Current Challenges and Perspectives in Breast Cancer in Elderly Women: The Senologic International Society (SIS) Survey.

Objective: Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives. Materials and Methods: The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives. Results: Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials. Conclusion: Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women.

Biologic meshes and synthetic meshes in cancer patients: a double-edged sword: differences in production of IL-6 and IL-12 caused by acellular dermal matrices in human immune cells.

PURPOSE: In 2005, Breuing et al. first described the use of acellular dermal matrices (ADMs) in breast cancer patients. ADMs are assumed to be safe to use in an oncologic setting, but data from controlled studies are still needed. Here, we investigate the effects of ADMs on the production of interleukin (IL)-6 and IL-12, key regulators of immune suppression and activation. METHODS: Strattice (ST), CollaMend (CM), and Biodesign (BD) biologic meshes and TiLoop, a synthetic mesh (TL), were used in this study. We isolated myeloid dendritic cells (MDCs), untouched plasmacytoid dendritic cells (pDCs), naïve B cells, and CD8+ T cells and co-cultured these cells with either the biologic meshes or TL. As positive controls, we used CpG ODN 2216 or lipopolysaccharide (LPS). The cytokine concentrations of IL-12p70 and IL-6 were determined after 7 days using sandwich ELISA sets. RESULTS: There were highly significant differences between the ADMs and TL in terms of their ability to stimulate immunologic responses. IL-6 expression was significantly increased in B cells (p = 0.0006131) and T cells (p = 0.00418) when comparing TL and ADMs. We also identified significant differences in IL-12 production by B cells (p = 0.0166) and T cells (p = 0.003636) when comparing TL and ADMs. CONCLUSIONS: Despite the assumed lack of an immunological response to ADMs, in our experimental study, human immune cells reacted with significantly different cytokine profiles. These findings may have implications for the potential activation or suppression of effector cells in cancer patients and could explain some of the post clinical post surgical signs of ADMS like skin rush and seroma.

Neoadjuvant radiotherapy followed by mastectomy and immediate breast reconstruction : An alternative treatment option for locally advanced breast cancer.

BACKGROUND: The optimal sequence of mastectomy with immediate breast reconstruction (IBR) and radiotherapy (RT) for the treatment of locally advanced breast cancer (LABC) is still under debate. Increased rates of postoperative complications are described following postmastectomy RT. Neoadjuvant RT aims to improve the aesthetic results and simplify the reconstructive pathway. PATIENTS: A total of 22 patients diagnosed with LABC and treated with neoadjuvant RT followed by mastectomy and IBR between 04/2012 and 03/2015 were retrospectively analyzed. RT consisted of external beam RT to the breast and the regional lymphatics, if indicated. Both implant-based and autologous tissue-transfer reconstruction techniques were used. RESULTS: At the time of RT, 10 patients had no prior surgery and 12 patients had previously undergone breast-conserving surgery (BCS) with positive resection margins without the possibility to perform a second BCS. Additional neoadjuvant chemotherapy was administered in 18 patients prior to RT. A complete pathological response was achieved in 55.0% of patients. The 2­year overall survival rate was 89.3%, the 2­year disease-free-survival 79.8% and the local-recurrence-free survival was 95.2%. The cosmetic result was excellent or good in 66% of the patients treated with upfront mastectomy and 37% of the patients who had previously undergone BCS. Among patients who received implant-based IBR, 4 patients developed serious wound-healing problems with implant loss. The most satisfactory results were achieved with autologous tissue reconstruction. CONCLUSION: A sequential neoadjuvant chemo-/radiotherapy to allow IBR following mastectomy in selected cases of LABC seems feasible and can be safely attempted. Careful patient selection, close monitoring, and continuous patient support is mandatory to ensure compliance in this treatment strategy.

Expression of the Tumor-associated Mucin 1 Epitope Analyzed with the Humanized PankoMab-GEX™ Antibody in Malignant and Normal Tissues of the Head and Neck.

