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G Sauter

Publications and source records attributed to G Sauter.

At least 91 records · Page 5Linked to original sources
PubMed1998

A scientific relational database combined with a report generator for endoscopy in networks: EndoNet.

BACKGROUND AND STUDY AIMS: The flexibility required in academic endoscopy units is not provided by the available database systems. In a project involving substantial cooperation between endoscopists and computer scientists, we have developed an adaptable database, combined with a report generator embedded in the hospital's intranet. PATIENTS AND METHODS: Six workstations in different areas of the hospital were clustered with a UNIX operating system to implement multi-user capability and access control. A relational database was used to design an application appropriate to the specific needs of the endoscopy unit in a teaching hospital engaged in scientific research. Both the terminology used in standardized endoscopy nomenclature and a free text block facility were included. A graphical user interface was developed to assemble pertinent data, generate the reports, and supervise the database. RESULTS: A total of 4936 examinations including 2988 patients were entered consecutively during continuous routine operation of the system. Complete report generation required five minutes (median; range 1-9 minutes). Both structured items and free text were used in all the reports. Querying of the database was possible, concerning matters such as the need for repeated endoscopic therapy in acute gastrointestinal bleeding (4%), the search for Helicobacter pylori in appropriate patients (64%), the rate of accidental pancreatic duct visualization in endoscopic retrograde cholangiography (24%), and links between examinations and active trials (2%). Indicating improved report quality, the number and the diameter of esophageal varices in patients with varices were more frequently reported with the new report system than with previous typed reports (P<0.001). An anonymous questionnaire revealed that the readability of the computer-generated reports was better than that of the previous typewritten reports (P=0.01). CONCLUSIONS: This report describes the creation of a database application and a report generator meeting the needs of scientific and routine use, and the successful application of this system in an academic endoscopy unit.

Computer Communication Networks↗
PubMed1998

Focal neuroendocrine differentiation lacks prognostic significance in prostate core needle biopsies.

PURPOSE: The biological behavior of prostate cancer is highly variable and cannot sufficiently be predicted by histological criteria alone. New prognostic factors are needed in core needle biopsies before initial treatment decisions. We investigate the prognostic significance of focal neuroendocrine differentiation in core needle biopsies of prostate cancer. MATERIALS AND METHODS: Core needle biopsies from 105 untreated patients (mean age 71 years) were immunohistochemically examined for focal neuroendocrine differentiation using an antibody against chromogranin A. Tumor cell proliferation was assessed with Ki-67 labeling index using MIB 1 antibody. The cause of death was determined by examination of records including autopsy reports. RESULTS: Focal neuroendocrine differentiation was found in 25% of the tumors. There was no association between the presence of focal neuroendocrine differentiation and Gleason score or Ki-67 labeling index. Tumor specific survival analysis revealed that high Gleason score and high Ki-67 labeling index were predictors of tumor specific death, whereas focal neuroendocrine differentiation failed to provide prognostic information. There was a significant increase in frequency and density of neuroendocrine differentiation between initial core needle biopsies and later specimens of secondary hormone resistant prostate cancer in 15 patients. CONCLUSIONS: In contrast to high Gleason score and high Ki-67 labeling index, focal neuroendocrine differentiation is not a prognostic factor in core needle biopsies of prostate cancer. Focal neuroendocrine differentiation seems to appear more frequently and intensively in hormone resistant prostate cancer, supporting a role of neuroendocrine cells in the development of hormone refractory disease.

Aged↗
PubMed1997

AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer.

Members of the recently recognized SRC-1 family of transcriptional coactivators interact with steroid hormone receptors to enhance ligand-dependent transcription. AIB1, a member of the SRC-1 family, was cloned during a search on the long arm of chromosome 20 for genes whose expression and copy number were elevated in human breast cancers. AIB1 amplification and overexpression were observed in four of five estrogen receptor-positive breast and ovarian cancer cell lines. Subsequent evaluation of 105 unselected specimens of primary breast cancer found AIB1 amplification in approximately 10 percent and high expression in 64 percent of the primary tumors analyzed. AIB1 protein interacted with estrogen receptors in a ligand-dependent fashion, and transfection of AIB1 resulted in enhancement of estrogen-dependent transcription. These observations identify AIB1 as a nuclear receptor coactivator whose altered expression may contribute to development of steroid-dependent cancers.

Amino Acid Sequence↗
PubMed1997

Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization.

