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D Oertli

Publications and source records attributed to D Oertli.

At least 37 records · Page 2Linked to original sources

[Small breast carcinomas--less axillary surgery?].

In view of introducing less invasive or selective axillary procedures for small breast cancers we investigated our own pT1 tumor patients. The incidence of pT1 carcinoma, the nodal involvement of pT1a, b and c, the axillary relapse and the overall survival were analyzed. From 1983 till 1997 185 consecutive patients have been treated for breast cancers with a diameter of < or = 20 mm. The survival data after Kaplan-Meier are based on a cohort of 117 patients with a median follow up of at least seven years. There were seven patients with a pT1a carcinoma, 30 with a pT1b and 148 with pT1c carcinoma. On an average 16 axillary lymph nodes were counted by the pathologists. The axillary involvement clearly depends on the size of the primary tumor: no nodal involvement in patients with pT1a carcinoma, 10% in patients with pT1b carcinoma and 30% in patients with pT1c carcinoma. Not one single axillary relapse was detected after this follow up time. The overall ten years survival for patients with pT1a was 100%, 91% for pT1b, but only 74% for pT1c carcinoma. Screening mammography is expected to detect more small breast cancers in pN0 stage. Risks and benefits of axillary dissection have to be carefully evaluated. Axillary involvement of small breast cancers is rare. Only a minority of patients will benefit from routine axillary lymphadenectomy, while the majority runs the risk of complications. The sentinel lymph node (SLN) procedure offers a selective approach to this dilemma.

Adult↗

Surgical approach to thyroid nodules and cancer.

Fine needle aspiration cytology is the mainstay of the diagnostic work-up of solitary thyroid nodules. Together with the patient's history and the clinical findings, cytology determines the indication for surgery. The minimal intervention for a suspicious nodule consists of thyroid lobectomy. If a diagnosis of malignancy is established, then we recommend total thyroidectomy for all follicular lesions that are larger than 1.5 cm and for high-risk papillary tumours. Near-total thyroidectomy may be appropriate for low-risk patients with papillary carcinoma in whom it is not intended to use radioactive iodine ablation. Whereas ipsilateral lymphadenectomy of the central (primary) compartment should routinely be performed, modified radical neck dissection is only indicated in evident nodal disease of the lateral (secondary) compartment(s). Patients with incidentally discovered differentiated thyroid carcinomas generally do not require complete thyroidectomy unless the tumours are larger than 1.5 cm in diameter or nodal involvement is present. A detailed description of the surgical technique for thyroidectomy and lymphadenectomy is given and an overview of surgical complications is provided.

Frozen Sections↗

[Malignant pheochromocytoma in the 17th week of gestation].

INTRODUCTION: Pheochromocytoma during pregnancy is rare and represents a high risk for mother and fetus. Due to the variable clinical presentation it may be mistaken for preeclampsia. CASE: A 34-year-old primipara with hypertension up to 240/120 mmHg. After diagnosis of a pheochromocytoma its resection together with lymph node metastasis in the 17th week of gestation was performed. CONCLUSION: The definitive diagnosis is confirmed by elevation of serum catecholamines and their metabolites in a 24-h urine collection. Localization during pregnancy can be made by ultrasound and MRI. The definitive treatment is surgical removal after administration of adrenergic blockers. If discovered later in pregnancy, delivery by elective caesarean section followed by tumor resection is recommended. Since about 10 % of pheochromocytomas are malignant, postpartum screening is required to detect and treat extraadrenal or metastatic tumors by MIBG scintigraphy, chemotherapy or surgical procedures.

Adrenal Gland Neoplasms↗

[Hyperthyroidism and thyroid carcinoma--coincidence or association?].

In a series of 617 patients undergoing thyroidectomy, 86 cases (13.9%) were identified as having hyperthyroidism. Forty-nine out of these 86 patients suffered from Graves disease. Histopathologic evaluation revealed a low grade papillary thyroid carcinoma in two out of the 86 specimens from the hyperthyroid patients. Therefore, the incidence of malignancy among all our patients with hyperthyroidism is 2.3% and among those with Graves disease is 4.1%. Patients with hyperthyroidism and concurrent nodular or diffuse goiter are at possible risk for thyroid carcinoma. The indication for surgical resection is given in these cases where the success of thyroistatic treatment is low and where patients are at higher risk for thyroid malignancy. In a short review of the literature, we discuss the coincidence of the two pathologic entities and their possible association.

Carcinoma, Papillary↗

Enhanced generation of cytotoxic T lymphocytes using recombinant vaccinia virus expressing human tumor-associated antigens and B7 costimulatory molecules.