BACKGROUND: During neoplasia, glycosylation changes. In this setting, mucins, especially mucin 1 (MUC1), become carriers for oncofetal carbohydrates and relieve invasive growth. The recently described tumor-associated MUC1 epitope TA-MUC1 is primarily restricted to malignancies and is overexpressed in these tissues. The humanized monoclonal antibody PankoMab-GEX specifically recognizes TA-MUC1. MATERIALS AND METHODS: Laryngeal cancer specimens (n=125) and normal tissue of head and neck (n=7) were used in this study. Paraffin-embedded sections were incubated with PankoMab-GEX. Staining reaction was carried out using peroxidase (POD) labeling and diaminobenzidine (DAB). Breast cancer tissue was used as positive control and negative control used non-specific mouse IgM. Semi-quantitative evaluation by two independent double-blinded investigators, including a pathologist, used the immunoreactive score (IRS) of Remmele and Stegner. RESULTS: A total of 31 out of 125 laryngeal cancer specimens were classified as G1. Of these, 22 (71%) were completely negative for TA-MUC1, the remaining 9 showed very weak staining, with an IRS of 2. A total of 94 cases of cancer specimens were classified as G2 and G3; 34 of them were also negative, but 60 had an IRS of up to 9. All investigated normal tissue of the upper aerodigestive tract was completely negative for TA-MUC1. CONCLUSION: G1 tumors are completely negative or do not reach an IRS relevant range. The finding that G1 tumors are completely negative for TA-MUC1 or have IRS≤2 can be helpful for histopathological examination, especially concerning tumor grading. Therefore, this antibody holds great potential for use as a therapeutic antibody in laryngeal cancer.

Glycodelin A - a famous lipocalin and its role in breast cancer.

Lipocalins are a large protein family with only little sequence homology but highly conserved structural similarity. Many lipocalins play crucial roles in the generation of epithelial cancer, influencing pathways which regulate cell motility, cell differentiation and neovascularisation. Thereby they can be used as biomarkers of cancer, in most cases for a rather good prognosis. Glycodelin is a lipocalin existing in three isoforms which differ only by glycosylation, but which have different functions. In breast cancer, glycodelin A is known to contribute to a more differentiated cell morphology and is a biomarker for a favourable prognosis, but also plays a role in angiogenesis. Glycodelin A is a useful prognostic marker as it can be detected in serum samples, but is also a target for therapeutical interventions.

Prophylactic mastectomy with immediate reconstruction combined with simultaneous laparoscopic salpingo-oophorectomy via a transmammary route: a novel surgical approach to female BRCA-mutation carriers.

INTRODUCTION: Breast reconstruction with salpingo-oophorectomy can easily be performed in patients with genetic mutations increasing the risk for mammary and ovarian carcinoma. However, many patients are skeptical about having several surgeries, as they may result in additional anesthesiological risks as well as multiple visible scars. Therefore, the purpose of this study was to evaluate the feasibility of prophylactic mastectomy and breast reconstruction combined with simultaneous transmammary salpingo-oophorectomy for BRCA carriers. MATERIALS AND METHODS: Of the six patients (1 %) who chose prophylactic mastectomy with salpingo-oophorectomy at our hospital four patients had BRCA-1 mutations, one patient had a BRCA-2 mutation and one patient had a family inheritance pattern with no mutations. All patients chose to reduce their risk for mammary and ovarian cancer by undergoing bilateral mastectomy and bilateral salpingo-oophorectomy. Prophylactic mastectomy with immediate reconstruction was performed, followed by bilateral salpingo-oophorectomy with a procedure that relies on transmammary access and reduces the number of necessary surgeries without compromising cosmetic results, surgical risks and operating time. RESULT: The mean age of the patients was 46.7 ± 1.8 years (SD). The mean operative time was 190.2 ± 13.7 min. No complications were observed during the operations. The mean intra-operative loss of blood was 363.3 ± 77.9 ml. The operative method was successful in all six cases and was performed with no complications. All of the patients were satisfied with the cosmetic results. CONCLUSION: In conclusion, prophylactic mastectomy and breast reconstruction combined with simultaneous laparoscopic salpingo-oophorectomy via transmammary access is feasible, easy to perform and provides an intriguing and novel approach to female BRCA carriers who desire operative prophylactic measures in one surgical session with no visible abdominal scars and no additional risks and complications.

Significance of the tumor protease cathepsin D for the biology of breast cancer.

Cathepsin D is a protease involved in the metastasis and angiogenesis of mammary carcinomas. This review analyzes the significance of the tumor protease cathepsin D in mammary carcinomas as a tumor marker. We present a systematic overview based on a selective Medline search. Cathepsin D is expressed in mammary carcinomas and exhibits higher expression in invasive ductal carcinomas compared with lobular carcinomas. Nodal positive carcinomas showed reduced cathepsin D expression compared to lymph node metastases, and increased expression has been observed in hormone-receptor negative tumors. Thus, the expression of cathepsin varies between the two histological types. Increased cathepsin-D expression in acinar affection has also been described. The lack of an association of cathepsin D with known prognostic factors such as CA15-3, ERalpha and ERbeta does not prevent it from being using as a tumor marker. Cathepsin has already been used along with other genes as a prognostic parameter for carcinoma patients in gene arrays.

