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C Wittekind

Publications and source records attributed to C Wittekind.

At least 109 records · Page 6Linked to original sources
PubMed1997

K-RAS-2 gene mutations as predictors of metachronous colorectal adenomas.

BACKGROUND: Mutations of K-RAS-2 gene and tumour suppressor genes have been found in both colorectal adenomas and carcinomas. The aim of this study was to investigate the prognostic value of K-RAS-2 gene mutations found in initial colorectal adenomas for predicting the risk of metachronous adenomas. METHODS: Genomic DNA was extracted from formalin-fixed and paraffin-embedded adenomas larger than 5 mm in diameter removed at the initial total colonoscopy between 1980 and 1982. All patients underwent colonoscopic follow-up for at least 10 years. The sequence of exon 1 of the K-RAS-2 oncogene was amplified with the polymerase chain reaction technique and screened for mutation by single-strand conformation polymorphism analysis. All suspected mutations were confirmed by direct DNA sequencing. The predictive value of K-RAS-2 gene mutations for the risk of metachronous adenomas was assessed by chi-square testing and logistic regression analysis. RESULTS: Of 54 patients 39 (72%) were male and 15 (28%) female. At the time the initial adenoma was removed, 31 (57%) patients were younger than 60, whereas 23 (43%) were 60 years or older. Point mutations of the K-RAS-2 oncogene were found in the index adenomas of 15 (27.7%) patients. Mutations were found more frequently in large (> or = 20 mm) adenomas and in adenomas with severe dysplasia (P = 0.0011 and P = 0.0310, respectively). There were no significant associations between K-RAS-2 mutations and anatomic location, histologic type, or number of synchronous initial lesions. Mutations were found predominantly at codon 12 with transversions from GGT to GTT (57%), from GGT to GAT (36%), and from GGT to TTT (one patient). The single mutation found at codon 13 showed a transversion from GGC to GAC. There were significant associations between size (> or = 20 mm) and K-RAS-2 mutation of the initial adenomas and the size (> 5 mm) of metachronous adenomas (P = 0.0259 and P = 0.0265, respectively). However, multivariate analysis showed that K-RAS-2 mutations did not provide a significant additional contribution to the prognostic value of the size of the initial adenoma (odds ratio, 7.62; 95% confidence interval (CI), 1.68-34.48) and the amount of villous structure (odds ratio, 0.22; 95% CI, 0.05-0.90) it contained. CONCLUSIONS: Patients with large (> or = 20 mm) adenomas and adenomas with K-RAS-2 mutations found at the initial examination have a significantly higher risk of developing large (> 5 mm) metachronous adenomas during surveillance. Multivariate analysis of initial adenoma characteristics showed that the risk of metachronous colorectal adenomas can be adequately estimated by the size and the histologic type of the largest initial adenoma and that K-RAS-2 mutations are of secondary importance only. Further studies based on a larger series will have to identify the adenoma characteristics that will help to improve follow-up strategies.

Adenoma↗
PubMed1997

Melanosis coli--a harmless pigmentation or a precancerous condition?

UNLABELLED: Melanosis coli has long been considered as a harmless pigmentation of the colorectum associated with the use of laxatives containing anthraquinone. Recent experimental and clinical studies, however, have provided some evidence of a possible association between melanosis coli/laxative use and colorectal cancer. METHODS: In 2.229 consecutive patients we retrospectively analyzed the association of melanosis coli and laxative use with colorectal neoplasia. All the patients had undergone total colonoscopy, and the colorectal neoplasias had been examined histopathologically in accordance with the WHO classification. Information concerning laxative use, bowel habits and family history of colorectal cancer was obtained from the medical records. The statistical analysis was done using the Mantel-Haenszel-test for linear association. RESULTS: The presence of colorectal cancer was not associated with melanosis coli or laxative use. However, colorectal adenomas were found significantly more frequently in patients with melanosis coli than in those without melanosis (p = 0.0002). But adenomas associated with melanosis coli were significantly smaller than those not associated with melanosis (p < 0.0001), and were located predominantly in the proximal colon (p = 0.0002). In the patients with melanosis coli the relative risk was significantly higher for tubular (1.80; 95% CI: 1.26-2.56) and tubulovillous adenomas (2.03; 95% CI: 1.09-3.76), but not for villous adenomas. No significant differences were found in the grade of dysplasia of adenomas in patients with, and those without, melanosis coli. CONCLUSION: There appears to be no association between colorectal cancer and melanosis coli or laxative use. Colorectal adenomas are more frequently found in patients with melanosis coli. Colorectal adenomas do not contain the melanin-like pigmentation. The association of adenomas with melanosis coli can be explained by the ease of detection of even tiny polyps as white spots within a dark-colored colonic mucosa.