In this work, we addressed the possibility to enhance the "in vitro" generation of CTLs recognizing tumor-associated antigens (TAAs) by using an inactivated recombinant vaccinia virus encoding B7.1 and B7.2 costimulatory molecules (rVV-B7.1/2). Antigen presenting cells (APCs) infected by rVV-B7.1/2 and pulsed with MART-1/Melan-A27-35 HLA-A2.1-restricted peptide induced significantly higher specific cytotoxic activity than peptide-loaded APCs infected by wild-type VV, both in VV-sensitized and naive donors. When APCs were infected with a rVV encoding both MART-1/Melan-A27-35 and B7-1/2 (rVV-B7.1/2-M), a significantly more effective CTL generation was observed as compared with cultures stimulated by APCs infected with a rVV encoding the TAA epitope only (rVV-M). These enhancing effects were detectable irrespective of a previous VV-specific sensitization. Most importantly, fibroblasts, devoid of antigen-presenting capacity upon peptide pulsing or infection with rVV-M, could be turned into effective APCs after infection by rVV encoding TAA epitopes and costimulatory molecules. In these experiments, by using separate recombinant viral constructs, we observed a predominant role of B7-1 as compared with B7-2 in the induction of TAA-specific CTLs. Taken together, our data indicate that replication-incompetent rVV encoding TAA epitopes and costimulatory molecules are able to induce highly effective generation of tumor-specific CTLs. Therefore, these vectors could represent valuable clinical tools for immunotherapy of melanoma patients.

Antigen-Presenting Cells↗

[Is infra-inguinal venous bypass less successful in the woman?].

In the present study the influence of gender in peripheral arterial reconstructions was evaluated. Between 1986 and 1990 we performed 173 infrainguinal vein bypass procedures in 117 men and 56 women. All procedures were carried out for chronic critical leg ischaemia. Bypasses in men were femoral to popliteal in 68%, and femoral to infragenicular in 32% in cases. The corresponding values in women were 52% and 48%. Perioperative 30-day mortality was 2% in men and 2% in women. Long-term survival at 5 years was 50% in men and 44% in women. Life-table primary 5-year patency rates were 81% for men and 74% for women. Limb salvage results at 5 years were 87% for men and 84% for women. The results indicate that in our experience with autogenous vein longterm graft patency and limb salvage results in women are identical to those obtained in men. Infrainguinal arterial reconstruction can be performed in women with mortality rates similar to those of men.

Adult↗

[The Advanced Breast Biopsy Instrumentation (ABBI), a system for stereotactic excision of mammographically suspect nonpalpable findings in the breast].

Advanced Breast Biopsy Instrumentation (ABBI) allows radiologically guided stereotactic excision of non-palpable radiodense lesions with high accuracy. Tissue cylinders of 5, 10, 15 or 20 mm diameter and of variable lengths can be removed very accurately under local anaesthesia and on an outpatient basis. Thirty-six patients with suspicious clusters of microcalcifications (n = 29) and with round lesions (n = 7) of the breast were qualified for ABBI. We were able to perform the excisional biopsy in a total of 34 patients. The breast of one woman was too small to safely fit into the system and in another woman the lesion could not be visualized by the system. In 2/34 cases (6%), the excision was imprecise due to slight dislocation of the breast parenchyma by the advancing cylinder knife. In one case (3%), ABBI missed the target within a dense mastopathic breast. In all cases the excisions were well tolerated. No wound complications occurred and the cosmetic result was excellent. Histology revealed 28 benign (82%) and 6 malignant (18%) lesions. Among the 27 small microcalcifications there were 3 invasive carcinomas, 3 ductal carcinomas in situ (DCIS), 1 lobular hyperplasia, 14 mastopathies, 1 fibroadenoma, 1 duct papilloma and 4 calcifications in scars. Four of the 7 round-shaped lesions were found to be fibroadenomas, 1 lobular hyperplasia, and 2 mastopathies. With the ABBI system, non-palpable breast lesions can be precisely localized and excised.

Adult↗

[Open antireflux surgery].

