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Biomedical subjects

B Rau

Publications and source records attributed to B Rau.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Radiochemotherapy plus hyperthermia in rectal carcinoma].

In locally advanced rectal cancer (uT3/uT4) resectability as well as local control is reduced. In the patients combined preoperative radiochemotherapy demonstrated an increase of resectability and a reduction of local recurrence. Radiotherapy was applied in standard blocks, 5 x 1.8 Gy up to 45 Gy. Chemotherapy consisted out of two cycles of 5-Fluorouracil (300-350 mg/m2/d) and Leucovorin (50 mg). Prior to radiotherapy additionally thermotherapy was carried out using the SIGMA 60 applicator BSD 2000 once a week. The hyperthermia method is based on heating up affected tissue compartments to temperature above 42 degrees Celsius without damaging surrounding tissue compartments. In regional hyperthermia tumors in the abdominal region are treated by emitting radio waves into the patient. 4-6 weeks after radiochemotherapy, surgery was performed. The therapeutic toxicity was acceptable and the resectability rate was up to 90%. Response rate to treatment was 60%. Our data with preoperative combined treatment in locally advanced rectal cancer revealed encouraging downstaging, local control, and survival rates.

Chemotherapy, Adjuvant↗
PubMed2001

[Minimal invasive surgery. Aspects of surgical oncology of the gastrointestinal tract].

The general potential and current position of minimally invasive surgery for the surgical treatment of malignant tumours of the gastrointestinal tract are discussed. A reliable validation of these procedures for tumour surgery is still impossible due to the lack of long-term results, the selective experience, and the ongoing process of learning and development. However, it seems clear that minimally invasive procedures will have an important position within surgical oncology. This is especially true with respect to improved staging of gastrointestinal tumours by laparoscopy and various palliative procedures that may be performed laparoscopically. Minimally invasive procedures may suffice for the treatment of certain, highly selected cases of preneoplastic and early cancerous lesions. The definitive acceptance of minimally invasive procedures in the future will require further clinical, preferably randomised trials, comparing the advantages of the minimally invasive access route to possible long-term disadvantages with regard to recurrence-free and overall survival.

Gastrointestinal Neoplasms↗
PubMed2001

[Value of laparoscopic ultrasound for staging of gastrointestinal tumors].

BACKGROUND: The objective of this study was to evaluate the impact of laparoscopic ultrasound on the staging of gastrointestinal tumors prospectively. METHODS: Between 1993 and 2000 staging laparoscopy was performed on 668 patients with various neoplasms. Laparoscopy provided adequate information regarding resectability in 366 patients. Laparoscopic ultrasonography was performed in 302 patients (45%) using an intraoperative ultrasound unit (B & K) and a semiflexible ultrasound probe (5-7.5 MHz). The results of staging laparoscopy were compared to the preoperative staging and histopathology. RESULTS: Compared to preoperative staging laparoscopic ultrasound provided additional information of therapeutic relevance in 46 of 302 cases (15%). In a group of 384 patients with tumors of the upper gastrointestinal tract, laparoscopic ultrasound was performed in 186 cases and showed occult liver metastases, M1-lymph nodes, or nonresectable disease in 26 patients. Overall, this technique improved the staging of esophageal, gastric and pancreatic cancer in 12%, 3%, and 12% of the patients, respectively. Laparoscopic ultrasound proved to be most useful in esophageal and pancreatic cancer with a rate of 52% and 20% information additional to laparoscopy. The relative contribution of laparoscopic ultrasound to the staging of gastric cancer was only 10%. CONCLUSION: Laparoscopic ultrasound improves the diagnostic accuracy of staging laparoscopy. However, routine use of this technique is only justified, if neoadjuvant therapy--particularly in controlled trials--is considered in patients with advanced gastrointestinal cancer.

Carcinoma, Squamous Cell↗
PubMed2001

Prevention of severe change in acute pancreatitis: prediction and prevention.