Adenoma↗
PubMed1997

The prediction of lymph node metastases in colorectal cancer by expression of the nucleoside diphosphate kinase/nm23-H1 and histopathological variables.

OBJECTIVE: To ascertain the risk of locoregional lymph node metastases from colorectal cancer, we compared microscopic pathological characteristics of the primary tumor with the expression of the nm23-H1 protein. METHODS: The nm23-H1 expression of 100 colorectal carcinomas and corresponding non-neoplastic mucosa was analyzed immunohistochemically at the time of primary curative surgery (R0 resection). Conventional histopathological factors (depth of infiltration, grade of differentiation, invasion of lymph vessels or veins) that are proven indicators for metastatic involvement of locoregional lymph nodes were examined in all cases. RESULTS: Of 45 tumors with lymph node metastases, 42 (93%) had a low nm23-H1 expression whereas only 35 (78%) were of high-risk histology (G3, G4, or lymphatic invasion). Therefore, nm23-H1 expression within the primary tumor indicated the lymph node status with a sensitivity of 93% and a negative predictive value of 92%. The classic pathohistological factors (high risk vs low risk) had a sensitivity of 78% and a negative predictive value of 77%, respectively. CONCLUSION: Reduced expression of nm23-H1 within primary colorectal carcinomas could serve as an additional independent marker in estimating the nodal metastatic potential of these tumors.

Antigens, Neoplasm↗
PubMed1997

[Adrenal gland incidentaloma is not a "time bomb"--arguments for follow-up control].

Adrenal masses are nowadays more and more diagnosed incidentally. In the vast majority of cases these "incidentalomas" are benign adrenocortical adenomas which do not compel operative therapy. In about 12% of patients an endocrine activity is detected. With Increasing tumor size the risk of malignancy increases. This article summarizes recommendations, only to allow patients with endocrine activity or an increased risk of malignancy to be selected for surgery. A small uncertainty will always remain, but may be minimized by an individually tailored follow-up.

Adrenal Gland Neoplasms↗
PubMed1996

Impact of arterialization on hepatic oxygen supply, tissue energy phosphates, and outcome after liver transplantation in the rat.

The importance of arterial reconstruction in experimental orthotopic rat liver transplantation is widely acknowledged in the literature. Non-rearterialization of the graft leads to impaired microcirculation and, in chronic models, to severe hepatobiliary damage, together with bile duct proliferation and fibrosis in such livers. The aim of the current study was to investigate the impact of rearterialization on hepatic oxygen tension (pO2), hepatic tissue content of adenine nucleotides, early graft function, and postoperative outcome. Orthotopic liver transplantation was performed in 27 male inbred rats. Ten rats underwent rearterialization and while 17 did not. A group of sham-operated animals (n = 6) served as controls. After reperfusion, liver grafts without arterial reconstruction showed significantly reduced levels of oxygen tension (mean +/- SD, 3.79 +/- 2.20 vs. 10.03 +/- 2.84 mmHg; P < 0.05) and a clear shift toward lower pO2 values in the pO2 histograms, as compared with arterialized grafts. Without arterialization, the level of liver ATP was 65% of that in sham animals, compared with 84% in arterialized livers. Without arterialization, bile secretion was reduced (0.42 +/- 0.04 vs. 0.71 +/- 0.06 mg/min x g liver; (P < 0.001), and the postoperative course of serum alanine transaminase, bilirubin, and alkaline phosphatase revealed severe hepatobiliary damage. These findings allow us to conclude that graft rearterialization is essential to ensure both an adequate oxygen supply and maintenance of tissue ATP. Arterialization may thus be a necessary part of liver transplantation models in this animal species, and should be considered when designing studies on the biochemical, microcirculatory, and histopathological status of the graft.

