Long-term satisfaction of patients after laparoscopic and robotic-assisted hysterectomy.

INTRODUCTION: Da-Vinci-Xi is the most recent device used in gynecologic robotic surgery. The aim of the present study was to compare the long-term satisfaction of patients who had undergone conventional laparoscopic hysterectomy or robotic assisted laparoscopic hysterectomy using the Da-Vinci-Xi surgical system. METHODS: All hysterectomies performed at the University Hospital of Luebeck from 2018 to 2019 were reviewed. Postoperative outcomes were compared between women who had undergone total hysterectomy with da Vinci Xi (n = 42) or conventional laparoscopy (n = 97). Postoperative outcomes included pain, elimination of complaints after surgery, bladder function, sexual function, satisfaction with the cosmetic outcome, positive experiences after robotic surgery, and satisfaction with the surgeon's preoperative explanation. Obese patients were evaluated separately in a subgroup analysis. RESULTS: Both groups had similar baseline characteristics and complication rates. Preoperative complaints subsided after surgery in a little more than 90% of patients. No significant differences were noted between groups in this regard (p = 0.262), or with reference to postoperative pain after one week (p = 0.866) and one month (p = 0.580), stress incontinence (p = 0.343), sexual function (p = 0.766) and the cosmetic outcome of the abdominal incisions (p = 0.273). The majority of patients who had undergone robotic surgery (96.8%) would be willing to undergo the procedure again if necessary. The subgroup analysis of obese patients revealed no significant differences. CONCLUSION: The Da-Vinci-Xi device did not improve the long-term surgical satisfaction of normal-weight or obese patients who underwent hysterectomy compared with patients who underwent conventional laparoscopy performed by experienced laparoscopic surgeons.

Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer.

PURPOSE: Insulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC. DESIGN: Patients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses. RESULTS: 170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82-1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01). CONCLUSION: Addition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.

Influence of the second stage of labor on maternal and neonatal outcomes in vaginal births after caesarean section: a multicenter study in Germany.

BACKGROUND: The American College of Obstetricians and Gynecologists (ACOG) introduced a new standard of care in 2014, extending the duration of the second stage of labor in order to reduce caesarean delivery (CD) rates and its severe complications. The aim of the present study is to evaluate success rates of trial of labor after caesarean section (TOLAC), as well as maternal and neonatal outcomes after the establishment of the recent guidelines. METHODS: A retrospective study was performed at two large departments in Germany from January 2008 to January 2018. Patients undergoing TOLAC were divided into two groups. Group I (958 patients) was constituted before the establishment of the current guidelines, and Group II (588 patients) after the establishment of the guidelines. A subgroup analysis was performed to compare neonatal outcomes after successful TOLAC and operative vaginal delivery with those after failed TOLAC and secondary CD. RESULTS: The success rate of vaginal births after cesarean section (VBAC) fell from 66.4% in Group I to 55.8% in Group II (p < 0.001). The median duration of the second stage of labor was statistically significantly longer in Group II than in Group I (79.3 ± 61.9 vs. 69.3 ± 58.2 min) for patients without previous vaginal birth. The incidence of operative vaginal delivery decreased from Group I to Group II (9.6% vs. 6.8%). The incidence of third- and fourth-degree perineal lacerations, blood loss and emergency CD were similar in the two groups. Concerning the neonatal outcome, our groups did not differ significantly in regard of rates of umbilical artery cord pH < 7.1 (p = 0.108), the 5-min Apgar scores below 7 (p = 0.224) and intubation (p = 0.547). However, the transfer rates to the neonatal care unit were significantly higher in Group II than in Group I (p < 0.001). Neonatal outcomes did not differ significantly in the subgroup analysis. CONCLUSION: Extending the second stage of labor does not necessarily result in more vaginal births after TOLAC. Maternal and neonatal outcomes were similar in both groups. Further studies will be needed to evaluate the role of operative vaginal delivery and the duration of the second stage of labor in TOLAC.