Little is known about the genetic changes underlying invasive tumor growth in bladder cancer. Because alterations that are linked to invasive tumor growth may be detectable in minimally invasive (stage pT1) but not in noninvasive (stage pTa) tumors, we searched for genetic differences between 28 pTa and 28 papillary pT1 bladder tumors by comparative genomic hybridization. Losses of 9q (54%), 9p (39%), and Y (28%) and gains of 1q (14%) were most prevalent in pTa tumors. These changes may play a role in the initiation of noninvasive papillary bladder cancer. The total number of aberrations was higher in pT1 tumors (6.5 +/- 5.4) than in pTa tumors (2.3 +/- 2.1; P = 0.0003), suggesting an increased genetic instability at stage pT1. Specific alterations, which were significantly more frequent in pT1 than in pTa tumors (P < or = 0.05), included deletions at 2q (36% of pT1 tumors), 8p (32%), and 11p (21%) and gains at 1q (54%), 8q (32%), 3p, 3q, 5p, 6p, and 10p (18% each). These loci are candidates for carrying genes involved in invasive tumor growth in bladder cancer. High-level amplifications at 1q22-24, 3p24-25, 6p22, 8p12, 8q21-22, 10p12.1-14, 11q13, 12q15-21, 13q31-33, Xp11-13, and Xq21-22.2 may pinpoint the location of oncogenes with relevance for bladder cancer.

Chromosome Aberrations↗
PubMed1997

p53 protein expression but not mdm-2 protein expression is associated with rapid tumor cell proliferation and prognosis in renal cell carcinoma.

The clinical course of renal cell carcinoma (RCC) is highly variable. Overexpression of the p53 protein has been suggested as a possible prognostic parameter in RCC. Overexpression of the mdm-2 oncogene product has been shown to interact with the p53 function. To investigate the immunohistochemical overexpression of mdm-2 protein in comparison with that of p53 protein in RCC, 50 nonpapillary pT3 RCCs were immunostained for p53 protein (DO-7) and mdm-2 (IF2). Tumor growth fraction (Ki-67 labeling index; MIB-1) was determined by immunohistochemistry. p53 positivity was detected in 16% of tumors. mdm-2 overexpression was seen in 30% of RCCs. There was a significant association between p53 and mdm-2 immunostaining (P = 0.0006), suggesting that mdm-2 protein may contribute to p53 protein stabilization in RCC. p53 overexpression was associated with a high Ki-67 LI (P = 0.0002), suggesting that p53 overexpression is involved in growth control in RCC. Survival analysis showed that Ki-67 LI (P = 0.04) and p53 overexpression were associated with poor prognosis (P = 0.0021), whereas mdm-2 overexpression was not related to patient outcome (P = 0.73). A Cox regression analysis revealed tumor stage (P < 0.001) and p53 overexpression (P < 0.05) to be independent prognostic parameters. It is concluded that p53 but not mdm-2 may be of practical relevance in predicting patient prognosis in RCC.

Carcinoma, Renal Cell↗
PubMed1997

DNA aberrations in urinary bladder cancer detected by flow cytometry and FISH.

Detection of molecular alterations is of potential significance for diagnosis and prognosis in bladder cancer. Fluorescence in situ hybridization (FISH) allows visualization and quantitation of genes and chromosomes on a cell by cell level and can easily be applied to urinary cells. To evaluate the sensitivity of FISH for detection of DNA aberrations in bladder cancer, formalin-fixed tissues of 293 tumors were examined by FISH and flow cytometry (FCM). Centromere probes for the chromosomes X, Y, 1, 7, 9, and 17 were used for FISH analysis. FISH was more sensitive for detection of quantitative DNA aberrations than FCM. An aberration of at least one chromosome was found in 107 of 108 tumors (99%), which were tetraploid, aneuploid, or multiploid, and in 29 of 49 tumors (59%), which were diploid, by FCM. The frequency of FISH aberrations showed greater differences between pTa (47%) and pT1 tumors (85%; P < 0.0001) than between stages pT1 and pT2-4 (98%). The marked genetic difference between pTa and pT1 tumors argues against the concept of grouping pTa and pT1 tumors together as "superficial bladder cancer." The frequency of tumors with chromosomal aberrations detected by FISH increased with the number of chromosomes examined. Aneusomy was seen in 68% of grade 1 tumors examined for > or = 4 chromosomes, suggesting that the cytological diagnosis of bladder cancer recurrences could be substantially improved by FISH.

Carcinoma, Transitional Cell↗
PubMed1997

Preoperative risk assessment of hepatic resection for malignant disease.

