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Biomedical subjects

H G Bender

Publications and source records attributed to H G Bender.

At least 37 records · Page 2Linked to original sources

[Surgical procedure after primary chemotherapy of breast carcinoma--an unresolved clinical problem].

Neoadjuvant chemotherapy has more and more become clinical routine during the past years. Results from large randomized trials like NSABP-B18 show that survival parameters are not affected if sequence of therapy is changed. Survival parameters have been intensively studied, but surgical standards after primary chemotherapy are much less well defined. Results from the early trials comparing lumpectomy or quadrantectomy with mastectomy are generally transposed to the neoadjuvant situation. In this context the "result of downstaging" is surgically treated like otherwise the primary tumor would have been treated. Though local recurrence rates reported after primary chemotherapy are not increased within the whole population this may not be correct for subgroups. E.g. within the NSABP-B18 trial significantly higher local recurrence rates are reported for those patients who initially were proposed to have mastectomy and who actually received lumpectomy after effective primary chemotherapy. Another unresolved problem is surgery after complete remission, which as histopathology demonstrates corresponds often not to pathological complete remission. Therefore in most cases the initially involved area is resected, which may result in a more radical surgical approach to complete remission than to partial remission. Further standardisation of surgical approach to patients after neoadjuvant chemotherapy should be evaluated within phase III trials.

Breast Neoplasms↗

[Reconstructive surgery of the efferent urinary tract in pelvic exenteration of gynecological tumors].

In locally advanced or recurrent tumors of the female genital tract anterior or total exenteration may be mandatory in case of tumor invasion into the lower urinary tract or if a second course of radiation therapy is not feasible. The management of resection and reconstruction of the affected lower urinary tract has to be well integrated into the gynecological therapeutic concept. In 11/32 patients the reconstruction of the partially resected lower urinary tract was feasible with preservation of a functionally intact urinary bladder. Urinary diversion following pelvic exenteration was achieved in 13/17 patients with a continent urinary reservoir and in 4/17 patients with an ileal conduit. Operative reinterventions were needed only in patients with continent urinary diversion in 5 cases. All these patients had a past history of primary radiation therapy of their gynecological tumor. In the remaining other 11 patients with a history of primary radiation therapy no complications occurred. 9 of 32 patients survived the operative procedure 40.8 (25-57) month with no evidence of recurrent tumor. Continent urinary diversion represents an excellent therapeutic option for replacement of function lost due to exenterative pelvic surgery. Stringent selection of patients is mandatory to consider the presented therapeutic concept a reasonable tool in the management of the described clinical situations.

Adult↗

Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer.

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has proven useful in the differentiation of various tumour entities, including breast cancer. In patients with primary breast cancer we performed a 3-h imaging protocol to examine possible improvements in tumour detectability and image contrast. Twenty-nine patients with primary breast cancer with a diameter of >/=2 cm that was demonstrated to be malignant by biopsy or surgery were injected with 370-740 MBq 18F-FDG and scanned in the prone position. Data were acquired 0-40 min, 1.5 h and 3.0 h after injection. After correction for measured attenuation, decay and scatter and iterative reconstruction, standardised uptake values (SUVs) and tumour-to-non-tumour and tumour-to-organ ratios were calculated. Visual analysis was performed using transverse, sagittal and coronal slices as well as 3D reprojection images. Tumour-to-non-tumour and tumour-to-organ ratios were significantly higher for the 3-h images than for the 1.5-h images. SUVs did not increase to the same extent. Lesion detectability was 83% in 1.5-h images compared to 93% in 3-h images. We conclude that tumour contrast in breast cancer is improved by starting the PET acquisition at 3 h p.i. rather than at 1.5 h p.i.

Adult↗

Psychosomatic aspects of urinary incontinence.

Psychosomatic aspects of urogynecological disorders may play an important role in their clinical presentation. 72 patients presenting to the urogynecological clinics and a control group of 34 healthy women were included in this study. After informed consent had been obtained, all patients were subjected to (1) a detailed enquiry about personal- and medical history (2) psychological tests (Freiburg's personality inventory, a questionnaire focused on anxiety and anger, and Beck's depression inventory) and (3) routine urodynamic measurement. Patients with stress incontinence had a mean duration of symptoms of 59 months. In 67% there was a combination with clinical urge symptoms. 53% of the patients did not have regular sexual intercourse. Of those who had regular intercourse 23% had incontinence during intercourse and 25% were anorgasmic. 59% of the patients had dysmenorrhea and a negative attitude to their menarche. Urodynamic evaluation showed stress, urge or no incontinence in 39%, 12% and 39%, respectively. Analysis of the psychosomatic tests did not show a specific psychosomatic influence. Negative sexual life correlated with depressive mood, which was not based on the urogynecological problem. There was no causal relationship between personality traits and urogynecological problems. The individual perception of incontinence, however, may depend on or influence personality structure.

