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S Kanzler

Publications and source records attributed to S Kanzler.

At least 19 recordsLinked to original sources

[Massive hemorrhage in a 28-year-old male patient with intestinal Behçet's disease].

A 28-year-old man was admitted to the emergency room of our hospital after syncope and acute gastrointestinal bleeding. On the basis of numerous oral and genital ulcerations as well as uveitis anterior and erythema nodosum, the diagnosis of Behçet's disease had been confirmed previously. The bleeding focus could not be detected by endoscopy. During the next days recurrent massive hemorrhages occurred in spite of immunosuppressive therapy with steroids. Angiography revealed a circumscribed bleeding source in the colon transversum near the left colonic flexure, which was treated by superselective coil embolization. A massive hemorrhage reoccurred and required a surgical approach with a Hartmann procedure. Histology depicted bleeding into the submucosa and mucosa and an ulcer in this area as well as lymphatic infiltration of the mucosa. Immunosuppressive therapy was intensified with azathioprine and resulted in a dramatic improvement of the oral and genital ulcers. In addition, no further gastrointestinal hemorrhage occurred. Due to its higher prevalence in patients from eastern Asia, Behçet's disease poses an important differential diagnosis of intestinal hemorrhage in patients of this descent.

Adult↗

[Immunotherapy of colorectal cancer--overview and perspectives].

The specific immunotherapy of colorectal cancer initially revealed promising results. However, a significant clinical benefit for patients has still to be proven in phase III trails. In order to compare the different clinical approaches and early phase I - II studies, there is an urgent need for the establishment and acceptance of new standardized diagnostic tools for detecting and quantifying induced and clinical relevant immune responses in patients. Whether or not subgroups with a certain genetic background, such as specific HLA alleles, reveal a better benefit from tumour vaccinations needs to be further analysed. Currently, only two specific antibodies, targeting membraneous receptors or their ligands, such as EGF or VEGF, have been approved by diverse national drug authorities. The question as to whether these antibodies also induce an antibody-dependent cellular toxicity (ADCC) is currently being analysed.

Antibodies, Monoclonal↗

[Combined simulation training: a new concept and workshop is useful for crisis management in gastrointestinal endoscopy].

INTRODUCTION: Crisis management as well as realistic emergency situations can be trained in the new developed simulation workshop "Gastrointestinal Endoscopy and Crisis Resource Management" by combining a full-scale simulator and the Erlanger Endoscopy Trainer. The aim of the current study was to evaluate the efficiency of the newly developed simulation workshop. METHODS: Endoscopists with more than 12 months experience can train their endoscopic skills and crisis resource management with the help of different simulators. In addition, two different scenarios (GI bleeding with significant blood loss and sedation overdoses) embedded in a realistic surrounding (emergency room) have to be managed by the participants. Vital parameters, endoscopic skills, as well as personal interactions were recorded and graded. RESULTS: 100 participants took part in the newly developed workshop (between June and December 2003). The participants showed a significantly better endoscopic performance and a significantly better crisis management after the standardized training program. CONCLUSIONS: Simulation training plays an essential role in aviation and minimizes the risk for human errors. In the current study it is clearly shown that simulation training is also useful in gastrointestinal endoscopy. The newly developed workshop may thus be of crucial importance to improve personal crisis management. Simulation also leads to an improvement of endoscopic and emergency skills. Accordingly, simulation training should be recommended or offered as an education option in gastrointestinal endoscopy.

Computer-Assisted Instruction↗

Prospective comparison of cardiopulmonary events during minilaparoscopy and colonoscopy under conscious sedation.