Loss of LDOC1 expression by promoter methylation in cervical cancer cells.

Cervical cancer lacks reliable prognostic factors for both progression and chemotherapeutic responsiveness. The expression of the LDOC1 tumor suppressor candidate was therefore investigated. In four of six cervical cancer cell lines tested, expression of LDOC1 was silenced. Downregulation of LDOC1 could also be shown in biopsies of cervical cancer specimens. PCR-based promoter methylation analysis revealed a significant association between promoter methylation and the loss of LDOC1 expression, which could be reverted by DNA methyltransferase inhibitors. This indicates that silencing of LDOC1 is a frequent event in cervical cancer and may be of interest as a molecular marker in cervical cancer.

Multicentric and multifocal versus unifocal breast cancer: differences in the expression of E-cadherin suggest differences in tumor biology.

BACKGROUND: The aim of this study was to evaluate the expression of the cell adhesion-related glycoproteins MUC-1, ß-catenin and E-cadherin in multicentric/multifocal breast cancer in comparison to unifocal disease in order to identify potential differences in the biology of these tumor types. METHODS: A retrospective analysis was performed on the expression of MUC1, ß-catenin and E-cadherin by immunohistochemistry on tumor tissues of a series of 112 breast cancer patients (total collective) treated in Munich between 2000 and 2002. By matched-pair analysis, 46 patients were entered into two comparable groups of 23 patients after categorizing them as having multicentric/multifocal or unifocal breast cancer. Matching criteria were tumor size, histology grade and lymph node status; based on these criteria, patients were distributed equally between the two groups (p = 1.000 each). Data were analyzed with the Kruskal-Wallis and the Mann-Whitney tests. RESULTS: In the matched groups, we found a significantly down-regulated expression of E-cadherin in multicentric/multifocal breast cancer compared to unifocal disease (p = 0.024). The total collective showed even higher significance with a value of p < 0.0001. In contrast, no significant differences were observed in the expression of ß-catenin between multicentric/multifocal and unifocal tumors (p = 0.636 and p = 0.914, respectively). When comparing the expression of MUC1, E-cadherin and ß-catenin within the unifocal group, we found a significant positive correlation between E-cadherin and ß-catenin (p = 0.003). In the multicentric/multifocal group we observed, in contrast to the unifocal group, a significant decrease of MUC1 expression with increased grading (p = 0.027). CONCLUSION: This study demonstrates that multicentric/multifocal and unifocal breast cancers with identical TNM-staging clearly differ in the expression level of E-cadherin. We suggest that the down-regulation of E-cadherin in multicentric/multifocal breast cancer is causally connected with the worse prognosis of this tumor type.

Effects of phytoestrogen extracts isolated from pumpkin seeds on estradiol production and ER/PR expression in breast cancer and trophoblast tumor cells.

Phytoestrogens have a controversial effect on hormone-dependent tumours. Herein, we investigated the effect of the pumpkin seed extract (PSE) on estradiol production and estrogen receptor (ER)-α/ER-ß/progesterone receptor (PR) status on MCF7, Jeg3, and BeWo cells. The PSE was prepared and analyzed by mass spectrometry. MCF7, Jeg3, and BeWo cells were incubated with various concentrations of PSE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the PSE on ER-α/ER-ß/PR expression was assessed by immunocytochemistry. The PSE was found to contain both lignans and flavones. Estradiol production was elevated in MCF7, BeWo, and Jeg3 cells in a concentration-dependent manner. In MCF7 cells, a significant ER-α downregulation and a significant PR upregulation were observed. The above results after properly designed animal studies could highlight a potential role of pumpkin seed's lignans in breast cancer prevention and/or treatment.

The inhibin-ßC subunit is down-regulated, while inhibin-ßE is up-regulated by interferon-ß1a in Ishikawa carcinoma cell line.