Adenine Nucleotides↗
PubMed1996

Posttraumatic aneurysm of the right atrium.

We report on an acquired right atrial false aneurysm, which was removed under extracorporeal circulation. The patient remembered three occasions of blunt chest trauma with rib fractures. Clinical symptoms were ongoing dyspnea, chest pain, and atrial fibrillation.

Aneurysm, False↗
PubMed1996

[The development of metastases and their classification].

PURPOSE: The process of metastasis has been elucidated by thorough morphological studies on resection specimens and new findings in the field of molecular biology in recent years. The successful surgical removal of distant metastases lead to the necessity of a detailed and precise classification system of distant metastases. PATIENTS AND METHODS: The new molecular findings as well as data obtained from morphological studies and the results of a international field study on behalf of the UICC lead to the proposed system presented here as a new classification system for metastases. RESULTS: A general classification of distant metastases of any primary tumor should separate 5 different categories: M1 for non-regional lymph node metastases only, M2 for liver metastases only, M3 for lung metastases only, M4 for bone metastases only and M5 for metastases in 2 or more of these organs or others. In case of liver metastases of colorectal carcinoma, 2 different classifications were proposed; a clinical classification based on locoregional tumor status, number of liver metastases and involved lobes and a post-surgical classification depending on locoregional tumor status and size of metastases removed surgically and assessed by the pathologist. CONCLUSION: More detailed knowledge of the metastatic process and success in surgical treatment makes a detailed and exact classification system for distant metastases essential. This should be used as a fundamental base for future therapeutical and prognostic studies.

Classification↗
PubMed1996

Expression of c-erbB2 oncogene product in different tumours and its standardised evaluation.

In order to evaluate the reliability and reproducibility of the immunohistochemical demonstration of the c-erbB2 oncoprotein and define criteria for positivity assessment in paraffin-embedded material from different tumours, we examined immunohistochemically 79 gastric, 100 colorectal and 20 bladder carcinomas using 5 different c-erbB2 antibodies. To determine criteria for the evaluation of c-erbB2 positivity, the observed immunohistochemical staining was compared with the actual protein prevalence, determined by Western blot analysis of each tumour. The comparison of protein levels obtained from Western blot with corresponding immunohistochemistry revealed that positive staining can only be considered to be specific for c-erbB2 oncoprotein if: (i) there is a definite staining along the tumour cell membrane with no predominant immunoreactivity inside the tumour cell cytoplasm, (ii) the intensity of immunoreactivity is comparable with a positive standard (e.g. in this study breast carcinoma) and (iii) the surrounding normal, non-neoplastic tissue shows no immunoreactivity. The graduation of staining intensities did not correlate to the actual amount of protein detected in Western blots. This study stresses the importance of defined and controlled criteria for evaluation of c-erbB2 oncoprotein positivity in immunohistochemistry.

Blotting, Western↗
PubMed1996

[Principles of lymphogenic and hematogenous metastasis and metastasis classification].

The process of lymphatic and hematogenous metastasis has been elucidated in recent years by thorough morphological studies on resection specimens and new findings in the field of molecular biology. However, this process is far from being completely understood. Metastasis is a multistep process requiring numerous interactions of tumor cells with the surrounding matrix. Especially, adhesion, invasion of basement membranes and passage through extracellular matrix are active processes taking place in the tissue of the primary tumor and later on in host tissues. Metastases to distant organs can be the result of a venous invasion of the primary tumour as well as lymphovenous short-circuits or by the thoracic duct. Using immunohistological methods, tumor cells can be detected in lymph nodes, blood and bone marrow. This not termed metastasis, these cells are classified as isolated tumor cells (M1(i)). The frequency of lymph node metastasis depends on the intensity of histological examination. In colorectal carcinomas the risk of metastatic lymph nodes can be estimated by conventional parameters such as pT category of the primary tumor, histological grade or invasion of lymphatic vessels. The benefit of applying molecular markers (such as nm23-H1) is unclear. The successful removal of hepatic metastasis of colorectal carcinomas requires a more precise classification. A proposal of a more detailed and clarified classification will be discussed.

