[The results of five years follow-up prospective study of vaginal prolapse repaired by prolift total mesh surgery or sacrospinous fixation]. / Resení sestupu trí kompartmentu pomocí syntetického implantátu a sakrospinózní fixace: kohortová prospektivní studie s délkou follow-up peti let.

OBJECTIVE: The aim of the study is to compare the results of five years follow-up prospective study of vaginal prolapse repaired by prolift total mesh surgery or sacrospinous fixation. STUDY DESIGN: A single-center prospective, cohort study, in patients with defect grade II and more by POP-Q. SETTING: The Institute for the Care of Mather and Child; 3rd Medical Faculty Charles university, Prague. METHODS: Comparison of the preoperative state and the five years after the operation according POP Q, ICIQ-SF, PISQ 12, VAS. Comparison of intraoperative and postoperative complications. RESULTS: The study was attended by 142 patients; 75 patients underwent surgery Prolift Total and 67 patients sacrospinous fixation by Amreich Richter. On clinical examination at 5-year follow-up, we observed 15 (20.0%) case of anatomical failure in the Prolift group and 30 (44.8%) in the SSF group. Anatomic failure was defined clinically as Ba, C or Bp at the hymen or below. In assessing the overall condition before and five years after surgery using a VAS occurred in patients in the cohort Prolift Total decrease to 2.9 (± 1.9) from the original 7.8 (± 1.8). VAS in SSF group decreased after 5 years to 4.2 (± 2.7) of the original 7.8 (± 1.4). Values ICIQ-SF, analyzing the state of voiding PT group showed a decline from the original 6.7 (± 6.9) to 5.5 (± 5.3). A similar trend was evident even after the SSF. Parameters questionnaire PISQ-12 showed a positive increase from the original 28.6 (± 9.5) to 31.8 (± 7.9) points. PISQ-12 was improved from 28.7 (± 9.8) to 32.2 (± 7.5). CONCLUSION: Recurrences were observed more frequently in patients after sacrospinous fixation, while the quality of life questionnaires yielded comparable postoperative results. Quantity of intraoperative complications is low and both groups do not differ.

[Reconstruction of the posterior and central compartment with the Prolift Posterior: cohort study with a 5-year follow-up]. / Rekonstrukce defektu zadního a stredního kompartmentu pomocí kotveného implantátu Prolift Posterior: kohortová studie s petiletým follow-up.

OBJECTIVE: To analyse the results of the long-term prospective follow-up study of vaginal prolapse reconstructed using a Prolift Posterior. STUDY DESIGN: Prospective, cohort study. SETTING: Institute for the Care of Mother and Child, Prague. METHODS: Over a 5-year period (I/2006 - XII/2011) we prospectively followed a cohort of patients with posterior vaginal wall defect who underwent surgical reconstruction using a monofilament polypropylene implant Prolift Posterior (Gynecare, Ethicon, Inc., Piscataway, NJ, USA). Patients were invited for review at six weeks, three months, six months, 12 months and then yearly up to five years. Postoperative follow-up included the clinical examination and subjective evaluation using VAS, PISQ 12 and ICIQ SF. RESULTS: One hundred twenty-four women were included in the study, of which 14 (11.3%) had no prolapse surgery in their health history. There were no concomitant vaginal procedures such as hysterectomy or another implant surgery. The average operation time and blood loss were 64.25 min (min. 10, max. 205 min) and 115 ml (min. 10 ml, max. 1000 ml), respectively. Only one patient had a blood loss 1000 ml. There were no injuries of the urinary bladder or intestines during the needle insertion of the mesh. In the five-year period, the recurrence of posterior vaginal wall defect was observed in 4 cases (3.3%). The average time to the posterior vaginal wall recurrence prolapse was 19.5 months (min. 6, max. 36). De novo prolapse in the anterior compartment was observed in 25 patients (20.5%). CONCLUSION: In this prospective single centre study, we observed anatomical improvement in the implanted compartment with low recurrence rate. During five years follow-up period there was de novo anterior vaginal wall defect observed in 20.5% cases. The question of implant employment in urogynecology remain to be answered, however, our results show that implants have their position in reconstructive surgery.

[Cooperation between mammologist and radiodiagnostic in the management of mammary leasions in the University Hospital Kralovské Vinohrady]. / Spolupráce mamologa a radiodiagnostika pri managementu mamárních lézí ve FNKV.