INTRODUCTION: Inhibins are important regulators of the female reproductive system. Recently, two new inhibin-subunits ßC and ßE have been described, although, their function is still quite unclear. Interestingly, there is an association between interferon and TGF-ß expression. Therefore, the aim of this study was to determine expression changes of inhibin-ßC and -ßE subunits in endometrial Ishikawa carcinoma cell line after stimulation with interferon-ß1a. MATERIALS AND METHODS: The Ishikawa cell line was cultured until confluence was observed (after 2 days). After adding interferon-ß1a (1,000 IE/ml), Ishikawa cells were analyzed for inhibin-ßC and -ßE subunits by RT-PCR. The fibroblast cell line BJ6 served as negative control. Experiments were performed in triplicates. RESULTS: The endometrial adenocarcinoma cell line Ishikawa synthesized the inhibin- ßC and -ßE subunits. The fibroblast cells BJ6 did not demonstrate an inhibin -ßC and -ßE mRNA expression, while inhibin-ßC subunit is down-regulated and inhibin-ßE is up-regulated in Ishikawa carcinoma cell line after stimulation with interferon-ß1a in Ishikawa. DISCUSSION: We demonstrated for the first time a functional relationship between interferon and the novel inhibin-ßC and -ßE subunits. It might be possible that interferon exerts a possible apoptotic function through the ßE-subunit, while, by down-regulating the ßC isoform, cell proliferation is inhibited. However, the precise function of the novel ßC- and ßE-subunits are still not known in human endometrial tissue and a possible association with interferon is still unclear and warrants further research.

Analysis of Epithelial Growth Factor-Receptor (EGFR) Phosphorylation in Uterine Smooth Muscle Tumors: Correlation to Mucin-1 and Galectin-3 Expression.

Uterine fibroids are the commonest uterine benign tumors. A potential mechanism of malignant transformation from leiomyomas to leiomyosarcomas has been described. Tyrosine phosphorylation is a key mechanism that controls biological functions, such as proliferation and cell differentiation. The aim of the current study was to evaluate the phosphorylation of epithelial growth factor-receptor (EGFR) in normal myometrium, uterine myomas and uterine leiomyosarcomas. Formalin-fixed paraffin-embedded tissue samples from normal myometrium, leiomyomas and leiomyosarcomas were studied. Samples were immunohistochemically (IHC) assessed using the anti-EGFR phosphorylation of Y845 (pEGFR-Y845) and anti-pEGFR-Y1173 phosphorylation-specific antibodies. IHC staining was evaluated using a semiquantitative score. The expression of pEGFR-Y845 was significantly upregulated in leiomyosarcomas (p < 0.001) compared to leiomyomas and normal myometrium. In contrast, pEGFR-Y1173 did not differ significantly between the three groups of the study. Correlation analysis revealed an overall positive correlation between pEGFR Y845 and mucin 1 (MUC1). Further subgroup analysis within the tumoral group (myomas and leiomyosarcomas) revealed an additional negative correlation between pEGFR Y845 and galectin-3 (gal-3) staining. On the contrary no significant correlation was noted within the non-tumoral group. An upregulated EGFR phosphorylation of Y845 in leiomyosarcomas compared to leiomyomas implicates EGFR activation at this special receptor site. Due to these pEGFR-Y845 variations, it can be postulated that MUC1 interacts with it, whereas gal-3 seems to be cleaved from Y845 phosphorylated EGFR. Further research on this field could focus on differences in EGFR pathways as a potentially advantageous diagnostic tool for investigation of benign and malignant signal transduction processes.

Her-2/neu expression is a negative prognosticator in ovarian cancer cases that do not express the follicle stimulating hormone receptor (FSHR).

BACKGROUND: Anti-Her-2 treatment is successfully administered to Her-2 overexpressing breast cancer patients and significantly implicates upon their survival. Building on these promising results, anti-Her-2 treatment protocols were tested as an option for epithelial ovarian cancer (EOC) as well. However Her-2 signalling is known to be modulated by G-protein coupled receptors (GPCR). Since a common GPCR in ovarian cancer is the FSH receptor (FSHR), we investigated the prognostic significance of Her-2 in patients that had been stratified according to their FSHR status. FINDINGS: A total number of 153 EOC patients were included in this study. Her-2 positivity was assessed using a standard protocol. Intriguingly Her-2 turned out to be an independent prognostic marker for poor overall survival only in those patients that did not express FSHR. This did neither apply for the whole panel nor in case of FSHR co-expression. CONCLUSIONS: We thus conclude that Her-2 can be a negative prognosticator only in FSHR negative EOC cases. Hence by stratifying EOC patients according to their FSHR expression status, we introduce a diagnostic protocol to effectively select EOC patients that would most probably respond to anti-Her-2 treatment. This observation could be of clinical importance in terms of selecting the patient that would most likely benefit from anti-Her-2 treatment.