BACKGROUND AND STUDY AIMS: Cardiorespiratory parameters were examined throughout diagnostic minilaparoscopy procedures. The same parameters were analyzed during colonoscopy, and the data were compared. PATIENTS AND METHODS: Sixty-five consecutive unselected patients undergoing minilaparoscopy (group 1: ASA I, n = 34; group 2: ASA II/III, n = 31) and 61 consecutive unselected patients undergoing colonoscopy (group 3: ASA I, n = 31; group 4: ASA II/III, n = 30) were included. Oxygen saturation (Sao (2)), heart rate (HR) and mean arterial pressure (RRm) were measured continuously, and 12-lead electrocardiography (ECG) recordings were made at specific times during each procedure. RESULTS: Minor differences were observed, particularly after premedication, probably due to different dosage regimens and timing in the two examination techniques. After premedication, testing for differences from baseline values showed a minor decrease in Sao (2) and RRm in the minilaparoscopy groups in comparison with the colonoscopy groups (median Sao (2), group 1: 99.9 % +/- 0 vs. group 3 : 100 % -1, P = 0.0078; median RRm, group 1: 99.5 - 4 mm Hg vs. group 3 : 96 -16 mm Hg, P = 0.046, and median RRm, group 2 : 110 + 1 mm Hg vs. group 4 : 101 -13.5 mm Hg, P = 0.0007). HR increased in minilaparoscopy in comparison with colonoscopy (median HR: group 2 : 77 + 4 beats/min vs. group 4 : 75.5 +/- 0 beats/min; P = 0.01). Comparison of defined relevant pathological changes in Sao (2), RRm, HR, and ECG showed no significant differences. DISCUSSION: These data indicate that diagnostic minilaparoscopy under conscious sedation is only associated with limited risk in patients with compensated cardiopulmonary diseases. This is probably due to the low insufflation pressure used.

Blood Pressure↗

Minilaparoscopy in the diagnosis of peritoneal tumor spread: prospective controlled comparison with computed tomography.

BACKGROUND: Early diagnosis of peritoneal spread in malignant disease prevents unnecessary laparotomies. Minimally invasive laparoscopy with the patient under conscious sedation is a new, easily feasible diagnostic technique. This study compares prospective and controlled diagnostic minilaparoscopy with computed tomography (CT) scan for the diagnosis of peritoneal metastases. METHODS: In this study, 56 patients with malignant disease were prospectively investigated with diagnostic minilaparoscopy and CT scan. RESULTS: The study criteria were fulfilled by 54 patients. Minilaparoscopy detected peritoneal carcinosis in 28 of 54 cases, whereas CT detected the disease in 14 of 54 cases. For 36 patients, the diagnosis could be verified by histologic examination of peritoneal biopsies or laparotomy. In this group, minilaparoscopy detected peritoneal carcinosis in 25 of 36 cases, whereas CT detected the disease in 12 of 36 cases. CONCLUSIONS: Minilaparoscopy was more sensitive than CT in detecting peritoneal carcinosis (100% vs 47.8%; p < 0.01). Considering its low grade of invasiveness and superior sensitivity, minilaparoscopy should be regarded as the procedure of choice for the early detection of peritoneal carcinosis.

Adult↗

[Autoimmune liver disease: diagnosis and therapy].

Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and overlap syndromes of these three disease entities are regarded as autoimmune liver diseases. These conditions are important differential diagnoses of elevated liver function tests as about 10 % of liver transplantations in Europe and North America are for these indications. The diagnosis is often difficult but can be facilitated by sequential measurement of relevant autoantibodies, exclusion of other liver disease, ultrasound, ERCP and liver histology. In AIH immunosuppressive therapy has been shown to prevent or stop the development of cirrhosis and improve the prognosis of the patients decisively. In other autoimmune liver diseases this evidence is missing making individual therapeutic decisions necessary. Ursodesoxycholic acid (UDCA) seems to slow disease progression in particular in early stages of PBC.

Adult↗

Current practice in managing patients on anticoagulants and/or antiplatelet agents around the time of gastrointestinal endoscopy -- a nation-wide survey in Germany.