Adult↗

Reliability and clinical application of fetal RhD genotyping with two different fluorescent duplex polymerase chain reaction assays: three years' experience.

OBJECTIVE: This study was designed to evaluate accuracy and clinical usefulness of fetal RhD genotyping with fluorescent duplex polymerase chain reaction. STUDY DESIGN: Two RhD-specific gene fragments (exon 10 in polymerase chain reaction 1 and exon 7 in polymerase chain reaction 2) were amplified in samples from 213 fetuses. RESULTS: Amplification failed in 0.9% of the specimens, and equivocal results were found in 1.4% of the specimens. Of the analyses, 6.6% had to be repeated. The concordance of genotyping and serotyping was 99.0% for each polymerase chain reaction. False-positive results were noted in 4 fetuses. Concordant findings from both assays indicated the correct serotype for all fetuses. In 44 alloimmunized pregnancies, further invasive procedures were avoided for 5 of the 6 genotypically RhD-negative fetuses. Only two of 38 RhD-positive fetuses had a hemoglobin level <8 g/dL at first fetal blood sampling. CONCLUSIONS: Fetal genotyping at distinct regions of the RhD gene is reliable and improves the care management of sensitized women.

Amniotic Fluid↗

Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation.

Amplification of the cyclin-dependent kinase 4 (CDK4) gene, located at 12q13-q14, has been found as an alternative genetic alteration to CDKN2A inactivation in various human tumors including malignant gliomas and sarcomas. In the present study, we have evaluated the frequency of the CDK4 gene amplification in sporadic breast cancer by applying a nonradioactive quantitative differential polymerase chain reaction based on fluorescent DNA technology. Fluorescent-labeled polymerase chain reaction products were analyzed with an automated DNA sequencer. Amplification of CDK4 gene was detected in 15 (15.8%) of 95 breast cancers. All tumors with CDK4 gene amplification showed high CDK4 protein expression determined by immunohistochemistry. Furthermore, the mean Ki-67 labeling index in tumors with CDK4 gene amplification was significantly higher than in those without CDK4 gene amplification. No significant associations were observed between CDK4 gene amplification and any specific histopathological parameter. The findings of this study provide the first evidence of CDK4 gene amplification in breast cancer and suggest that CDK4 gene amplification appears to be of importance in the pathogenesis of a subset of sporadic breast cancer.

Breast Neoplasms↗

CDKN2A gene inactivation in epithelial sporadic ovarian cancer.

The tumour suppressor gene CDKN2A, located on chromosome 9p21, encodes the cell cycle regulatory protein p16. Inactivation of the CDKN2A gene could lead to uncontrolled cell growth. In order to determine the role of CDKN2A in the development of sporadic ovarian cancer, loss of heterozygosity at 9p21-22, homozygous deletion, mutation and methylation status of the CDKN2A gene as well as CDKN2A expression were examined in a panel of serous papillary ovarian cancer. The frequency of loss of heterozygosity (LOH) for one or more informative markers at 9p21-22 was 65% (15/23). The most common deleted region was located between interferon (IFN)-alpha and D9S171. Homozygous deletions and mutations of the CDKN2A gene were not found. There was no evidence of methylation in exon 1, but methylation in exon 2 of CDKN2A gene was found in 26% (6/23). Absence of CDKN2A gene expression was shown in 27% (6/22) at mRNA level and 21% (4/19) at protein level. These data suggest that the CDKN2A gene is involved in the tumorigenesis of ovarian cancer, but the mechanisms of CDKN2A gene inactivation in serous papillary ovarian cancer remains unclear.

Chromosome Mapping↗

Mutations and amplification of oncogenes in endometrial cancer.

Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer.

DNA Primers↗

[Not Available].

Endometriosis is one of the most frequent gynecological disorders in the reproductive age. Discrepancies between clinical findings and subjective Symptoms cause the question of the determing factors for the subjective experience. In the present study an hermeneutic, sense-orientated approach was employed by using qualitative methods of research. Eleven interviews with endometriosis patients were recorded on tape and transcribed, followed by an individual-case and a comparative analysis in partly deductively and inductively defined categories. The psychosexual development has been found as negatively influenced. Endometriosis patients show conflicting concepts of their sex-specific role. A found aggression conflict manifests itself in the pain Sensation, at an intrapsychic land an interpersonnel level: it influences the relations with other persons, in particular, the doctor-patient relationship. Changes of sense in the doctor-patient-relationship and recent concepts of psychosomatic disorders are discussed.