Epidemiological datas describing up to date status of diagnostics and oncological parameters (incidence, mortality, prevalence, total number of pacients with breast cancer) are given in the article. Further changes are comented in this field after start of mammografic screening programme in our country in the year 2002. Authors evaluated possibilities of clinical diagnostics performed by mammologist in his ambulance and possibilities and types of invasive and noninvasive (immaging) diagnostic methods performed by radiodiagnostic according mammologist indication. Management of benign and malignant leasions detected and treated in the mammological centre of the University Hospital Královské Vinohrady are mentioned.

[The injury of bladder without penetrate during the TVT surgery for stress incontinence]. / Nepenetrující poranení mocového mechýre pri antiinkontinencní operaci (TVT).

OBJECTIVE: The aim of this article is alert to possibile of non-penetrating injury of bladder and risk of extraperitoneal bleeding during the TVT surgery when the tape is inserted by retropubic path. This type of injury can't be find by cystoscopy and there can be a serious blood loss in to the interstitial space. According this fact, there is a great importance of this injury and there is an urgent need to prompt reaction on this situation. In this way, we do prevent serious risk of health damage. DESIGN: Case report. SETTING: Department of Obstetrics and Gynaecology, 3rd Faculty of Medicine, Charles University, Faculty Hospital Královské Vinohrady, Prague. METHODS: The different authors presents various percentage of complications in the case of TVT surgery. The differences follow from size of patient´s group, type of surgical procedure, type of the tape and the way of tape insertion. Nevertheless, differences between these results are statistically nonsignificant. CONCLUSIONS: The operation´s complications and early after operation´s complications can arise in the course of any surgery and iatrogenic complications also belong to this group. Minimally invasive surgery is certainly make not an exception. The most often signs of these complications are abdominal pain, presence of blood in urine, anemia, malfunction of bladder and possible breakdown of intestinal activity. If the conservative methods failed, we have to perform operating inspection. The cooperation with surgeon or urologist is certainly needed.

Expression of steroid receptor coactivator 3 in ovarian epithelial cancer is a poor prognostic factor and a marker for platinum resistance.

BACKGROUND: Steroid receptor coactivator 3 (SRC3) is an important coactivator of a number of transcription factors and is associated with a poor outcome in numerous tumours. Steroid receptor coactivator 3 is amplified in 25% of epithelial ovarian cancers (EOCs) and its expression is higher in EOCs compared with non-malignant tissue. No data is currently available with regard to the expression of SRC-3 in EOC and its influence on outcome or the efficacy of treatment. METHODS: Immunohistochemistry was performed for SRC3, oestrogen receptor-α, HER2, PAX2 and PAR6, and protein expression was quantified using automated quantitative immunofluorescence (AQUA) in 471 EOCs treated between 1991 and 2006 with cytoreductive surgery followed by first-line treatment platinum-based therapy, with or without a taxane. RESULTS: Steroid receptor coactivator 3 expression was significantly associated with advanced stage and was an independent prognostic marker. High expression of SRC3 identified patients who have a significantly poorer survival with single-agent carboplatin chemotherapy, while with carboplatin/paclitaxel treatment such a difference was not seen. CONCLUSION: Steroid receptor coactivator 3 is a poor prognostic factor in EOCs and appears to identify a population of patients who would benefit from the addition of taxanes to their chemotherapy regimen, due to intrinsic resistance to platinum therapy.

Site-specific CpG methylation in the CCAAT/enhancer binding protein delta (CEBPδ) CpG island in breast cancer is associated with metastatic relapse.

BACKGROUND: The CCAAT/enhancer binding protein delta (CEBPδ) is a member of a highly conserved family of basic region leucine zipper transcription factors. It has properties consistent with a tumour suppressor; however, other data suggest that CEBPδ may be involved in the metastatic process. METHODS: We analysed the expression of CEBPδ and the methylation status of the CpG island in human breast cancer cell lines, in 107 archival cases of primary breast cancer and in two series of metastatic breast cancers using qPCR and pyrosequencing. RESULTS: Expression of CEBPδ is downregulated in primary breast cancer by site-specific methylation in the CEBPδ CpG island. Expression is also downregulated in 50% of cases during progression from primary carcinoma to metastatic lesions. The CEBPδ CpG island is methylated in 81% metastatic breast cancer lesions, while methylation in the CEBPδ CpG island in primary cancers is associated with increased risk of relapse and metastasis. CONCLUSION: CCAAT/enhancer binding protein delta CpG island methylation is associated with metastasis in breast cancer. Detection of methylated CEBPδ genomic DNA may have utility as an epigenetic biomarker of primary breast carcinomas at increased risk of relapse and metastasis.

