PubMed Health⌕ Search

Biomedical subjects

Urs Haller

Publications and source records attributed to Urs Haller.

12 recordsLinked to original sources

Patients' satisfaction with the preoperative informed consent procedure: a multicenter questionnaire survey in Switzerland.

OBJECTIVE: To assess patients' satisfaction with the preoperative informed consent procedure in obstetrics and gynecology. PATIENTS AND METHODS: Between March 2001 and April 2002, patients from 11 Swiss hospitals, representing 3 linguistic areas of Switzerland, were given a questionnaire and a standardized operation-specific leaflet and engaged in a structured conversation. The questionnaire and operation-specific leaflet were designed in collaboration with the Swiss Patient Organization, the judiciary service of the Swiss Medical Association, and the Swiss Society of Obstetrics and Gynecology. RESULTS: A total of 3888 (56%) of 6970 women received the questionnaire and were enrolled in the study. Most of the patients considered the written and oral information to be good or excellent, and more than 80% did not desire further written information. Forty-five percent would have preferred to receive this structured Information the same day the decision to undergo an invasive procedure was made, and mere than half of the patients were reassured by the information provided. However, in 7% anxiety increased. In the multivariate analysis, Turkish (odds ratio [OR], 6.7; 95% confidence Interval [CI], 2.0-22.4; P=-.002) and Serbo-Croat (OR, 8.0; 95% CI, 2.4-27.4; P=.001) language and a poor rating of the written description of the planned operation (OR, 3.1; 95% CI, 1.1-9.0; P=-.03) were the only variables significantly associated with discontent. CONCLUSIONS: The combined written and oral preoperative information presented is well adapted to patients' Informative wishes and needs; it allows for a structured conversation, facilitates documentation, and offers valid legal proof that adequate information has been provided. Therefore, close collaboration between the national patient organization and the expert Judiciary and medical societies of the corresponding country is strongly recommended to Improve the Informed consent procedure.

Adolescent↗

Catamenial pneumothorax revisited: clinical approach and systematic review of the literature.

BACKGROUND: Catamenial pneumothorax is a rare entity of spontaneous, recurring pneumothorax in women. It has been associated with thoracic endometriosis, yet varying clinical courses and the lack of consistent intraoperative findings have led to conflicting etiologic theories. METHODS: We discuss etiology, clinical course, and surgical treatment of 3 women with catamenial pneumothorax. In addition, the world literature since the first description is reviewed. RESULTS: Three women (31, 32, and 39 years old) had recurrent, menses-associated, right-sided spontaneous pneumothoraces. They had undergone video-assisted thoracoscopic surgery previously, with various unsuccessful procedures. Finally, with video-assisted thoracoscopic surgery multiple small perforations in the tendinous part of the right diaphragm with adjacent endometrial implants were detected. After plication of the involved area, 2 patients have been free of recurrence for 22 and 13 months, respectively. Laparoscopic evaluation in 1 woman with a further recurrence revealed asymptomatic pelvic endometriosis. This patient has been free of recurrence since initiation of luteinizing hormone-releasing hormone analog therapy for 17 months. In a review of 229 cases of catamenial pneumothorax in the literature, adequate information was given for 195 patients (85.2%). One hundred fifty-four (79%) were treated surgically, with detailed findings reported for 140 (91%). Thoracic endometriosis was diagnosed in 73 patients (52.1%), and 54 (38.8%) showed diaphragmatic lesions. Pleurodesis, with or without diaphragmatic repair or wedge resection, was performed in 81.7% of the cases. CONCLUSIONS: Catamenial pneumothorax may be suspected in ovulating women with spontaneous pneumothorax, even in the absence of symptoms associated with pelvic endometriosis. During video-assisted thoracoscopic surgery, inspection of the diaphragmatic surface is paramount. Plication of the involved area alone can be successful. In complicated cases, hormonal suppression therapy is a helpful adjunct.

Adult↗

Photodynamic endometrial ablation: morphological study.

