Guideline-Based Strategies in the Surgical Treatment of Female Urinary Incontinence: The New Gold Standard is Almost the Same as the Old One.

The modern sling procedures for treating female stress urinary incontinence encompass numerous methods, materials and manufacturers. On the basis of the current S2e guidelines, the methods used most frequently in the diagnosis of and therapy for stress urinary incontinence in women are critically illustrated. An individualised procedure is necessary for the choice of the surgical method, especially in the presence of accompanying pathologies. This article is intended to help the treating physician to carry out quality-assured diagnostics and therapy for the patient and to offer the best possible urogynaecological management. In addition to the complications and chances of success of the surgical options, the legal aspects of therapy planning are also taken into consideration.

Diagnosis and Therapy of Female Pelvic Organ Prolapse. Guideline of the DGGG, SGGG and OEGGG (S2e-Level, AWMF Registry Number 015/006, April 2016).

Aims: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). This is a guideline published and coordinated by the DGGG. The aim is to provide evidence-based recommendations obtained by evaluating the relevant literature for the diagnostic, conservative and surgical treatment of women with female pelvic organ prolapse with or without stress incontinence. Methods: We conducted a systematic review together with a synthesis of data and meta-analyses, where feasible. MEDLINE, Embase, Cinahl, Pedro and the Cochrane Register were searched for relevant articles. Reference lists were hand-searched, as were the abstracts of the Annual Meetings of the International Continence Society and the International Urogynecological Association. We included only abstracts of randomized controlled trials that were presented and discussed in podium sessions. We assessed original data on surgical procedures published since 2008 with a minimum follow-up time of at least 12 months. If the studies included descriptions of perioperative complications, this minimum follow-up period did not apply. Recommendations: The guideline encompasses recommendations for the diagnosis and treatment of female pelvic organ prolapse. Recommendations for anterior, posterior and apical pelvic organ prolapse with or without concomitant stress urinary incontinence, uterine preservation options, and the pros and cons of mesh placements during surgery for pelvic organ prolapse are presented. The recommendations are based on an extensive and systematic review and evaluation of the current literature and include the experiences and specific conditions in Germany, Austria and Switzerland.

Complications following Tension-Free Vaginal Tapes: Accurate Diagnosis and Complications Management.

The sling procedures are the gold standard for SUI treatment. They are highly effective but not free from complications. The most common adverse effect for the surgery with the implant insertion is: overactive bladder occurring de novo after the surgery, voiding dysfunctions, urine retention, and unsatisfactory treatment outcome. The most important question that arises after 20 years of sling procedures is how to manage the complications and what can be offered to complicated patients. The above review summarises the ultrasound findings in complicated cases and shows the scheme of management of the clinical problems concerning the tape location in suburethral region.

[Tethered tape or the fourth factor. A new cause of recurrent stress incontinence after midurethral tape procedures vaginal tape insertion]. / "Tethered tape" oder der 4. Faktor. Eine neue Ursache der Rezidivbelastungsinkontinenz nach miturethralen Bändern.

BACKGROUND: This is the first report of a newly identified cause of recurrent stress urinary incontinence (SUI) after midurethral tape insertion. PATIENTS AND METHODS: This article reports a series of cases with primary or secondary tape failure including clinical presentation and findings, the results of pelvic floor (PF) ultrasound, and the (surgical) correction of malpositioned vaginal tapes. RESULTS: A vaginal tape for treating SUI must be accurately placed under the mid-third of the urethra and at a distance of 3-5 mm from the urethra. Alignment parallel to the urethra in the urethrovaginal septum is also essential for adequate function. A tethered tape refers to the adhesion of a tape edge to the anterior vaginal wall either during primary wound closure or due to secondary ingrowths and is typically associated with recurrent SUI during activities or changes in posture. Less common is SUI through an increase in pressure from cranially, which occurs when coughing or laughing. "Vaginal polyps" may point to imminent vaginal erosion of the tape. In the sagittal plane, the PF examination will identify an oblique orientation of the tape at rest, an abnormal closeness of the tape to the transducer, and changes in tape shape upon manipulation of the vaginal probe. Once the diagnosis has been established, a tethered tape is easy to correct by realignment or tightening to accomplish correct positioning parallel to the urethra. This measure restores tape function and continence. CONCLUSION: Primary or secondary failure of a tension-free vaginal tape may be caused by a tethered tape. This complication can be diagnosed on the basis of characteristic findings at PF ultrasound. In most women, the tape position can be corrected and there is no need for tape removal.