A risk factor analysis of complications after surgery for vulvar cancer.

INTRODUCTION: Despite the less frequent use of surgery in patients with vulvar cancer, the high rates of postoperative complications are still a matter of concern. The aim of the present study was to identify risk factors that influence postoperative complications rates in vulvar cancer and identify specific clinical parameters that may influence their incidence. MATERIALS: Patients who underwent curative-intent surgery for squamous cell carcinoma of the vulva from 2003 to 2018 were selected. All patient characteristics were analyzed as risk factors for the development of postoperative lymphocele, lymphedema, and wound dehiscence. The patients were followed up for 2 years postoperatively. RESULTS: The investigation comprised 121 patients, of whom 18.1% developed wound dehiscence, 17.7% a lymphocele, and 20.4% lymphedema. We found no significant evidence of an association between patient's characteristics and postoperative complications. The depth of tumor invasion and the appearance of lymph-node metastasis were significantly associated with postoperative complications. Free resection margins of 5 mm or more were associated with a reduced risk of postoperative complications compared to resection margins less than 5 mm. No complications were encountered after sentinel node biopsy (SNB). Complication rates were associated with inguinofemoral lymphadenectomy, but not with the extent of lymphadenectomy. The development of a lymphocele or wound dehiscence may be correlated with the development of long-term lymphedema. CONCLUSION: FIGO stage at diagnosis influences the risk of postoperative complications. The use of SNB minimized postoperative complications. Correlations between the free microscopic resection margin distance and the risk of postoperative wound dehiscence must be investigated further.

Incidence of unexpected uterine malignancies after electromechanical power morcellation: a retrospective multicenter analysis in Germany.

PURPOSE: During the last decade, electromechanical power morcellation (EMM) was more frequently used but it may be associated with the dissemination of occult malignancies. The aim of the present study was to determine the frequency of unexpected uterine malignancies after EMM. METHODS: This retrospective study consisted of patients who were treated at three departments of Gynecology in Germany from 2008 to 2017. We identified women who underwent an operation with the use of EMM. Clinical records, risk factors, and the outcomes of the patients were reviewed. RESULTS: We performed an analysis of 1683 patients who had undergone laparoscopic supracervical hysterectomy (LASH), total hysterectomy, or myomectomy (LM) (48.6%, 8.4%, and 43.0%, respectively). Unexpected malignancies were detected in 4 of 1683 patients (0.24%). In all cases, the malignancy proved to be a sarcoma and was detected after LASH. All patients with occult sarcomas were older than 45 years and the most common (75%) risk factor was the appearance of a solitary tumor. The patients underwent secondary laparotomy for complete oncological staging, and no histological dissemination of the sarcoma was registered. Two patients had a recurrence. At the final follow-up investigation all four patients were in good general health. CONCLUSION: Occult malignancies are liable to spread after EMM, although the overall risk of being diagnosed with an occult malignancy and the risk of dissemination appear to be low. Once the preoperative diagnostic investigation has yielded no suspicious findings, laparoscopic morcellation may be considered a safe method, especially LM in patients of reproductive age.

Accuracy of frozen section at early clinical stage of endometrioid endometrial cancer: a retrospective analysis in Germany.

