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Biomedical subjects

J Mueller

Publications and source records attributed to J Mueller.

At least 55 records · Page 3Linked to original sources
PubMed2000

Limited resection for early adenocarcinoma in Barrett's esophagus.

OBJECTIVE: To assess the extent of disease in patients with pT1 esophageal adenocarcinoma and to evaluate the feasibility and outcomes of a limited surgical approach. SUMMARY BACKGROUND DATA: Radical esophagectomy with systematic lymphadenectomy is widely advocated as the treatment of choice in patients with early adenocarcinoma of the distal esophagus. This approach, however, is associated with substantial complications and long-term side effects. The extent of resection necessary to achieve cure in such patients is not clear. METHODS: Seventy-one patients with pT1 adenocarcinoma of the distal esophagus underwent transmediastinal or transthoracic esophagectomy with two-field lymphadenectomy. Twenty-four patients with uT1N0 tumors underwent a limited resection of the distal esophagus and esophagogastric junction, regional lymphadenectomy, and reconstruction by interposition of an isoperistaltic pedicled jejunal segment. The two groups were compared for extent and multicentricity of the primary tumor and associated high-grade dysplasia, pattern of lymph node metastases, complications, deaths, and outcome of surgical treatment. RESULTS: Multicentric tumor growth or associated high-grade dysplasia was observed in 60.6% of the resection specimens. Complete resection of the tumor and the entire segment with intestinal metaplasia was achieved in all patients, irrespective of the surgical approach. Patients undergoing limited resection had fewer complications. Lymph node metastases or micrometastases were present in none of the 38 patients with tumors limited to the mucosa (pT1a) versus 10 of the 56 (17.9%) patients with tumors invading the submucosa (pT1b). Distant lymph node metastases occurred only in patients with more than three positive regional lymph nodes. Lymph node metastases were prognostic, but the pT1a/pT1b category and the surgical approach were not. The mean Gastrointestinal Quality of Life Index after limited resection did not differ from that of healthy controls: 20 of the 24 patients were completely asymptomatic. CONCLUSIONS: In patients with early adenocarcinoma in the distal esophagus, resection of the distal esophagus and esophagogastric junction, with regional lymphadenectomy and jejunal interposition, is an attractive limited surgical alternative to radical esophagectomy.

Adenocarcinoma↗
PubMed2000

Evaluation of c-erbB-2 overexpression and Her-2/neu gene copy number heterogeneity in Barrett's adenocarcinoma.

Amplification of the Her-2/neu gene is accompanied by overexpression of its cell surface receptor product, c-erbB-2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett's adenocarcinoma (BCA) (n = 6) and dysplasia adjacent to the carcinoma (n = 4). In addition, fluorescence in situ hybridisation (FISH) was performed in primary BCA (n = 5) and dysplastic areas (n = 4). For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoral heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogeneous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoral gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her-2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c-erbB-2 protein overexpression and Her-2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c-erbB-2 status in small biopsies and possibly influence the effectiveness of a potential c-erbB-2 targeting therapy. Figures on http://www.esacp.org/acp/2000/20-1/walch.htm+ ++.

Adenocarcinoma↗
PubMed2000

International comparability of the pathological diagnosis for early cancer of the digestive tract: Munich meeting.