Staining of MUC1 in ovarian cancer tissues with PankoMab-GEX detecting the tumour-associated epitope, TA-MUC1, as compared to antibodies HMFG-1 and 115D8.

PankoMab-GEX is a novel humanized and glycooptimized antibody, which recognizes a novel specific tumour epitope of MUC1 (TA-MUC1). The aim of this study was to evaluate PankoMab-GEX binding to a variety of ovarian cancer specimens (n=156) and to normal ovarian tissue. In addition, PankoMab-GEX staining was compared to that of the well-known anti-MUC1 antibodies HMFG-1 and 115D8. PankoMab-GEX showed positive reactivity in serous (100% of cases, mean IRS 8.23), endometrioid (95% of cases, mean IRS 6.40), mucinous (58% of cases, mean IRS 4.17), and clear cell (92% of cases, mean IRS 7.58) carcinomas. In contrast to HMFG-1, healthy ovarian tissue was not recognized by PankoMab-GEX. Staining with antibody 115D8 was increased with staging. Cytoplasmic PankoMab-GEX staining increased with tumour grade, but no correlation was found with staging. Univariate Kaplan-Meier analysis revealed a tendency of reduced survival of patients with high expression of TA-MUC1. The findings are encouraging with respect to a potential use of PankoMab-GEX as a new therapeutic antibody for the treatment of ovarian cancer patients.

Bilateral prophylactic skin-reducing nipple-sparing mastectomy with immediate breast reconstruction using only a vascularized dermal-subcutaneous pedicle: technique and possible advantages.

PURPOSE: To present a new surgical technique regarding breast reconstruction after skin-reducing nipple-sparing mastectomy. METHOD: The current trend for immediate breast reconstruction after skin-reducing mastectomy mainly supports the insertion of subpectoral implants or the use of autologous breast reconstruction techniques. Herein for the first time, we present a case of bilateral prophylactic skin-reducing nipple-sparing mastectomy with immediate breast reconstruction, using only a dermal-cutaneous pedicle. RESULTS: The postoperative course was uneventful. Forty days postoperatively the aesthetic result was excellent. CONCLUSIONS: We believe that such technique in selected cases can present several advantages as low cost, reduced possibilities for complications associated to implant insertion or autologous reconstruction techniques and an easier mammography follow-up.

Diagnostic biomarkers of pro-inflammatory immune-mediated preterm birth.

PURPOSE: Pro-inflammatory immunity, either infectious or sterile-derived, is one of the major causes of preterm birth and associated with enhanced maternal and fetal morbidity and mortality. Diagnosing intrauterine inflammation at an early stage is tremendously important. Amniotic fluid interleukin (IL)-6 concentration is currently the most investigated diagnostic tool for detecting intrauterine inflammation. METHODS: Amniotic fluid samples were obtained from women with no signs of intrauterine infection [amniocentesis (n = 82), cesarean section (n = 110), spontaneous delivery (n = 20) and those with clinical signs of intrauterine infection or inflammation (AIS, n = 16)]. Amniotic fluid was screened by commercial ELISAs for IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, growth regulated oncogene-α (gro) α, macrophage inflammatory protein (MIP) 1α, MIP1ß, histone, tumor necrosis factor (TNF) α, proIL1ß and interferon γ-induced protein (IP) 10. RESULTS: ProIL-1ß, MIP1ß, IL-10 and IL-8 levels were significantly elevated in the AIS group, whereas IL-4 levels were significantly lower in the AIS group. No significant differences were found regarding IL-2, IL-6, IL-12, IL-15, IL-17, GROα, MIP1α, histone, TNFα, ProIL1ß and IP10. CONCLUSION: MIP1ß, IL-4, IL-8, IL-10 and proIL-1ß might be potential singular biomarkers in diagnosing intrauterine inflammation. The combinations of elevated levels of IL-17/GROα, MIP1ß/IL-15 and histone/IL-10 are new potentially advantageous biomarker combinations.

Decidual macrophages are significantly increased in spontaneous miscarriages and over-express FasL: a potential role for macrophages in trophoblast apoptosis.

