Search PubMed⌕ Search

Biomedical subjects

A Frilling

Publications and source records attributed to A Frilling.

At least 55 records · Page 3Linked to original sources
PubMed2001

Current status of liver transplantation for treatment of hepatocellular carcinoma.

Hepatocellular carcinoma accounts for more than 5% of all malignancies with a continuous increase worldwide. The most important risk factor is liver cirrhosis, frequently associated with hepatitis B virus or hepatitis C virus infection. Liver resection is the only treatment that can potentially achieve cure. In carefully selected patients with a tumor smaller than 5 cm the 5-year survival is around 50%. The presence of liver cirrhosis and portal hypertension limits the feasibility of hepatic resection. Child-Pugh A patients without major associated risk factors may be considered as the ideal target group for resection. A significant local disease recurrence rate of more than 70% at 5 years is the main problem of hepatic resection. Orthotopic liver transplantation offers the possibility of removing a potentially multicentric tumor and the underlying end-stage liver disease. Due to pure selection of suitable candidates the initial reports on the efficacy of liver replacement in a cohort of patients with hepatocellular carcinoma were disappointing. Taking the shortness of donor organs and the high posttransplant tumor recurrence rate into account, several groups developed criteria qualifying transplantation. A tumor size of >6 cm and gross intrahepatic portal vein involvement seem to be of significant prognostic importance. Patients with smaller solitary tumors or less than 3 tumors with a total tumor diameter of <8 cm have the same survival after transplantation as those with benign liver disease. Living donor liver transplantation offers a new approach to overcome the organ shortage and to theoretically extend the indication for transplantation in hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed2001

[Molecular diagnosis of multiple type 2 endocrine neoplasia].

The paper reviews the data on the molecular structure of the protooncogene RET encoding for receptor-type protein kinase, on the mechanism of transformation of the normal protooncogene RET to a dominant transforming oncogene, and on RET mutations detected in patients with the MEN-2 syndrome. Moreover, it presents the authors' own findings. The familial medullary thyroid carcinoma burdened genealogy shows a new point mutation TCG(Ser)-->GCG(Ala) in codon 891, in the exon 15 of the protooncogene RET. This mutation was not detected in the chromosomes of healthy individuals. Analyzing the linkage with two known and two new polymorphic markers showed that there was a cisaggregation of informative polymorphic markers, phenotypic manifestation of the disease, and mutations in the genealogy in question. In the protooncogene RET, there were two new polymorphisms: G/A at position 24 in intron 14 and C/T in codon 836 (exon 14). The rate of the polymorphism encountered in codon 836 proved to be similar for the Russians and the Germans (0.96%), which was also seen for two earlier described polymorphisms in codon 691 (0.80 and 0.81, respectively) and in codon 904 (0.21 and 0.22). At the same time, there were statistically significant differences in the rates of intron 14 polymorphism (0.87 and 0.77, respectively). In a family having MEN 2, a proband displayed TGC-->CGC mutation in codon 634 of the gene RET in the heterozygous state. The mutation results in substitution of cysteine amino acid residue in the cysteine-rich extracellular domain of protein kinase encoded by the gene RET for arginine. The results of molecular analysis were used to confirm its clinical diagnosis and to indicate that effective care should be delivered in MEN 2a.

Alleles↗
PubMed2000

[Minimally invasive parathyroidectomy with local anesthesia in conjunction with ultrasonography, sestamibi scintigraphy and intraoperative parathyroid hormone measurement].

INTRODUCTION: The standard procedure in patients with primary hyperparathyroidism (pHPT) includes cervical exploration and identification of all four enlarged parathyroid glands. New localization techniques, i.e., ultrasonography associated with color duplex sonography, 99mTc-sestamibi scintigraphy and the possibility of intraoperative parathormone (iPTH) measurement permit minimally invasive parathyroidectomy (MIP). Three different methods have been established: minimally invasive open parathyroidectomy, endoscopic parathyroidectomy and video-assisted parathyroidectomy. We present our experience with open MIP with the patient under local anesthesia (LA). METHODS: In 25 patients with pHPT the operation was started under local anesthesia. Preoperatively, ultrasonography and sestamibi scintigraphy were performed in each patient. iPTH measurement was carried out intraoperatively. RESULTS: In 23 patients (92%) the operation was done successfully in LA. There were no postoperative complications. During follow-up none of the patients developed hypercalcemia again. CONCLUSION: MIP in connection with ultrasonography, sestamibi scintigraphy and intraoperative PTH measurement offers a promising treatment for patients with pHPT.