Humans↗
PubMed1996

K-ras point mutations are rare events in premalignant forms of Barrett's oesophagus.

OBJECTIVE: In Barrett's adenocarcinomas, in contrast to squamous oesophageal carcinomas, K-ras point mutations are thought to be a frequent event. The frequency of K-ras point mutations in premalignant forms of Barrett's oesophagus (metaplasia, dysplasia) leading to adenocarcinoma with increased risk is currently not known. To establish the frequency of K-ras mutations in premalignant forms of Barrett's oesophagus, we investigated oesophageal biopsy specimens with Barrett's metaplastic and dysplastic epithelium for point mutations in the K-ras gene/codons 12, 13. DESIGN: A total of 412 biopsies from patients with Barrett's oesophagus were histologically classified into biopsies with metaplasia (n = 252), dysplasia (n = 105) and adenocarcinoma (n = 11), as well as biopsies distant from disease (normal, n = 37 and hyperplastic squamous epithelium, n = 7). METHODS: DNA from biopsy specimens was amplified by polymerase chain reaction (PCR) with a modified primer for generating a restriction site in the case of wild type in codon 12. Wild-type or point mutations in the K-ras gene/codons 12, 13 were detected by restriction fragment length analysis of the PCR products. RESULTS: Point mutations in K-ras/codon 12 were found in 9 biopsies (n = 1 in metaplasia, n = 4 in dysplasias, n = 4 in adenocarcinomas). All the other biopsies showed the wild type of K-ras/codon 12. No K-ras/codon 13 mutation (GGCgly-->GACasp) was observed. CONCLUSION: Mutations in K-ras/codon 12 were rarely found in premalignant forms of Barrett's oesophagus. Whereas the screening for K-ras point mutations in metaplastic sites of Barrett's epithelium seems not to be of practical value, the screening for mutations in dysplastic lesions might be helpful to estimate the individual risk for progression of Barrett's epithelium to adenocarcinoma. A further evaluation in larger numbers of patients is needed.

Adenocarcinoma↗
PubMed1995

Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma.

PURPOSE: Reduced expression of the metastasis suppressor gene nm23-H1 has previously been correlated with high tumor metastatic potential and fatal clinical outcome in some tumors (e.g., breast). For colorectal carcinomas, the findings are equivocal. METHODS: We have used a monoclonal antibody against nm23-H1 to investigate the expression in colorectal carcinomas at the time of primary curative surgery (R0 resection) to assess if there was any relation between nm23-H1 expression and stage or histologic grade at the time of primary tumor removal. RESULTS: Of 100 colorectal carcinomas studied (Stages I, II, and III according UICC, all resected curatively), nm23-H1 immunoreactivity was weak in 41 (41 percent), moderate in 24 (24 percent), and strong in 35 (35 percent) cases. The grade of positivity against nm23-H1 was significantly lower in advanced stages of the disease (Stages II or III) (P < 0.001, chi-squared = 52.8). In tumors with low or weak immunoreactivity against nm23-H1, frequency of lymph node metastases was significantly higher compared with those with moderate or strong staining (P < 0.001; chi-squared = 50.58). Therefore, with a sensitivity of 93 percent and a specificity of 58 percent, low nm23-H1 immunoreactivity of the primary tumor, assessed at the time of surgery, is an indicator of the presence of lymph node metastases. CONCLUSIONS: Immunohisto-chemical evaluation of nm23-H1 in the primary tumor or in a biopsy is a useful predictor of stage of disease and presence of lymph node metastases in colorectal carcinomas and may have clinical significance, e.g., in predicting optimal therapeutic regimes.

Biomarkers, Tumor↗