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Biomedical subjects

M Rothmund

Publications and source records attributed to M Rothmund.

At least 73 records · Page 4Linked to original sources
PubMed2000

Pancreaticoduodenal endocrine tumors in multiple endocrine neoplasia type 1: surgery or surveillance?

BACKGROUND: The management of pancreaticoduodenal endocrine tumors (PETs) remains controversial in multiple endocrine neoplasia type 1 (MEN 1). METHODS: Twenty-one patients with MEN 1 and PETs were analyzed for outcome of surgery and surveillance with special regard to the genotype based on MEN1 gene mutation analysis. RESULTS: Nine patients had gastrinomas, 5 had nonfunctioning tumors, 4 had insulinomas, 2 had insulinomas and gastrinomas, and 1 had a VIPoma. Seven patients (33%) had malignant tumors. Sixteen patients (76%) were initially treated by pancreatic resections or tumor enucleations or both. Six patients underwent reoperations for recurrences or lymph node metastases or both. Fifteen of the 16 operated patients are alive, and 12 have no evidence of disease after a median follow-up of 78 months (range, 1-198 months). Five patients with gastrinomas or nonfunctioning tumors, but no symptoms, underwent surveillance; 1 of them developed lymph node metastases. Patients with truncating mutations in the N- or C-terminal region (exons 2, 9, or 10) of the MEN1 gene had a significantly higher rate of malignant tumors (55% vs 10%; P <.05) than patients with other mutations. CONCLUSIONS: An aggressive surgical approach is justified for PETs in patients with MEN 1. However, MEN1 gene mutations in exons 3 to 8 seem to be associated with mild behavior of PETs, possibly allowing surveillance in asymptomatic patients.

Adult↗
PubMed2000

Multiple primary tumors as an indicator for p16INK4a germline mutations in pancreatic cancer patients?

Multiple primary tumors in pancreatic cancer patients might indicate a genetic predisposition to the development of malignancies. In this study we evaluated whether the mutation rate of the TP53 and p16INK4a genes of pancreatic cancers differs in pancreatic cancer patients with and without multiple primaries. Furthermore, we investigated whether pancreatic cancer patients with multiple primaries carry germline mutations in either p16INK4a, TP53, or BRCA2 tumor suppressor genes to detect a genetic alteration that predisposes to the development of different primaries. Fourteen (23%) of 60 pancreatic cancer patients developed histologically verified additional primaries during their lifetimes. Normal constitutional and tumor DNA of the 14 patients with a positive cancer history, but negative family history, were analyzed for p16INK4a, TP53, and BRCA2 mutations by single-strand conformational variant (SSCV) analysis and direct sequencing. Hypermethylation of the p16INK4a promoter region in pancreatic cancers was identified by methylation-specific polymerase chain reaction (PCR; MSP). Four of 14 pancreatic carcinomas carried somatic intragenic p16INK4a mutations, and another four tumors revealed hypermethylation of the p16INK4a promoter region. Somatic intragenic TP53 mutations were identified in six of 14 tumors. None of the pancreatic cancer patients carried TP53 or BRCA2 germline mutations. In contrast, one of 14 pancreatic cancer patients with multiple primaries carried the p16INK4a mutation A68V in his germline. This mutation was localized in the conserved second ankyrin repeat of p16INK4a and did not occur in 100 control patients. The frequency of somatic TP53 and p16INK4a mutations in pancreatic cancer is similar in patients with and without multiple primaries. TP53 and BRCA2 germline mutations seem not to be significantly associated with the occurrence of multiple primaries in pancreatic cancer patients. However, p16INK4a germline mutations might be causative for tumor development in some pancreatic cancer patients with multiple primaries. The genetic investigation of patients with accumulation of different cancers even without a positive family history may be a new approach for the understanding of the relation of different cancers.

Adult↗
PubMed2000

Low frequency of p16(INK4a) alterations in insulinomas.

