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Biomedical subjects

B Gerber

Publications and source records attributed to B Gerber.

At least 55 records · Page 3Linked to original sources

Ultrasonographic detection of asymptomatic endometrial cancer in postmenopausal patients offers no prognostic advantage over symptomatic disease discovered by uterine bleeding.

The aim of this study was to investigate whether endometrial carcinoma (EC) screening by transvaginal sonography (TVS) has a prognostic advantage over symptomatic EC. In a retrospective study, 190 postmenopausal patients with symptomatic EC and 123 asymptomatic patients with suspicious endometrium detected by TVS were analysed regarding clinical, socio-economic and histopathological findings. Total bleeding time and the International Federation of Gynecology and Obstetrics (FIGO) tumour stage were evaluated with respect to their effect on survival. In 123 asymptomatic patients with suspicious endometrium, 16 (13%) EC, 61 (50%) polyps, 21 (17%) hyperplasias, 23 (19%) atrophias, 1 (0.8%) myoma and 1 (0.8%) metastasis were found. TVS findings in asymptomatic patients resulted in unnecessary operations, which were associated with considerable costs totalling at least 116256. Compared with screened asymptomatic patients, symptomatic patients were significantly (P<0.05) older, more frequently obese, and hypertensive, had a larger proportion of cases living in rural areas and visited their gynaecologists rarely. The bleeding time of symptomatic patients strongly correlated with the tumour stage (P<0.0001). Depending on the bleeding time, the 5-year disease-free survival and overall survival rates were 77% and 86% (no bleeding), 83% and 98% (<8 weeks), 74% and 90% (8-16 weeks), and 62% and 69% (>16 weeks), respectively. The corresponding tumour stage-related data for disease-free and overall survival were 100% (Ia; both rates), 87% and 95% (Ib), 66% and 93% (Ic), 63% and 78% (II) and 36% (III/IV; both rates), respectively. Postmenopausal vaginal bleeding represents an early symptom of EC, but it is not always perceived as problematic by the patients. There is no prognostic advantage for screened compared with symptomatic patients, who had bleeding of shorter than 8 weeks. Moreover, patients who are at a high risk for EC tend to avoid TVS screening. Finally, endometrial screening often results in unnecessary operations, which are associated with increased morbidity and costs.

Aged↗

Differences between synthetic oligosaccharide immunoabsorbents in depletion capacity for xenoreactive anti-Galalpha1-3Gal antibodies from human serum.

Extracorporeal immunoabsorption for removal of anti-Galalpha1-3Gal (anti-Gal) antibodies in putative pig-to-human xenotransplantation is considered a major prophylactic measure to avoid hyperacute and acute vascular rejections. However, the efficacy of the procedure does depend on choosing the appropriate oligosaccharide epitopes for the binding of human anti-Gal. The synthetic oligosaccharides Galalpha1-3Gal (B-disaccharide, Bdi) and Galalpha1-3Galbeta1-4Glc ('type 6' trisaccharide, Tri6), covalently coupled to Sepharose via polyacrylamide (Sorbents Bdi and -Tri6, respectively), as well as a mixture thereof (Sorbent Mix), were examined for their efficacy to absorb anti-Gal from 20 human serum samples. Sorbent Bdi removed 81% of anti-Gal IgM and 85% of -IgG when assessed on Bdi by ELISA, but only 49% of IgG and 75% of IgM when assessed on Tri6. Sorbent Tri6 and -Mix showed significantly better absorption capacities in so far as Sorbent Tri6 removed 65% of anti-Gal IgM and 80% of -IgG as assessed on Bdi and 85% of IgM/87% of IgG when tested on Tri6, and Sorbent Mix absorbed > 90% anti-Gal of both isotypes of either specificity. Direct hemagglutination of rabbit erythrocytes (ER) was reduced by 75% (median value, range 0-94%) and the median cytotoxicity to PK15 target cells by > 94% after absorption on Sorbent Mix. Neither the decrease in ER agglutination titers nor the reduction of PK15 cytotoxicity revealed significant differences between the three immunoabsorbents tested. The large variation ranges of absorption efficacies within the 20 tested sera suggest that "tailor-made" immunoabsorption treatments may be needed for putative xenotransplant recipients.

