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Biomedical subjects

J Mueller

Publications and source records attributed to J Mueller.

At least 37 records · Page 2Linked to original sources

Tricuspid valve dysfunction and surgery after orthotopic cardiac transplantation.

OBJECTIVE: The study examines the prevalence of tricuspid regurgitation and biopsy-induced flail tricuspid leaflets after orthotopic heart transplantation and evaluates the results of the tricuspid valve surgery. METHODS: By a computerized search of the databases 647 of 889 patients who survived heart transplantation for more than 30 days were identified for this study. The primary tool for rejection monitoring in our institution is the daily observation of intramyocardial ECG (IMEG) based on day-by-day changes of the maximal QRS complex amplitude. Endomyocardial biopsy with 45-cm-long sheath bioptome was performed only in doubtful IMEG and echocardiographic data and at times of annual routine heart catheterization. Tricuspid regurgitation was diagnosed clinically and by echocardiography as mild, moderate and severe. Eleven patients received prosthetic valve replacements (four bioprostheses and seven mechanical valves) and six patients underwent valve reconstruction. The choice of xenograft valve was dictated by the condition of renal function. Patient survival and incidence of tricuspid regurgitation and freedom from operation for severe tricuspid regurgitation were analyzed with Kaplan-Meier method. RESULTS: The prevalence of tricuspid regurgitation was 20.1%. Mild and moderate tricuspid regurgitation was seen in 14.5 and 3.1% of the patients, respectively, who were responsive to medical therapy and remained clinically stable in NYHA class I-II. Severe tricuspid regurgitation was seen in 16 (2.5%) patients who presented signs of an acute right heart dysfunction. Tricuspid valve pathology at operation revealed biopsy-induced rupture of the Chordae tendineae at various valve segments mostly the anterior and posterior leaflets. There was one hospital death (<30 day) and five late deaths due to infection, arrhythmia and trauma and no procedural-related or directly cardiac related death. Ten patients (62.5%) are alive at a mean follow-up time of 29.9 months (range 4-81 months) and nine survivors are in NYHA class I-II and one in class III. CONCLUSIONS: Severe tricuspid regurgitation in transplanted hearts is associated mainly with biopsy-induced injury or endocarditis. Other regimes of rejection monitoring may help to eliminate this complication. Apart from our preference of valve repair, the choice of valve substitute may be influenced by the presence or the prospect of chronic renal failure. Heart transplant patients can safely undergo valve surgery with acceptable mortality, low morbidity and excellent intermediate-term clinical results. Mild to moderate functional tricuspid regurgitation is responsive to medical therapy and non-progressive and occur in 17.6% of orthotopic transplanted hearts without having a detrimental effect on the right ventricular performance.

Aged↗

Molecular genetic changes in metastatic primary Barrett's adenocarcinoma and related lymph node metastases: comparison with nonmetastatic Barrett's adenocarcinoma.

Lymph node metastasis is one of the strongest negative prognostic factors for patients with Barrett's adenocarcinoma (BCA). However, despite the importance of the metastatic process in BCA, the molecular basis of it remains poorly understood. To search for cytogenetic events associated with metastasis in regional or distant lymph nodes in BCA, we investigated 8 primary BCA and their lymph node metastases and compared them with 18 nonmetastatic BCA. In metastatic primary BCA, we observed significantly more DNA gains on 3q (P = .013), 17q (P = .019), and 22q (P = .021) compared with nonmetastatic primary BCA. No statistically significant correlation could be observed between DNA copy number changes and the histopathologic stage, grade, or survival (P > .05). The most frequent alteration observed only in lymph node metastases but not in the related primary tumor was loss of 2q (5 of 8). Coamplification of 7p and chromosome 17 was found in 6 of 8 lymph node metastases. A comparison of DNA copy number changes between primary tumors and their corresponding metastases indicated a high degree of genetic heterogeneity. Fluorescence in situ hybridization analysis demonstrated the involvement of the Her-2/neu gene in primary BCA and its related lymph node metastases. Each of the investigated primary tumors and related lymph node metastases also showed striking heterogeneity with respect to Her-2/neu, with several areas displaying different levels of amplification. In summary, our data indicate that DNA copy number changes on 2q, 3q, 7p, 17q, and 22q may be involved in the metastatic process in BCA. Furthermore, the striking genetic heterogeneity that we found between primary BCA and its lymph node metastases may underlie BCA's poor responsiveness to therapy and could help explain why prognostic biomarkers measured exclusively in primary tumors give an incomplete view of the biologic potential of BCA.