Can we place tension-free vaginal tape where it should be? The one-third rule.

OBJECTIVES: The tension-free vaginal tape (TVT) insertion technique generally does not take into account individual urethral length. In this study we investigated whether preoperative sonographic measurement of individual urethral length allows for reliable TVT positioning under the midurethra, which is a critical segment for the continence mechanism. METHODS: Urethral length was measured by preoperative introital ultrasonography in 102 consecutive female patients with stress urinary incontinence. TVT procedures were performed as recommended by the manufacturer. The suburethral incisions were initiated at one-third of the sonographically measured urethral length. TVT position and tape-urethra distance were followed up 6 months postoperatively. RESULTS: At 6-month examination of the 102 study participants, 93.1% were cured and 6.9% showed improved continence. TVTs were found in the target range of 50-70% of the urethral length in 88.2% of the cohort. Women with the TVT in the 50-70% urethral length range and a 3-5-mm tape-longitudinal smooth muscle distance had a greater likelihood of being cured without complications (P < 0.001). CONCLUSIONS: Preoperative sonographic measurement of urethral length, combined with the one-third rule, may aid in reliable midurethral TVT positioning.

Anti-inflammatory effects of atorvastatin on peripheral blood mononuclear cells and synovial fibroblasts in rheumatoid arthritis.

OBJECTIVE: Statins, such as atorvastatin (ATV), are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors known to exert lipid-lowering but also anti-inflammatory, effects. In this study, we analysed the in vitro effects of ATV on peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), a chronic inflammatory joint disease. METHODS: PBMCs isolated from 25 RA patients and 20 healthy blood donors were stimulated in vitro with 0.1 microM ATV for 24 h. PBMC cultures were analysed for cell surface markers to characterize T-cell subtypes (CD4, CD8, CD69, HLA-DR) by flow cytometry and for T helper cell type 1 (Th1) and type 2 (Th2) cytokines [interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-10] in culture supernatants by enzyme-linked immunosorbent assay (ELISA). Furthermore, RNA isolated from ATV-stimulated RA-FLS pre- and post-ATV stimulation was analysed by microarray and quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Flow cytometric analysis of T-cell subsets revealed no significant differences for CD4, CD8, CD69, and HLA-DR surface marker expression of PBMCs in RA patients and healthy controls after ATV stimulation. However, the proportion of IFN-gamma expressing CD4+ T cells and the IFN-gamma cytokine concentrations in culture supernatants were significantly reduced in T-cell cultures from RA patients. In ATV-stimulated FLS a significant downregulation of proinflammatory cytokine (IL-6) and chemokine (IL-8) expression was detected (p<0.001). CONCLUSIONS: Our study demonstrates a marked in vitro anti-inflammatory activity of ATV in RA including a systemic effect on a pathogenic CD4+ T-cell population (Th1) and a local effect on FLS. These findings may provide a scientific rationale for statins as add-on therapy in RA.

Role of bladder neck mobility and urethral closure pressure in predicting outcome of tension-free vaginal tape (TVT) procedure.