Adult↗

[Preoperative chemotherapy in primary operable breast cancer with a dose-dense combination of doxorubicin and docetaxel (ADoc) - Experience of the GEPARDO-GABG study group].

OBJECTIVE: The German Adjuvant Breast Cancer Study Group (GABG) conducts trials of preoperative chemotherapy in patients with primary breast cancer using a combination of doxorubicin and docetaxel (ADoc). - PATIENTS AND METHODS: We conducted a parallel-grouped phase IIa-study with 42 patients with a conventionally dosed and a dose-dense ADoc-schedule (4 cycles of Doxorubicin 50 mg/m(2), Docetaxel 75 mg/m(2) i. v. day 1, q day 15 or 22; G-CSF day 3-15 only for the dose-dense schedule) and a randomized phase IIb-study (GEPARDO-Study) with 250 patients with ADoc +/- Tamoxifen. Biological factors were determined immunohistochemically on 197 core biopsies before treatment. A comparison to a sequential AC-Doc regimen including 913 patients has been completed recently. - RESULTS: ADoc can be applicated on schedule in 93 % of all patients. The dose-dense regimen shows a tendency to more toxicity but also to more efficacy. The rate of complete pathological remissions (pCR) was 9.7 %. No difference was found between chemo- and chemoendocrine treatment. Clinically negative lymphnodes and a negative estrogen receptor status is predictive for a higher pCR-rate. To date no differences in toxicity could be found between ADoc and AC-Doc. - CONCLUSIONS: The dose-dense ADoc regimen is well tolerated and highly effective as preoperative therapy of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Effectiveness of Trastuzumab (Herceptin) in a patient with locally recurrent breast cancer after cardiac failure caused by severe cytotoxic pretreatment.

In HER2-positive breast cancer patients, the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) may improve overall survival. No reports exist regarding the application of trastuzumab in patients with cytotoxically induced cardiac failure and decreased left ventricular ejection fraction or about locally recurrent and advanced disease. In this case report, trastuzumab resulted in a complete and long-lasting response of recurrent and locally advanced breast cancer and was well tolerated in a severely cytotoxically pretreated patient with cardiac failure. We encourage other oncologists to offer trastuzumab also to severely cytotoxically pretreated patients with conditions after cardiac insufficiency or with locally advanced breast cancer.

Antibodies, Monoclonal↗

Effects of adjuvant tamoxifen on the endometrium in postmenopausal women with breast cancer: a prospective long-term study using transvaginal ultrasound.

PURPOSE: To study the value of transvaginal ultrasound (TVS) in endometrial screening of postmenopausal breast cancer patients treated with tamoxifen. PATIENTS AND METHODS: In 247 tamoxifen-treated (20 to 30 mg/d for >/= 2 years) women and 98 controls, the endometrium was prospectively followed-up by means of TVS every 6 months for up to 5 years. Patients with homogeneous endometrium of more than 10-mm thickness were then scanned repeatedly every 3 months. RESULTS: The mean endometrial thickness was 3.5 +/- 1.1 mm before treatment and increased to a maximum of 9. 2 +/- 5.1 mm after 3 years of tamoxifen application (P: <.0001), which was significantly (P: <.0001) thicker compared with controls. Fifty-two asymptomatic patients with thickened or morphologically suspect endometrium underwent hysteroscopy and dilatation and curettage (D&C), resulting in four uterine perforations. Histopathologically, atrophy was found in 38 patients (73.1%), polyps in nine, hyperplasia in four, and endometrial cancer in one case. In 20 screened patients who reported vaginal bleeding, five atrophies (25%), five polyps, four hyperplasias, and two endometrial cancers were found. Before hysteroscopy and D&C were performed, 36 (69.2%) of 52 asymptomatic and four (20%) of 20 symptomatic patients were scanned by repeated TVS over 2 to 30 months. Invasive diagnostic procedures were significantly (P: <.05) more frequent in younger and obese patients. In the controls, one asymptomatic polyp and one symptomatic hyperplasia were found. CONCLUSION: In tamoxifen-treated patients, TVS offered a high false-positive rate, even with a cutoff value of 10 mm for endometrial thickness and repeated TVS scans. Increased iatrogenic morbidity and only one asymptomatic endometrial carcinoma do not warrant endometrial screening by TVS in tamoxifen-treated patients.