BACKGROUND/AIMS: The molecular mechanisms contributing to the tumorigenesis of insulinomas are poorly understood. Disruption of the cell cycle due to inactivation of the p16(INK4a) tumor-suppressor gene was identified in a variety of human tumors, including gastrinomas and nonfunctioning endocrine pancreatic carcinomas. In this study the role of p16(INK4a) in the tumorigenesis of insulinomas was evaluated. METHODS: Seventeen insulinomas (14 benign, 3 malignant) were analyzed for genetic alterations in the p16(INK4a) tumor-suppressor gene by SSCP, PCR-based deletion and methylation-specific assays. p16 expression was determined by immunohistochemistry. RESULTS: One malignant insulinoma showed a homozygous deletion of p16(INK4a) and another two benign insulinomas revealed aberrant methylation of the p16(INK4a) promoter region. All three tumors lacked p16 expression according to immunohistochemistry. None of the insulinomas carried intragenic p16(INK4a) mutations. In total, 17% of insulinomas had p16(INK4a) alterations. CONCLUSIONS: The p16(INK4a) tumor-suppressor gene contributes to tumorigenesis in only a small subset of insulinomas.

Cell Cycle↗
PubMed2000

Hydrogel-based non-autologous cell and tissue therapy.

Many diseases are closely tied to deficient or subnormal metabolic and secretory cell functions. Milder forms of these diseases can be managed by a variety of treatments. However, it is often extremely difficult or even impossible to imitate the moment-to-moment fine regulation and the complex roles of the hormone, factor or enzyme that is not sufficiently produced by the body. Immunoisolated transplantation is one of the most promising approaches to overcome the limitations of current treatments. Non-autologous (transformed) cell lines and allogeneic and xenogeneic cells/tissues that release the therapeutic substances are enclosed in immunoprotective microcapsules. The microcapsules avoid a lifetime of immunosuppressive therapy while excluding an immune response in the host. Research in this direction has shown the feasibility of microcapsules based on hydrogels (particularly of alginate) for transplantation of non-autologous cells and tissue fragments. Numerous technical accomplishments of the immunoisolation method have recently made possible the first successful long-term clinical applications. However, realizing the potential of immunoisolated therapy requires the use of several factors that have received limited attention in the past but are important for the formulation of hydrogel-based immunoisolation systems that are highly versatile, potentially economical and can gain medical approval.

Alginates↗
PubMed1999

[Can diagnostic scoring systems help decision making in primary care of patients with suspected acute appendicitis?].

BACKGROUND AND OBJECTIVE: To assess two recently developed scoring systems with respect to making or excluding the diagnosis of acute appendicitis. PATIENTS AND METHODS: Data on 2359 patients with typical signs of acute appendicitis (AA) were analysed, the results of two diagnostic scoring systems being compared with the diagnosis made by an experienced surgeon. RESULTS: AA was confirmed in 662 of the 22,359 patients (prevalence 28%). Sensitivity, specificity, positive and negative predictive values and overall accuracy for diagnosis with the Ohmann scoring system were 0.63, 0.93, 0.77, 0.86 and 0.84; with the Eskelinen score the values were 0.79, 0.85, 0.68, 0.81 and 0.835; and by the surgeon they were 0.90, 0.94, 0.85, 0.96 und 0.93. The negative appendectomy or laparotomy rate was 14.3 an 12.3 respectively with the Ohmann score, 29.5 and 26.6 with the Eskelinen score. The numbers of potential and of nondiagnosed perforations were 41% and 37% respectively with the Ohman score and 26.6% and 16.3% with the Eskelinen score. The number of missed cases of AA was lowest with the Ohman scoring system, compared with 1.8% for the surgeon. After excluding AA, both scoring systems had a specificity of -0.99, with a positive probability rate of at least 27 (Eskelinen score) up to 87 (Ohman score). CONCLUSION: Both diagnostic scoring systems are better for excluding than correctly diagnosing AA; the decision to exclude could be made with a high degree of accuracy. Either scoring system may therefore be used in primary care of patients suspected of AA to help decide on referral to hospital.