Anticoagulants and antiplatelet agents are widely used in the prophylaxis and management of thromboembolic and cardiovascular diseases. Gastrointestinal bleeding is a well-known complication of these agents. Modification of anticoagulant and antiplatelet therapy is often required in patients undergoing surgical procedures and specific recommendations for the perioperative period have been issued. Fewer data exist with regard to the use of these agents around the time of endoscopic procedures. A survey of the American Society for Gastrointestinal Endoscopy (ASGE), performed several years ago, showed a wide variation between endoscopists in the management of anticoagulants and antiplatelet agents in the periendoscopic period. Subsequently, guidelines have been proposed by the ASGE as well as the German Society for Gastroenterology (DGVS). The aim of this study was to investigate the current practices among German endoscopists regarding the use of these medications in patients undergoing endoscopic procedures and to assess their adherence to published guidelines. Our data demonstrate that, in spite of the dissemination of guidelines, there is still a wide variation in the periendoscopic management of patients who are at increased risk for bleeding due to anticoagulants, especially in patients taking antiplatelet agents.

Anticoagulants↗

Minimal change esophagitis: prospective comparison of endoscopic and histological markers between patients with non-erosive reflux disease and normal controls using magnifying endoscopy.

INTRODUCTION: More than half the patients with gastroesophageal reflux disease (GERD) show no endoscopic abnormality or minimal change esophagitis (non-erosive reflux disease, NERD). We investigated the value of endoscopic and histological markers for the prediction of NERD before and after treatment with 20 mg esomeprazole. METHODS: Between July and October 2002, consecutive patients presenting for upper endoscopy were stratified into GERD and non-reflux patients (control group) with the help of a questionnaire. The endoscopist was blind to the presence of reflux symptoms. Using magnifying endoscopes minimal change esophagitis was defined by the presence of vascular injection or vascular spots above the Z-line, villous mucosal surface and islands of squamous cell epithelium below the Z-line. Targeted and random biopsies were taken below and above the Z-line. Patients with endoscopically visible classical signs of esophagitis (Los Angeles A-D) or histologically proven Barrett's esophagus were not further investigated in the study (drop out). The esophageal specimens were histologically evaluated for erosions, infiltration with leukocytes, hyperplasia of basal cells and length of papillae. Patients with NERD were treated with 20 mg esomeprazole/day for 4 weeks and reevaluated by endoscopy as described before. RESULTS: 39 patients with heartburn and 39 patients without reflux symptoms (controls) were finally included in the analysis (per protocol). Patients with NERD significantly (p = 0.005) more often showed endoscopic signs of minimal change esophagitis (27/39) than the control group (8/39). An increased length of papillae (14/39 versus 2/39; p = 0.005) and basal cell hyperplasia (17/39 versus 4/39; p = 0.009) were significantly more common in the heartburn group. After treatment with esomeprazole, no significant endoscopic or histological differences between the NERD and control group could be observed. CONCLUSIONS: Minimal change esophagitis can be seen with high resolution magnifying endoscopy. By combining endoscopic and histological markers NERD can be predicted with a sensitivity of 62% and a specificity of 74%. Treatment with esomeprazole for 4 weeks reverses the slight alterations to normal.

Anti-Ulcer Agents↗

Value of chromoendoscopy and magnification endoscopy in the evaluation of duodenal abnormalities: a prospective, randomized comparison.

BACKGROUND AND STUDY AIMS: Endoscopic staining methods are increasingly being used to evaluate lesions in the esophagus and colon. The aim of this prospective study was to investigate chromoendoscopy and magnification endoscopy for the evaluation of mucosal lesions in the duodenum. PATIENTS AND METHODS: Consecutive patients were randomly assigned to undergo conventional endoscopy without staining (group A) or intravital staining of the duodenal mucosa with indigo carmine and evaluation with a conventional video endoscope (group B) or a magnification endoscope (group C). Visible lesions were characterized before and after staining, and biopsies were taken for histological assessment. RESULTS: A total of 118 patients was examined. Chromoendoscopy detected significantly more lesions in the duodenal bulb (98 vs. 28; P = 0.0042) in more patients (29 vs. 15; P = 0.0025) compared with conventional endoscopy (group A). After mucosal staining, there was no difference between video endoscopy and magnification endoscopy with regard to the number or extent of the lesions identified. Significantly more targeted biopsies were possible after intravital staining. The most commonly identified lesions on targeted biopsies included (staining/control groups): gastric metaplasia (14/3), hyperplastic Brunner's glands (6/3), inflammatory changes (7/6), villous atrophy (1/3), adenoma (1/0). CONCLUSIONS: Intravital staining of the duodenum with indigo carmine may be useful for detecting mucosal abnormalities, delineating their extent, and allowing targeted biopsies. Magnification endoscopy, when used in addition to chromoendoscopy, does not appear to further increase the diagnostic yield for detecting duodenal abnormalities.