PURPOSE: The aim of this study was to estimate the accuracy of intra-operative frozen section (FS) diagnosis during hysterectomy for early-stage endometrial cancer (EC). METHODS: At the Department of Obstetrics and Gynecology, University of Luebeck, between 2009 and 2014, the intra-operative FS pathology of 164 patients with pre-operative endometrial curettage, showing G1 or G2 endometrioid EC at an early clinical stage (FIGO I-II), was compared retrospectively with the final paraffin section reports. The accuracy of myometrial invasion (MI) in all patients and separately in stage FIGO I patients was calculated and the under- or overtreatment of the patients was analyzed. A subgroup analysis was performed focusing on the percentage of inadequate staging by FS with clinical consequences. RESULTS: Concordance of FS and final pathology results in terms of FIGO stage was 85.2%, with an under-diagnosis rate of 14% and an over-diagnosis rate of 0.8%. The subgroup analysis rate of patients who were inappropriately operated using FS was 6.6%, while 3.3% underwent a secondary operation. The overall accuracy of FS in predicting MI was 93.3% and in patients with stage FIGO I, 92.7%. Sensitivity, specificity, PPV and NPV were 98.25%, 89.06%, 88.89% and 98.28%, respectively, and in stage FIGO I, 98.25%, 84.62%, 90.32% and 97.06%, respectively. CONCLUSION: The authors consider that intra-operative FS is a reliable diagnostic method to identify the clinical stage of EC and especially MI, to determine the necessity of lymphadenectomy. Further development of diagnostic techniques is essential to maximize diagnostic accuracy.

The prognostic impact of age in patients with triple-negative breast cancer.

The purpose of this study was to assess the prognostic impact of age in patients with triple-negative breast cancer (TNBC). 1,732 patients with primary TNBC were analyzed. Five age cohorts (≤30, 31-40, 41-50, 51-60, and >60 years) at diagnosis were correlated with clinical/pathological parameters. Univariate and multivariate analyses were used to examine the effect of age on disease-free (DFS), distant disease-free (DDFS), and overall survival (OS). In patients with TNBC, increasing age at diagnosis was inversely correlated with tumor grade (P < 0.0001); likelihood of being non-Caucasian (P = 0.0001); likelihood of getting chemotherapy (P < 0.0001); and positively correlated with DFS (P = 0.0003); DDFS (P < 0.0001); and OS (P < 0.0001). The median DFS for patients 31-40 and older than 60 years was 4 years [95 % confidence interval (95 % CI) 2-5] and 8 years (95 % CI 5-14, respectively, P = 0.0003). The DDFS and OS were also statistically significantly shorter for younger patients. In multivariate analysis, tumor size, nodal stage, tumor grade, and age remained significant independent prognostic variables. Clinical characteristics of TNBC differ by age group, patients ≤40 years have poorer survival despite more aggressive systemic therapy.

First-Day-of-Life Rectal Swabs Fail To Represent Meconial Microbiota Composition and Underestimate the Presence of Antibiotic Resistance Genes.

The human gut microbiome plays a vital role in health and disease. In particular, the first days of life provide a unique window of opportunity for development and establishment of microbial community. Currently, stool samples are known to be the most widely used sampling approach for studying the gut microbiome. However, complicated sample acquisition at certain time points, challenges in transportation, and patient discomfort underline the need for development of alternative sampling approaches. One of the alternatives is rectal swabs, shown to be a reliable proxy for gut microbiome analysis when obtained from adults. Here, we compare the usability of rectal swabs and meconium paired samples collected from infants on the first days of life. Our results indicate that the two sampling approaches display significantly distinct patterns in microbial composition and alpha and beta diversity as well as detection of resistance genes. Moreover, the dissimilarity between the two collection methods was greater than the interindividual variation. Therefore, we conclude that rectal swabs are not a reliable proxy compared to stool samples for gut microbiome analysis when collected on the first days of a newborn's life. IMPORTANCE Currently, there are numerous suggestions on how to ease the notoriously complex and error-prone methodological setups to study the gut microbiota of newborns during the first days of life. Especially, meconium samples are regularly failing to yield meaningful data output and therefore have been suggested to be replaced by rectal swabs as done in adults as well. We find this development toward a simplified method to be producing dramatically erroneous results, skewing data interpretation away from the real aspects to be considered for neonatal health during the first days of life. We have put together our knowledge on this critical aspect with careful consideration and identified the failure of rectal swabs to be a replacement for sampling of meconium in term-born newborns.