Adenoma↗
PubMed2000

Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation.

Immunosuppressive therapy in patients after liver transplantation requires careful monitoring of blood levels for immunosuppressive agents such as cyclosporin A. A variety of drugs are capable of interfering with the metabolism of cyclosporin A. We observed a 63-year-old patient who received a liver allograft for cryptogenic liver cirrhosis in 1998. This patient developed severe acute rejection 14 months after transplantation which was associated with a sudden drop in cyclosporin A levels. Two weeks previously, he had started taking the herbal drug Hypericum perforatum (2 x 900 mg/day) for increasing episodes of depression. The cyclosporin A dosage later had to be doubled, which caused some side effects. Finally, an assessment of oral cyclosporin A resorption suggested an enhanced cyclosporin A metabolism. Hypericum perforatum was stopped. Both cyclosporin A dosage and blood levels immediately returned to normal. The liver function recovered completely. In conclusion, this observation is a previously undescribed drug interaction of a widely used herbal drug (Hypericum perforatum, i.e. St. John's wort) in a patient after liver transplantation.

Antidepressive Agents↗
PubMed2000

Absence of H- and K-ras oncogene mutations in sporadic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) occurs sporadically (sMTC) or as part of the inherited cancer syndrome, multiple endocrine neoplasia type 2 (MEN 2). While the occurence of the MEN 2 syndrome is associated with mutations in the RET protooncogene, the reason for carcinogenesis in sMTC still remains unclear. Ras is a frequently mutated oncogene in a broad spectrum of human tumors and has been found in about 50% of follicular, papillary or anaplastic thyroid carcinomas. The purpose of this study was to determine, whether mutations in the ras oncogene could play a possible role in the carcinogenesis of sMTC. In this study we analyzed 15 sMTC for mutations in the hotspots codon 12, 13 and 61 of the H- and K-ras oncogene. We used the direct sequencing technique. In none of the examined tumors we were able to detect a mutation in the codon 12, 13 and 61 of the H-ras and K-ras oncogene. Based upon these results, we conclude that H- and K-ras do not play an important role in the carcinogenesis of sMTC.

Base Sequence↗
PubMed2000

Value of preoperative diagnostic modalities in patients with recurrent thyroid carcinoma.

BACKGROUND: Patients with well-differentiated thyroid cancer (WDTC) regularly have an excellent prognosis. However, tumor recurrence either involving the thyroid bed or the regional lymph nodes, or both, can be associated with significant morbidity and even mortality. The aim of the follow-up after primary surgery is to detect recurrent disease at its earliest stage. We assessed the value of different diagnostic methods in detecting locoregional recurrence in patients with WDTC. METHODS: We prospectively identified 150 patients with WDTC. Of those, 43 (28.7%) presented with recurrent disease. Ultrasonography-guided fine needle biopsy (US-FNB), iodine 131 ((131)I) wholebody scintigraphy, thyroglobulin (Tg) measurement, and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) were carried out. RESULTS: Ultrasonography detected malignant lesions in 95.3% of the patients. The true positive rate of US-FNB was 95.3%. (131)I scanning had true positive, false negative, and false positive results in 54.2%, 40.0%, and 5.7% of the cases, respectively. In 85.7% of the patients, Tg levels were within pathologic range. Among the 13 patients who underwent FDG-PET, 84.6% showed pathologic uptake indicating malignancy. US and US-FNB provided the highest specificity for detecting recurrence (P <.001). CONCLUSIONS: In patients with WDTC and locoregional recurrence, US and US-FNB are the most sensitive methods in detecting local recurrence or regional lymph node metastases. FDG-PET is valuable in case of negative (131)I scanning results and elevated serum Tg levels. The method has limitations in finding minimal disease.

Adult↗
PubMed2000

Increased major histocompatibility complex (MHC) expression in nontoxic goiters is associated with iodide depletion, enhanced ability of the follicular thyroglobulin to increase MHC gene expression, and thyroid autoantibodies.