Adolescent↗

Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics.

BACKGROUND: Antibodies to soluble liver antigen/liver pancreas (SLA/LP) are specific markers of autoimmune hepatitis. Their target antigen has recently been cloned. AIMS: To establish standardised immunoassays using the recombinant antigen, and to assess the frequency and significance of seropositivity in patients from different countries. METHODS: An enzyme linked immunoassay was developed using purified recombinant antigen and validated by testing sera from 200 healthy blood donors and 1026 patients with various liver and non-liver diseases. The assay was then applied to 454 sera from 419 patients with autoimmune hepatitis from different countries. All sera were also tested by inhibition immunoassay and western blot. RESULTS: Antibodies were reliably detected by the recombinant immunoassay and occurred exclusively in patients with autoimmune liver disease. Twenty three of 149 patients from the USA (15%), 23/132 from Brazil (17%), 21/108 from Germany (19%), and 2/30 from Japan (7%) were seropositive. Clinical features at presentation were similar between seropositive and seronegative patients. However, relapse after corticosteroid withdrawal or during maintenance therapy occurred more commonly in seropositive patients. CONCLUSIONS: Antibodies to SLA/LP can be reliably detected by these standardised immunoassays based on recombinant antigen. Antibodies to SLA/LP occur with similar frequencies in different geographical regions, races, and age groups, and are of exquisite diagnostic specificity. Whether SLA/LP positive patients represent a clinically distinct subgroup remains to be determined; relapse during treatment reduction appeared to be more common in the SLA/LP group.

Adolescent↗

Hepatocellular expression of a dominant-negative mutant TGF-beta type II receptor accelerates chemically induced hepatocarcinogenesis.

The potent growth-inhibitory activity of cytokines of the transforming growth factor-beta (TGF-beta) superfamily and their widespread expression in epithelia suggest that they may play an important role in the maintenance of epithelial homeostasis. To analyse TGF-beta mediated tumor suppressor activity in the liver, we generated transgenic mice overexpressing a dominant negative type II TGF-beta receptor in hepatocytes under control of the regulatory elements of the human C-reactive protein gene promoter. Transgenic animals exhibited constitutive and liver-specific transgene expression. The functional inactivation of the TGF-beta signaling pathway in transgenic hepatocytes was shown by reduced TGF-beta induced inhibition of DNA synthesis in primary hepatocyte cultures. Liver morphology and spontaneous tumorigenesis were unchanged in transgenic mice suggesting that interruption of the signaling of all three isoforms of TGF-beta in hepatocytes does not disturb tissue homeostasis in the liver under physiological conditions. However, following initiation with the carcinogen diethylnitrosamine and tumor-promotion with phenobarbital transgenic mice exhibited a moderate albeit significant increase in the incidence, size and multiplicity of both preneoplastic tissue lesions in the liver and of hepatocellular carcinomas. These results give in vivo evidence for a tumor suppressor activity of the endogenous TGF-beta system in the liver during chemical hepatocarcinogenesis.

Animals↗

[Presence of SLA/LP autoantibodies in patients with primary biliary cirrhosis as a marker for secondary autoimmune hepatitis (overlap syndrome)].

