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Biomedical subjects

H Kölbl

Publications and source records attributed to H Kölbl.

At least 19 recordsLinked to original sources
PubMed2007

[Pathoanatomical preparation and reporting for dysplasias and cancers of the cervix uteri: cervical biopsy, conization, radical hysterectomy and exenteration].

A careful macroscopic description with selection of representative tissue for histological examination is required for quality assurance, for assessing prognostic factors and for answering legal questions in (pre)cancerous lesions of the cervix uteri. Exact and standardized gross inspection and preparation are decisive for the quality of the histopathological statement. The extent of cervical carcinomas should be given in three dimensions, including the relative depth of invasion into the cervical wall. The report should include size, type (according to the WHO classification) and grading of the tumor, the presence of lymphatic as well as blood vessel invasion and perineural involvement. The statement for resection margins should include the vaginal, parametrial, rectal and vesical directions. It is also mandatory to document the number of lymph nodes with metastatic disease in relation to the total number of nodes investigated. The staging should follow the TNM system. In the handling of conisation specimens, it is important to appropriately document localization, horizontal expansion, depth of invasion including microinvasion of any dysplastic or malignant lesions. Clockwise dissection of the conisation specimen, total submission, and step sections are recommended. The preparation of exenteration specimens is a highly skilled job: the exact tumor dimension should be given in its relation to all resected organs and structures with special focus on resection margins.

Biopsy↗
PubMed2006

[Urinary incontinence and urodynamics].

Incontinence can be the result of impaired functioning of the detrusor muscle and/or the sphincter mechanism. For this reason, the pathomorphology and the pathophysiology should be documented before surgery, so that if it is not successful it is possible to deduce what alterations have been caused by an operation and the reason why the treatment has not been successful. Vaginal reconstruction of the pelvic floor following vaginal prolapse is a safe, effective surgical procedure, particularly for older women. Abdominal fixation of the vaginal stump through open or laparoscopic sacrocolpopexy gives long-lasting and anatomically favourable results especially for younger women who are sexually active, but is associated with a higher mortality rate. Incontinence treatment in men is itself gradually becoming accepted as a subspecialty. Pharmacological treatment that is used for urge incontinence takes the form of substances that relax or desensitize the detrusor (antimuscarinics, oestrogens, alpha-blockers, beta-mimetics, botulinum toxin A, resiniferatoxin, vinpocetin), while stress incontinence requires stimulation of the sphincter and pelvic floor (alpha-mimetics, oestrogens, duloxetin). Bladder function disturbances in children can be classified by noninvasive methods, but the therapy remains a difficult endurance test for the children, their parents and the doctor, often extending over years.

Adult↗
PubMed2006

[Massive adenomyosis in a patient with uterus septus completus].

Septate uterus is a malformation caused by the defective resorption of the Müllerian ducts. It may be incomplete, or -- less frequently -- complete. We present a case of a uterus septus completus with special emphasis on the endometrial changes. We describe a 46-year-old female patient (nullipara) with a known uterus septus suffering from hypermenorrhea. Sonography demonstrated a massively enlarged uterus with several nodes. Hysterectomy was performed and tissue specimens were routinely processed. Macroscopical examination revealed a 1 230 g-weight uterus septus completus. In particular, the myometrium was enlarged and exhibited a cystic cut surface with several nodes measuring up to 4.5 cm. Histologically, we found prominent adenomyosis with several leiomyomas. Patients with uterine malformations are known to suffer from endometrial dysfunction, most commonly due to endometriosis. However, massive adenomyosis in combination with leiomyomas, as presented in this case report, has not been described so far. These endometrial changes are important, since they significantly contribute to infertility.

Adenomyoma↗
PubMed2006

[Plastic reconstructive procedures of vulvar carcinoma: results and complications].