In over 80% of patients with gastroesophageal reflux disease, the Nissen antireflux fundoplication gives good long-term results. Dysphagia, inability to belch or vomit as well as the gas bloat syndrome are possible sequelae after fundoplication. The frequency of these symptoms could be reduced by modification of the original Nissen-Rossetti fundoplication into the so-called "floppy" Nissen fundoplication, a short and loose wrap of mobilized gastric fundus. Failures of the antireflux procedure are mainly due to disruption or displacement of the wrap with the telescope phenomenon. Here, reoperation with refashioning of the original wrap may lead to same functional results like a primary fundoplication. Technical alternatives may selectively be chosen, when gastroesophageal reflux disease is complicated by fixated hiatal hernia, esophageal shortening, or serious esophageal motility disorders. Such specific anatomic or functional abnormalities are detected by preoperative endoscopy, barium swallow, 24-h pH monitoring, and manometry. Alternative techniques are mainly transthoracic repairs, including the Nissen fundoplication, Collis gastroplasty, and the Belsey Mark IV. Modifications of the 360 degrees Nissen operation are partial fundoplications like the Hill repair and the Toupet dorsal fundoplication. Because of a high failure rate in the long-term follow-up, application of the ligamentum teres cardiopexy and of the Angelchik prosthesis is not recommended.

Follow-Up Studies↗

Efficacy of specific aseptic precautions for preventing propofol-related infections: analysis by a quality-assurance programme using the explicit outcome method.

Specific aseptic precautions have been recommended for preventing infectious complications of propofol because its lipid base can support bacterial growth if contaminated. To study whether the precautions used at our institution prevent propofol-related infections, we retrospectively analysed the data covering 1 January, 1995 until 30 June, 1996 held in our quality-assurance database. The database contains prospectively collected, detailed and standardized information of each patient's risk factors, anaesthetic and surgical data, and postoperative outcome. Surgical patients who had received propofol for anaesthesia did not have a higher incidence of postoperative infection, thus demonstrating the efficacy of our aseptic precautions.

Adult↗

[B7 costimulation molecules improve induction of tumor specific cytotoxic T-cells against MART-1(27-35)].

The expression of B7-1/2 molecules in addition to TAA in APC significantly improves the generation of specific CTL in vitro. Moreover, human fibroblasts, usually devoid of APC capacity, can be engineered into effective APC upon infection with recVV encoding costimulatory molecules together with specific epitopes. The generation of artificial APC by infection of non professional APC with appropriately engineered recVV is a new concept that may be useful in the implementation of immunotherapy strategies.

Antigens, CD↗

[Recombinant vaccinia viruses as efficient vectors of biologically active, human B7 costimulation molecules].

A specific antigenic ligand and a costimulatory signal are required for optimal T cell activation. We constructed and tested recombinant Vaccinia viruses (recVV) expressing hB7-1 or hB7-2 as a gene expression vector system for delivery of costimulatory function in vitro. Upon infection with replication incompetent and non-cytopathic recVV B7, all human tumour cell lines tested expressed the recombinant molecules. Cell lines expressing recombinant B7 molecules provided effective costimulation for proliferation of resting CD4+ T helper cells in the presence of suboptimal PMA concentrations. The costimulatory effect could be blocked with soluble CTLA-4 proteins. RecVV B7-1 infected EBV transformed B-lymphocytes overexpressed the costimulatory molecules resulting in enhanced costimulation. The capacity of these cells to stimulate autologous CD4+ memory cells of VV immunocompetent donors was not impared by the recVV infection indicating an intact capacity for processing and presenting antigenic proteins in the context with MHC Class II molecules remained. RecVV encoding human B7 molecules therefore appear to be promising experimental and clinical tools to enhance immune responses.

B-Lymphocytes↗

[Initial experiences with the Advanced Breast Biopsy Instrumentation (ABBI), a system for stereotactic excision of non-palpable breast lesions].

The advanced breast biopsy instrumentation (ABBI) allows the radiologically guided stereotactic excision of non-palpable radiodense lesions with high accuracy. Forty-six patients with suspicious clusters of microcalcifications (n = 37) and with round lesions (n = 9) of the breast were investigated using the ABBI. Tissue cylinders were successfully removed in 98% of cases. No wound complications occurred and cosmesis was excellent. Histopathology revealed 35 benign (76%) and 11 malignant (24%) lesions. With the ABBI system, non-palpable breast lesions can be precisely localized and excised.

Adult↗

Nonreplicating recombinant vaccinia virus encoding human B-7 molecules elicits effective costimulation of naive and memory CD4+ T lymphocytes in vitro.