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate whether the presence of SLA/LP-autoantibodies in PBC-patients gives evidence for a secondary AIH, also called AIH/PBC-overlap-syndrome. PATIENTS AND METHODS: Out of 233 consecutive patients with PBC who had been followed between October 1980 and April 2000, we evaluated the data of anti-SLA/LP-positive patients and compared them to patients with an anti-SLA/LP-negative AIH/PBC overlap syndrome as well as to patients with a classical course of AIH and PBC. RESULTS: In total we could identify nine PBC patients with anti-SLA/LP antibodies (six women/three men) or 3.9% of the study population, Anti-SLA/LP-positive PBC patients were slightly younger at diagnosis in comparison to anti-SLA/LP-negative PBC-patients (49.9 vs. 53.2 years). Transaminases and gamma-globulins were significantly higher in anti-SLA/LP-positive PBC-patients in comparison to anti-SLA/LP-negative PBC-patients (mean: 235 vs. 55 IU/l and 27.6 vs. 19.5 g/l). Anti-SLA/LP-positive patients significantly more frequently had an HLA-type that is characteristic for AIH (B8; DR3; DR4). Immunosuppressive therapy reduced inflammatory activity and cholestasis significantly. Relapses were frequent after reduction or discontinuation of immunosuppressive therapy. CONCLUSION: The presence of SLA/LP autoantibodies in PBC patients has a high specificity for a secondary AIH (AIH/PBC overlap syndrome). These patients have a good response to immunosuppressive therapy. The autoantibody profile and immunogenetics may help in future to identify PBC patients that benefit most from immunosuppressive therapy.

Adult↗

Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta.

Although many patients with chronic viral hepatitis C infection suffer from progressive liver disease, the rate of fibrosis progression is highly variable and some patients do not show any measurable progression. However, our ability to predict which patients progress is very limited. Since transforming growth factor-beta (TGF-beta) is a key mediator of liver fibrogenesis, we assessed the predictive role of TGF-beta for fibrogenesis in chronic hepatitis C. We studied 39 patients with chronic hepatitis C in whom two liver biopsies were taken at least 12 months apart, and who did not receive therapy during this period. TGF-beta was measured by bioassay and by ELISA in serum samples taken at the time of the first biopsies, and TGF-beta was determined semiquantitatively by immunostaining of liver biopsy sections. Fibrosis was scored blinded in the biopsy samples by two pathologists independently. There was a close correlation between TGF-beta serum levels and the rate of fibrosis progression. Patients with no progression of fibrosis had significantly lower (59 ng/mL +/- 22) TGF-beta serum levels than patients with progressive disease (115 ng/mL +/- 20), and a TGF-beta level below 75 ng/mL was predictive for stable disease. Immunohistology for TGF-beta in biopsy samples was also predictive for progressive liver disease with fibrosis progression found in those patients displaying staining of hepatocytes and sinusoidal cells. No such correlation was found with other markers such as procollagen III peptide, viral load or transaminase levels. These results further support the role of TGF-beta in liver fibrogenesis, and offer an opportunity to predict clinical disease progression, which may help in selecting patients who are in need of therapeutic interventions.

Alanine Transaminase↗

Long-term management and prognosis of autoimmune hepatitis (AIH): a single center experience.