Bacterial infection of pancreatic necrosis is the most frequent local complication of severe acute pancreatitis and is responsible for the majority of deaths in this disease. The development of systemic complications of severe acute pancreatitis such as septic multiple organ failure is closely related to infected necrosis. In this review, the factors predisposing to a severe course of acute pancreatitis are discussed as are clinical and laboratory markers which allow identification of patients at risk. Prevention of complications of acute pancreatitis is difficult. A variety of drugs including antiproteases and antiinflammatory agents have been shown to be of no benefit with regard to the reduction of severe complications. At present, based on the results of controlled trials, there is the widespread belief that prophylactic antibiotics are capable of reducing the incidence of infected pancreatic necrosis. New approaches for the prevention of systemic complications of severe acute pancreatitis are total enteral nutrition and local arterial infusion of antibiotics and antiproteases into the celiac trunk.

Abscess↗
PubMed2001

The voltage-gated sodium channel gene SCN2A and idiopathic generalized epilepsy.

We tested the hypothesis that genetic variation in the human sodium channel gene SCN2A confers liability to idiopathic generalized epilepsy (IGE). We performed a systematic search for mutations in 46 familial IGE cases and detected three novel polymorphisms, however, allele frequencies did not differ significantly between patients and controls. A rare mutation (R1918H) was identified in one patient but was absent in one further affected family member. Thus, our results do not suggest a major role of SCN2A in the etiology of IGE.

Alleles↗
PubMed2001

Differential and mutually exclusive expression of CD95 and CD95 ligand in epithelia of normal pancreas and chronic pancreatitis.

Acinar regression in chronic pancreatitis may be due to immune attack in parenchymal areas neoexpressing HLA-DR molecules. CD4+Th1 cytotoxic T cells induce apoptosis of their targets via oligomerizing CD95 (APO-1/Fas) death receptors on target cells by their CD95 ligand (CD95L). We determined the expression of CD95 and CD95L in epithelia of normal and chronically inflamed pancreatic tissues. We applied RT-PCR and Western blotting for CD95L expression profiles, serial frozen section immunohistochemistry to detect CD95, CD95L, and HLA-DR molecules, CD3, CD4, CD11c, and S-100 protein (S100p). Normal pancreases and chronic pancreatitis contain CD95L message and protein. Immunohistochemistry revealed a mutually exclusive expression of CD95 and CD95L. Physiologically, acini were CD95-/CD95L+, ducts were CD95-/CD95L-, and islets were CD95-/CD95L+. In areas of lymphohistiocytic infiltration, mainly consisting of CD3+CD4+ T cells and CD11c+, CD4+/-, S100p+ interstitial dendritic cells, and in areas of initial fibrosis, acini and ducts were HLA-DR+, acini CD95+/CD95L-, and ducts CD95+/CD95L-. Islet cells were CD95-/CD95L+ in both conditions. IFNgamma levels in protein lysates, as measured by an immunoassay, were significantly higher in chronic pancreatitis than in normal pancreas (p < 0.0003). In vitro, IFNgamma down-modulated CD95L message and protein in ASPC1 and BxPc3 pancreatic carcinoma cells. In conclusion, pancreatic epithelia differentially express CD95 and CD95L in a mutually exclusive manner. In chronic pancreatitis the CD95-/CD95L+ status is conserved in islet cells even in the vicinity of lymphohistiocytic infiltrates, whereas it is lost in acini coexpressing HLA-DR. As a potential consequence, and possibly triggered by local release of IFNgamma, CD4-Th1 cells may cognately interact with and successfully attack exocrine cells by triggering CD95 on their target without being killed by epithelial, CD95L-mediated, counterattack.

Antibodies, Monoclonal↗
PubMed2001

Differential effects of caspase-1/interleukin-1beta-converting enzyme on acinar cell necrosis and apoptosis in severe acute experimental pancreatitis.