Clinical, laboratory, functional, and volumetric data of 340 consecutive patients undergoing hepatic resection for malignant disease between November 1990 and June 1995 were analyzed. The operative mortality was 3.3% (8/244 patients). Among 178 patients with liver metastases and 66 with primary hepatobiliary tumors the hospital mortality was 4.1% (10/244 patients) and morbidity 22.0% (54/244 patients). Survival after hepatectomy was strongly influenced by the extent of resection quantified by the parenchymal hepatic resection rate. The prediction of fatal postoperative complications can be improved for patients with hepatic metastases by calculating the liver resection index (sensitivity 75%, specificity 83%).

Adult↗
PubMed1997

DNA aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma.

Inactivation of the p53 gene plays a key role in tumour biology, probably through a disturbed cell cycle control and an increased genetic instability in p53-inactivated tumours. To learn more about the relationship between p53 alterations, proliferation and genetic instability (DNA aneuploidy) in lung cancer patients, specimens of 220 surgically resected lung carcinomas with clinical follow-up information were examined by immunohistochemistry (p53; CM1) and flow cytometry. Nuclear p53 positivity--found in 49.5% of the tumours--was associated with both high S-phase fraction (SPF) and DNA ploidy aberrations. SPF was higher in p53-positive tumours (15.9 +/- 10.2) than in p53-negative tumours (10.3 +/- 8.7; P = 0.03). The rate of p53 positivity was higher in 101 DNA-aneuploid and DNA-multiploid tumours (55%) than in 27 diploid and peridiploid carcinomas (33%; P = 0.0512). These results are consistent with an in vivo role of p53 inactivation for increased proliferative activity and development of genomic instability in lung cancer. There was no association between SPF and prognosis. Although prognosis was worse in DNA-aneuploid and multiploid tumours than in diploid, peridiploid and tetraploid carcinomas (P = 0.029), DNA ploidy was not an independent predictor of poor prognosis in multivariate analysis. These data show that DNA-flow cytometry has little prognostic value for patients with resected non-small-cell lung carcinoma.

Aneuploidy↗
PubMed1997

Safety and efficacy of repeated shockwave lithotripsy of gallstones with and without adjuvant bile acid therapy.

BACKGROUND & AIMS: The value of adjuvant bile acid dissolution therapy after extracorporeal shockwave lithotripsy (ESWL) of gallbladder stones is under debate. A double-blind, randomized, multicenter trial was conducted to determine the safety and efficacy of repeated ESWL with and without adjuvant bile acid therapy. METHODS: At five centers, 153 patients with gallstones and good gallbladder emptying were randomized to undergo up to six high-energy lithotripsy sessions combined with ursodeoxycholic acid (UDCA, 750 mg/day; n = 77) or placebo (n = 76). RESULTS: Six months after the initial treatment, 77% of patients with small single stones (< or = 20 mm in diameter), 60% with large single stones (> 20 mm in diameter), and 41% with multiple stones were free of stones. Administration of UDCA had no effect on stone disappearance in the whole study group but tended to improve stone disappearance rates in patients with large single stones and tended to decrease biliary adverse effects in patients with multiple stones. CONCLUSIONS: Repeated high-energy ESWL without adjuvant bile acid therapy represents a safe and effective treatment in patients with small single stones and good gallbladder emptying. In patients with large single stones and multiple stones, adjuvant bile acid therapy may be beneficial.

Adjuvants, Pharmaceutic↗
PubMed1997

Epidermal growth factor receptor expression is associated with rapid tumor cell proliferation in renal cell carcinoma.

Epidermal growth factor receptor (EGF-r) expression and tumor cell proliferation rate have been proposed as potential prognostic parameters in renal cell carcinoma (RCC). In this study, immunohistochemical stains using antibodies to EGF-r and the cell proliferation marker Ki-67 (MIB-1) were used to study the relationship between EGF-r expression, tumor cell proliferation, and prognosis in 50 non-papillary RCC extending beyond the renal capsule (pT3). A high Ki-67 labeling index (LI) was associated with poor patient prognosis (P < .05). Thirty-eight cases (76%) expressed strong cell membrane immunoreactivity for EGF-r. There was a tendency toward a shortened survival for EGF-r-positive tumors (P = .08). Tumor growth fraction (Ki-67 LI) was significantly higher in EGF-r-positive tumors than in EGF-r-negative tumors (P < .05), suggesting that rapid tumor proliferation might be responsible for the poor prognosis associated with EGF-r-positive RCC.