Endometriosis↗

Chronic pelvic pain syndrome (CPPS) and chronic vulvar pain syndrome (CVPS): evaluation of psychosomatic aspects.

The purpose of our study was to examine the chronic pelvic pain syndrome (CPPS) and the chronic vulvar pain syndrome (CVPS) as two psychosomatic gynecological syndromes. Sociodemographic data were collected from 106 CPPS and 36 CVPS in-patients (under internal and external supervision). Sixty-eight CPPS and 24 CVPS patients were examined using psychological tests (Freiburg Personality Inventory (FBI) and Giessen Test (GT)) and compared with a control group of 34 healthy women. Descriptive statistics, the chi-square test, multi-variant analyses, and regression analyses were used for statistical evaluation. There was a significantly higher incidence of sexual abuse and severe psychological disturbances in the CPPS group (p < 0.03). Sexual abuse was found to be a significant predictor of the CPP syndrome. The CPPS and CVPS patients were significantly more depressed than the control group (p < 0.03). CPPS and CVPS are two distinct psychosomatic gynecological syndromes accompanied by different psychological disturbances.

Adult↗

[Diagnostic and therapeutic concepts of HPV infection in HIV-positive women].

Among HIV-seropositive women there is a high prevalence of anogenital human papillomavirus (HPV) infection. HPV-DNA is more frequent detected in cervicovaginal-lavage specimens from HIV-seropositive women as in those from HIV-seronegative women. We and others suggest that HIV-infection increases the risk to have HPV-associated lesions of the lower female genital tract, especially the risk for developing a squamous intraepithelial lesion of the cervix. In this report we describe the current diagnostic and therapeutic strategies in HIV-seropositive women with HPV-infection. The gynecological examination should be performed at six to twelve month intervals, including the colposcopy and the Pap smear test. We hope to improve the quality of our screening program by doing an additional HPV-test. At last we investigate the CD4+ T-lymphocyte counts because it is observed that women with low CD4+ cell counts (< 200/microliter) were more likely to have persistent HPV-infection as those with higher counts (> 500/microliter). The treatment method is dependent on the development of the HPV-associated lesion and the clinical status of the HIV infected women. In cases with external warts local application of Condylox should be the first line treatment. Probably in about few months we could use other drugs like Wartec or Aldara in Germany. But the effectiveness of these drugs in HIV-positive women has to be proven yet. In the cause of persistence of external warts or recurrence of the disease the systemical application of Intron A or Roferon A is possible. The CO2-lasertreatment is performed under colposcopic guidance, especially in cases with multicentric condylomatous lesions. The treatment of cervical intraepithelial neoplasia (CIN) by CO2-laservaporisation or Loop Electrosurgical Excision Procedure (LEEP) is based on the clear colposcopic visualisation of the upper limit of the lesion. If CIN reaches the endocervix, being out of colposcopic view, and the squamocolumnar junction is localised in the endocervical canal conisation by laser or cold knife has to be performed. Before performing the treatment of CIN one should exclude multicentric cervical, vaginal and vulval intraepithelial neoplasia by colposcopy, because multicentric intraepithelial neoplasia of the lower female genital tract is more frequently than in HIV-seronegative women. Multicentric disease seems to be one cause of the high recurrence of HIV-seropositive women. However, higher levels of immunosuppression (CD4+ T-lymphocyte counts < 200/microliter) are also important determinants of recurrence of the disease. Therefore, an accurate short-term follow-up with colposcopy, Pap test and HPV test should be carried out after the treatment of HIV-seropositive women with low CD4+ counts.

Comorbidity↗

Psychosomatic aspects of vulvodynia. Comparison with the chronic pelvic pain syndrome.