We constructed recombinant vaccinia viruses (recVV) encoding the human T-cell costimulatory molecules B7-1 and B7-2. To abrogate the vaccinia virus transcription termination signal for early genes, the cDNA of B7-1 had to be modified by a T through C sense mutation at position 766. Upon infection with replication incompetent and noncytopathic recVV, several tumor cell lines as well as cultured human fibroblasts expressed the costimulatory molecules. All these cells were capable of providing effective costimulation for proliferation of resting CD4(+) T-cells after infection with recVV encoding B7 molecules. The costimulatory effect could be blocked with CTLA-4 IgG fusion protein, the soluble ligand for B7. RecVV-induced overexpression of B7 on syngeneic EBV-transformed lymphoblastoid B-cells was able to costimulate the proliferative response of CD4(+) memory cells against VV antigens. The possibility of easily engineering a variety of human cells using recVV encoding human B7 molecules holds implications for the future design of vaccination strategies.

B7-1 Antigen↗

Generation of tumoricidal cytotoxic T lymphocytes from healthy donors after in vitro stimulation with a replication-incompetent vaccinia virus encoding MART-1/Melan-A 27-35 epitope.

Active specific immunotherapy targeting tumor-associated antigens (TAA) requires reagents of high immunogenicity and safety. To address this issue, we constructed a recombinant vaccinia virus carrying a minigene insert encoding the HLA-A2.1-restricted MART-1/Melan-A27-35 melanoma TAA (rVV-M). To facilitate the entry of the antigenic epitope into the endoplasmic reticulum, a sequence coding for adenovirus E3/19K leader peptide was added. This rVV-M was made replication-incompetent by treatment with psoralen and UV light. Infection with rVV-M rendered HLA-A2.1 EBV-transformed lymphoblastoid cells sensitive to the cytotoxic effects of HLA-class-1-restricted, MART-1/Melan-A27-35-specific cytotoxic T lymphocytes (CTL). The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC). MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses. Infection with rVV-M elicited a higher CTL response than addition of exogenous peptide, whereas, when a similar protocol was used to stimulate PBMC of healthy donors, significant and specific cytotoxic activity could be observed only upon rVV-M infection but not upon exogenous peptide addition. All CTL generated upon rVV-M stimulation were also able to efficiently kill melanoma cell lines expressing both MART-1/Melan-A and HLA-A2.1. In addition, TNF-alpha production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes. This safe and highly immunogenic reagent could be of use in TAA-targeted clinical immunotherapy.

Amino Acid Sequence↗

Induction of antigen-presenting capacity in tumor cells upon infection with non-replicating recombinant vaccinia virus encoding murine MHC class II and costimulatory molecules.

The possibility of inducing antigen-presenting capacity in cells normally lacking such capacity, currently represents a major goal in vaccine research. To address this issue we attempted to generate 'artificial' APC able to stimulate CD4+ T cell responses when tumor cells were infected with a single, recombinant, vaccinia virus (rVV) containing the two genes encoding murine MHC class II I-Ak and a third gene encoding the murine B7-1 (mB7-1) costimulatory molecule. To minimize the cytopathic effect and to improve safety, in view of possible in vivo applications, we made this rVV replication incompetent by Psoralen and long wave UV treatment. Tumor cells infected with rVV encoding I-Ak alone, pulsed with hen egg white lysozyme peptide (HEL46-61), induced IL-2 secretion by an antigen-specific T hybridoma. Tumor cells infected with the rVV encoding mB7-1 provided costimulation for activating resting CD4+ T cells in the presence of ConA. Tumor cells infected with the rVV encoding I-Ak and mB7-1, and pulsed with chicken ovotransferrin peptide (conalbumin133-145), induced a significantly higher response in a specific Th2 cell clone (D10.G4.1) as compared to cells infected with rVV encoding I-Ak molecules only. Thus, this replication incompetent rVV represents a safe, multiple gene, vector system able to confer in one single infection step effective APC capacity to non-professional APCs.

Amino Acid Sequence↗

Artificial antigen-presenting cells engineered by recombinant vaccinia viruses expressing antigen, MHC class II, and costimulatory molecules elicit proliferation of CD4+ lymphocytes in vitro.

The current study was designed to test the ability of recombinant Vaccinia virus (rVV) encoding essential components of an artificial antigen-presenting cell to activate antigen-specific T cells in vitro. We have constructed a set of rVV encoding separately or in combination a CD4+ T cell-specific epitope (the 133-145 peptide of chicken conalbumin), the MHC class II molecule I-Ak, and costimulatory molecules (mB7-1 and mB7-2). Cultured cells infected with rVV encoding both the antigen and the presenting MHC, but not either one alone, could activate cloned CD4+ T cells specific for the virus-encoded epitope. Additional co-expression of mB7-1 and mB7-2 resulted in further enhancement of T cell response. Thus, our rVV vector expressing four different foreign gene products elicited the highest proliferation rates of antigen-specific cloned T cells.

Amino Acid Sequence↗