There is recent experimental evidence that inhibition of caspase-1/interleukin-1beta converting enzyme (ICE) significantly ameliorates overall severity and survival in severe acute experimental pancreatitis. However, little is known about the effects of this approach on the dynamics and mechanisms of local acinar cell damage, which we aimed to investigate in the present study. Severe acute pancreatitis (SAP) was induced by retrograde infusion of 4% sodium taurocholate in rats treated with isotonic saline or a highly selective, irreversible inhibitor of ICE. After 3, 6, and 24 hours, 3 and 7 days, acinar cell death by necrosis and apoptosis, as well as intrapancreatic and systemic interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) expression, was assessed. Treatment with the ICE inhibitor significantly reduced the extent of acinar cell necrosis accounting for major parenchymal destruction. In contrast, apoptosis was confined to the postacute course of the disease and was closely related to tubular complex formation, both remaining unchanged. Whereas intrapancreatic IL-1beta mRNA expression was highly up-regulated in both treated and untreated animals, active IL-1beta protein expression and subsequent neutrophil tissue infiltration was dramatically decreased in the ICE-inhibited group. Parallel to the onset of enhanced apoptotic acinar cell death and tubular complex formation, TNF-alpha mRNA and protein expression was up-regulated, with levels being lower in ICE inhibitor-treated rats. We conclude that activation of caspase-1/ICE plays a central role in the progression of acinar cell death by necrosis in SAP. Herein, IL-1beta-mediated neutrophil infiltration seems to be a crucial step in enhanced cellular destruction. In contrast, acinar cell apoptosis contributes to ductal transformation and is independent of this mechanism, but may be influenced by TNF-alpha.

Acute Disease↗
PubMed2001

Modulation of endogenous nitric oxide synthase in experimental acute pancreatitis: role of anti-ICAM-1 and oxygen free radical scavengers.

OBJECTIVE: To evaluate, in an experimental model of acute pancreatitis, the impact of nitric oxide on the disease process and the interaction between nitric oxide and oxygen free radicals. SUMMARY BACKGROUND DATA: Nitric oxide and oxygen free radicals are involved in the pathophysiology of acute pancreatitis. It is well established that oxygen free radicals play an important role in the development of pancreatic cell damage and remote organ failure, but the impact of nitric oxide on the disease process and the interactions between the two radical species remain controversial. METHODS: Necrotizing pancreatitis (NP) was induced in Wistar rats by intraductal sodium taurocholate infusion after pretreatment with isotonic saline (NP-S), superoxide dismutase/catalase (NP-SOD/CAT), or an anti-ICAM-1 antibody (aICAM-1). Sham-operated rats received isotonic saline (SHX). After an observation period of 5 minutes and 24 hours, the pancreas was removed for microscopy, glutathione, and myeloperoxidase (MPO) analysis. The inducible NO synthase (NOS-2) was detected by Western blotting or RT-PCR. Serum was analyzed for nitrite/nitrate (NO2-/NO3-) and S-nitrosothioles (RSNO), while plasma was used to assay for trypsinogen activation peptides (TAP). RESULTS: NP-S animals showed a significant decrease in GSH levels after NP-induction as compared with animals under therapy. Increased MPO levels in the NP-S group were significantly reduced by aICAM-1 while SOD/CAT injection showed no changes. Serum NO-derivatives peaked at 12 hours while TAP levels had a maximum at 6 hours after NP induction, and were lower after aICAM-1 application SOD/CAT treatment increased both parameters. Extended acinar cell damage and inflammatory infiltrate developed in NP-S animals and was significantly improved by SOD/CAT and aICAM-1 treatment. RT-PCR and Western-blot analysis revealed NOS-2 expression in the NP-S group, which was reduced by radical scavengers and aICAM-1. CONCLUSION: Enhanced nitric oxide synthase expression and increased nitric oxide derivatives are found during severe acute pancreatitis. Oxygen free radicals and neutrophils seem to be potent and important regulation mechanisms for nitric oxide synthase activity and nitric oxide-mediated toxicity but imply only a secondary role for nitric oxide in the local pathologic mechanism of this disease.

Animals↗
PubMed2001

Clinical relevance of caspase-1 activated cytokines in acute pancreatitis: high correlation of serum interleukin-18 with pancreatic necrosis and systemic complications.