Disseminated ectopic pregnancy after salpingotomy in a 30-year-old patient.

We present a case of a 30-year old patient who devoloped a disseminated abdominal pregnancy after receiving a salpingotomy due to a prior tubal pregnancy.

Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients.

INTRODUCTION: NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor that has been characterized as an intracellular immune checkpoint in effector T cells and, therefore, may control tumor development and growth. The prognostic impact of NR2F6 in endometrial cancers is evaluated in this study. MATERIALS AND METHODS: Expression analysis of NR2F6 in 142 endometrial cancer patients was performed by immunohistochemistry of primary paraffin­embedded tumor samples. Staining intensity of positive tumor cells was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: Forty five of 116 evaluable samples (38.8%) showed an overexpression of NR2F6. This leads to an improvement of the overall survival (OS) and progression-free survival (PFS). In NR2F6-positive patients, the estimated mean OS was 156.9 months (95% confidence interval (CI) 143.1-170.7) compared to 106.2 months in NR2F6-negative patients (95% CI 86.2-126.3; p = 0.022). The estimated PFS differed by 63 months (152 months (95% CI 135.7-168.4) vs. 88.3 months (95% CI 68.5-108.0), p = 0.002). Furthermore, we found significant associations between NR2F6 positivity, MMR status, and PD1 status. A multivariate analysis suggests NR2F6 to be an independent factor influencing the OS (p = 0.03). CONCLUSION: In this study, we could demonstrate that there is a longer progression-free and overall survival for NR2F6-positive patients with endometrial cancer. We conclude that NR2F6 might play an essential role in endometrial cancers. Further studies are required to validate its prognostic impact.

Thymosin beta 15A (TMSB15A) is a predictor of chemotherapy response in triple-negative breast cancer.

BACKGROUND: Biomarkers predictive of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) of breast cancer are urgently needed. METHODS: Using a training/validation approach for detection of predictive biomarkers in HER2-negative breast cancer, pre-therapeutic core biopsies from four independent cohorts were investigated: Gene array data were analysed in fresh frozen samples of two cohorts (n=86 and n=55). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in formalin-fixed, paraffin-embedded (FFPE) samples from two neoadjuvant phase III trials (GeparTrio, n=212, and GeparQuattro, n=383). RESULTS: A strong predictive capacity of thymosin beta 15 (TMSB15A) gene expression was evident in both fresh frozen cohorts (P<0.0001; P<0.0042). In the GeparTrio FFPE training cohort, a significant linear correlation between TMSB15A expression and pCR was apparent in triple-negative breast cancer (TNBC) (n=61, P=0.040). A cutoff point was then defined that divided TNBC into a low and a high expression group (pCR rate 16.0% vs 47.2%). Both linear correlation of TMSB15A mRNA levels (P=0.017) and the pre-defined cutoff point were validated in 134 TNBC from GeparQuattro (pCR rate 36.8% vs 17.0%, P=0.020). No significant predictive capacity was observed in luminal carcinomas from GeparTrio and GeparQuattro. CONCLUSION: In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.

An unprecedented occult non-communicating rudimentary uterine horn treated with laparoscopic excision and preservation of both fallopian tubes: a case report and review of the literature.

BACKGROUND: Müllerian duct anomalies are congenital malformations of the female genital tract and may be of various types. For decades they have been classified according to the American Society of Reproductive Medicine, which mentions unicornuate uterine malformations as the second subgroup. They result from the arrested development of one of the Müllerian ducts and appear in approximately 1/1000 women. These anomalies are usually diagnosed in the second decade of life, because they tend to remain asymptomatic until adolescence and their initial symptoms may vary. Patients present with symptoms such as dysmenorrhea, infertility, and chronic or acute abdominal pain. CASE PRESENTATION: We report on a 21-year-old Caucasian German patient who suffered from dysmenorrhea for 7 years. After a transvaginal ultrasound and magnetic resonance tomography of the pelvis was performed, the patient underwent a diagnostic hysteroscopy and operative laparoscopy, and was finally diagnosed with a Müllerian duct anomaly presenting with a non-communicating rudimentary uterine horn. The left tube arose directly in orthotopic location from the cornua of uterus, with no connection to the rudimentary uterine horn or structure. CONCLUSION: The anatomic features of this case have not been reported previously and were not consistent with any existing classification. More cases are needed in order to confirm our hypothesis. Gynecologists should always consider Müllerian anomalies as an important differential diagnosis in young patients with abdominal pain.

