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Biomedical subjects

Daniel Oertli

Publications and source records attributed to Daniel Oertli.

25 records · Page 2Linked to original sources
PubMed2003

Multiple endocrine neoplasias type 2A and thyroid medullary carcinoma: an interdisciplinary challenge.

The diagnosis and treatment of multiple endocrine neoplasias type 2A (MEN 2A) requires interdisciplinary management. The association of RET proto-oncogene mutations and medullary thyroid carcinoma (MTC) in children is well-known, but the optimal timing for elective surgery is controversial. Besides the risk of MTC, associated anomalies like hyperparathyroidism have to be considered. We report the results of molecular genetic investigations, the pentagastrin stimulation test, pre- and postoperative staging, and histologic examinations of four children who had a positive family history for MEN 2A. Histologic specimens of the removed thyroid glands showed MTC in all four cases. The patients had an uneventful postoperative clinical course. In view of the recent literature and our patients' results, we suggest a concept for diagnostic strategy and timing of the elective thyroidectomy.

Adolescent↗
PubMed2002

Rapid induction of specific cytotoxic T lymphocytes against melanoma-associated antigens by a recombinant vaccinia virus vector expressing multiple immunodominant epitopes and costimulatory molecules in vivo.

A specific cellular immune response directed against a panel of three defined tumor-associated antigen (TAA) epitopes was induced in metastatic melanoma patients by a prime-boost strategy taking advantage of an innovative recombinant vaccinia virus as evaluated by quantitative assessment of cytotoxic T lymphocytes (CTLs) with corresponding specificity. The immunization protocol consisted of the administration of psoralen-UV-treated and replication-incompetent recombinant vaccinia virus encoding the three immunodominant HLA-A*0201-restricted epitopes Melan-A(27-35), gp100(280-288), and tyrosinase(1-9) together with two costimulatory molecules, B7.1 and B7.2, in the context of systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment. Boosts were subsequently applied with corresponding synthetic nonapeptides and GM-CSF. Specific CTL induction was assessed by tetramer staining and CTL precursor (CTLp) frequency evaluation. Within 12 days of injection of the recombinant vector, cytotoxic T cell responses specific for engineered epitopes were detectable in three of three patients. During the vaccination treatment, antigen-specific CTLp frequencies exceeding 1:10,000 peripheral CD8(+) T cells could be observed. Tetramer staining also revealed significant increases in specific CD8(+) T cell numbers. We conclude that active specific antitumor vaccination can raise a concurrent and specific cellular immune response against a panel of molecularly defined antigens, thereby increasing the chance of an immune hit against neoplastic cells with heterogeneous antigen expression. Data from this study emphasize the potency of a recombinant vaccinia virus vector encoding multiple minigenes and costimulatory molecules in the context of exogenously administered GM-CSF. Clinical effectiveness of this immunologically active protocol should therefore be explored in appropriately selected groups of patients.

Antigens, Neoplasm↗
PubMed2002

Laparoscopic adrenalectomy: the new standard?

PRINCIPLES: Since 1994 we have been removing most non-malignant classified pathologies of the adrenal gland laparoscopically. Does this minimal invasive procedure involve advantages over the conventional approach? METHODS: Retrospective analysis of 22 all-consecutive laparoscopic adrenalectomies in 21 patients (10 women, 11 men, age 26-70 years, mean 43 years, 11 right, 9 left, one bilateral in MEN IIa syndrome). These procedures were performed between 1994 and 2001 transperitoneally in the lateral decubitus position, recently by use of the Ultracision device and once with a handport. These results are compared with 20 consecutive open transperitoneal unilateral adrenalectomies with similar pathologies (13 women, 7 men, age 28-77 years, median 51.5 years, 8 right, 12 left) carried out between 1988 and 1993. RESULTS: The mean operating times were 150 and 115 minutes with the laparoscopic and the open procedure respectively (p <0.011). On the other hand, mean hospital stay (6 versus 15 days, p <0.00001), intraoperative blood loss (200 versus 300 ml, p <0.04) and postoperative need for analgesics were significantly shorter or lower. Two out of the first five laparoscopic operations had to be converted into open adrenalectomy due to intraabdominal adhesions and a diaphragmatic injury with pneumothorax. In both groups three complications occurred (14% and 15%). CONCLUSION: Laparoscopic adrenalectomy is a safe, effective and useful procedure involving a shorter hospital stay, lower intraoperative blood loss and a lower postoperative analgesics requirement compared with the open approach. The laparoscopic approach is the procedure of choice for all benign adrenal pathologies.