OBJECTIVES: There is recent experimental evidence that caspase-1 activation plays an instrumental role in the pathomechanism of severe acute pancreatitis. Besides interleukin-1beta, interleukin-18, a recently described proinflammatory cytokine, is cleaved into its biologically active form by caspase-1 as well. Interleukin-18 is known to have potent properties concerning the activation of the Th1-lymphocyte subset via costimulation of interferon-gamma production. In contrast to interleukin-1beta, little is known about the clinical impact of interleukin-18 in the course of acute pancreatitis. DESIGN: Cohort study comparing patients with mild and severe acute pancreatitis associated with local and systemic complications during the course of the disease. SETTING: Surgical and anesthesiological intensive care unit as well as wards of the department of general surgery. PATIENTS: We included 68 patients with acute pancreatitis in the present study. In terms of local complications, pancreatic necrosis was present in 37 patients, of whom 21 developed pancreatic infections. Systemic complications included pulmonary, renal, or cardiocirculatory insufficiency and were observed in 40, 18, and 25 patients, respectively. Severe multiple-organ dysfunction syndrome involving all three organ systems occurred in 18 patients, all suffering from pancreatic necrosis. INTERVENTIONS: Serum samples were collected over 14 consecutive days after study inclusion. Ascites or peripancreatic exudate was obtained by ultrasound-guided fine needle aspiration in 14 cases. Sera and local aspirates were stored at -70 degrees C until analysis. MEASUREMENTS AND RESULTS: Interleukin-18 and interferon-gamma were measured by commercially available enzyme-linked immunosorbent assays. Interleukin-18 concentrations were significantly increased after the fourth day of disease onset until the end of the observation period in patients who developed pancreatic necrosis and systemic complications such as pulmonary, renal, and cardiocirculatory failure as well as severe multiple-organ dysfunction syndrome. However, no correlation was found between the development of pancreatic infections and interleukin-18 concentrations. In contrast with interleukin-18, interferon-gamma concentrations did not show any significant difference with respect to the presence or absence of either systemic or local complications. Local interleukin-18 concentrations in ascites or peripancreatic exudate were up to 20-fold higher than systemic concentrations, whereas interferon-gamma concentrations did not differ. CONCLUSIONS: Serum interleukin-18 concentrations are significantly elevated in patients with acute pancreatitis complicated by pancreatic necrosis and remote organ failure. The present data suggest an important role of caspase-1 dependent cytokine activation in the pathomechanism of severe acute pancreatitis beyond the experimental setting. In this context, interleukin-18 may serve as a potential target for new therapeutic approaches.

APACHE↗
PubMed2001

Early severe acute pancreatitis: characteristics of a new subgroup.

This study focuses on patients with severe acute pancreatitis complicated by organ failure within the initial phase of the disease. Data of 158 patients with severe acute pancreatitis (SAP) admitted to hospital within 72 hours after onset of symptoms were prospectively documented and analyzed for the occurrence of early severe acute pancreatitis (ESAP). ESAP was defined as presence of organ failure (OF) at admission. Forty-seven (30%) patients had ESAP, compared with 111 patients without OF (SAP group). In a multivariate analysis, the main factor predisposing to ESAP was the presence of extended pancreatic necrosis (odds ratio, 3.8), whereas biliary pancreatitis was associated with a slightly lower risk compared with alcoholic pancreatitis (odds ratio, 0.34). Compared with SAP, patients with ESAP more frequently developed intractable organ failure, which posed the indication for surgical treatment. Surgical necrosectomy due to progressive OF had to be performed in 89% of the ESAP patients and in 60% of the SAP patients. The incidence of infected pancreatic necrosis did not differ between both groups (23 vs. 21%). Mortality was significantly higher in ESAP (42 vs. 14%; p = 0.0003). ESAP is characterized by the presence of extended pancreatic necrosis and a complicated clinical course. Intractable organ failure is a frequent finding. Given the poor prognosis of ESAP, these patients should be treated in specialized intensive care units.