BACKGROUND AND OBJECTIVES: Endometriumablation provides an alternative treatment modality to hysterectomy for dysfunctional uterine bleeding (DUB). Its feasibility was demonstrated in animal studies. The purpose of this study was the evaluation of histological changes following photodynamic endometrial ablation in patients. STUDY DESIGN/MATERIALS AND METHODS: 5-Aminolevulinic acid (ALA) was topically applied in three premenopausal and one postmenopausal patient 4-6 hours before laser-illumination. ALA-concentration: 100-400 g/ml, NaOH-titration (pH 5.5). Volume applied, 1.5-2.0 ml; intrauterine balloon-lightdiffuser; wavelength, 635 nm; lightdose, 160 J/cm(2). Hysterectomy was performed 3-152 days after photodynamic ablation. Histological examination was carried out on endometrium sections stained with hematoxylin and eosin (H&E). RESULTS: Necrosis including the full thickness of the endometrium was found 3 days after photodynamic endometrial ablation. Specimens collected after 35 and 152 days did not exhibit fibrosis or adhesions. Foci of preserved endometrium were detected in all patients. CONCLUSIONS: Photodynamic endometrial ablation is selective and does not cause endometrial fibrosis or adhesions.

Adult↗

Fluorescence hysteroscopy using 5-aminolevulinic: a descriptive study.

BACKGROUND AND OBJECTIVES: To assess the feasibility of fluorescence hysteroscopy following topical ALA application and to describe the optical appearance of normal and neoplastic endometrium. STUDY DESIGN/MATERIALS AND METHODS: Fifty-four patients scheduled for routine hysteroscopy and D&C were assigned to the study group using topically applied ALA. Two milliliters of a 2% 5-ALA-solution at pH = 4.0 (ASAT AG/Zug, Switzerland) was administrated into the uterine cavity 4 hours before fluorescence hysteroscopy, using a STORZ-D-Light (Tuttlingen, Germany) system. Hysteroscopic findings were compared to the histological diagnosis of hematoxylin & eosin (H&E) stained sections. In the study group, 60 histological specimens were taken (47 materials of curettage and 13 targeted biopsies). The percentage of fluorescence positive patients was calculated. RESULTS: The rate of fluorescent endometrial samples was low in atrophic endometrium 1/16 (6.2%). Endometrial carcinoma were diagnosed in two patients. Both cases exhibited selective and intense PpIX-mediated red fluorescence. Fluorescence hysteroscopy could not differentiate between hyperplastic areas with or without atypia. Minimal uterine cramps or discomfort following ALA instillation were complained by 30 (56%) patients, no pain was indicated by 24 patients (44%). CONCLUSIONS: Fluorescence hysteroscopy following intrauterine application of ALA is feasible. Cancerous, hyperplastic, and secretory endometrial tissue showed high red fluorescence.

Administration, Topical↗

Role of p53 and ATM in photodynamic therapy-induced apoptosis.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) induces cell death through a laser light-activated photosensitizer and is a treatment option for tumors resistant to radio- and chemo-therapy. STUDY DESIGN/MATERIALS AND METHODS: We investigated whether m-THPC-PDT induces cell death by necrosis and/or apoptosis, and whether these responses are modulated by p53 and/or ATM, two cancer-associated genes. Sensitivity of atm(+/+)p53(+/+), atm(+/+)p53(-/-), and atm(-/-)p53(-/-) mouse embryonic fibroblasts to m-THPC-PDT performed at a wavelength of 652 nm was determined by the MTT assay, trypan blue-exclusion, and the TUNEL and caspase3-cleavage apoptosis assays. c-Abl protein level was determined by immunoblotting. RESULTS: m-THPC-PDT rapidly induced cell death in a substantial fraction of cells by p53- and Ataxia telangiectasia mutated (ATM)-independent non-apoptotic processes. However, in the subset of apoptotic cells, apoptosis was reduced by loss of p53 and was even more reduced by the additional loss of ATM. Apoptosis correlated inversely with c-Abl level. CONCLUSIONS: p53 and ATM are not required for necrosis, but may be required for PDT-mediated apoptosis.

Animals↗

p53-deficient cells display increased sensitivity to anthracyclines after loss of the catalytic subunit of the DNA-dependent protein kinase.