Adult↗

FasL:Fas ratio--a prognostic factor in breast carcinomas.

Programmed cell death (apoptosis) is primarily mediated by Fas ligand (FasL; CD95L) and the Fas receptor (Fas; CD95). In this study, FasL was detected by immunohistochemical analysis in 85% of breast carcinomas and 14% of fibroadenomas randomly chosen, indicating that high expression of FasL might play a role in tumor pathology. FasL and Fas levels as well as FasL:Fas ratios were further ascertained in 215 human breast tumors, including 199 invasive ductal carcinomas, by real-time quantitative reverse transcription-PCR and compared with expression levels and ratios found in 25 normal human tissues, in 37 fibroadenomas, and in 5 normal breast tissues. Among breast carcinomas, high FasL mRNA expression seems to be positively correlated with histological grading (n = 212; P<0.0001). A ratio of FasL:Fas mRNA transcripts >1 is found to be significantly associated with decreased patient's disease-free survival (n = 211; P<0.03) and increased mortality (n = 211; P = 0.19). A FasL:Fas ratio >1 is related to tumor progression scored by histological grading (n = 212; P<0.02). The selection process leading to highly aggressive breast tumor variants might be enhanced by FasL-mediated tumor fratricide, eventually a possible target for novel therapeutic strategies.

Adolescent↗

Expression of the apoptosis-inducing ligands FasL and TRAIL in malignant and benign human breast tumors.

Apoptosis-inducing ligands such as Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been found to play an important role in cell regulation. Different malignant tumors show an altered expression of these ligands and their respective receptors compared to normal tissues. The purpose of this study was therefore to investigate expression of TRAIL, FasL, and its receptor Fas on protein and mRNA levels in breast carcinomas (n=40), fibroadenomas (n=7), and normal breast tissues (n=5). Immunohistochemical reaction demonstrated that FasL was strongly expressed in breast cancer tissues (34/40) while only one fibroadenoma and one normal breast tissue reacted weakly positive for FasL. All fibroadenomas and normal breast tissues as well as the majority of breast cancer tissues expressed Fas on protein level. Quantitative RT-PCR analysis detected high expression of FasL mRNA in breast cancer tissues and fibroadenomas, whereas fibroadenomas showed the highest Fas mRNA copy numbers, followed by breast cancer tissues and normal breast tissues (P<0.05). Compared to FasL expression, TRAIL could be detected in less breast cancer tissues on protein level (21/40) and was found in only one fibroadenoma and none of the normal breast tissues. Thus, it can be concluded that malignant breast tumors show an altered expression of the two apoptosis-inducing ligands FasL and TRAIL.

Apoptosis↗

[Detection of atypical site of "sentinel lymph nodes" by lymph drainage scintigraphy in patients with breast carcinoma].