Acute Disease↗
PubMed2001

Anti-ICAM-1 antibody modulates late onset of acinar cell apoptosis and early necrosis in taurocholate-induced experimental acute pancreatitis.

The hallmark of severe acute pancreatitis (SAP) is massive acinar cell death by necrosis. However, programmed, apoptotic acinar cell death has also been observed. Little is known about the dynamics, localization, and inductive factors of acinar cell apoptosis in SAP. We therefore induced SAP in rats by retrograde infusion of 3% sodium taurocholate. Starting as early as 5 minutes after taurocholate administration, small scattered groups of acinar cells showed zymogen degranulation, loss of cell polarity, cytoplasmic microvacuolization, and nuclear shrinkage, but no DNA degradation, thus featuring necrosis. The areas of necrotic acini extended at later time points giving rise to larger areas of complete parenchymal breakdown after 6 hours. Parenchymal degradation was paralleled by neutrophil infiltration and significant tumor necrosis factor (TNF)-alpha mRNA up-regulation. Up to the 12-hour interval, apoptotic acinar cells detected by TUNEL were as rare as in healthy pancreata. At 24 hours, however, the acinar apoptotic rate in nonnecrotic parenchyma had dramatically increased. Pretreatment of rats with anti-ICAM-1 antibody prior to pancreatitis induction led to a significant reduction of neutrophil infiltration along with decreased TNF-alpha mRNA expression throughout the 24-hour observation period without affecting the presence and dynamics of necrosis. However, anti-ICAM-1 pretreatment decreased the extent of acinar cell damage by necrosis and extensively suppressed acinar cell apoptosis. We conclude that taurocholate induces two sequential patterns of acinar cell death in terms of very early necrosis followed by late apoptosis during the postacute phase of SAP. The progression of necrosis and the late apoptotic acinar cell death seem to be influenced by the local presence of neutrophils via a TNF-alpha-dependent mechanism. In addition to augmenting necrosis, neutrophils might have an apoptosis-inducing potential in SAP.

Acute Disease↗
PubMed2001

Management of patients with extended pancreatic necrosis.

BACKGROUND: Extended pancreatic necrosis pose a considerable therapeutic problem in patients with necrotizing pancreatitis. AIM: Factors that limit conservative treatment in patients with extended pancreatic necrosis were analyzed. METHODS: The clinical course of 61 patients with an extent of necrosis of more than 50% of the gland (according to contrast-enhanced CT scan) were analysed with special regard to systemic complications. Indications for surgical treatment were either persistent organ failure or pancreatic infection. RESULTS: 10 patients were managed by conservative treatment, 51 (84%) patients underwent operation. Indications for surgery were sepsis with or without organ failure in 17 patients, persistent organ failure in another 17 patients, persistent SIRS in 13 patients and local complications in 4 patients. Pancreatic infection was present in 25 patients. The incidence of systemic complications did not differ between infected and sterile necrosis, but they occurred earlier in sterile necrosis. CONCLUSIONS: Persistent organ failure is limiting conservative treatment during the early course in patients with sterile necrosis. The latter course is characterized by a high incidence of pancreatic infection and septic organ failure.

APACHE↗
PubMed2001

[Infected necroses and pancreatic abscess: surgical therapy].

Infected pancreatic necrosis and pancreatic abscesses are severe complications of necrotizing pancreatitis. Compared to infected necrosis, pancreatic abscess is associated with lower mortality. Surgical treatment is the current standard. Necrosectomy is performed as a single-step operation in combination with postoperative drainage/lavage or as scheduled reoperation. In selected cases, pancreatic abscesses can be successfully drained by percutaneous interventional drainage. Mortality in infected necrosis is 20-30% and 5-10% in patients with pancreatic abscess.

Abscess↗
PubMed2000

Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters.