OBJECTIVE: To examine psychosomatic aspects of vulvodynia (VD) in comparison with the chronic pelvic pain syndrome (CPPS). STUDY DESIGN: Sixty-seven VD patients and 97 CPPS patients were examined with psychological tests (Freiburg Personality Inventory, Giessen Test) and compared with a control group of 34 healthy women. Sociodemographic data and psychoanalytic diagnoses were collected for 36 VD patients and 106 CPPS patients (inpatients). Descriptive statistics, chi 2 test and multivariant analyses were used. RESULTS: CPPS patients had significantly higher somatization than VD patients (P < .004). Both CPPS and VD patients, as inpatients, were significantly more depressive than the control group. In milder forms of VD, the patients (outpatients) exhibited no depression. The incidences of sexual abuse and severe psychological disturbances were significantly higher in the CPPS group (P < .01). CONCLUSION: VD and CPPS are two, distinct psychosomatic gynecologic syndromes and indicate psychosomatically oriented therapy.

Adult↗

[Chronic pelvic pain and chronic vulvodynia as multifactorial psychosomatic disease syndromes: results of a psychometric and clinical study taking into account musculoskeletal diseases].

OBJECTIVE: Chronic Pelvic Pain Syndrome (CPPS) and vulvodynia (CVPS) are two gynecological syndromes with psychosomatic implications. The purpose of the study was to examine multifactorial psychosomatic syndromes taking into account musculoskeletal diseases. PATIENTS AND METHODS: The psychosomatic data acquired in respect of 106 CPPS and 36 CVPS patients was evaluated. In addition, these patients were subject to orthopedic clinical examinations and the results compared with a control group without pain (n = 35). 68 CPPS and 24 CVPS patients took part in psychological tests, the results of which were compared with those of a control group of healthy women (n = 34). RESULTS: There was a significantly higher incidence of sexual abuse among the CPPS group. Sexual abuse and somatization were found to be significantly predictive factors. The CPPS and CVPS patients were significantly more depressive than the healthy group. The two clinical groups differ in that the CPP syndrome is significantly more frequently linked with a so-called early disturbance. The incidence of musculoskeletal diseases was higher in the case of the CPPS patients. CONCLUSIONS: Interdisciplinary psychosomatic treatment, which also includes nongynecological disorders, especially musculoskeletal diseases, is necessary in the case of both these syndromes.

Adolescent↗

[Tumor risk consultation for predisposed women from high risk cancer families].

Germline mutations of the cancer susceptibility genes BRCA1 and BRCA2 seem to lead to a very high risk for breast and/or ovarian cancer. Therefore, genetic counselling and identification of high-risk families may be essential to offer the opportunity to participate in a specific early cancer detection program and to provide individualized psychological support. In a two year period (August 1994-August 1997) 304 consultees present for genetic counselling at the interdisciplinary cancer genetic clinic (Department of Obstetrics & Gynecology and Human Genetics, Heinrich-Heine-Universität, Düsseldorf). For genetic testing a BRCA1/2 mutation detection strategy including protein truncation test (PTT), single strand conformation polymorphism (SSCP), and direct DNA sequencing is used. 161 families fulfilled the inclusion criteria; at present, 72 families for whom complete analytical material is available are analyzed. Although genetic testing for BRCA1 and BRCA2 is technically challenging, women with a family history of multiple sporadic breast/ovarian cancers and those with a hereditary BRCA1 and BRCA2 gene defect may be distinguished. For the first group of consultees this may ease their concern, for the second group preventive measures including an early cancer detection or prevention program, psychological support or prophylactic surgery may be discussed.

BRCA1 Protein↗

[Diagnosis and therapy of breast carcinoma--an interdisciplinary challenge].

Screening studies in patients older than 50 years show a reduction of mortality and an increase of early stages. Newly diagnosed breast cancer confronts the patient and the clinician with multiple treatment decisions. Breast conserving surgery has become standard therapy for early breast cancer. Key elements in the selection of patients for treatment with local or transferred tissue or mastectomy include preoperative mammography, careful pathologic evaluation of the needle or core biopsy specimen, and an assessment of the patients desires in order to balance the risk of local recurrence against preservation of a cosmetically acceptable breast. MR-mammography and sonography complement mammography to define the extent of the disease preoperatively. This review examines some of the local treatment options, the choice between breast conserving treatment and mastectomy, how best to treat the axilla, the optimal sequencing of local and systemic therapy. Breast conserving therapy with radiation has been recognized as a standard strategy, because of the low incidence of local failure and minimal postoperative deformity compared with that of quadrantectomy without radiation. High-dose chemotherapy is being evaluated in the treatment of metastatic and high-risk primary breast cancer.

Adult↗

[Pattern of various cytokeratins of normal vulva, vulvar intraepithelial neoplasia (VIN) and vulvar carcinoma].