OBJECTIVE: Sentinel lymph node (SLN) localization in breast cancer allows biopsy of directly tumor drained lymph nodes. The objective was to study the association of tumor and SLN localization. PATIENTS AND METHODS: SLN was identified in 39 (81%) of 48 patients with histologically proven breast cancer, clinically and sonographically unsuspected axillary lymph nodes after peritumoral application of 40-50 Mbq 99mTc-Nanocolloid. Patients age, tumor size and localization, histology and localization of the SLN as well as removed axillary lymph nodes were analyzed. RESULTS: Axillary lymph node metastases were found in 11 (28%) of 39 patients. Involvement of the SLN was confirmed by intraoperative frozen sections (n = 9) and paraffin embedded histology (n = 1). One (9%) patient with a positive node revealed a false-negative SLN. In 24 patients with a tumor in the lateral hemisphere of the breast the SLN were identified in the ipsilateral axilla. In 6 (40%) of 15 patients with a central or medial localized tumor the SLN was observed infraclavicular (n = 3), parasternal (n = 2) or in the contralateral axilla (n = 1). In the latter one the SLN of the contralateral axilla showed metastases, whereas the simultaneous SLN and all removed lymph nodes of the ipsilateral axilla were not involved. More than one SLN were found in 12 (31%) of the 39 cases. CONCLUSION: A correlation between tumor localization and localization of the SLN is suggested, but the lymph drainage seems more variable in cases of medial tumor size. Using blue dye for map of extraaxillary SLN seems inappropriate. Currently the diagnostic and therapeutic impact of the detection of extraaxillary SLN is still unclear.

Adult↗

[Skin sparing mastectomy with autologous immediate reconstruction: oncological risks and aesthetic results].

OBJECTIVE: Is the oncological safety of skin sparing mastectomy (SSM) with immediate autologous reconstruction and improved aesthetic results comparable to postoperative findings in patients treated with modified radical mastectomy (MRM)? MATERIAL AND METHODS: Sixty patients with T1-2 breast carcinomas and contraindications for breast conserving therapy were treated by SSM and compared to 81 patients of the same age groups and MRM with regard to oncological and aesthetic data. In 33 (55%) patients the nipple areola complex (NAC) could be spared. For autologous tissue TRAM- and Latissimus dorsi-flaps were used. The mean follow-up was 40 (range 20-71) months. RESULTS: The observed local recurrence rates were not significantly different (p = 0.443) after SSM (n = 3; 5.0%) or MRM (n = 5; 6.2%). Distant metastases and death were seen in 26.7% and 15.0% (SSM), respectively, and in 25.9% and 13.5% (MRM), respectively. Body mass index, operation time and postoperative haemoglobin concentration differed between both groups significantly (p < 0.001) but not the rate of complications (p = 0.232). Aesthetic results of SSM were judged as excellent or good in 90.0% of patients and in 83.4% of surgeons. Nine patients (11.1%) underwent a secondary breast reconstruction after MRM. Furthermore, 12 (14.8%) patients with MRM would prefer a SSM with immediate reconstruction in a similar situation. CONCLUSION: Skin-sparing mastectomy improves aesthetic results to a high degree without increasing of local or distant recurrence rates. Skin-sparing mastectomy should be offered to selected patients with breast cancer as an alternative to modified radical mastectomy.

Adult↗

Sensory preconditioning in honeybees.

Sensory preconditioning means that reinforcement of stimulus A after unreinforced exposure to a compound AB also leads to responses to stimulus B. Here, we describe and analyze sensory preconditioning in an insect, the honeybee Apis mellifera. Using two-element odorant compounds in classical conditioning of the proboscis extension reflex, we found (i) that sensory preconditioning is not due to stimulus generalization, (ii) that paired, but not unpaired, presentation of elements supports sensory preconditioning, (iii) that simultaneous, but not sequential, exposure to the elements of the compound supports sensory preconditioning and (iv) that a single presentation of the compound yields maximal sensory preconditioning. The results are discussed with respect to configural and chain-like associative explanations for sensory preconditioning. We suggest an experience-dependent step of compound processing, establishing configural units, as an additional explanation for sensory preconditioning.

Animals↗

Human chorionic gonadotrophin-beta transcripts correlate with progesterone receptor values in breast carcinomas.