Decidual macrophages (DM) are the second most abundant population in the fetal-maternal interface. Their role has been so far identified as being local immuno-modulators favoring the maternal tolerance to the fetus. Herein we investigated tissue samples from 11 cases of spontaneous miscarriages and from 9 cases of elective terminations of pregnancy. Using immunohistochemistry and dual immunofluorescence we have demonstrated that in spontaneous miscarriages the DM are significantly increased. Additionally, we noted a significant up-regulation of macrophage FasL expression. Our results further support a dual role for DM during pregnancy and miscarriages. We hypothesize that the baseline DM population in normal pregnancy is in line with an M2 phenotype supporting the ongoing gestation. In contrast, during spontaneous miscarriages, the increased FasL-expressing population could be a part of an M1 phenotype participating in Fas/FasL-related apoptosis. Our results highlight a new aspect of macrophage biology in pregnancy physiology and pathophysiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact.

Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid.

BACKGROUND: Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated. FINDINGS: Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age. CONCLUSION: Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.

Clinical relevance of occult stress urinary incontinence (OSUI) following vaginal prolapse surgery: long-term follow-up.

INTRODUCTION AND HYPOTHESIS: Patients with genital prolapse and occult stress urinary incontinence (OSUI) are typically treated with prolapse surgery and anti-incontinence surgery based on either a one-step approach or a two-step approach. The aim of our study was to determine whether anti-incontinence surgery is necessary based on the occurrence of OSUI in a study cohort with a long follow-up period. METHODS: Prolapse surgery was performed using a vaginal approach. Preoperatively, a stress test, a pad test and an assessment of the urodynamics were performed with and without prolapse reduction. Over a follow-up period of 2-8 years, the patients with preoperative evidence of OSUI underwent urogynaecological examinations, stress tests and pad tests. RESULTS: Of 113 patients with preoperative evidence of OSUI, 57 (50.4 %) were followed up for an average of 5.7 years (range 2-8) after prolapse surgery. Of 57 patients, 16 (28.1 %) had objective and/or subjective stress urinary incontinence (SUI) during the follow-up period, but only 3 patients (5.3 %) required subsequent tension-free vaginal tape (TVT) surgery. In 17 of 57 patients (29.8 %), prolapse recurred. CONCLUSIONS: Despite the preoperative evidence of OSUI, the manifestation of SUI rarely occurs, with 28.1 % of patients experiencing SUI over long-term follow-up after vaginal prolapse surgery. Anti-incontinence surgery was necessary in only three cases (5.3 %). These results indicate that with the one-step approach, 54 of 57 patients (94.7 %) would have received prophylactic anti-incontinence surgery unnecessarily. In conclusion, we recommend the two-step approach in the management of vaginal prolapse surgery in patients with OSUI.

Expression of different carbohydrate tumour markers and galectins 1 and 3 in normal squamous and malignant epithelia of the upper aaerodigestive tract.

AIM: Tumour markers hold a great relevance in the diagnosis and the follow-up treatment of different kinds of human carcinoma. Although head and neck cancer occurs frequently, there is still lack of appropriate tumour markers. Our investigation on the expression of sialyl Lewis A (CA19-9) in laryngeal carcinomas, consists of systematical analysis of oncofetal carbohydrates and of galectins 1 and 3 in different normal and malignant tissues of the aerodigestive tract. MATERIALS AND METHODS: Paraffin-embedded sections of normal tongue, vocal cord, larynx, pharynx and epiglottis, representing normal control tissue and laryngeal cancer tissue were incubated with monoclonal antibodies against sialyl Lewis A and X (sLeA and X), Lewis Y (LeY), the Thomsen-Friedenreich (TF) antigen and galectin 1 and 3 (Gal-1 and -3). A staining reaction was carried out with ABC-peroxidase and diaminobenzidine (DAB). Tissue of breast cancer was used as a positive control. Mouse IgM, as isotype control antibody, was used as a negative control. Semi quantitative evaluation was carried out double-blinded, by two independent investigators, including a pathologist. RESULTS: Squamous epithelia of all investigated normal tissues of the aerodigestive tract show nearly the same pattern. Most impressive findings are the very weak expression of Gal-1 and the total absence of the TF antigen. Laryngeal cancer reveals high amounts of sLeA, Gal-1 and the TF antigen. CONCLUSION: On the basis of our findings in normal tissue of the aeradigestive tract, these three markers qualified as potential tumour markers for carcinoma of the aerodigestive tract. In particular, the high expression of TF in cancer tissue and its absence from the normal tissue is promising for its establishment as a new tumour marker in this field.