[Reproductive functions in women after cancer therapy]. / Reprodukcní funkce u onkologických pacientek.

Improvement in early diagnostics and treatment options led to an increase in the number of young oncological patients in reproductive age. These young oncological patietns have life-long consequences of treatment, such as infertility, early menopause and sexual dysfunctions. There is the possibility of maintening fertility by assisted reproduction methods. So far, ovarian stimulation followed by ICSI and cryopreservation of embryos seem to be the most successful method. Unfortunately, this method is suitable only for patients with a stable partner where there is no risk of delay because of necessary stimulation of ovulation. For patients without a partner, it is possible to freeze stimulated oocytes. Cryopreservation of immature oocytes followed by in vitro maturation seems to be a very promising method. Freezing ovarial tissues followed by transplantation is at this point only an experimental procedure. The authors present their experience with in vitro maturation of oocytes of 28 women with pregnancy rate 14.3%. Twenty-seven cases of infertility with a high risk of ovarial hyperstimulation syndrome and one case of breast cancer patient before chemotherapy were chosen for IVM.

NT5E CpG island methylation is a favourable breast cancer biomarker.

BACKGROUND: Relapse risk assessment and individual treatment recommendations remain suboptimal for breast cancer patients. In the light of existing preclinical and clinical data, we studied NT5E (5'-nucleotidase, ecto) expression and NT5E CpG island methylation in breast cancer. METHODS: We used RT-PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse NT5E in breast carcinoma cell lines and primary and breast carcinomas. RESULTS: NT5E CpG island methylation was inversely associated with NT5E expression in breast carcinoma cell lines. In clinical series, patients whose primary tumours had NT5E CpG island methylation were less likely to develop metastasis (P=0.003, OR=0.34, 95% CI: 0.17-0.69). In 3/4 paired samples, NT5E was methylated in primary tumours and demethylated in CNS metastases. Patients progressing to non-visceral as compared with visceral metastases were more likely to have NT5E CpG island methylation in primary tumours (P=0.01, OR=11.8). Patients with tumours lacking detectable methylation had shorter disease-free survival (DFS) (P=0.001, HR=2.7) and overall survival (OS) (P=0.001, HR=3). The favourable prognostic value of NT5E methylation was confirmed in oestrogen receptor negative (P=0.011, HR=3.27, 95% CI: 1.31-8.12) and in triple negative cases (P=0.004; HR=6.2, 95% CI: 1.9-20). Moreover, we observed a more favourable outcome to adjuvant chemotherapy in patients whose tumours were positive for NT5E CpG island methylation: DFS (P=0.0016, HR=5.1, 95% CI: 1.8-14.37) and OS (P=0.0005, HR=7.4, 95% CI: 2.416-23.08). CONCLUSION: NT5E CpG island methylation is a promising breast cancer biomarker.

Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas.

BACKGROUND: Calcium is an important intracellular messenger that mediates many biological processes that are relevant to the malignant process. Calcium ion channels are key in controlling the intracellular calcium, and little is known about their role in human cancer. METHODS: We used qPCR and pyrosequencing to investigate expression and epigenetic regulation of the calcium channel regulatory subunit α(2)δ-3 (CACNA2D3) in breast cancer cell lines, primary cancers and metastatic lesions. RESULTS: Expression of CACNA2D3 mRNA is regulated in breast cancer cell lines by methylation in the CpG island located in the 5' regulatory region of the gene. Expression is upregulated by azacytidine (AZA) in cells with CpG island methylation but unaffected in cells lacking methylation. In primary breast carcinomas, methylation is more common in cancers, which subsequently relapse with loco-regional and, particularly, visceral metastatic disease in both oestrogen receptor-α (ER)-positive and -negative cases. Furthermore, CACNA2D3 CpG island is frequently methylated in breast cancer that has metastasised to the central nervous system. CONCLUSION: Methylation-dependent transcriptional silencing of CACNA2D3 may contribute to the metastatic phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for risk of development of metastatic disease.

High frequency of complex TP53 mutations in CNS metastases from breast cancer.