Acute Disease↗
PubMed1999

Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors.

Tumors of the endocrine pancreas are extremely rare, and molecular mechanisms leading to their development are not well understood. A candidate tumor suppressor gene, DPC4, located at 18q21, has recently been shown to be inactivated in half of pancreatic adenocarcinoma xenografts. The close anatomical relationship of the exocrine and endocrine pancreas prompted us to determine the role of DPC4 in the tumorigenesis of 25 pancreatic islet cell tumors (11 insulinomas, nine non-functioning endocrine carcinomas, three gastrinomas, two vipomas). A mutation screening of the highly conserved COOH-terminal domain of DPC4 (exons 8-11) was performed by single-strand conformational variant (SSCP) analysis and a PCR-based deletion assay. Five of nine (55%) non-functioning endocrine pancreatic carcinomas revealed either point mutations, small intragenic deletions or homozygous deletion of DPC4 sequences compared to none of the insulinomas, gastrinomas or vipomas. These results suggest that DPC4 is an important target gene promoting tumorigenesis of non-functioning neuroendocrine pancreatic carcinomas.

Adenoma, Islet Cell↗
PubMed1999

[Validation of a diagnostic scoring system (Ohmann score) in acute appendicitis].

A diagnostic scoring system, recently published by Ohmann et al. in this journal, was validated by analyzing the clinicopathological data of a consecutive series of 2,359 patients, admitted for suspicion of acute appendicitis. The results of the scoring system were compared to the results of clinical evaluation by junior (provisional) and senior surgeons (final clinical diagnosis). To assess the diagnostic ability of the score, the accuracy and positive predictive value were defined as the major diagnostic performance parameters; the rate of theoretical negative laparotomies and that of diagnostic errors served as the major procedural performance parameters. Of 2,359 patients admitted for suspected acute appendicitis, 662 were proven to have acute appendicitis by histology, for a prevalence of 28%. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the provisional clinical diagnosis were 0.50, 0.94, 0.77, 0.83, and 0.82; 0.93, for the score 0.63, 0.93, 0.77, 0.86 and 0.84, and for the final clinical diagnosis 0.90, 0.94, 0.85, 0.96, and 0.93, respectively. Of the main diagnostic performance parameter, the accuracy of the score was significantly better than that of provisional clinical diagnosis (P < 0.05, chi 2 test). The score yielded a rate of negative appendecomies and laparotomies of 14.3 and 12.3%. With respect to the rate of overlooked cases of acute apendicitis, the score demonstrated a superior performance, with only 6 cases missed (0.9%). However, the number of patients with acute appendicitis, including those with perforated disease, who were not identified by the score, was almost four times that of the final clinical diagnosis (245 vs 63). With regard to the main procedural performance parameter, the score resulted in a significantly smaller number of diagnostic errors than the provisional clinical investigator (P < 0.05, chi 2 test). The results of this study indicate that the diagnostic scoring system might be helpful when experienced investigators or additional diagnostic modalities such as ultrasonography are not available. It may therefore be of value in the preclinical evaluation of patients with suspected acute appendicitis and may be instrumental as a quality control tool and in clinical guidelines.

Acute Disease↗
PubMed1999

[Benign ulcer in the gastric tube 9 years after esophagectomy for adenocarcinoma].

Esophagectomy for esophageal carcinoma is associated with significant morbidity. Long-term survival rates are usually poor. Common problems in the early postoperative period are pulmonary complications and leakage at the collar anastomosis causing local infection, sepsis and subsequent anastomotic strictures. There are only a few reports in the literature about benign ulcerations in the gastric tube after resection of the esophagus for carcinoma. We report a patient with a huge benign ulcer in the gastric tube penetrating into the right lung 9 years after esophagectomy for carcinoma. Several aspects of possible etiologic factors and different prophylactic approaches as well as therapeutic aspects are discussed.