Carcinoma, Renal Cell↗
PubMed1997

Cholesterol 7 alpha-hydroxylase activity in hypothyroidism and hyperthyroidism in humans.

Alterations of serum cholesterol levels are well recognized findings in hypothyroidism and hyperthyroidism. It remains unclear, whether thyroid hormones may affect serum concentrations of cholesterol through changes in the activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolic conversion of cholesterol to bile acids. We determined serum concentrations of the bile acid precursor 7 alpha-hydroxy-4-cholesten-3-one, which reflects cholesterol 7 alpha-hydroxylase activity in the liver, in 19 patients with hypothyroidism and in 10 patients with hyperthyroidism before and after treatment, respectively. In patients with hypothyroidism, serum concentrations of cholesterol and LDL-cholesterol decreased by 33% (p < 0.0005) and 39% (p < 0.0005), respectively, after replacement therapy with thyroid hormones. In contrast, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one (21.7 +/- 15.8 ng/ml vs 24.5 +/- 18.1 ng/ml before treatment, n.s.) as well as serum HDL-cholesterol were unchanged during substitution therapy. In patients with hyperthyroidism, serum concentrations of cholesterol and LDL-cholesterol increased by 27% (p < 0.01) and 39% (p < 0.01) after antithyroid treatment, respectively. Again, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one did not change significantly during treatment (15.8 +/- 12.6 ng/ml vs 14.7 +/- 8.1 ng/ml before treatment, n.s.). These findings indicate that in humans, thyroid hormones influence serum lipid concentrations by other mechanisms than by affecting the activity of cholesterol 7 alpha-hydroxylase.

Adenoma↗
PubMed1997

Frequent homozygous deletion of cyclin-dependent kinase inhibitor 2 (MTS1, p16) in superficial bladder cancer detected by fluorescence in situ hybridization.

Deletion of all or part of chromosome 9 is a well-described genetic alteration in bladder tumors. It has been proposed that inactivation of a tumor-suppressor gene on chromosome 9 is an important event in tumor development. Recent reports have supported cyclin-dependent kinase inhibitor 2 (CDKN2, also known as MTS1, INK4, p16) at 9p21 as a candidate tumor-suppressor gene in solid tumors. However, the prevalence of CDKN2 mutations in primary bladder tumors has been controversial. Therefore, we applied gene-specific probes for CDKN2 and the interferon alpha gene (IFNA), also located at 9p21, to characterize further the genomic deletions at this locus in bladder cancer. Seventeen superficial (pTa or pT1) bladder tumor specimens were examined for gene deletion by fluorescence in situ hybridization. Dual-labeling hybridization with a repetitive pericentromeric probe for chromosome 9 and a gene-specific probe for CDKN2 was performed to characterize the gene copy number in relation to the chromosome 9 copy number on a cell-by-cell basis. Homozygous deletion for CDKN2 without homozygous IFNA deletion was found in 5 of 17 tumors tested. Both genes were deleted in one additional case, and one tumor showed deletion of IFNA without deletion of CDKN2. Homozygous deletion at the 9p21 locus was found only in tumors having monosomy for the chromosome 9 centromeric signal. These results indicate that the homozygous deletion of the CDKN2 gene is a frequent and early event in superficial bladder cancer.

Adult↗
PubMed1997

Chromosome 8p deletions are associated with invasive tumor growth in urinary bladder cancer.

Alterations of chromosome 8, including deletions of 8p, occur frequently in many tumors. In this study, fluorescence in situ hybridization was used to study the relationship between 8p deletions, 8q gains, and phenotype in bladder cancer. Cells from 87 tumors were examined by dual-labeling fluorescence in situ hybridization with a centromere 8 probe (pJM12) and P1 probes for 8p22, 8p12, 8q12, and 8q24. Both 8p22 deletions and 8q24 gains were strongly associated with tumor phenotype. There was a marked difference in 8p22 deletions between noninvasive (pTa) tumors (3/33) and minimally invasive (pT1) tumors (8/19; P = 0.005) whereas there was no significant difference between pT1 and muscle-invasive (pT2-4) tumors (19/35; P = 0.3926). Six tumors with 8p22 deletion were examined at 8p12. Three of these tumors showed no 8p12 deletion, narrowing down the site of a putative tumor suppressor gene distal to 8p12. In one other case, there was a marked increase in 8p12 copy number (> 40 per cell; amplification), suggesting the presence of an oncogene involved in bladder cancer at 8p12. The marked difference in 8p22 deletions between noninvasive (pTa) and minimally invasive (pT1) tumors is consistent with a role of a putative tumor suppressor gene on 8p for development of invasive tumor phenotype.