PURPOSE: Preoperative radiochemotherapy (RCT) is a widely used means of treatment for patients suffering from primary, locally advanced, or recurrent rectal cancer. We evaluated the efficacy of treatment due to additional application of regional hyperthermia (HRCT) to this conventional therapy regime in a Phase II study, employing the annular phased-array system BSD-2000 (SIGMA-60 applicator). The clinical results of the trial were encouraging. We investigated the relationship between a variety of thermal and clinical parameters in order to assess the adequacy of thermometry, the effectiveness of hyperthermia therapy, and its potential contribution to clinical endpoints. METHODS AND MATERIALS: A preoperative combination of radiotherapy (1.8 Gy for 5 days a week, total dose 45 Gy applied over 5 weeks) and chemotherapy (low-dose 5-fluorouracil [5-FU] plus leucovorin in the first and fourth week) was administered to 37 patients with primary rectal cancer (PRC) and 18 patients with recurrent rectal cancer (RRC). Regional hyperthermia (RHT) was applied once a week prior to the daily irradiation fraction of 1.8 Gy. Temperatures were registered along rectal catheters using Bowman thermistors. Measurement points related to the tumor were specified after estimating the section of the catheter in near contact with the tumor. Three patients with local recurrence after abdominoperineal resection, had their catheters positioned transgluteally under CT guidance, where the section of the catheter related to the tumor was estimated from the CT scans. Index temperatures (especially T(max), T(90)) averaged over time, cumulative minutes (cum min) (here for T(90) > reference temperature 40.5 degrees C), and equivalent minutes (equ min) (with respect to 43 degrees C) were derived from repetitive temperature-position scans (5- to 10-min intervals) utilizing software specially developed for this purpose on a PC platform. Using the statistical software package SPSS a careful analysis was performed, not only of the variance of thermal parameters with respect to clinical criteria such as toxicity, response, and survival but also its dependency on tumor characteristics. RESULTS: The rate of resectability (89%) and response (59%) were high for the PRC group, and a clear positive correlation existed between index temperatures (T(90)) and thermal doses (cum min T(90) >/= 40.5 degrees C). Even though the overall 5-year survival was encouraging (60%) and significantly associated with response, there was no statistically significant relationship between temperature parameters and long-term survival for this limited number of patients. However, nonresectable tumors with higher thermal parameters (especially cum min T(90) >/= 40.5 degrees C) had a tendency for better overall survival. We found even higher temperatures in patients with recurrences (T(90) = 40.7 degrees C versus T(90) = 40.2 degrees C). However, these conditions for easier heating did not involve a favorable clinical outcome, since surgical resectability (22%) and response rate (28%) for the RRC group were low. We did not notice any other dependency of thermal parameters to a specific tumor or patient characteristics. Finally, neither acute toxicity (hot spots) induced by hyperthermia or RCT nor perioperative morbidity were correlated with temperature-derived parameters. Only a higher probability for the occurrence of hot spots was found during treatment with elevated power levels. CONCLUSION: In this study with two subgroups, i.e., patients with PRC (n = 37) and RRC (n = 18), there exists a positive interrelationship between thermal parameters (such as T(90), cum min T(90) >/= 40,5 degrees C) and clinical parameters concerning effectiveness. Additional hyperthermia treatment does not seem to enhance toxicity or subacute morbidity. Procedures to measure temperatures and to derive thermal parameters, as well as the hyperthermia technique itself appear adequate enough to classify heat treatments in

Age Factors↗
PubMed2000

The voltage-gated sodium channel beta2-subunit gene and idiopathic generalized epilepsy.

Recent identification of ion channel gene mutations in Mendelian epilepsies suggests that genetically driven neuronal hyperexcitability plays an important role in epileptogenesis. In this study, we tested the hypothesis that genetic variation in the human SCN2B gene confers liability to common subtypes of idiopathic generalized epilepsies (IGE). A systematic search for mutations was performed in 92 IGE patients. We detected a novel single nucleotide polymorphism (SNP), however, allele frequencies did not differ between IGE patients and controls (chi2 = 0.19, df = 1, p = 0.744). Furthermore, a missense mutation in codon 209 (Asn209Pro) was identified in one patient, but was found to be absent in an affected sibling of the index patient. Thus, our results do not suggest a major role of the SCN2B gene in the etiology of common IGE subtypes.

Adult↗