DNA-dependent protein kinase (DNA-PK) is involved in non-homologous end joining which repairs DNA double-strand breaks introduced by irradiation and radiomimetic agents. DNA-PK interacts with p53 but may also have p53-independent functions. The present study investigated whether disruption of the gene for the catalytic subunit DNA-PKcs affects chemosensitivity in p53-deficient cells. Drug sensitivity of DNA-PKcs(+/+)/p53(+/+), DNA-PKcs(+/+)/p53(-/-), DNA-PKcs(-/-)/p53(+/+), and DNA-PKcs(-/-)/p53(-/-) mouse lung-fibroblasts was determined by the MTT assay, the clonogenic assay, and trypan blue exclusion. Susceptibility to apoptosis was determined by DNA fragmentation (TUNEL) and by caspase-3 cleavage. We show that p53-deficient cells were 2 to 3-fold resistant to treatment with doxorubicin, epirubicin, cisplatin, and docetaxel as compared to wild-type cells. We further demonstrate that the additional loss of DNA-PKcs function in p53-deficient cells resulted in a 2-fold increase in sensitivity to doxorubicin and epirubicin as documented by the MTT assay, clonogenic assay, and trypan blue exclusion. Doxorubicin-induced hypersensitivity in these cells correlated with a transient G2/M checkpoint activation but did not seem to correlate with apoptosis. The data indicate that additional loss of DNA-PKcs in p53-deficient cells reverses anthracycline-resistance imposed by p53-deficiency, and that DNA-PKcs modulates p53-independent pathways responding to DNA damage induced by anthracyclines. They also indicate that processes other than apoptosis may contribute to the increased cytotoxicity to anthracyclines. DNA-PKcs may thus be a potential target for functional inhibition, which might increase the efficacy of some anti-tumour agents in the treatment of cancers mutated in the p53 gene.

Animals↗

The effect of loss of Brca1 on the sensitivity to anticancer agents in p53-deficient cells.

BRCA1 is implicated in cellular responses to DNA damage, thereby substantially contributing to maintenance of the genome integrity. Mutations in the BRCA1 gene occur in breast and ovarian cancer and mutations that disable p53 are frequently found in human cancers, often accompanied by mutations in additional genes, contributing to tumor progression or high-grade malignancy. Therefore, the role of BRCA1 in the sensitivity to anticancer agents in p53-deficient cells was investigated using p53-deficient mouse knockout cell lines either deficient or proficient in Brca1 function. We report that Brca1-deficiency in p53-null cells was associated with increased sensitivity to the topoisomerase I poisons camptothecin and topotecan, the topoisomerase II poisons doxorubicin, mitoxantrone and etoposide, and to the platinum compounds carboplatin and oxaliplatin, but not to the antimetabolites 5-fluorouracil and gemcitabine and the taxanes docetaxel and paclitaxel. The increased growth inhibition to doxorubicin after loss of Brca1 correlated with increased cell killing caused by increased apoptosis. The data presented here indicate that Brca1 modulates p53-independent DNA damage response pathways and they support the case of a role of Brca1 to protect cells from apoptosis-mediated cell death in p53-deficient cells. These results suggest a higher chemotherapy susceptibility of cells disabled in both functions and they foster the concept that functional inhibition of BRCA1 may be a valuable adjunct to anticancer agents to increase the efficacy of chemotherapy in the treatment of p53-mutated cancers.

Animals↗

Effects of chlorin-mediated photodynamic therapy combined with fluoropyrimidines in vitro and in a patient.

Although photodynamic therapy (PDT) is becoming an additional cancer therapy, only little is known about its interactions with other drugs and treatment modalities in vitro and in vivo. We investigated the combination of 5-fluoro-2'-deoxyuridine (5FdUr), a chemotherapeutic drug, with 5,10,15,20-tetra( m-hydroxyphenyl)chlorin (mTHPC), a potent photosensitizer. Two cell lines, MCF-7 and LNCaP, were either simultaneously or consecutively incubated with both drugs and irradiated with laser light to activate mTHPC, and cell survival was determined. The combination of the two treatments was additive or antagonistic in LNCaP cells but additive or synergistic in MCF-7 cells depending on the protocol and concentration of 5FdUr. In one patient with multiple basal cell carcinoma, the effect of the combination of 5-fluorouracil administration followed by PDT resulted in significantly stronger effects than expected, leading to severe oedema, redness and ulceration. The healing process was delayed by 2 months compared to PDT alone. It is therefore important to find optimal conditions under which PDT and chemotherapy combinations do not fall outside the therapeutic window.