PURPOSE: This study describes the results of the plastic reconstructive measures in 207 patients with a primary or a recurrent vulvar cancer. These procedures were analysed in sight of surgical excision, previous therapy, and detailed postoperative results. METHODS: All procedures and clinical parameters were recorded standardized in a data bank and analysed using statistical methods. RESULTS: In 123 local (cutaneous or fasciocutaneous) and 84 regional (myocutaneous) flaps we found a primary healing in about 2/3 of the cases. Local flaps exhibited secondary healing in 31 %, regional flaps in 20 %. This often involved the donor sites and generally did not present any permanent problems. Pronounced healing disturbances (necrosis of more than 10 %) was not achieved in local flaps, in regional flaps it aroused in 5.9 %. Gluteal femoral flaps were used most frequently and showing the best results of all myocutaneous flaps. They were comparable with the local reconstructions by a high degree of reliability and healing. In 15 cases a tissue-loss was observed. In these patients, elevated risk factors, certain oncological characteristics and technical problems could be demonstrated. CONCLUSION: Plastic surgery enlarges the spectrum of operative therapy of vulvar cancer, especially in extensive or recurrent tumors, leading to a favourable oncological outcome and good cosmetic results. Severe healing disturbances are rare and can be controlled.

Adult↗
PubMed2005

[Recommendations for the handling and oncologic pathology report of lymph node specimens submitted for evaluation of metastatic disease in gynecologic malignancies].

The nodal status is one of the strongest prognostic factors in gynecologic malignancies. Metastatic involvement of regional and distant lymph nodes represents the selection basis for adjuvant therapy in a large number of solid neoplasms. The number of resected lymph nodes is one of the most important parameters in the quality control of the surgical procedure, in particular with respect to radicality. The present paper provides recommendations for gross dissection, laboratory procedures and reporting for lymph node biopsies, lymph node dissections and sentinel lymph node biopsies (SLN) for cancers of the vulva, vagina, uterine cervix, endometrium, Fallopian tubes and the ovaries, submitted for the evaluation of metastatic disease. The pathologic oncology report should include information about the number and size of resected lymph nodes, the number of involved lymph nodes with the maximum size of metastases and the presence of paranodal infiltration. In addition, the detection of isolated tumor cells should be reported, particularly with respect to the detection method (immunostains or molecular methods). In cases of metastatic disease and carcinoma of unknown primary (CUP-syndrome), information should be given regarding the primary tumor.

Female↗
PubMed2004

[Inhibins and Activin A in hypertensive Disorders of Pregnancy and HELLP-Syndrome].

OBJECTIVE: Are serum concentrations of the ovarian glycoproteins inhibin A, inhibin B, pro-alpha-C and activin A different in normotensive, chronical hypertensive or pregancies complicated by preeclampsia or HELLP-syndrome? What are the clinical consequences? METHODS: Serum concentrations of inhibin A, inhibin B, pro-alpha-C, and activin A of 99 women (37 normotensive patients, 23 patients with chronical hypertension, 25 women with preeclampsia and 14 patients with HELLP-syndrome) at different stages of pregnancy were determined by high specific ELISAS. RESULTS: During pregnancy serum levels of all parameters increased continually and fell rapidly within parturition. Activin A and inhibin B levels showed significant higher serum concentrations in patients with preeclampsia and - even more pronounced - in patients with HELLP-syndrome. Normotensive and chronically hypertensive patients were not different. CONCLUSION: Activin A and inhibin A appear to be viable candidates as laboratory parameters for detection of pregnancy induced hypertension. Maybe furthermore both parameters will allow the discrimination between chronic hypertension and hypertension induced by pregnancy.

Activins↗
PubMed2004

Importance of ets1 proto-oncogene for breast cancer progression.

Ets proteins are transcription factors, which share a unique DNA binding domain, the Ets domain. Some members of the Ets family are implicated in tumorigenesis. Ets1, the founder of the Ets family, is predominantly expressed in invasive tumors and able to activate certain genes encoding ECM-degrading proteases. We used RNA-interference in combination with DNA chip analysis to identify Ets1-regulated genes in MDA-MB-231 breast cancer cells. Of the Ets1-responsive proteases, matrix metalloproteases MMP1 and MMP9, but not MMP3 or uPA, showed reduced RNA levels when endogenous Ets1 expression was suppressed. These data suggest that Ets1 regulates only a certain subset of ECM-degrading proteases. How Ets1 is regulated in invasive breast cancer cells is unknown. The observations that protein kinase C inhibitors abrogated Ets1 expression and that protein kinase C was able to increase Ets1-dependent transcription imply that protein kinase C is a potential regulator of Ets1 activity in breast cancer cells.