BACKGROUND: Controlled trials have firmly established the need for immunosuppressive therapy in autoimmune hepatitis. However, reports about long-term management and prognosis of the disease are scarce. PATIENTS AND METHODS: We reviewed the charts of 103 consecutive patients with a well-documented long-term course of autoimmune hepatitis who had been carefully managed over a mean observation period of 95 months (12-405 months). RESULTS: Under immunosuppressive therapy 94 patients (91.2%) reached complete remission after a mean treatment duration of 3 +/- 3 months. 28 of the 103 patients (27.2%) were eligible for a trial of treatment withdrawal after a mean treatment duration of 32.2 months (range: 12-81 months). 21 of these patients (75%) had a relapse following treatment withdrawal. 13.6% of patients had intolerance of or severe side effects to azathioprine. There was no increase in tumor risk during a cumulative observation period of 423 patient-years of azathioprine therapy. Corticosteroid side effects occurred mostly during induction therapy, but were usually minor and resolved upon dose reduction. During a cumulative observation period of 842 patient-years no liver related deaths occurred and no patient had to be referred to liver transplantation, even though 30 patients (29.1%) had histological evidence of cirrhosis at presentation. The overall 5- and 10-year survival of patients with autoimmune hepatitis was identical to an age- and sex-matched control population. CONCLUSION: Our study shows that the majority of patients with AIH do achieve a complete remission within 3 months, but require long-term or permanent immunosuppressive therapy that is usually well tolerated. Long-term survival in well-managed patients is excellent.

Adolescent↗

Autoimmune hepatitis in the elderly.

OBJECTIVES: Autoimmune hepatitis (AIH) is widely believed to be a disease of young women and menopause. Little is known about the frequency and clinical characteristics in patients aged > or =65 yr. METHODS: We reviewed charts of 120 consecutive outpatients with known AIH to identify patients who were diagnosed at the age of 65 or older. These 20 patients (median age, 69 yr) were compared to the same number of younger patients (median age, 24 yr) with well-documented AIH from the same cohort. RESULTS: Seventeen percent (20/120) of our patients were > or =65 yr at the time of diagnosis. In the older patients median time to diagnosis was significantly longer than in the younger patients (8.5 vs 3.5 months). Patients most commonly presented with an acute icteric hepatitis. Complete remission was achieved to a similar extent (18/20 and 17/20 patients). Fewer older patients expressed human leukocyte antigen A1-B8 (p = 0.005). CONCLUSIONS: Diagnosis of AIH often seems to be delayed in the elderly, presumably because AIH is erroneously considered to be a disease of young age. Presentation with acute icteric hepatitis is similar to that of younger patients, supporting the assumption that beneficial effects of hormonal changes associated with menopause are not as pronounced in AIH as in other autoimmune diseases. Human leukocyte antigen type seems to have an influence on the age of onset of AIH. Prognosis is excellent, and AIH should be considered in the older patient to avoid delayed initiation of immunosuppressive therapy.

Aged↗

Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis.

BACKGROUND: Autoantibodies are a hallmark of autoimmune hepatitis, but most are not disease specific. Autoantibodies to soluble liver antigen (SLA) and to liver and pancreas antigen (LP) have been described as disease specific, occurring in about 30% of all patients with autoimmune hepatitis, but no standardised assays are available. Methods We tested 2000 serum samples from patients with various liver diseases and controls for SLA autoantibodies by inhibition ELISA. Serum samples positive for SLA antibodies were used for immunoscreening of cDNA expression libraries. Identified clones were tested against a panel of serum samples positive for SLA and LP autoantibodies and control serum samples, and the epitope mapped by deletion mutants and exonuclease digestion. FINDINGS: SLA and LP autoantibodies were identical. Of 2000 serum samples screened, 35 were positive for SLA autoantibodies. These positive samples came from patients with autoimmune hepatitis; three from patients with an overlap syndrome (primary biliary cirrhosis and secondary autoimmune hepatitis). Expression cloning and absorption experiments identified a 422 aminoacid protein present in two splice variants as the sole target antigen. Aminoacids 371-409 were critical for immune recognition. INTERPRETATION: The identified cDNA encodes the primary target antigen of SLA/LP autoantibodies. The SLA/LP antigen has a previously unknown aminoacid sequence, and presumably codes for an unindentified enzyme, suggested to be UGA-suppressor tRNA-associated protein. SLA/LP autoantibodies are disease specific and recognise a dominant epitope, suggesting a specific antigen-driven immune response. Identification of the SLA/LP target antigen will allow establishment of a reliable, widely available diagnostic assay. Furthermore, its role in the pathogenesis of autoimmune hepatitis can now be studied.

Autoantibodies↗