Apoptosis↗

Frequency and distribution pattern of distant metastases in breast cancer patients at the time of primary presentation.

INTRODUCTION: For routine staging of patients with primary breast cancer, clinical practice guidelines of many medical societies recommend chest X-ray, liver ultrasound and bone scan. With respect to expanding health care costs and patients' psychological distress it has been supposed, that there might be a group of breast cancer patients, who do not need these imaging studies. METHODS: Four hundred and eighty-eight consecutive patients with primary breast cancer who had primary surgery at our institution and complete work-up for distant metastases including chest X-ray, liver ultrasound, and bone scan were studied. RESULTS: We found distant metastases at the time of primary diagnosis in 19 patients (3.9%). Bone metastases were found in 2.7%, liver metastases in 1.0%, and pulmonary metastases in 0.4%. However, in breast tumors smaller than 1 cm, no metastatic lesions were found, whereas 18.2% of the patients with pT4 tumors had metastases. In 2.4% of screening imaging studies, metastases were ruled out by additional imaging. CONCLUSION: Based on our data and a review of the literature, we suggest that chest X-ray, liver ultrasound and bone scan can be omitted in the staging of asymptomatic patients with pT1a or pT1b disease.

Adult↗

Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5-aminolevulinic acid.

BACKGROUND AND OBJECTIVES: To determine the feasibility of photodynamic therapy (PDT) of vulvar and vaginal condyloma and intraepithelial neoplasia (VIN, VAIN) and to compare PDT results with conventional treatments. STUDY DESIGN/MATERIALS AND METHODS: Thirty-eight patients with vulvar or vaginal intraepithelial neoplasia (VIN) grade II/III (n = 22) or condyloma (n = 16) had 10% 5-aminolevulinic acid (ALA)-gel applied topically. After 2-4 hours, 80-125 J/cm(2) laser light at a wavelength of 635 nm was applied. PDT was compared to conventional treatments for condyloma (CO(2) laser evaporation) and for VIN III (laser evaporation, surgical excision). RESULTS: The complete clearance rate for condyloma treated by PDT was 66% and the rate for IN was 57% (as determined by biopsy). Of the neoplasia patients, none with hyperkeratotic VIN (n = 4) responded, and only one of four with increased pigmentation cleared. No scarring occurred, and postoperative discomfort lasted 4.9 +/- 3.4 days. Reduced disease-free survival (DFS) was associated with multifocal VIN (P = 0.02, OR 2.17, 95% CI 1.15-4.08), but DFS did not vary with treatment mode. CONCLUSIONS: Although PDT is not equally efficacious for all subgroups, PDT for condyloma and intraepithelial neoplasia appears to be as effective as conventional treatments, but with shorter healing time and excellent cosmetic results.

Administration, Topical↗

Axillary staging using positron emission tomography in breast cancer patients qualifying for sentinel lymph node biopsy.

Axillary lymph node dissection (ALND) is the standard of care for nodal staging of patients with invasive breast cancer. Due to significant somatic and psychological side effects, replacement of ALND with less invasive techniques is desirable. The goal of this study was to evaluate the clinical usefulness of axillary lymph node (ALN) staging by means of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in breast cancer patients qualifying for sentinel lymph node biopsy (SLNB). FDG-PET was performed within 1 week before surgery in 24 clinically node-negative breast cancer patients with tumors smaller than 3 cm. Sentinel lymph nodes (SLNs) were identified by preoperative lymphoscintigraphy following peritumoral technetium 99m-labeled colloid albumin injection, and by intraoperative gamma detector and blue dye localization. Following SLNB, a standard ALND was performed. Serial sectioning and immunohistochemistry of the SLN as well as standard histologic examination of the non-SLN was performed. FDG-PET detected all primary breast cancers. Staging of ALNs by PET was accurate in 15 of 24 patients (62.5%), whereas PET staging was false negative in 8 of 10 node-positive patients and false-positive in 1 patient. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for nodal status was 20%, 93%, 67%, and 62%, respectively. The mean diameter of false-negative ALN metastases was 7.5 mm (range 1-15 mm). Lymph node staging using FDG-PET is not accurate enough in clinically node-negative patients with breast cancer qualifying for SLNB and should not be used for this purpose.

Adult↗