OBJECTIVE: To investigate how urethral mobility and urethral closure pressure affect the outcome of tension-free vaginal tape (TVT) insertion for stress incontinence. METHODS: A total of 191 consecutive women with genuine stress urinary incontinence with or without intrinsic sphincter deficiency were evaluated prospectively with multichannel urodynamics, 24-h voiding diaries, clinical stress tests and introital ultrasound measurements preoperatively and 6 months after surgery. Additional introital ultrasound examinations were performed immediately after the operation, at 12 months and annually thereafter. 177/191 patients had completed a 36-month follow-up at the time of writing. Urethral mobility was described as linear dorsocaudal movement (LDM), with hypermobility being defined as LDM > 15 mm on sonography. Intrinsic sphincter deficiency was defined by a maximum urethral closure pressure (MUCP) of <20 cm H(2)O. RESULTS: The overall cure rate at the 36-month follow-up was 89.5% (Kaplan-Meier estimator), with secondary cure (within 6 months of surgery) in 10.5% of these patients. The operation failed in 4.2% of the women and recurrence was seen in 6.3% of the cases. Bladder neck mobility was significantly reduced at the 6-month follow-up (P < 0.001). Compared with primary cure, therapeutic failure and secondary cure were associated with a significantly lower postoperative bladder neck mobility (P < 0.05). Postoperative hypermobility reduced the risk of therapeutic failure. In addition, women with therapeutic failure or secondary cure had a significantly lower MUCP than did those with primary cure (P < 0.01). CONCLUSION: The effectiveness of the TVT sling appears to depend on adequate postoperative urethral mobility and urethral closure pressure.

Changes in the RANK ligand/osteoprotegerin system are correlated to changes in bone mineral density in bisphosphonate-treated osteoporotic patients.

INTRODUCTION: Since the soluble receptor activator of the NF-kappaB ligand (sRANKL) as well as the endogenous anti-resorptive cytokine osteoprotegerin (OPG) are produced by osteoblasts and given that these cells undergo significant changes during antiresorptive treatment, we hypothesized that treatment with bisphosphonates (BP) would be accompanied by changes in serum OPG and sRANKL levels. METHODS: In a prospective, randomized controlled trial of previously untreated postmenopausal women with osteoporosis, oral BP therapy (daily doses of either 10 mg alendronate or 5 mg risedronate) in combination with calcium/vitamin D was compared to calcium/vitamin D treatment alone (control group). Follow-up at 2, 6 and 12 months was completed for 56 patients. Standardized spinal X-rays were performed at baseline, and DEXA measurements at the femoral neck and trochanter were made at baseline and after 1 year. Serum OPG and sRANKL levels were measured with a polyclonal antibody-based ELISA system. RESULTS: After 1 year, there was a non-significant loss in neck and trochanteric bone mineral density (BMD) in the CTR group and a mean increase of 3.3% and 4.6% in the combined BP group (both p<0.0001), respectively. Serum levels of C-terminal telopeptides of type I collagen (sCTX) and osteocalcin decreased by 12% and 10% at 12 months in the CTR group and by 43% and 23% in the combined BP group, respectively (all significant). OPG serum levels in the CTR group decreased significantly by 9% at 2 months (p<0.005) and remained below pre-treatment levels at later time points. Both the alendronate- and risedronate-treated patient groups showed unaltered OPG levels after 2 months, but they had significantly increased serum levels at 6 and 12 months. Levels of sRANKL were unchanged throughout the treatment period. Univariate regression analysis demonstrated that changes in serum OPG levels after 12 months of BP treatment were positively and better correlated to BMD changes (trochanter: r=0.59, p<0.0001; neck: r=0.50, p<0.001) than those of sCTX, which showed the expected negative correlation to BMD change (trochanter: r=-0.35, p=0.03; neck: r=-0.23, p=0.16). With multiple regression analyses at 12 months, R2 values for 1-year changes in trochanteric BMD of 0.33 (OPG alone) and 0.23 (sCTX alone) were significantly improved to the 0.57 when OPG and sCTX changes were combined (p<0.001). Results for the femoral neck were also statistically significant R2=0.35, p<0.001). BMD and OPG changes in the CTR group were not correlated with each other. CONCLUSIONS: We conclude that with BP treatment, changes in serum OPG levels, unlike changes in sCTX levels, are positively correlated to changes in BMD response. The BP-related changes in serum OPG levels during treatment could result from effects on osteoclastogenesis and osteoclast apoptosis as well as from a direct stimulatory effect on osteoblastic OPG production. These changes in OPG levels may be used to predict the individual response of patients to BP treatment.