Recent studies suggest that thyroglobulin (TG) accumulated in the follicular lumen of colloid nodular goiters can increase major histocompatibility complex (MHC) class I gene expression in FRTL-5 thyrocytes. Iodide deficiency, also present in these patients, was separately suggested to enhance thyroidal MHC class I and class II gene expression in vivo and in vitro. To test the clinical relevance of these observations, we examined 41 nontoxic goiters surgically removed from patients who had compression problems. Northern analysis revealed that there was a mean 3.9-fold increase in MHC class I expression and a 8.3-fold increase in class II expression by comparison to 9 normal glands. In situ hybridization showed that thyrocytes were the main source of class I and class II transcripts; histological examination revealed that lymphocytic infiltration was minimal to non-existent. The iodine content of the 41 nontoxic goiters was significantly lower than in normal glands, consistent with increased MHC class I and class II. There is also a profound accumulation of TG in the follicles of the nontoxic goiters, and TG purified from the follicles of these glands increased MHC class I gene expression in FRTL-5 thyroid cells significantly more than TG from normal glands per mg protein. Nearly all patients with nontoxic goiter had low, but significantly elevated, levels of antibodies against thyroid peroxidase and/or against TG in their sera compared with those in normal individuals. Moreover, there was a positive correlation between the titer of the serum antibodies against thyroid peroxidase and against TG and MHC class I and class II expression in the thyroid. The data support the possibility that the TG accumulated in the follicular lumen of nontoxic goiters together with relative iodine deficiency contributes to increased MHC expression in thyroid cells in vivo and that increased MHC gene expression contributes to the ability of thyroid antigens to trigger an autoimmune reaction.

Adult↗
PubMed2000

Telomerase activity in neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors span a rather heterogenic group of tumors, which differ in malignant potential. Very few is known about the tumorigenesis of neuroendocrine tumors. Telomeres seem to stabilize chromosomes and prevent DNA degradation and provide a signal of cellular senescence. During each cell cycle of replication, telomeres are progressively shortened. Non-diseased somatic cells, when the telomere length is reduced to a critical point, exit from the cell cycle and become senescent. In tumor cells, telomere shortening is prevented by the DNA-complex telomerase. Aim of this study was to evaluate the role of telomerase activity in the pathogenesis of neuroendocrine tumors and whether it can be a clinically useful marker for malignant potential. METHODS: Telomerase activity was determined in frozen tissue samples of 31 patients with neuroendocrine tumors by means of the "telomeric repeat amplification protocol" (TRAP)-assay. Classification of the tumors was done by the clinical course and histologic examination. There were 11 benign and 20 malignant neuroendocrine tumors. Telomerase activity was expressed as percentage of the positive control. RESULTS: 25 tumors had a telomerase activity between 0-5% of the positive control (group I), 5 tumors between 5-20% (group II) and 1 tumor over 20% (group II). We were not able to distinct malignant from benign tissue by means of the telomerase activity assay. There was no association with telomerase activity and clinicopathological parameters. CONCLUSIONS: The data indicate that telomerase activity does not seem to be associated with the tumorigenesis of neuroendocrine tumors and can therefore not be used as a suitable marker for malignancy.

Adult↗
PubMed1999

No correlation between RET immunostaining and the codon 918 mutation in sporadic medullary thyroid carcinoma.

INTRODUCTION: Medullary thyroid carcinoma (MTC) occurs sporadically or as part of the inherited cancer syndrome, multiple endocrine neoplasia (MEN) type 2. The MEN2 gene has been identified as the RET proto-oncogene. Mutations in the RET proto-oncogene are associated with the pathogenesis of MTC. Approximately 23-40% of sporadic MTCs (sMTCs) have a somatic RET codon 918 mutation within the catalytic core of the tyrosine kinase, which is a mutation found in over 98% of all MEN 2B cases as a germline mutation. METHODS: In order to elucidate the role of this mutation, we examined 40 sMTCs for the codon 918 mutation. Simultaneously, we looked for overexpression of the RET protein by means of immunohistochemistry with a newly developed RET antibody. RESULTS: In 8 of 40 tumors (20%), we were able to find a RET codon 918 mutation. Nine of 40 tumors (22.5%) showed immunoreactivity with the RET antibody. CONCLUSION: The presence of the somatic RET codon 918 mutations did not correlate with the presence of positive RET immunostaining.

Carcinoma, Medullary↗
PubMed1999

Telomerase activity in benign and malignant adrenal tumors.

