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Biomedical subjects

T Sutter

Publications and source records attributed to T Sutter.

13 recordsLinked to original sources
PubMed2001

Diagnosis and therapy of sporadic and familial medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy. About 75% are sporadic (sMTC) while the remaining 25% are hereditary (hMTC). The treatment of choice for both sMTC and hMTC is surgery. An adequate initial operation provides the best chance of cure. Hence, the diagnosis of MTC should be made preoperatively. In sMTC, ultrasound, ultrasound-guided fine-needle aspiration cytology and measurement of calcitonin levels (basal and after injection of calcitonin-stimulating reagents, e.g., pentagastrin) are sensitive diagnostic tools. In hMTC, identification of a germline mutation in the proto-oncogene RET is sufficient for making the diagnosis. Total thyroidectomy is recommended in all patients, sporadic and hereditary. In addition, lymphadenectomy of the cervicocentral and both cervicolateral compartments should be performed. The only indication to perform a less extensive operation may be given in young patients with hMTC. Sufficient treatment of MTC beyond local disease is still non-existent. Future research should concentrate on this issue.

Adolescent↗
PubMed1999

Repeat mediastinal lymph-node dissection for palliation in advanced medullary thyroid carcinoma.

BACKGROUND: In medullary thyroid carcinoma (MTC), the effectiveness of repeat mediastinal lymph-node dissection for palliation of specific symptoms caused by discrete mediastinal lesions is unclear in non-bulky tumor disease. METHODS: Between November 1994 and August 1998, five symptomatic MTC patients with radiologic evidence of mediastinal tumor and elevated calcitonin levels were subjected to repeat mediastinal lymph-node dissection. RESULTS: At reoperation, an average of 7 of 25 (28%) removed cervical and 5 of 9 (56%) dissected mediastinal lymph-nodes were positive on histopathology. A substantial fraction of these were excised from anatomical regions inaccessible through a purely cervical or partial sternotomy approach. Clinical symptoms were effectively palliated in all five patients. Basal serum calcitonin levels fell only moderately, suggesting distant micrometastases. Mortality was nil. Morbidity encompassed two cases of hypoparathyroidism and a lymphatic fistula that closed spontaneously on total parenteral nutrition. One patient later required cervical reoperation deferred at secondary surgery. All five patients have since remained free of cervical and mediastinal tumor at a mean follow-up of 15 months. CONCLUSIONS: In mediastinal lymph-node metastases, repeat lymph-node dissection is warranted for palliation of discrete anatomic lesions inaccessible through a cervical approach.

Adult↗
PubMed1997

Expression of cyclins D1 and E in human colon adenocarcinomas.

Cyclins D1 and E play critical roles in the progression of cells through the G1 phase of the cell cycle. Amplification and/or overexpression of the cyclin D1 gene and aberrant expression of cyclin E have been described in several forms of human cancer. In the present study, we examined the expression of these two genes by Western, Northern and Southern blot analyses in a series of primary human colon carcinomas of various stages and degrees of differentiation and in paired adjacent normal mucosa samples, and also in a series of human colon carcinoma cell lines. About 50% of the colon carcinomas displayed a two to five fold increase in the expression of cyclin D1 mRNA and protein, when compared with the paired normal mucosa samples. Six out of eight carcinomas examined showed a four to nine fold increase in cyclin E mRNA and about 50% of the carcinomas displayed a two to three fold increase in cyclin E protein. Low molecular weight cyclin E-related proteins were observed in four out of ten carcinomas. These changes in cyclins D1 and E occurred in both early and late stage tumors. Three of the six cell lines examined displayed a high expression of cyclin D1 mRNA and protein. A very high level of cyclin E mRNA expression was seen in HCT116 cells and this was associated with the presence of low molecular weight cyclin E-related proteins. None of the primary colon carcinomas nor the six cell lines examined displayed amplification of either the cyclin D1 or cyclin E genes. Thus, an aberrant expression of both cyclins D1 and E occurs in a significant fraction of human colon carcinomas.

Adenocarcinoma↗
PubMed1996

Increased expression of cyclin D1 and the Rb tumor suppressor gene in c-K-ras transformed rat enterocytes.