Updated recommendations on ultrasonography in urogynecology.

Ultrasound is a supplementary, indispensable diagnostic procedure in urogynecology; perineal, introital, and endoanal ultrasound are the most recommended techniques. The position and mobility of the bladder neck can be demonstrated. In patients undergoing diagnostic work-up for urge symptoms, ultrasound occasionally demonstrates urethral diverticula, leiomyomas, and cysts in the vaginal wall. These findings will lead to further diagnostic assessment. The same applies to the demonstration of bladder diverticula, foreign bodies in the bladder, and bullous edema. With endoanal ultrasound, different parts of the sphincter ani muscle can be evaluated. Recommendations for the standardized use of urogenital ultrasound are given.

The OPG/RANKL/RANK system in metabolic bone diseases.

The OPG/RANKL/RANK cytokine system is essential for osteoclast biology. Various studies suggest that human metabolic bone diseases are related to alterations of this system. Here we summarize OPG/RANKL/RANK abnormalities in different forms of osteoporoses and hyperparathyroidism. Skeletal estrogen agonists (including 17beta-estradiol, raloxifene, and genistein) induce osteoblastic OPG production through estrogen receptor-alpha activation in vitro, while immune cells appear to over-express RANKL in estrogen deficiency in vivo. Of note, OPG administration can prevent bone loss associated with estrogen deficiency as observed in both animal models and a small clinical study. Glucocorticoids and immunosuppressants concurrently up-regulate RANKL and suppress OPG in osteoblastic cells in vitro, and glucocorticoids are among the most powerful drugs to suppress OPG serum levels in vivo. As for mechanisms of immobilization-induced bone loss, it appears that mechanical strain inhibits RANKL production through the ERK 1/2 MAP kinase pathway and up-regulates OPG production in vitro. Hence, lack of mechanical strainduring immobilization may favor an enhanced RANKL-to-OPG ratio leading to increased bone loss. As for hyperparathyroidism, chronic PTH exposure concurrently enhances RANKL production and suppresses OPG secretion through activation of osteoblastic protein kinase A in vitro which would favour increased osteoclastic activity. In sum, the capacity for OPG to antagonize the increases in bone loss seen in many rodent models of metabolic bone disease implicates RANKL/OPG imbalances as the likely etiology and supports the potential role for a RANKL antagonist as a therapeutic intervention in these settings.

Determination of bladder neck position by intraoperative introital ultrasound in colposuspension: outcome at 6-month follow-up.

OBJECTIVE: To determine whether open colposuspension modified by intraoperative ultrasound to prevent overcorrection is a safe and effective procedure. METHODS: Ninety women operated on for urodynamically proven genuine stress urinary incontinence underwent intraoperative introital ultrasound in a prospective observational clinical study. The positions of the bladder neck and proximal urethra were assessed by determining the parameters height (H), distance (D) and the urethrovesical angle (beta) perioperatively and for up to 6 months postoperatively. Colposuspension of the bladder neck was performed with a vertical height correction, DeltaH (resting H(intraop) - resting H(preop)) of 1 to 10 mm. Bladder neck positions were determined on an individual basis by introital ultrasound before, during and after surgery. RESULTS: Surgical elevation of the bladder neck (median height correction, DeltaH 4 mm) resulted in a median intraoperative elevation of 9 mm (6 months: 8 mm). All postoperative measurements showed a significant reduction of the median linear movement of the bladder neck during straining (P < 0.0001). Anti-incontinence surgery resulted in a significant reduction of funneling and hypermobility 6 months after surgery (P < 0.0001). At 6-month follow-up, 94% (85/90) of the women were continent. Evaluation immediately after surgery showed voiding difficulties and urge symptoms in 9% (8/90) of the patients each and de novo urge incontinence in 1% (1/90). CONCLUSIONS: Intraoperative introital ultrasound can help to optimize the colposuspension procedure. Ultrasonographic measurement of height H allows for objectively assessing the surgical procedure and can reduce postoperative complications by preventing excessive correction.