BACKGROUND: Brain metastasis from breast cancer is usually associated with a poor prognosis and early death. Alteration of p53 may contribute to malignant progression by abrogation of apoptosis induced by oncogene activation and by acquisition of gain-of-function properties, which promote tumour aggression. Mutation in TP53 occurs at high frequency in carcinomas of the lung and gastro-intestinal tract, but is much less frequent, at 25%, in primary breast cancer. The frequency of TP53 alteration in the central nervous system (CNS) metastatic breast cancer is not known. METHODS: In all, 23 cases of histologically confirmed CNS metastatic breast cancer were identified and the coding sequence of TP53 determined. TP53 was also sequenced in two control series of primary breast carcinomas from independent clinical centres. RESULTS: We demonstrate a strikingly high frequency of TP53 mutation in the CNS metastatic lesions with an over-representation of complex mutations (non-sense/deletions/insertions). Complex mutations occur in metastatic lesions in both triple-negative breast cancer and hormone receptor/HER2-positive cases. Analysis of paired primary carcinomas and brain metastatic lesions revealed evidence for both clonal selection and generation of new mutations (missense and complex) in progression from a primary breast carcinoma to brain metastasis. CONCLUSION: Mutation in TP53 is the most common genetic alteration reported during metastasis to the brain in breast cancer.

The role of steroid receptor coactivator-3 (SRC-3) in human malignant disease.

BACKGROUND: The p160 steroid receptor coactivator (SRC) family is critical to the transcriptional activation function of nuclear hormone receptors. A key member of this family is SRC-3, initially found to be amplified and expressed in breast cancer it has subsequent been shown to be expressed in malignant disease arising from a wide range of other organs. An understanding of the potential role of SRC-3 in the pathogenesis and its possible prognostic role in a broad range of tumours will improve our general understanding of carcinogenesis as well as potentially leading to a new prognostic marker as well as new therapeutic targets. METHODS: Relevant papers were identified by searching the PubMed and MEDLINE databases for article published until 28th February 2009. Only articles published in English were considered. The search terms included "SRC-3", "AIB1" in association with the following terms: "human", "cancer" and "malignant disease". The search focused on malignant disease arising outside of the mammary gland. Full articles were obtained and references were checked for additional material when appropriate. RESULTS: SRC-3 is amplified and expressed in a wide spectrum of human malignant diseases and appears to be a potential prognostic marker in a number of different tumours. CONCLUSION: SRC-3 appears to be implicated in the possible risk of developing prostate and ovarian cancer. Its presence appears to be a marker of aggressive disease. Further research is required to determine its predictive and prognostic utility given the relative paucity of studies for each specific malignant disease.

Reconstruction of maxilla alveolus for application of dental implant in patients with cleft defect.

The prospective study of dental implant application into the reconstructed maxilla alveolus of cleft patients was started in 2001. Its aims are to specify precisely the indications, conditions and techniques, as well as the factors justifying the assumption that the results will be successful. Indication was based on an examination by a multidisciplinary therapeutic team (plastic surgeon, dental surgeon, orthodontist, and prosthetist), with the proviso that the patient should have a positive approach. Successful orthodontic treatment of intergnathic relation and shape of the dental arches served as the basis. It was followed by a reconstruction of the defective alveolus using autologous cancellous bone grafts, harvested from an iliac crest. Dental implants were inserted 12-15 weeks after the transplantation and subsequently a prosthetic component was applied with a time delay of at least 2 months. After the orthodontic preparation, reconstruction of the alveolus has so far been performed in 38 patients. Their age was at least 14 years, i.e. the age when growth of the orofacial region was finalised or already complete. The crucial tasks at this stage are to form a stable, three-dimensional voluminous alveolar crest, and to cover the grafts with a sufficient amount of quality soft tissue. We needed an average amount of 3.7 ccm of cancellous bone graft for the reconstruction. This amount can be harvested only from an enchondral bone. For soft tissue shell the mucoperiosteal shift of flap from cleft segment was used. In more serious cases contralateral or even bilateral shift was performed. The relief of tissue tension was performed by double cut-back. Using the approach described we attained a 84.2% success rate. Our results and experience derived within this project show that the success rate of this procedure depends on the continuous flow of the alveolar arch with a good intergnathic relation, with a length of defect between crowns of border teeth of at least 8 mm. The original osseous walls of the defect must definitely be of suitable height. On-lay augmentation does not work in these cases. A subsequent pitfall lies in resorption of transplanted bone, which may be reduced due to an early load by a dental implant. During the three months after the reconstruction a spongy osseous graft matures enough to ensure the primary stability of a fixture. We emphasise the necessity of close co-operation of the therapeutic team in such cases.