Activating mutations in the c-K-ras gene occur in about 40% of human colorectal carcinomas, yet the role of this oncogene in tumorigenesis is not known. We have developed a model cell culture system to study this problem, utilizing the immortalized but non-tumorigenic epithelial cell line IEC18, originally derived from normal rat intestine epithelium. These cells were cotransfected with the drug resistance selectable marker tk-neo and the plasmid pMIKcys, which encodes a mini human c-K-ras gene (15 kb) containing a cysteine mutation at codon 12. Drug resistant clones were isolated. Clones which also expressed the activated c-K-ras gene displayed a transformed morphology, decreased doubling time, increased level of diacylglycerol, anchorage independent growth in soft agar and an aneuploid karyotype and they were also tumorigenic when injected into nude mice. These clones also displayed increased expression, at both the mRNA and protein levels, of cyclin D1 and Rb. These findings may be of clinical relevance since human colorectal tumors also frequently display increased expression of both cyclin D1 and Rb. This model system may be useful for understanding the role and interrelationship between activation of the c-K-ras oncogene and increased expression of cyclin D1 and Rb in colorectal tumorigenesis.

Animals↗
PubMed1996

Frequent K-ras mutations in small bowel adenocarcinomas.

The reasons for the relatively rare occurrence of small bowel adenocarcinomas when compared to the high frequency of colonic adenocarcinomas are unknown. Activating mutations in the K-ras oncogene occur in about 40% of colonic adenocarcinomas, possibly reflecting the consequences of carcinogenic exposure. To study whether the low incidence of small bowel adenocarcinomas might be due to the absence of activation of cellular oncogenes in small bowel adenocarcinomas, we examined the frequency of K-ras mutations in small bowel adenocarcinomas. K-ras mutations were determined using a polymerase chain reaction (PCR)-based method to detect codon 12 mutations by restriction fragment length polymorphism. PCR amplification was successful in six of nine small bowel adenocarcinoma samples, and revealed point mutations of K-ras at codon 12 in five of these six cases. We conclude that the small bowel might be exposed to carcinogens similar to those responsible for colorectal cancer, but may have developed protective mechanisms against cancer formation.

Adenocarcinoma↗
PubMed1996

Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis.

BACKGROUND & AIMS: Cyclin D1 gene amplification and/or overexpression occurs in several human cancers. The level of expression of cyclin D1 protein during the multistage process of human colon carcinogenesis was determined. METHODS: Cyclin D1 protein abundance was determined by immunostaining samples of normal colonic mucosa(n=23), transitional normal mucosa adjacent to adenomas or adenocarcinomas (n=41), hyperplastic polyps (n=8), adenomatous polyps (=35), and adenocarcinomas (n=27), using a polyclonal anti-human cyclin D1 antibody. RESULTS: Cyclin D1 nuclear staining occurred in 30% of adenocarcinomas and 34% of adenomatous polyps but not in hyperplastic polyps or normal or transitional mucosa. Nuclear staining did not correlate with sex, age, size, or dysplasia of the adenomatous polyps or with differentiation and Dukes' staging of the adenocarcinomas. Left-sided colon neoplasms showed nuclear staining more frequently than those right-sided lesions. Diffuse or supranuclear cytoplasmic staining occurred in about one third of hyperplastic polyps, adenomas, and adenocarcinomas and in transitional mucosa adjacent to adenocarcinoma. CONCLUSIONS: Increased nuclear expression of cyclin D1 occurs in around one third of colonic tumors as an early event during multistage process of colon carcinogenesis. Increased expression of cyclin D1 may perturb cell-cycle control in benign adenomas and thereby enhance tumor progression.

Adenocarcinoma↗
PubMed1990

[Long-term results of 370 profunda-plasties].

Three hundred and seventy profundaplasties were performed from January 1977 to December 1987. This procedure was considered indicated in stage IIb in 41%, in stage III in 25.8%, in stage IV in 22.8% and in acute ischemia in 10.4%. The operative mortality was 3%, the five-year-survival rate 53%. Local complications were observed in 12.6%. After 8 years, 76% of the limbs had been saved, although 92 reoperations had been required. According to our experience we consider profundaplasty as an alternative to bypass procedures, especially in multi-level-disease.