The presence of specific keratins can be of diagnostic value for studying normal and neoplastic epithelium of the vulva. The aim of the present study was to investigate normal, preneoplastic and neoplastic epithelium of the vulva. Keratins 5, 6 and 18, identified by a polyspecific anti-human CK antibody (clone LP 34, DAKO), and the keratin subtypes 7, 10, 14, 18, 19 and 20 of normal, dysplastic and malignant vulval epithelium (paraffin-embedded sections) were detected by immunohistochemical APAAP staining. Keratins 5, 6, and 18 (clone LP 34) and keratin subtype 10 are expressed in the upper third of the normal vulval epithelium. In mild and moderate intraepithelial neoplasia only a few cells express these keratins. In patients with severe intraepithelial neoplasia (VIN III) the expression of these keratins seems to be associated with recurrence of the disease. In biopsy specimens of patients without recurrence we find positive results for keratins 5, 6 and 18 (clone LP 34) and keratin 10. If patients have a recurrence of the disease, expression of these keratins is only diffuse or is absent. The expression of these keratin subtypes in vulval carcinomas is mostly seen in differentiated cells. There was no association between recurrence and keratin pattern. We have not found any other expression of the tested keratin subtypes in VIN and in vulval carcinoma.

Biomarkers, Tumor↗

Mechanisms of steroid hormone action and resistance in endometrial and breast cancer.

The detection of molecular alterations that lead to the development, progression, and formation of metastases in human endometrial and breast cancer may contribute to a better understanding of tumour biology as well as the development of specific preventative and therapeutic strategies. Endometrial and breast cancers both emerge during a multistep process. Cytogenetic and molecular genetic analysis of cancer samples suggest that tumour development involves: (1) alterations of hormonal interactions, and (2) accumulation of various genetic alterations. Steroid hormones act directly via corresponding steroid hormone receptors or indirectly via alterations of protein kinases or (proto-)oncogenes. Oncogene amplification with concomitant overexpression of the oncoprotein seems to be specific for certain cancer types and to mediate cellular proliferation. Loss of normal tumour suppressor protein function can occur through sequential gene mutation events (somatic alteration) or through a single mutational event of a remaining normal copy, when a germline mutation is present. The second event is usually chromosome loss, mitotic recombination, or partial chromosome deletion. These alterations of interactions or different regulatory cellular pathways may lead to primary or secondary hormonal resistance during therapeutic interventions.

Breast Neoplasms↗

Patterns of allelic loss on chromosome 17 in sporadic breast carcinomas detected by fluorescent-labeled microsatellite analysis.

Loss of heterozygosity (LOH) on chromosome 17 is a frequent genetic alteration in breast cancer. To assess whether the location of potential tumor suppressor genes is compatible with the LOH pattern in individual tumors, we analyzed allele loss on chromosome 17 in 121 invasive ductal breast carcinomas and 16 benign breast tumors with 14 polymorphic microsatellite markers (4 on 17p and 10 on 17q). Fluorescent polymerase chain reaction (PCR) for typing microsatellites coupled with DNA fragment analysis in an automated DNA sequencer was applied. Frequencies of LOH varied from 29.4% (D17S1322) to 57.4% (TP53-Alu). No LOH could be detected in benign breast tumors. In 54 tumors the deletion patterns were consistent with the complete loss of 17p (n = 28), 17q (n = 9) or the whole chromosome 17 (n = 17). Five smallest regions of overlap (SROs) were identified in tumors with interstial deletion patterns. On 17p, two foci were detected affecting the TP53 locus and the hypermethylated in cancer I (HICI) region (17p13.3). On 17q, SRO1 was localized between markers THRAI and D17S855, centromeric to the breast/ovarian cancer gene BRCAI; SRO2 was flanked by markers AFM234 and NMEI, and SRO3 was centered between markers MPO and GH. Associations between LOH and histopathological characteristics were determined. Significant correlations were found between higher grade and loss of the TP53 gene (marker TP53, P = 0.019), loss of the BRCAI region (P < 0.009), LOH of marker AFM155 (P = 0.003) and marker NMEI (P = 0.026). For positive estrogen receptor status, only LOH of the THRAI marker correlated significantly, whereas highly significant correlations were determined between positive progesterone receptor and markers centromeric to the BRCAI region D17S250 (P = 0.00002), THRAI (P = 0.0006), and the intragenic BRCAI markers [D17S1322 (P = 0.021), D17S855 (P = 0.029)]. Results presented in this study identify five independent regions of chromosome 17 which are likely to contain potential tumor suppressor genes involved in the carcinogenesis of sporadic breast cancer.

Alleles↗