Large differences have been found between Western and Japanese pathologists' diagnosis of adenoma/dysplasia versus early carcinoma for gastric, esophageal. and colorectal epithelial neoplastic lesions. In this study we examined whether differences in experience in gastrointestinal pathology can to some extent explain these differences in diagnostic practice. Three Japanese, one British, and two German pathologists with much experience and one North American pathologist with less experience in routine diagnostic work reviewed 52 microscopic slides: 16 gastric, 24 esophageal, and 12 colorectal biopsy and resection specimens obtained from patients with lesions ranging from early carcinoma to adenoma, dysplasia, and regenerative epithelium. The extent of agreement between the diagnoses of the four individual Western pathologists and the most common Japanese diagnoses was assessed by kappa statistics. For the 16 gastric lesions, a diagnosis of suspected or definite carcinoma was made by the Japanese pathologists in 69%-75% of the slides, by three experienced Western pathologists in 56%-63% (high kappa values: 0.61, 0.64, 0.65), and by the less experienced Western pathologist in only 31% of the slides (low kappa value: 0.10). For the 24 specimens of esophageal squamous lesions, carcinoma in situ and suspected or definite carcinoma were diagnosed by the Japanese in 96%-100% and by the Western pathologists in 63%-88% of the slides (low kappa values: 0.17, 0.25, 0.25, 0.27). For the 12 colorectal lesions, the Japanese diagnosed suspected or definite carcinoma in 58%-83%, whereas all Western pathologists followed the World Health Organization definition of colorectal carcinoma and diagnosed suspected or definite carcinoma in only 0-42% of the slides (kappa values: 0.04, 0.10,0.12, 0.49). In conclusion, there were few differences in diagnoses between experienced Western and Japanese pathologists for gastric lesions but considerable differences for esophageal and colorectal lesions. The differences in the diagnosis of adenoma/dysplasia versus early carcinoma between Western and Japanese pathologists found in previous studies may in large part be attributable to differences in experience with regard to gastric neoplasia and to differences in interpretation and nomenclature with regard to esophageal and colorectal neoplasia.

Biopsy↗
PubMed2000

Loss of heterozygosity and microsatellite instability as predictive markers for neoadjuvant treatment in gastric carcinoma.

We analyzed a group of gastric carcinomas treated with a cisplatin-based neoadjuvant chemotherapy regimen for microsatellite instability (MSI) and loss of heterozygosity (LOH) to determine whether there is any relation between microsatellite alterations and therapy response. Pretherapeutic endoscopic biopsies of 37 patients were studied at 11 microsatellite loci. Thirteen (35%) had a complete or partial clinical response (responders), and 24 (65%) had only a minor or no response (nonresponders). High-grade MSI was found in two tumors, both nonresponders, whereas low-grade MSI was found in five biopsies, including three non-responders and two responders. Regarding LOH, the most obvious differences between the groups were observed on chromosome 17p13, the location of the p53 gene, with 7 of 12 (58%) and 3 of 20 (15%) of the informative tumors exhibiting LOH in responders and nonresponders, respectively (P = 0.018). A statistically significant difference was also observed in the fractional allelic loss (FAL) ratio of the groups. Among the 13 responding patients, 7 (54%) tumors exhibited high FAL (>0.5-0.75), 2 (15%) showed medium FAL (>0.25-0.5), and 4 (31%) demonstrated low FAL values (0-0.25), whereas among the 22 nonresponding patients, 2 (9%) tumors showed high FAL, 5 (23%) showed medium FAL, and 15 (68%) showed low FAL (P = 0.020). These data suggest that LOH at chromosome 17p13 is associated with a good clinical response to cisplatin-based chemotherapy, suggesting that altered p53 function might render cells more sensitive to therapy. Furthermore, the association of FAL with therapy response indicates that gastric carcinomas with a high level of chromosomal alteration may be more sensitive to this type of chemotherapy.

Adult↗
PubMed2000

[Morphologic response evaluation of neoadjuvant chemotherapy of gastric carcinoma].

A primary goal of the histopathologic evaluation of the gastric resection specimen is the determination of prognostically relevant factors, but it is not known whether, following neoadjuvant therapy, these factors have the same influence on prognosis. The goal of this study was to investigate prognostically relevant macroscopic and microscopic findings after neoadjuvant chemotherapy. The resection specimens of 36 patients with locally advanced gastric carcinoma who had been treated with Etoposide, Adriamycin and Cisplatin were investigated with respect to tumor size, Lauren type, ypTNM, UICC R-status, lymphangiosis, and degree of regression. On the basis of these factors, a prognosis score was developed that included both the degree of regression (grade 1-3), staging parameters (UICC T-category, R-status), tumor size and lymphatic vessel invasion. All of the parameters were weighted according to a score (1 point--best, 3 points--worst). The points were added for each individual case and the cases were divided into three prognosis groups, Group A: 5-7 points (n = 5), Group B: 8-10 points (n = 15), and Group C: > or = 11 points (n = 16). When compared with survival by the Kaplan-Meier method, these three prognosis groups showed highly significant differences (p < 0.0001). These results demonstrate that it is possible to accurately predict survival using resection specimens following neoadjuvant chemotherapy, which could lead to the identification of subgroups for which additional, further adjuvant therapy might be useful.