[Introital and perineal sonography in diagnosing stress urinary incontinence - possible clinical applications]. / Introitus- und Perinealsonographie in der Diagnostik der Stressharninkontinenz - Möglichkeiten der klinischen Anwendung.

Urogynecological ultrasound as a part of the diagnostic work-up of stress urinary incontinence enables the morphologic and dynamic assessment of the lower urinary tract and has replaced radiography in the primary diagnostic work-up of stress urinary incontinence. It is possible to classify the sonographically identified changes of the endopelvic fascia, whereby any dynamic changes must be interpreted in context with the clinical findings. Stress urinary incontinence, besides voiding dysfunction, recurrent urinary tract infections and dyspareunia, may be associated with urethral diverticula, which can be detected by ultrasound. Postoperative voiding problems, de novo urgency or recurrent urinary tract infections can be assessed by demonstrating possible causes, such as haematomas, overcorrection with postvoid residual, misplacement of the tape at the level of the bladder neck or intravesical displacement of suture or tape material. Introital and perineal ultrasound might also be used for monitoring the proper placement of sutures to reduce postoperative complications.

Introital ultrasound of the lower genital tract before and after colposuspension: a 4-year objective follow-up.

OBJECTIVE: To assess the topography of the bladder neck by introital ultrasound before and after open colposuspension. METHODS: Three hundred and ten women with urodynamically proven stress urinary incontinence were included in this long-term study to investigate the position and function of the bladder neck at rest and during straining. Height (H), distance (D), and urethrovesical angle of the bladder neck (beta) were measured by means of preoperative and postoperative introital ultrasound. Women were followed up; 152 of them (49%) completed 48 months of follow-up. RESULTS: At the 6-month follow-up examination, 90.0% of the women were continent (279/310), 3.5% (11/310) showed voiding difficulties, 3.5% (11/310) had urgency, and 1.6% (5/310) had developed de novo urge incontinence. At the 48-month follow-up, 76.8% of the patients were still continent. All postoperative measurements yielded significantly lower values for angle beta at rest and during straining compared with the preoperative results (P < 0.0001). The median linear movement of the bladder neck during straining decreased from 18.0 mm before surgery to 6.4 mm at the 48-month follow-up (P < 0.0001). The median level of ventrocranial elevation of the vesicourethral junction was 14.3 mm immediately after surgery, 9.9 mm after 6 months and 6.6 mm after 48 months. The degree of surgical bladder-neck elevation was associated with postoperative urgency/de novo urge incontinence (P < 0.0001) and voiding difficulty (P < 0.0001). CONCLUSIONS: The colposuspension procedure reduces angle beta at rest and during straining, restricts linear movement with straining, and elevates the bladder neck. Perioperative introital ultrasound improves understanding of this surgical procedure and might help to prevent postoperative complications.

[Ultrasound imaging of the lower urinary tract in women before and after colposuspension: a 6-month follow-up]. / Introitussonographie des unteren Genitaltraktes vor und nach Kolposuspension: eine sechsmonatige Nachbeobachtung.