The pathophysiological role for the expression of human chorionic gonadotrophin (hCG) in malignant neoplasms is currently speculative. We investigated the overall expression of genes hCG-beta 5, 3, 8 and 7 in breast carcinoma (n=214), fibroadenoma (n=37) and macromastia (n=10) by quantitative reverse transcriptase-PCR. Eighty (37.4%) of the breast cancer samples revealed positive hCG-beta mRNA expression and the mean value was 67. 9 copies per 200 ng total RNA (range: 0-1743; 95% confidence interval (CI) for mean: 44-92). Fibroadenomas had more frequently detected (56.8%) and greater hCG-beta copy numbers (mean 86.9; range: 0-845; 95% CI for mean: 35-138). Macromastia probes yielded no positive hCG-beta mRNA. The hCG-beta mRNA expression was significantly different in the three histological subgroups (P=0. 006). Among breast carcinomas, a positive correlation was detected between hCG-beta mRNA copy numbers and progesterone receptor (PgR) values (P<0.001). No significant differences were seen regarding disease-free (P=0.87) and overall survival (P=0.20) depending on hCG-beta mRNA status. Finally, our findings do not support a role for hCG-beta in malignant transformation of human breast cells and indicate a possible involvement of hCG-beta in benign breast disease. The relationship with PgR expression may suggest that progestins regulate the expression of hCG in breast epithelial cells.

Adult↗

[Diagnosis and treatment of temporal paragangliomas: an analysis of 21 cases treated in Bern between 1992 and 1999].

INTRODUCTION: Paragangliomas are usually benign tumours stemming from the neural crest which may have neuroendocrine activity. Because of hypervascularisation they usually lead to pulsatile tinnitus. Local expansion initially causes middle ear and later inner ear hearing loss, and cranial nerve dysfunction. PATIENTS/METHODS: Signs and symptoms, demographic data, tumour stages, treatments and outcomes were analysed for the 21 patients treated at our clinic between 1992 and 1999. Among 16 surgically treated patients 3 type A and 4 type B tumours were treated by mastoidectomy and middle ear reconstruction. For the 8 type C and one type D tumours, angiography was performed preoperatively, usually followed by selective embolisation of tumour vessels, in 7 cases with additional permanent occlusion of the internal carotid artery. These 9 tumours were removed through an infratemporal approach with partial petrosectomy, preservation of the inner ear and facial nerve rerouting, followed in 8 cases by middle ear occlusion. The patient with a type D2 tumour had a two-stage otological and neurosurgical operation. One patient with type C3 tumour only underwent radiation therapy. 4 patients have had no treatment so far: 2 had small type A tumours and one a type C3 tumour but contraindications for surgery. A last patient with a slowly growing type D2 tumour cannot be operated on due to general health problems. RESULTS: All patients with type A and B tumours had normal to subnormal postoperative hearing and normal facial nerve function. In one case with a type C tumour the middle ear reconstruction led to normal hearing thresholds. After rerouting of the facial nerve, transient palsy was noted in 6 out of 9 cases. In 3 patients a slight permanent impairment of facial nerve function (House-Brackman II) remained. 4 patients had some dysfunction of cranial nerves IX-XII postoperatively. After a follow-up of up to 8 years (mean 5 years) no recurrence was observed in the surgically treated patients. The patient treated by radiation had further tumour growth and another treatment is being planned. Among the 4 patients followed without treatment, no tumour growth has been observed up to now in 3 patients. DISCUSSION: Our study confirms that the well standardised conservative surgical treatment allows reliable removal of paragangliomas in most cases, and involves low morbidity.

Cranial Nerve Diseases↗

Differential diagnosis of peri- and postmenopausal ovarian cysts.