Adult↗
PubMed1999

Behavior and occurrence of estrogens in municipal sewage treatment plants--I. Investigations in Germany, Canada and Brazil.

The developed method enables the quantification of estrogens in sewage samples down to 1 ng/l and in river water down to 0.5 ng/l. Mean recoveries of the analytes in ground water after SPE extraction, clean-up and derivatization generally exceeded 75%. The determined R.S.D. varied from 0 to 14% at a spiking level of 0.05 microgram/l. Even in the raw influent and the final effluent from municipal STPs the mean recoveries of estrogens were mostly above 70%. Using this method the behavior and occurrence of natural estrogens and synthetic contraceptives in municipal sewage treatment plants (STP) were investigated in German and Canadian facilities. In the sewage of a German municipal STP close to Frankfurt/Main 17 beta-estradiol and estrone were determined, with mean concentrations of 0.015 microgram/l and 0.027 microgram/l, respectively. In two investigated municipal STPs, 17 beta-estradiol and 16 alpha-hydroxyestrone were eliminated with a higher efficiency than 17 alpha-ethinylestradiol and estrone. In Canadian and German STP discharges estrone, 17 beta-estradiol, 17 alpha-ethinylestradiol and 16 alpha-hydroxyestrone were frequently detected within the lower ng/l-range. A maximum concentration was found for estrone with 70 ng/l. In 15 investigated German rivers and streams only estrone was present with a maximum concentration of 1.6 ng/l.

Animals↗
PubMed1999

Behaviour and occurrence of estrogens in municipal sewage treatment plants--II. Aerobic batch experiments with activated sludge.

Aerobic batch experiments containing a diluted slurry of activated sludge from a real sewage treatment plant (STP) near Frankfurt/Main were undertaken, in order to investigate the persistence of natural estrogens and contraceptives under aerobic conditions. The batch experiments showed that while in contact with activated sludge the natural estrogen 17 beta-estradiol was oxidized to estrone, which was further eliminated in the batch experiments in an approximate linear time dependence. Further degradation products of estrone were not observed. 16 alpha-hydroxyestrone was rapidly eliminated, again without detection of further degradation products. The contraceptive 17 alpha-ethinylestradiol was principally persistent under the selected aerobic conditions, whereas mestranol was rapidly eliminated and small portions of 17 alpha-ethinylestradiol were formed by demethylation. Additionally, two glucuronides of 17 beta-estradiol (17 beta-estradiol-17-glucuronide and 17 beta-estradiol-3-glucuronide) were cleaved in contact with the diluted activated sludge solution and thus 17 beta-estradiol was released. The glucuronidase activity of the activated sludge was further confirmed by the cleavage of 4-methylumbelliferyl-beta-D-glucuronide (MUF-beta-glucuronide) in a solution of a activated sludge slurry and Milli-Q-water (1:100, v/v). The turnover rate obtained was approximately steady state, with a turnover rate of 0.1 mumol/l for the released MUF. Hence, it is very likely that the glucuronic acid moiety of 17 beta-estradiol glucuronides and other estrogen glucuronides become cleaved in a real municipal STP, so that the concentrations of the free estrogens increase.

Aerobiosis↗
PubMed1999

Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations.

E-cadherin, a transmembrane cell adhesion molecule, has been observed to have an altered pattern of immunoreactivity in several types of carcinomas. In lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with immunohistochemistry using the HEC-D1 antibody. Normal protein expression similar to that in the adjacent nonmalignant mucosa was seen in 6 cases, whereas 23 tumours had reduced or absent E-cadherin expression. In the 8 cases with no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis failed to reveal any cDNA mutations despite the negative immunohistochemistry. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein processing levels and mutations in other parts of the gene that were not investigated by the cDNA analysis (e.g. intronic sequences), which could play a role in causing abnormal processing of the E-cadherin protein.

Adult↗