OBJECTIVE: To evaluate the position of the bladder neck before and after open Burch colposuspension, using introital ultrasound. DESIGN: Retrospective longitudinal study using pre- and post-operative sonographic assessment of the position and function of the bladder neck. SETTING: Urogynecology units at the universities of Marburg/Göttingen and Witten/Herdecke and the DRK district hospital in Alzey, Germany. PATIENTS: 310 women undergoing open Burch colposuspension for primary genuine stress incontinence between September 1992 and December 2001. METHOD: Two-dimensional introitus sonography of the bladder neck prior to, one week and six months after surgery. RESULTS: The median age at surgery was 55 years (26 - 85). Open colposuspension lead to a 90.0 % (279/310) cure rate at 6 months with only 3.5 % (11/310) of the patients showing persistent micturation problems. A further 11.6 % (36/310) had symptoms of urgency and in 7 patients (2.3 %) a de novo urge-incontinence occurred. Post-operative bladder neck angles and movements at rest and during valsalva manoeuvre were significantly reduced while the resting bladder neck position was significantly elevated (p < 0.0001). Anatomical elevation of the bladder neck after open colposuspension varied between 2 - 39 with a median of 14.3 mm of neck elevation after one week and 9.9 mm at 6 month, respectively. Incontinence surgery lead to a significant reduction of the urethral funneling (p < 0.0001). CONCLUSION: In our series, open Burch colposuspension decreased both the bladder neck angle and the linear movement at rest and on valsalva as a result of the surgically stabilized bladder neck. Thus, our results support the hammock hypothesis that even small changes in the position of neck position are sufficient to reverse incontinence. We believe that perioperative introitus sonography is a helpful tool for the clinical assessment and documentation of not only morphological but also functional changes of the female continence organ before and after open Burch colposuspension.

Uterine cervical metastasis of breast cancer: a rare complication that may be overlooked.

BACKGROUND: Metastasis of distant malignancies to the cervix uteri is a rare occurrence and the frequency is approximately 4% for all tumours. However, the frequency of cervical metastasis of breast cancer is much lower and is estimated to range between 0.8 and 1.7%. With the exception of ovarian metastases, secondary tumours of the female genital tract are rather uncommon. Therefore, these conditions pose diagnostic problems for the clinician. PATIENT: A 40-year-old woman with the diagnosis of invasive ductal cell carcinoma of the right breast underwent mastectomy with dissection of axillary lymph nodes in 1998. Subsequently, the patient received 6 cycles of chemotherapy with cyclophosphamide, methotrexate and fluorouracil. The initial tumour stage was pT2, pN0 (0/13), M0, G2. The oestrogen and progesterone receptors were positive and expression of the C-erb-B2 coding oncogene was negative. Gynaecological and ultrasonographic examination revealed a normal cervix without evident lesions. Exfoliative cytology was negative. 14 months after treatment the patient presented with an axillary relapse and surgery, second-line chemotherapy with doxorubicine and radiation therapy of the chest wall and the axilla were performed. The patient developed liver metastases 14 months later and at this time ultrasonographic pelvic examination revealed a 2.2 cm tumour of the cervix with good vascularisation. The patient had no clinical symptoms, i.e. no vaginal bleeding or discharge. Sonomorphologically this tumour appeared as a leiomyoma of the cervix. Cervical biopsies and curettage, however, revealed metastatic carcinoma expressing oestrogen and progesterone receptors consistent with the primary breast cancer. Under palliative chemotherapy with docetaxel progression of liver metastases and cervical metastasis occurred and the patient died 9 months later. CONCLUSION: Metastatic involvement of the cervix should be considered in women with a history of breast cancer who present with vaginal bleeding or suspicious changes of the cervix on transvaginal ultrasound. Therefore, gynaecological and ultrasonographic examination of the pelvis represent an important part of the follow- up investigations in women with primary breast cancer.

[Hormonal therapy and chemotherapy of endometrial cancer]. / Hormon- und Chemotherapie beim Endometriumkarzinom.