Histological analysis of surgically removed adrenal masses often fails to differentiate between benign and malignant tumors. In normal cells, the telomeric ends of the chromosomes are shortened with each cell division, leading to chromosome destabilization and cellular senescence after a critical number of cell cycles. In tumor cells, telomere shortening is prevented by a specific DNA polymerase, called telomerase. In an effort to clarify the role of telomerase in the pathogenesis of adrenal tumors, and to test whether its activity could serve as marker of malignancy, we measured telomerase activity in 41 human adrenal tissue samples that were classified both by the clinical course and by histological examination. Telomerase activity was determined by TRAP ELISA and expressed as high (>50% of positive control telomerase activity), medium (31-50%), low (11-30%), very low (< or = 10%), or absent (0%). The 8 normal adrenal tissue samples showed very low levels of telomerase activity. Mean telomerase activity also very low in 3/3 incidentalomas, 6/6 Cushing adenomas, 6/6 Conn adenomas, 7/7 adrenocortical carcinomas, 8/8 benign pheochromocytomas, and 2/3 malignant pheochromocytomas. In contrast, one malignant pheochromocytoma showed high telomerase activity. These data indicate that telomerase activity may not be a suitable marker for malignancy in the adrenal gland. Our results also challenge the current dogma of close correlation between cell dedifferentiation and telomerase activity.

Adenoma↗
PubMed1998

27-bp deletion in the ret proto-oncogene as a somatic mutation associated with medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) occurs as a sporadic tumor or in connection with the inherited cancer syndromes of multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Missense RET proto-oncogene mutations of one of cysteine codons in exons 10 and 11 are found in the majority of families with MEN 2A and or familial MTC. In MEN 2B, mutations at codon 918, exon 16, have been identified in most of the affected individuals. In a significant amount of sporadic MTC somatic codon 918 mutations appear. In addition to these, a 6-bp deletion including codon 630 and a 24-bp deletion including codon 634 combined with a 6-bp insertion have been observed. We report on a 27-bp deletion in exon 10 as a somatic mutation associated with a sporadic medullary thyroid carcinoma.

Amino Acid Sequence↗
PubMed1998

Treatment of liver metastases in patients with neuroendocrine tumors.

BACKGROUND: Hepatic metastases of neuroendocrine tumors demand differentiated therapeutic management due to the unique natural course and hormone secretion of the tumors. AIM: The purpose of the prospective nonrandomized study was to review the institutional experience with surgical treatment of hepatic neuroendocrine metastases. PATIENTS AND METHODS: From September 1992 until March 1996 29 consecutive patients with neuroendocrine tumors have been evaluated for surgical treatment of liver metastases. Of them, 11 (37.9%) fulfilled criteria for surgical treatment of hepatic secondary tumors. Extensive preoperative workup was carried out. Patients were divided in groups for curative or palliative resection. Liver transplantation was carried out in selected patients with disseminated liver metastases. RESULTS: Of 29 patients 4 (13.7%) underwent curative resection and in 3 patients (10.3%) palliative resection was performed. The patients who underwent curative resection are all biochemically and clinically tumor free at a mean postoperative follow-up of 22.3 months. Two patients who underwent palliative resection are alive at 40 and 29 months, respectively. From 12 patients evaluated for liver transplantation 4 were considered as suitable candidates. CONCLUSIONS: Liver resection can be recommended in patients with hepatic metastases of neuroendocrine tumors in terms of potential survival prolongation and palliation. Liver transplantation is generally acceptable treatment in highly selected group of these patients. Long-term results have to be awaited before definitive proof of the beneficial effect of surgical treatment.

Adult↗
PubMed1998

Use of somatostatin receptor scintigraphy to image extrahepatic metastases of neuroendocrine tumors.

BACKGROUND: The presence of lymph node metastases significantly influences the modality of treatment in patients with liver metastases of neuroendocrine tumors (NET). Somatostatin receptor scintigraphy (Octreo-Scan, Mallinckrodt-Diagnostica, Petten, the Netherlands) is a method for localization and staging NET. The aim of our prospective study was to evaluate the effectiveness of somatostatin receptor scintigraphy in the identification of extrahepatic tumor spread. METHODS: Thirty-five patients with liver metastases of NET were studied over a 5-year period. The presence of NET was confirmed histologically in all cases. To detect extrahepatic metastases or local tumor recurrence, conventional imaging techniques and somatostatin receptor scintigraphy were carried out. RESULTS: In correlation with the findings of conventional imaging methods, somatostatin receptor scintigraphy confirmed liver metastases in all patients. Additionally, 19 of 35 patients (54.2%) had extrahepatic tumor lesions not detected by other imaging techniques. Of those, 15 had extensive abdominal or thoracic lymph node metastases, 3 patients had bone metastases, and in 1 patient with bronchial carcinoid local tumor recurrence was detected. All 19 patients were excluded from further evaluation for liver resection or transplantation and subjected to conservative treatment. The somatostatin receptor scintigraphy sensitivity, confirmed at the time of operation, was 91.6%. In 1 patient, in whom cluster transplantation was performed, somatostatin receptor scintigraphy failed to disclose disseminated carcinosis of the pleural cavity, detected at autopsy (false-negative rate 8.3%). CONCLUSION: In our experience, somatostatin receptor scintigraphy provides a highly sensitive diagnostic method to localize metastases of NET. We recommend somatostatin receptor scintigraphy before liver surgery in every patient with hepatic metastases of NET to identify candidates suitable for resection.