Breast Neoplasms↗
PubMed2003

Multicenter phase II study of oral capecitabine (Xeloda(")) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapy.

BACKGROUND: Capecitabine is a rationally designed oral, tumor-activated fluoropyrimidine carbamate with high activity in metastatic breast cancer. This multicenter phase II study was designed to evaluate further the efficacy and safety of capecitabine in patients with metastatic breast cancer previously treated with a taxane-containing regimen. PATIENTS AND METHODS: All patients had to have documented progression after paclitaxel- or docetaxel-containing chemotherapy. Treatment comprised 3-week cycles of oral capecitabine 1250 mg/m(2) twice-daily for 14 days followed by a 7-day rest period. RESULTS: One hundred and thirty-six patients were enrolled. Disease stabilization occurred in 63 patients (46%) and the overall response rate was 15% (95% confidence interval 10% to 23%), providing an overall tumor control rate of 62%. Median time to progression was 3.5 months, median duration of response was 7.5 months and median overall survival was 10.1 months. Capecitabine was generally well-tolerated: most treatment-related adverse events were grade 1/2 in intensity; grade 3/4 treatment-related adverse events were hand-foot syndrome (13%), diarrhea (8%), vomiting (4%) and nausea (3%). There were no treatment-related deaths. CONCLUSIONS: This study confirms that capecitabine achieves a high tumor control rate in heavily pretreated patients with metastatic breast cancer. Due to its favorable safety profile and convenient oral administration, capecitabine can be given as an outpatient therapy. Capecitabine should be considered the reference treatment in this setting based on consistently high efficacy and good tolerability.

Administration, Oral↗
PubMed2001

An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria.

Infections with parasitic helminths are important causes of morbidity and mortality worldwide. New drugs that are parasite specific and minimally toxic to the host are needed to counter these infections effectively. Here we report the finding of a previously unidentified compound, nafuredin, from Aspergillus niger. Nafuredin inhibits NADH-fumarate reductase (complexes I + II) activity, a unique anaerobic electron transport system in helminth mitochondria, at nM order. It competes for the quinone-binding site in complex I and shows high selective toxicity to the helminth enzyme. Moreover, nafuredin exerts anthelmintic activity against Haemonchus contortus in in vivo trials with sheep. Thus, our study indicates that mitochondrial complex I is a promising target for chemotherapy, and nafuredin is a potential lead compound as an anthelmintic isolated from microorganisms.

Administration, Oral↗
PubMed2001

Prognostic significance of local recurrence in breast cancer after postmastectomy radiotherapy.

PURPOSE: We have retrospectively analyzed the impact of local recurrence in patients with adjuvant radiation therapy after mastectomy for breast cancer. PATIENTS AND METHODS: From January 1985 through December 1993, 959 patients were irradiated after mastectomy for breast cancer. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3-12.2 years). 368 (38%) were pre- and 591 (62%) postmenopausal. 35% had T3-4 tumors, 62% had axillary lymph node involvement, and 66% received additional systemic hormonal and/or cytotoxic therapy. Postmastectomy radiotherapy was administered in case of positive axillary nodes and in high-risk pN0-patients. The chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field with 50 Gy and the chest wall with an electron field with 44 Gy in 2-Gy fractions. RESULTS: The overall survival was 70.5% after 5 and 59.8% after 10 years. 53 patients (5.5%) developed a locoregional recurrence 2-96 months after treatment (median 26 months). The local control rate was 92.7% after 5 and 86.4% after 10 years. Axillary lymph node involvement was the most important and (in a multivariate analysis the only) risk factor for local recurrence (p = 0.0001). Patients with local control had a significantly better 10-year distant-disease-free survival and overall survival as compared to patients with local recurrence (44.5% vs 15.4%, p = 0.002 and 62.1% vs 34.8%, p = 0.004). Local recurrence increased the risk of death by a factor of 1.7 and in a Cox regression model, axillary lymph node status, T-category and local recurrence were significant prognostic factors for overall survival. In patients with local recurrence, the initial axillary lymph node status was the most important prognostic factor for survival after local recurrence. The 3-year survival after local relapse was 86% for patients with pN0 status vs 27% in with positive axillary nodes (p = 0.025). CONCLUSIONS: Local recurrence after treatment of breast cancer with mastectomy + radiotherapy +/- systemic therapy is associated with a significantly higher risk of distant metastases and death. In this analysis, local recurrence was a strong and, besides lymph node status and T category, an independent risk factor for survival. Minimizing the risk of local recurrence is therefore an essential goal of a curative treatment concept.