Adenocarcinoma↗

In vitro evaluation study of the membrane autotransfusion system experimental prototype: MATS-I.

Membrane Autotransfusion System (MATS) utilizing plasmapheresis technology has been developed in our laboratory. A specially designed polyethylene hollow fiber membrane was utilized. This study was conducted to evaluate performance of the first experimental prototype, MATS-I. The results of this study showed that the MATS-I could concentrate diluted blood at 10% of the initial hematocrit concentration (HCTi) into over 40% after passing through the system at a transmembrane pressure of 70 mm Hg. Moreover, the MATS-I can continuously treat 10,000 ml of diluted blood at various HCTi levels without deteriorating its performances. Even though the MATS-I met all required performances as an autotransfusion system, several areas of improvement of the system were necessary to meet various clinical needs. The next prototype, MATS-II, can be designed based on experiences obtained from the MATS-I. The MATS is smaller, more atraumatic and continuous, and is a faster system when compared to the currently available centrifugal autotransfusion devices.

Animals↗

Stromelysin-3 expression in noninvasive and invasive neoplasms of the urinary bladder.

Stromelysin-3 (ST-3) is a protease frequently expressed by fibroblasts surrounding invasive carcinomas. Based on its expression in some cases of breast carcinoma-in-situ, it has been thought to indicate a higher likelihood for subsequent invasion in preinvasive lesions. Carcinoma-in-situ (pTis) and noninvasive papillary tumor (pTa) of the urinary bladder are preinvasive lesions with an uncertain potential to become invasive. We studied the expression of ST-3 in pTis, pTa, and invasive bladder tumors to see whether it had an association with any established histopathologic variables and whether its expression might be an indicator of incipient invasion in the preinvasive lesions. Twenty-seven pTis, 27 pTa tumors, and 56 invasive bladder carcinomas were studied for ST-3 expression with immunohistochemistry and, in selected cases, with in situ hybridization. Staining for ST-3 was evaluated semiquantitatively. None of 27 pTis lesions, 4 of 27 pTa tumors, and 41 of 56 (73.2%) invasive carcinomas were positive for ST-3. Statistically significant associations were found in the invasive carcinomas between ST-3 expression and lymphatic vessel invasion, an infiltrative invasive pattern, and invasion into at least the muscle layer (pT2,3,4 v pT1). The expression of ST-3 in frankly invasive tumors was associated with a more aggressive tumor phenotype. Its expression in a small subgroup of pTa lesions may be indirect evidence that some tumors diagnosed as pTa have invasive potential.

Aged↗

Impact of cytokeratin-20 and carcinoembryonic antigen mRNA detection by RT-PCR in regional lymph nodes of patients with colorectal cancer.

The reported rates for tumour cell involvement in the locoregional lymph nodes of colorectal cancer vary greatly, depending on the method used and case selection. In order to further evaluate the clinical value of molecular biologic detection of tumour cells we investigated 102 histologically tumour-free (pN0) regional lymph nodes from 51 consecutive, completely resected (UICC R0) colorectal carcinoma specimens for the presence of tumour cell mRNA by RT-PCR specific for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20). Two lymph nodes located nearest to the primary tumour were investigated in each case. CK-20 mRNA was found in 31 of 51 patients (60.8%) and CEA mRNA in 30 of 51 patients (58.8%), respectively. Identical transcription patterns of CK-20 and CEA mRNA (both positive or both negative) were found in 38 of 51 patients (74.5%). There was a significantly higher proportion of cases with CEA positivity in the lymph nodes of tubulopapillary than of mucinous adenocarcinomas (P< 0.03). Detection of CK-20 and CEA mRNA correlated in nine of 12 cases (75.0%) with the risk of tumour recurrence (not significant) and showed a tendency towards shorter disease-free survival by univariate analysis (not significant). Our data indicate that CK-20 and CEA mRNA detection by RT-PCR may prove useful for the prediction of tumour recurrence of patients with pN0 colorectal carcinoma, although neither reach statistical significance in this series of patients.

Adenocarcinoma, Mucinous↗

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↗

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↗

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↗