Endometrial cancer is usually diagnosed at an early stage where surgery alone is the adequate therapy. Chemotherapy and hormonal treatment are therefore almost exclusively performed in palliative situations. Hormonal treatment with progestogens (medroxyprogesterone acetate and megestrol acetate) should be the therapy of choice primarily as these drugs are very well tolerated. Tamoxifen and GnRH analogs are further options but are seldom used. The response rates to hormonal treatment are relatively low (max. 25 %) with short remissions in most cases. - So far neither hormonal treatment nor cytotoxic chemotherapy has been shown to have substantial benefits in the adjuvant setting. In some selected high risk cases (serous papillary carcinomas, extra uterine manifestation) adjuvant chemotherapy may be an option following surgery, before or after radiotherapy. Age, general condition and morbidity of the patients need to be considered as limiting factors for chemotherapy. Crucial for the prognosis of all endometrial cancer patients however, is the stage adapted surgery. - Cytotoxic chemotherapy has failed to bring a break through in the therapy of advanced endometrial cancer. Cisplatin plus doxorubicin is the standard combination to date, with anthracyclines being the more important component. In a mono-therapy setting, doxorubicin and epirubicin are well tolerated and convenient in their efficacy. For recurrent and metastatic disease, docetaxel is being evaluated for efficacy and side effects in a multicenter phase II trial.

Migration, matrix production and lamellar bone formation of human osteoblast-like cells in porous titanium implants.

The goal of this study was to characterize growth, mineralization and bone formation of osteoblast-like cells in titanium pore channels of defined diameter. Titanium implants with continuous drill channels of diameters of 300, 400, 500, 600 and 1,000 microm were inserted into human osteoblast-like cell cultures. The ingrowth of the cells into the drill channels was investigated by transmitted-light microscopy and scanning electron microscopy. Immunofluorescence and histological analysis of 15-channel sections of each diameter were used to investigate the growth behavior and the matrix protein patterns. Mineralization was evidenced by Alizarin red staining and high-resolution microradiography. The ingrowth of human osteoblast-like cells in the drill channels occurred in a sequence of four characteristic stages. In stage 1, osteoblast precursor cells adhered to the wall of the channel and migrated three-dimensionally into the channel by forming foot-like protoplasmic processes. For all 15 sample drill channels that were investigated, the cell ingrowth over 20 days amounted on average to 793 microm (+/- 179) into 600-microm-diameter channels, where they migrated significantly faster than in all the other channels. In stage 2, approximately on day 5-7, the osteoblast-like cells began to anchor on the substrate wall by matrix proteins and to build up a dense network of matrix proteins in the drill channel. The mineralization of the extracellular matrix, while depending on cell stimulation, was initiated in stage 3, on average after 4 weeks. In drill channels of a diameter of 1,000 microm the cell growth was incomplete and no mineralization was found by radiological assessment. Starting in week 6, in the drill channels of diameters ranging from 300 to 600 microm, the network of extracellular matrix proteins and osteoblast-like cells began to form an osteon-like structure. Neither the highly developed migration behavior of osteoblastic cells nor the reorganization from a fiber-like matrix to a lamellar structure have so far been described for cell cultures.

[Diagnosis and therapy of uterine sarcoma]. / Diagnostik und Therapie der Uterussarkome.

Radical surgery in stage I and II uterine sarcoma removing all tumor manifestations is the only curative therapy option for early stage disease. Larger tumors (> 4 cm) and the presence of lymph node metastasis correlate with a high local recurrence rate. For these tumors adjuvant radiation and/or adjuvant chemotherapy may be recommended after surgical therapy. Adjuvant therapy however, should preferably be considered for uterine stromal sarcomas and mixed mesodermal tumors. The toxicity of radiation and/or chemotherapy is greater than any possible benefit for patients with leiomysarcomas as these tumors rarely respond to radiation or chemotherapy. For advanced (> stage I and II) and recurrent disease, curative therapy options are not available and palliative therapy for these patients has to take into consideration the negative side effects and weigh up quality of life against an often very limited possible benefit of such therapy.