Adult↗
PubMed2001

[New knowledge regarding tumor cell inactivation and histological evaluation after radiofrequency therapy. Single case observation and in vitro proof of a new hypothesis].

In a study, a radiofrequency (RF) treatment was performed on a patient with a small breast cancer after vacuum biopsy. As usual in cases with a malignant diagnosis, surgical excision and axillary dissection followed. Histopathology revealed some residual tumor in the margin of the cavity. It could not be distinguished from vital tumor on the hematotoxylin eosin (HE) stain. Based on the correlation of MRI and histopathology after subsequent surgical excision, we did, however, presume that the residual was contained within the zone of inactivation. Thus the hypothesis arose that, if too high temperatures can be avoided, it might be possible to inactivate tumor cells without significantly impairing histopathologic assessment. This hypothesis was supported by the following in vitro experiment performed on a fresh specimen: An RF treatment was performed using temperatures up to 70 degrees C only. Half of the specimen underwent HE-staining, the other half vitality testing. The results indicate that if a given temperature range is strictly observed it appears possible to inactivate tissue before tissue sampling, since histopathologic diagnosis will not be impaired. Further technologic improvements may eventually allow to develop a pre-treatment method which might permit to avoid potential hematogenous tumor spread during subsequent biopsy.

Biopsy↗
PubMed2001

[Operative standard therapy of micro- and macro-invasive carcinoma of the cervix].

Radical hysterectomy with bilateral lymphonodectomy represents one of the most important strategies in the treatment of cervical cancer, especially in early stage disease with small tumor volume. Nowadays, 5-year survival rates of patients with stage IB and IIA range between 87% and 92%. Ovary preserving management in cervical cancer is justified in early stage disease and younger women (< 45 years), and regarded as standard treatment. Therapy of microinvasive cervical cancer (Stage Ia1 und Ia2) depends on depth of invasion, superficial spread of lesion, and other prognostic criteria. Exact work-up of the cone is the basis for successful treatment. A great variety exists in regard to radicality of surgery in patients with cervical cancer--ranging between modified radical hysterectomy and radical hysterectomy with resection of the parametria to both pelvic side walls. Assessment of lymph node status is mandatory for individual treatment. Pelvic lymphonodectomy represents standard treatment at radical hysterectomy, and if positive, paraaortic lymphonodectomy is indicated. Micturition disorders, urinary incontinence, lymph cysts, bowel problems, thrombophlebitis, urogenital fistulas, and pulmonary embolism are the most frequent complications following radical hysterectomy. Today, there is an increasing competition between different therapy strategies in cervical cancer such as primary irradiation, chemoradiation, neoadjuvant chemotherapy, laparoscopic radical hysterectomy, vaginal radical hysterectomy combined with laparoscopic surgical staging. All these treatment modalities have to be compared with the "golden standard" comprising survival and recurrence rates functional results, morbidity, mortality and quality of life.

Cervix Uteri↗
PubMed2001

[Pregnancy, childbirth and the pelvic floor].