Chromosome Aberrations↗
PubMed1997

[Rudolf Virchow Prize 1997. Molecular cytogenetic analysis of superficial urothelial cancer of the bladder].

Development and progression of urinary bladder cancer is driven by an accumulation of genetic alterations. Most previous molecular and cytogenetic analyses of urinary bladder cancer were focused on advanced tumor stages. To learn more about molecular cytogenetic changes in early bladder cancer stages we analyzed 56 superficial carcinomas of the urinary bladder by comparative genomic hybridization (CGH). CGH is based on the simultaneous hybridization of differentially labeled tumor and normal DNA's to normal metaphase chromosomes. CGH allows the detection of all DNA sequence copy number changes (deletions, DNA sequence copy number gains, amplifications) of a tumor in one examination. Deletions were most frequently found at 9q (20 of 56 patients; 36%), chromosome Y (15 of 43 male patients; 35%), 9p (28%), 11q (16%), 11p (13%), and 10q (11%). DNA sequence copy number gains were most prevalent at 1q (34%), 8q (22%), 17q (15%), 20q (13%), and 12q (11%). There was a significant increase in the number of aberrations with tumor stage (pTa vs. pT1; p = 0.0003) and histologic grade (p = 0.0001). Several specific alterations were significantly more frequent in pT1 than in pTa tumors including deletions at 2q, 8p, and 11p as well as gains at 1q, 3p, 3q, 5p, 6p, 8q, and 10p. These loci are candidates for carrying genes involved in invasive tumor growth in bladder cancer. Overall, these data show that marked genetic differences exist between pTa and papillary pT1 bladder cancer. This challenges the concept of grouping these tumors together in one group as "superficial bladder cancer".

Awards and Prizes↗
PubMed1997

[Genomic changes in urinary bladder cancer].

Recent molecular studies on transitional cell carcinomas (TCC) of the urinary bladder suggest two genetically different tumor types with a varying degree of genomic instability-pTa (grade 1 and 2) tumors are usually "genetically stable". These tumors have rarely p53 alterations and contain only few genomic alterations (deletions, DNA sequence copy number gains, amplifications). Genomic changes in these tumors typically include losses of the chromosomes Y and 9 as well as 1q gains. TCC's with invasive growth pattern (pT1-4) are mostly "genetically instable". They have p53 alterations in about 50% of tumors, and often numerous DNA sequence copy number changes including deletions of 2q, 5q, 6q, 8p and 11p as well as gains at 1q, 3p, 3q, 5p, 6p, 8q und 10p. High level amplifications at various sites of the genome are also frequent in these "instable tumors". They may pinpoint the localization of overexpressed oncogenes. Further studies will have to investigate whether genetic analyses can add useful information to the currently used pathological (pTNM) and clinical (superficial/invasive) classifications of urinary bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1996

Formation of cholic acid and chenodeoxycholic acid from 7 alpha-hydroxycholesterol and 27-hydroxycholesterol by primary cultures of human hepatocytes.

It has been suggested that chenodeoxycholic acid is preferentially formed by the alternative or 'acidic' pathway of bile acid biosynthesis starting with 27-hydroxylation of cholesterol, while cholic acid is derived from 7 alpha-hydroxycholesterol which initiates the 'neutral' pathway. We have studied bile acid formation from each of these precursors using human hepatocytes cultured in a novel sandwich collagen configuration. Culture supernatants were analyzed using capillary gas chromatography and gas chromatography-mass spectrometry. 27-Hydroxycholesterol and 7 alpha-hydroxycholesterol were both found to be efficiently converted to cholic acid as well as chenodeoxycholic acid. Analysis of acidic intermediates after addition of 7 alpha-hydroxycholesterol to the cultures revealed a significant increase of side-chain oxygenated C24- and C27-steroids with a 3-oxo-7 alpha-hydroxy-delta 4-ring structure. These data indicate that (i) the 'neutral' pathway is connected to the 'acidic' pathway by side-chain oxidation of C27-steroids with a 3-oxo-7 alpha-hydroxy-delta 4-ring structure and that (ii) the relative formation of cholic acid and chenodeoxycholic acid is regulated by metabolic events distal to the initial hydroxylation at either position 7 or position 27 of the cholesterol molecule.

Adult↗