Bone Neoplasms↗
PubMed1998

Mutation of the RET proto-oncogene is correlated with RET immunostaining in subpopulations of cells in sporadic medullary thyroid carcinoma.

Mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, are associated with the pathogenesis of medullary thyroid carcinoma (MTC). Somatic mutations in RET, predominantly at codon 918, and very rarely at codon 883, have been found in a proportion of sporadic MTC. We have previously shown that approximately 80% of sporadic MTCs had at least one subpopulation with a somatic RET mutation. Uneven distribution of somatic mutation within a single tumor or among metastases from a single individual was notable. In the present study, we sought to correlate RET expression, as demonstrated by RET immunohistochemistry, with mutation status in sporadic MTC for each tumor. Seventy evaluable subpopulations, belonging to 28 unrelated sporadic cases, comprising primary MTC and metastases, were immunostained with two different polyclonal antibodies raised against the C-terminus of RET. The regional presence of codon 918 or 883 seemed to coincide with increased RET immunopositivity in at least 62 of 70 (89%, P < 0.000001) tumor subpopulations. The reasons for this concordance are not entirely clear but could be related to either RNA or protein stability. Preliminary studies have suggested that the presence of somatic codon 918 mutation in MTC has a prognostic significance. If these preliminary results prove true, then given our data, we can further explore the feasibility of RET immunocytochemistry as a rapid assessment for the presence of somatic codon 918 for molecular diagnostic and prognostic purposes.

Carcinoma, Medullary↗
PubMed1998

[Detection of H-ras and K-ras in tumors of gastrointestinal-pancreatic system].

The Gastro-Entero-Pancreatic System (GEP) defined a group of highly differentiated neuroendocrine tumors (Insulinomas, Gastrinomas, PP-omas, Somatostatinomas, Carcinoids). In this kind of tumors the multistage carcinogenesis is really unknown. Activated ras oncogenes could play an important role in initiation or process of carcinogenesis in different human cancers. The purpose of our study was to determe if H-ras or K-ras play a role in the carcinogenesis of GEP tumors. 20 paraffin embedded tumor tissues (1 Vipom, 1 Somatostatinom, 10 Carcinoids, 1 Gastrinoma, 4 livermetastasis of a Carcinoid, 3 Insulinomas) were analysed immunohistologic of H-ras and K-ras oncogene protein expression. Immunohistologic investigations showed a H-ras expression in 65% (13/20). K-ras protein could detected in 10% (2/20). On the basis of these data H-ras oncogene expression could play a role in the multistage carcinogenesis of GEP tumors.

Carcinoid Tumor↗
PubMed1998

[A new inherited RET proto-oncogene mutation associated with familial medullary thyroid carcinoma and polymorphisms in adjacent regions].

A new point mutation, TCG(Ser)-->GCG(Ala) in codon 891, exon 15 of the RET protooncogene was revealed in two patients from a pedigree with familial medullary thyroid carcinoma (FMTC), but not in healthy persons. A linkage analysis with two well-known and two new intragene polymorphisms showed that informative polymorphic markers, the phenotypic expression of the disease, and the mutation are cosegregated in the studied pedigree. Two new polymorphisms, G/A at position-24 of intron 14 and C/T in codon 836 of exon 14, were found in the RET protooncogene. The frequencies of allele 1 of the polymorphic site in codon 836 were the same (0.96) in the Russian and German populations. This was also characteristic of two polymorphisms revealed earlier, namely, the sites in codons 691 (0.80 and 0.81, respectively) and 904 (0.21 and 0.22). However, the frequency of allele 1 of the polymorphisms in intron 14 differed significantly (0.87 and 0.77, respectively).

Carcinoma, Medullary↗