OBJECTIVES: To test the value of preoperative and intracystic parameters in the differential diagnosis of ovarian cysts. METHODS: Criteria for admission of 58 patients were age > 47 years, complete history, detection of CA 125 serum level, and ultrasound findings. Tumor markers (CA 125, cancer-associated serum antigen (CASA), CA 72-4), hormones (estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH)), epidermal growth factor (EGF) receptor and c-erb B-2 amplification rate were detected in cyst fluid. RESULTS: Of the 58 subjects, 9 (15.4%) had functional cysts, 37 (63.8%) had benign tumors and 12 (20.8%) had malignant tumors. No functional ovarian cyst presented as echoic or multilocular cyst sonographically. The serum CA 125 values demonstrated significant differences between the non-malignant and malignant patient groups (P < 0.0005). The majority (63.8%, n = 37) of ovarian cysts were obtained at laparotomy, whereas only 36.2% (n = 21) were laparoscopically operated. The cyst fluid levels of FSH (P < 0.005) and LH (P < 0.05) were significantly lower in the functional group than in the benign or malignant group. Malignant cysts were significantly different from non-malignant cysts regarding low E2 (P < 0.01), high FSH (P < 0.05) and CASA (P < 0.02) values. There were no significant correlations between EGF receptor (P = 0.14) and c-erb B-2 (P = 0.06) gene amplification rates and malignant histology. CONCLUSIONS: Simple ovarian cysts combined with normal serum CA 125 levels are candidates for conservative follow-up or laparoscopy. The serum CA 125 is a powerful marker for prediction of histology in postmenopausal ovarian cyst. Laparoscopic surgery may be considered in patients with multilocular sonographic findings and normal CA 125 serum level. Combining serum CA 125 levels with cyst fluid parameters (E2, FSH, CASA) improves the sensitivity and specificity in predicting malignancy.

Age Distribution↗

Breast reconstruction with latissimus dorsi flap: improved aesthetic results after transection of its humeral insertion.

Does transecting the tendinous insertion of the latissimus dorsi on the humerus improve aesthetic results and avoid the displeasing bulge in the armpit that sometimes occurs when the latissimus dorsi is used for breast reconstruction? In a prospective study, 60 patients who were having breast cancer surgery and simultaneous breast reconstruction using the latissimus dorsi flap were randomized for cutting (n = 29) or leaving intact (n = 31) the tendinous muscle insertion on the humerus. The cosmetic outcome was evaluated by patients and surgeons 6 to 12 months postoperatively. Patients reported good cosmetic results in 29 of 31 cases with the humeral insertion left intact and in 26 of 29 cases when the tendon was cut (p = 0.59), as compared with 21 of 31 cases versus 25 of 29 cases (p = 0.091), according to the surgeon's evaluation. A lateral bulge was more frequently observed by the surgeons in the group with intact insertion (10 of 31 patients), as compared with the group with a transected humeral insertion (2 of 29 patients). Discomfort caused by this bulge was reported by 19 of 31 patients with intact insertion, but only 3 of 29 patients with the tendon cut (p < 0.0001). The additional transection of the tendon was not associated with any complications. The additional transection of the tendinous humeral insertion of the latissimus dorsi muscle improves aesthetic results and avoids a displeasing bulge in the axilla when the latissimus dorsi flap is used for breast reconstruction.

Breast Neoplasms↗

No evidence for olfactory blocking in honeybee classical conditioning

We use binary odorant compounds to investigate 'blocking' in honeybees which learn to associate an odorant (A-D) with a sucrose reward as the reinforcer (+). 'Blocking' means that learning about a stimulus B is reduced when trained in compound with a stimulus A that has previously been trained alone. Thus, reinforcement of B in these circumstances is not sufficient to induce learning. Such blocking is a frequently observed phenomenon in vertebrate learning and has also recently been reported in honeybee olfactory learning. To explain blocking, current models of conditioning include cognition-like concepts of attention or expectation which, consequently, seem also to apply to honeybees. Here, we first reproduce a blocking-like effect in an experimental design taken from the literature. We identify two confounding variables in that design and experimentally demonstrate their potential to support a blocking-like effect. After eliminating these confounding variables using a series of different training procedures, the blocking-like effect disappeared. Thus, convincing evidence for blocking in honeybee classical conditioning is at present lacking. This casts doubt on the applicability of cognition-like concepts to honeybees.

Journal Article↗