Adenocarcinoma↗
PubMed1999

[Reoperations for persistent or recurrent hyperparathyroidism].

Reoperations for persistent or recurrent primary or secondary hyperparathyroidism are demanding tasks mainly when localization of parathyroid tumor(s) was not successful. These procedures may harbor a risk for the patients and therefore need an expert surgeon who is familiar with even the most difficult situation. Important steps before surgery are confirmation of the diagnosis of persistent or recurrent disease and localization of the source of hormone access. Reoperations should be exclusively performed in centers where expert surgeons, radiologists, endocrinologists and nephrologists are available, as well as special technical equipment.

Adenoma↗
PubMed1999

Surgical treatment of pheochromocytomas: laparoscopic or conventional?

BACKGROUND: The use of minimally invasive techniques in the surgical treatment of pheochromocytoma is controversial because of possible intraoperative excessive hormone release resulting in cardiovascular instabilities. METHODS: Laparoscopic adrenalectomy was performed in nine patients with a total of 10 pheochromocytomas. Conversion was required in two cases. The relevant data were prospectively documented and compared with a historical group of nine patients who had undergone conventional transabdominal adrenalectomy for unilateral pheochromocytoma. RESULTS: The laparoscopic operations lasted significantly longer than the conventional procedures (median 243 min vs. 100 min, p < 0.01). Intraoperative cardiovascular instabilities (tachycardia, hypertension) occurred in seven laparoscopically and eight conventionally treated patients. All were easily controlled. Blood transfusions were necessary in four patients in the conventional and one patient in the laparoscopic group. Postoperative hospital stay and duration of analgetic treatment were significantly shorter after laparoscopic adrenalectomy. CONCLUSIONS: Laparoscopic adrenalectomy is a safe procedure for patients with pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1999

[Surgery for thyroid carcinoma].

Despite the low incidence of thyroid carcinoma this heterogenic group of tumors is the most common malignant endocrine disease. The spectrum of virulence in thyroid cancer ranges from a rather indolent course with almost normal survival rates to the most lethal, undifferentiated tumor with survival rates of only few weeks or months. Advances in diagnosis and therapy especially of hereditary medullary carcinoma have been made based on identification of the genetic defect causing the occurrence of this tumor. The key in therapy of thyroid carcinoma is in most of the cases the resection of the thyroid gland.

Combined Modality Therapy↗
PubMed1999

Pleiotropic effects of thyroid stimulating hormone in a differentiated thyroid cancer cell line. Studies on proliferation, thyroglobulin secretion, adhesion, migration and invasion.

Thyroid stimulating hormone (TSH) causes differentiation and epidermal growth factor (EGF) causes dedifferentiation of thyroid cells in vitro. In undifferentiated thyroid cancer cell lines, TSH stimulates tumor cell migration and invasion, a dedifferentiated function, presumably due to an escape of tumor cells from the control of differentiating growth factors. In a highly differentiated thyroid carcinoma cell line of Hürthle cell origin (XTC), we tested the hypothesis that TSH would stimulate thyroglobulin secretion (a differentiated function) more than EGF, and EGF would stimulate invasion (a de-differentiated function) more than TSH. Proliferation, adhesion, cell migration and invasion were measured by the MTT assay, human thyroglobulin by RIA and protease activity by substrate-gel zymography. TSH induced differentiated morphologic changes in XTC cells and stimulated secretion of human thyroglobulin in a dose dependent manner, whereas EGF did not. The effects of TSH on growth, adhesion, migration and invasion were dose dependent and biphasic, with an increase at low and a decrease at high concentrations of TSH. These effects were always more pronounced than those observed with EGE Gelatinolytic activity, consistent with metalloproteinase activity was revealed by zymography, but the pattern of secretion was not altered by neither TSH nor EGF. These results suggest, that TSH has pleiotropic effects on differentiated thyroid cancer cells in vitro that involve differentiated morphology and function but also affect features commonly associated with the malignant in vitro phenotype.

Cell Adhesion↗