Aged↗
PubMed1989

The value of cw-Doppler ultrasonography and DSA in the diagnosis of extra- and intracranial stenosis--a comparison with intraoperative findings.

The use of cw-Doppler sonography and digital subtraction angiography (DSA) for diagnosis of cerebro-vascular insufficiency (CVI) was evaluated in a retrospective study. 113 findings obtained by DSA and 315 findings obtained by cw-Doppler sonography were compared to the corresponding intraoperative finding. Furthermore, we examined the incidence of accompanying intracranial stenoses of the carotid artery. The impact of these stenoses on the CVI stage was analyzed by means of 200 transcranial Doppler sonographic studies. Cw-Doppler sonography (sensitivity: 95%) was clearly superior to DSA (sensitivity: 70%) for diagnosis of high grade and subtotal stenoses of the internal carotid artery (ICA). Sensitivity of both methods was insufficient for diagnosis of low grade stenoses (cw-Doppler: 50%, DSA 25%). Analysis of 200 transcranial Doppler sonographic studies did not reveal pathologic changes of intracranial vessels in 67% of all cases. This finding did not depend on the condition of the extracranial vessels and did also not depend on the CVI stage. Additionally, there was no correlation between the incidence and degree of intracranial stenoses and the CVI stage or the degree of stenosis of the ICA. These results support the view that Doppler sonography is the method of choice for diagnosis of high grade stenoses of the carotid artery. The use of DSA is limited to cases in which kinking or occlusion is suspected. Additional intracranial changes did not correlate with the CVI stage.

Angiography↗
PubMed1987

Correlation of biochemical (receptors, endogenous tissue hormones) and quantitative morphologic (stereologic) findings in normal and hyperplastic human prostates.

In previous light and electron-microscopic analyses human benign prostatic hyperplasia was shown to be predominantly a stromal disease; the aim of the present study was to correlate the stereological data with the levels of the endogenous tissue hormones (androgens, estrogens, progesterone) in normal (N) and hyperplastic human prostatic tissues (BPH). BPH tissue specimens were obtained by open prostatectomy (n = 25); normal prostatic tissue was obtained from kidney donors (n = 5). No statistically significant difference was found between normal and hyperplastic tissue. Testosterone BPH 0.69 +/- 0.44, N 0.25 +/- 0.12; 5 alpha-dihydrotestosterone BPH 7.0 +/- 2.9, N 4.2 +/- 0.7; progesterone BPH 0.059 +/- 0.022, N 0.058 +/- 0.005; estrone BPH 0.10 +/- 0.03, N 0.14 +/- 0.03; estradiol BPH 0.07 +/- 0.02, N 0.05 +/- 0.02; estriol BPH 0.02 +/- 0.01, N 0.04 +/- 0.02. Using a Spearman rank correlation coefficient a statistical analysis was performed for age, weight of the prostate, absolute stereological data and the endogenous prostatic hormones. As can be seen from the statistical analysis there is a poor correlation for 5 alpha-dihydrotestosterone and the amount of the glandular epithelium; otherwise no correlation of the endogenous tissue hormones with the stereological data investigated was found. These data show that the stromal overgrowth of benign hyperplasia is not reflected in the tissue hormone levels.

Gonadal Steroid Hormones↗
PubMedDate not supplied

Relation between number of hemopoietic stem cells in newborn mice and their radiosensitivity.

Fractionation of a radiation exposure causes greater damage in newborn mice than a single application since it induces radioresistant foetal hemopoietic stem cells to differentiate prematurely to more radiosensitive adult ones. In the present investigation, it was studied whether other agents that give rise to extensive stem cell destruction also lead to such a change in radiosensitivity. Indeed, treatment with cytostatic drugs which reduces the number of spleen colony forming units (CFU-s) and total cells also diminished the D0 value of the surviving cells 3 days later. Adriamycin was most effective in causing damage to hemopoietic stem cells and in inducing micronuclei in bone marrow; it also had the most marked action on the D0 of the surviving stem cells.

Aging↗