72 had alcohol-related cirrhosis. Oropharyngeal and esophageal malignancies after OLT were not observed in non-alcoholic patients. In contrast, these malignancies were diagnosed in three male patients who underwent transplantation for alcohol-induced cirrhosis (incidence 4.2%). Furthermore, all patients had a history of tobacco abuse. The tumors were located in the tongue of one patient and in the esophagus of two patients. While SCC of the tongue became apparent 5 years after OLT, esophageal SCC was detected 8 and 16 months after transplantation. Shortly before transplantation, endoscopy of the esophagus had not revealed evidence of pre-malignant dysplastic lesions in any of these patients. Thus, esophageal SCC may develop rapidly in patients undergoing transplantation for alcohol-related cirrhosis with a history of tobacco abuse before liver transplantation, which warrants careful post-transplant screening of these patients.

Adult↗

PubMed2003

Treatment of Crigler-Najjar type 1 disease: relevance of early liver transplantation.

BACKGROUND: Crigler-Najjar syndrome type 1 (CNS1) is characterized by severe unconjugated hyperbilirubinemia from birth, caused by total failure of UDP-glucuronyltransferase activity. Only orthotopic liver transplantation (OLT) offers the prospect of cure. However, because the onset of neurologic deficits is unpredictable, timing of OLT remains difficult. METHODS: In our transplant center, 3 patients underwent early OLT for CNS1. Two of them (7 yr, 12 yr) showed mild to moderate neurologic deficits only few weeks before OLT, another patient (4 yr) had no signs of bilirubin encephalopathy. All patients required extensive phototherapy to control bilirubin levels. Thus, OLT was performed shortly after the onset of neurologic symptoms or as a prophylactic procedure, respectively. RESULTS: OLT was uneventful in all recipients. One of the symptomatic patients (7 yr) completely recovered from neurologic deficits at 36 months on OLT, whereas the other patient (12 yr) significantly improved symptoms at 27 months of OLT. These patients, including the 4-year-old boy, attend school at appropriate grades now. CONCLUSIONS: Irreversible brain damage (kernicterus) may occur in the course of CNS1 disease. Because no alternative treatment options are available at this time, OLT should be performed as a preventive procedure to counteract severe CNS-related complications.

Child↗

PubMed2002

Interactive decision support in hepatic surgery.

BACKGROUND: Hepatic surgery is characterized by complicated operations with a significant peri- and postoperative risk for the patient. We developed a web-based, high-granular research database for comprehensive documentation of all relevant variables to evaluate new surgical techniques. METHODS: To integrate this research system into the clinical setting, we designed an interactive decision support component. The objective is to provide relevant information for the surgeon and the patient to assess preoperatively the risk of a specific surgical procedure. Based on five established predictors of patient outcomes, the risk assessment tool searches for similar cases in the database and aggregates the information to estimate the risk for an individual patient. RESULTS: The physician can verify the analysis and exclude manually non-matching cases according to his expertise. The analysis is visualized by means of a Kaplan-Meier plot. To evaluate the decision support component we analyzed data on 165 patients diagnosed with hepatocellular carcinoma (period 1996-2000). The similarity search provides a two-peak distribution indicating there are groups of similar patients and singular cases which are quite different to the average. The results of the risk estimation are consistent with the observed survival data, but must be interpreted with caution because of the limited number of matching reference cases. CONCLUSION: Critical issues for the decision support system are clinical integration, a transparent and reliable knowledge base and user feedback.

Carcinoma, Hepatocellular↗

PubMed2002

Successful liver transplantation of two brothers with crigler-najjar syndrome type 1 using a single cadaveric organ.