Pregnancy and vaginal delivery are responsible for the onset of genuine stress urinary incontinence, and pelvic floor damage. A striking dearth of prospective studies exists regarding the relationship of pregnancy and delivery to these problems. The vast majority of published data is based on analysis retrieved from questionnaires. Most damage of the pelvic floor obviously occurs during first delivery. Objective findings have demonstrated pudendal nerve damage mostly found after forceps delivery, increased duration of second stage of labour, third degree perineal tear and high birth weight. Episiotomy offers no protection against perineal tears and should be restricted to specified feto-maternal indications. Longitudinal studies are needed to assess long term consequences of pregnancy and child birth on both, lower urinary tract and pelvic floor function.

Female↗
PubMed2001

[Surgical concepts in female urinary stress incontinence].

Severe anatomical and functional defects and failure or rejection of conservative treatment are clear indications for surgical repair of sphincter incompetence. Adequate pretherapeutical diagnostic work-up should rule out other reasons for incontinence and additional pathology and allow adequate selection of the surgical technique. Prospective randomized studies as well as meta-analyses enable us to recognize suitable procedures; for primary surgery colposuspension and tension-free vaginal tapes (TVT), and in selected cases traditional slings can be recommended, whereas vaginal repairs, needle suspensions and the different injectables should not be encouraged for primary cases.

Female↗
PubMed2000

Could we treat more unruptured ectopic pregnancies with intramuscular methotrexate?

The main reason for the restricted use of methotrexate in the treatment of ectopic pregnancy (EP) obviously is the fear of tubal rupture in patients with lower abdominal pain after the administration of methotrexate. Therefore, we wanted to find out if patient characteristics at first presentation, such as age, pretreatment beta-hCG level, adnexal mass as visualized by transvaginal ultrasonography, or history of prior EP, would identify patients at risk for tubal rupture if they were hemodynamically stable and showed no signs of peritoneal irritation. We examined whether more patients could have been treated medically with methotrexate, because tubal rupture was unforeseeable at first presentation and inclusion criteria for methotrexate treatment were fulfilled. From January 1996 to August 1998, 122 patients diagnosed as having EP were treated at the Gynecologic Department of the University Hospital of Vienna. Inclusion criteria for medical treatment with intramuscular methotrexate (50 mg/ m(2) body surface area) were (1) hemodynamic stability, (2) an unruptured ectopic mass < or = 5 cm at the greatest dimension demonstrated at transvaginal ultrasonography; (3) beta-hCG level < or = 5,000 mIU/ml; (4) no cardiac activity of the extrauterine embryo; (5) wish of future fertility, and (6) informed consent. Patients with hemodynamic instability, severe abdominal pain, an ectopic mass > or = 5 cm at the greatest dimension, beta-hCG levels > or = 5,000 mIU/ml, cardiac activity of the extrauterine embryo, and no wish of future fertility, or disagreement with methotrexate treatment, primarily underwent surgery. Despite the fact that none of the above patient characteristics at first presentation identified patients at risk for tubal rupture, only 60/122 patients (49%) actually underwent medical treatment whereas our inclusion criteria would have granted medical treatment in 101/122 patients (83%). We determined the actual and maximal possible percentages of patients with unruptured EP eligible for medical treatment of EP with intramuscular single-dose methotrexate 50 mg/m(2) body surface area. Our data show that tubal rupture in hemodynamically stable patients is not foreseeable and should not lead to a restricted use of medical treatment in patients preferring methotrexate.

Adult↗
PubMed2000

Argadin, a new chitinase inhibitor, produced by Clonostachys sp. FO-7314.

A new chitinase inhibitor, designated as argadin (1), was isolated from the cultured broth of a fungal strain FO-7314. The strain was identified as Clonostachys sp. from the morphological characteristics. Argadin was purified from the cultured mycelium by a combination of cation exchange, adsorption and gel filtration chromatographic methods. The structure of argadin was elucidated as cyclo(Nomega-acetyl-L-arginyl-D-prolyl-homoseryl-histidyl-L- 2-aminoadipyl) in which homoseryl gamma-methylene bonded to histidyl alpha-amino residue. The IC50 value of argadin against Lucilia cuprina (blowfly) chitinase was 150 nM at 37 degrees C and 3.4 nM at 20 degrees C. Argadin arrested the moult of cockroach larvae upon injection into the ventral abdominal part.

Animals↗