Adenoma↗
PubMed2002

Cytotoxic T-cell induction in metastatic melanoma patients undergoing recombinant vaccinia virus-based immuno-gene therapy.

In an ongoing phase I/II study, metastatic melanoma patients were treated with a replication-incompetent recombinant vaccinia virus (rVV) encoding Melan-A(27-35), gp100(280-288), and tyrosinase(1-9) HLA-A*201-restricted epitopes together with B7.1 and B7.2 co-stimulatory molecules. rVV was administered in the context of systemic GM-CSF treatment. Boosts were subsequently administered 2 weeks apart with corresponding synthetic nonapeptides and GM-CSF. Two cycles of treatment were administered 2 weeks apart from each other. Specific immune responses were evaluated by quantitative assessment of cytotoxic T-lymphocyte precursor frequency and tetramer staining. By the time the two cycles had been completed, four out of five patients showed significant (greater than threefold) increases in gp100(280-288)-specific and four out of five, in Melan-A(27-35)-specific tetramer staining of CD8+ cells. Frequencies of CTL precursors specific for gp100(280-288), tyrosinase(1-9) and Melan-A(27-35) were also significantly increased in all five, and in four and four of the five patients, respectively, in some cases within 12 days after the first injection of the recombinant vector. Thus, the innovative vector under investigation is able to raise a concurrent and specific cellular immune response against a panel of molecularly defined antigens, thereby increasing the chance of an immune hit against neoplastic cells displaying heterogeneous antigen expression.

Epitopes↗
PubMed2002

Selective axillary surgery in breast cancer patients based on positron emission tomography with 18F-fluoro-2-deoxy-D-glucose: not yet!

We prospectively evaluated 31 patients with invasive breast cancer. Preoperative positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) for detection of axillary lymph node metastases was compared with the histopathologic status of the sentinel lymph node (SLN). Sensitivity of PET imaging was 43%, specificity and negative predictive value were 94 and 67%, respectively. The smallest metastasis detected by PET measured 3 mm in diameter. The results of this study suggest that detection of small axillary lymph node metastases is limited by the currently achievable spatial resolution of PET imaging. Selective axillary surgery in breast cancer patients based on 18F-FDG PET is yet not possible.

Aged↗
PubMed2002

Disseminated single tumor cells as detected by real-time quantitative polymerase chain reaction represent a prognostic factor in patients undergoing surgery for colorectal cancer.

OBJECTIVE: To evaluate the clinical relevance of real-time quantitative polymerase chain reaction (qPCR) detection of CEA and CK20 transcripts, as potentially related to tumor cell dissemination, in blood and peritoneal lavage from patients undergoing surgery for colorectal cancer. SUMMARY BACKGROUND DATA: Dissemination of single colorectal cancer cells in the peritoneal cavity, as well as in tumor drainage and peripheral blood vessels, might play a role in the metastasis process, thus affecting the clinical course. However, this phenomenon needs further elucidation. METHODS: In a prospective study the authors evaluated the potential of qPCR in the detection of CEA and/or CK20 transcripts in the peritoneal lavage fluid and in the peripheral and mesenteric venous blood of 39 patients undergoing curative resection for colorectal cancer. Peritoneal lavage and peripheral blood was sampled before and after tumor resection; mesenteric venous blood was sampled from the major tumor-draining vein immediately before clamping. After RNA extraction and reverse transcription, qPCR was performed using specific cDNA primers and probes for CEA and CK20. The dichotomous results from the qPCR were used as a predictor along with other covariates in Cox proportional hazard regression models of long-term outcome (disease-free survival and overall survival). RESULTS: Of 39 patients, 11 were positive. The median follow-up at analysis was 31 months for all patients. The dichotomous qPCR covariate was significant, with P =.001 and.0035 for disease-free survival and overall survival, respectively, in the proportional hazard regression models with only qPCR. In seven patients, disseminated colorectal cancer cells were found in the peritoneal lavage fluid but not in blood specimens; five of these patients (71%) had recurrence. CONCLUSIONS: These data suggest that detection of mRNA coding for CEA and/or CK20 using qPCR has potential clinical utility as a prognostic marker and should be evaluated in larger clinical studies. Identification of patients at high risk for metastatic disease after curative resection of colorectal cancer might be improved by analyzing peritoneal lavage specimens in addition to blood samples. This is based on the observation that in more than half of qPCR-positive patients, disseminated colorectal cancer cells were detected in peritoneal lavage specimens but not in blood samples, and that 71% of them had recurrence.

Adult↗