Crigler-Najjar type 1 disease (CNS1) is the result of a genetic defect, leading to complete functional loss of an enzyme which glucuronidates bilirubin. As a consequence, unconjugated bilirubin accumulates and may cause kernicterus, the most serious complication in adolescents. Phototherapy effectively adjusts bilirubin levels less than critical concentrations over many years but become less effective in elder children. Therefore, liver transplantation must be performed as definite therapy in these patients to avoid irreversible neurological deficits. Two brothers with CNS1, one without neurological deficits and one with moderate brain injury underwent orthotopic split liver transplantation from the same donor. The intra- and postoperative course of both patients was uneventful. Bilirubin levels normalized after transplantation in both recipients. Furthermore, mental and physical development considerably improved upon transplantation in the brother with neurological dysfunction. Therefore, orthotopic liver transplantation in CNS1 patients should be performed early enough to avoid irreversible brain damage, i.e., as a prophylactic procedure.

Adult↗

PubMed2002

Glutathione treatment protects the rat liver against injury after warm ischemia and Kupffer cell activation.

BACKGROUND/AIM: The generation of reactive oxygen species by activated Kupffer cells (KC) may contribute to reperfusion injury of the liver during liver transplantation or resection. The aim of our present studies was to investigate (1) prevention of hepatic reperfusion injury after warm ischemia by administration of the antioxidant glutathione (GSH) and (2) whether GSH confers protection through influences on KC toxicity. METHODS: Isolated perfused rat livers were subjected to 1 h of warm ischemia followed by 90 min of reperfusion without (n = 5) or with GSH or catalase (n = 4-5 each). Selective KC activation by zymosan (150 micro g/ml) in continuously perfused rat livers was used to investigate KC-related liver injury. RESULTS: Postischemic infusion of 0.1, 0.5, 1.0 and 2.0 mM GSH, but not 0.05 mM GSH prevented reperfusion injury after warm ischemia as indicated by a marked reduction of sinusoidal LDH efflux by up to 83 +/- 13% (mean +/- SD; p < 0.05) and a concomitant significant improvement of postischemic bile flow by 58 +/- 27% (p < 0.05). A similar protection was conveyed by KC blockade with gadolinium chloride indicating prevention of KC-related reperfusion injury by postischemic GSH treatment. Postischemic treatment with catalase (150 U/ml) resulted in a reduction of LDH efflux by 40 +/- 9% (p < 0.05). Accordingly, catalase as well as GSH (0.1-2.0 mM) nearly completely prevented the increase in LDH efflux following selective KC activation by zymosan in continously perfused rat livers. CONCLUSION: Postischemic administration of GSH protects the liver against reperfusion injury after warm ischemia. Detoxification of KC-derived hydrogen peroxide seem to be an important feature of the protective mechanisms.

Animals↗

PubMed2002

Detection of malignant hepatic lesions before orthotopic liver transplantation: accuracy of ferumoxides-enhanced MR imaging.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy of ferumoxides-enhanced MR imaging for screening malignant hepatic lesions before orthotopic liver transplantation. MATERIALS AND METHODS: The study comprised 48 patients who underwent MR imaging within 6 months before transplantation. Imaging techniques included unenhanced and ferumoxides-enhanced T1-weighted gradient-echo and T2-weighted fast spin-echo sequences and ferumoxides-enhanced T2(*)-weighted gradient-echo sequences. Qualitative and quantitative analyses were performed; the gold standard was the histopathologic reports of explanted livers. RESULTS: Twenty patients had malignant hepatic lesions, and 24 hepatocellular carcinomas were histopathologically proven. The mean area under the receiver operating characteristic curve and the mean sensitivity were significantly greater for the image sets with ferumoxides-enhanced gradient-echo sequences than for those without these sequences. The mean sensitivity and specificity of all sequences were 85% and 74% on a per-patient basis, respectively. The mean contrast-to-noise ratio was significantly greater for the ferumoxides-enhanced T2(*)-weighted gradient-echo sequences than for any other sequences and for the ferumoxides-enhanced T1-weighted gradient-echo sequences than for unenhanced sequences and the ferumoxides-enhanced T2-weighted fast spin-echo sequences. CONCLUSION: Ferumoxides-enhanced gradient-echo sequences improved the diagnostic accuracy and the sensitivity for detecting malignant hepatic lesions in patients with end-stage cirrhosis of the liver. However, the specificity was not improved even after the administration of ferumoxides because of the false-positive lesions that were mainly the result of fibrotic changes.

Adult↗