Sphingosine-kinase-1 expression is associated with improved overall survival in high-grade serous ovarian cancer.

PURPOSE: Sphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancer patients. METHODS: Expression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancer patients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: In our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively). CONCLUSION: Our data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancer patients.

Combination of osteopontin and activated leukocyte cell adhesion molecule as potent prognostic discriminators in HER2- and ER-negative breast cancer.

BACKGROUND: To analyse the discriminative impact of osteopontin (OPN) and activated leukocyte cell adhesion molecule (ALCAM), combined with human epidermal growth factor 2 (HER2) and oestrogen receptor (ER) in breast cancer. METHODS: Osteopontin, ALCAM, HER2 and ER mRNA expression in breast cancer tissues of 481 patients were analysed (mRNA microarray analysis, kinetic RT-PCR). Hierarchical clustering was performed in training cohort A (N=100, adjuvant treatment) and validation cohorts B (N=200, no adjuvant treatment, low-risk) and C (N=181, adjuvant treatment, high-risk). RESULTS: Negative/low ER and HER2, high OPN and low ALCAM mRNA expression helped to identify patients at particularly high risk, showing shorter DFS, P<0.001, and OAS, P=0.001. Although both validation cohorts showed diverse risk and treatment profiles, this marker constellation was concordantly associated with shorter DFS and OAS (P<0.001 and P=0.075 for cohort B and P=0.043 and P<0.001 for cohort C, respectively). In multivariate analysis, this algorithm was the main independent prognostic factor. Cohort B: DFS, P=0.0065, OAS, not significant; cohort C: DFS, P=0.026, OAS, P<0.001. CONCLUSION: Activated leukocyte cell adhesion molecule and OPN mRNA expression has a strong discriminative impact on survival within cancer patients with low or negative expression of ER and HER2, so called 'high-risk' breast cancers, and might help in identifying patients who could benefit from new treatment approaches like targeted therapies in the adjuvant setting.

Clinical relevance of the putative stem cell marker p63 in breast cancer.

P63 is a member of the p53 family. This protein is crucial for the maintenance of a stem cell population in the human epithelium and necessary for the normal development of all epithelial tissues including mammary glands. In normal breast tissue, the p63 seems to be a specific myoepithelial cell marker. P63 expression has been described in highly aggressive ER negative basal-like breast tumors. The value of p63 expression in ER positive disease is less clear. The expression levels of p63 mRNA by Affymetrix microarray analysis in a combined cohort of 2,158 ER positive breast cancers and its prognostic and predictive impact were analyzed. Tumor samples containing large amounts of benign breast tissue, which will interfere with p63 measurement, were excluded prior to the analysis. Survival analysis revealed a better prognosis of ER positive breast cancer expressing p63 (n = 410; P < 0.036). No correlation of p63 with standard parameters was observed. In a subgroup analysis, endocrine-treated patients with high p63 expression showed a better prognosis than low p63 expression (P = 0.06; n = 186). In untreated patients, this effect was less clear (n = 148; P = 0.5). P63 is a positive prognostic factor in endocrine-treated ER positive breast cancer and might influence responsiveness to endocrine treatment. Thus, p63 could be helpful as a predictive factor for endocrine therapy.

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.

Gene expression of topoisomerase II alpha (TOP2A) by microarray analysis is highly prognostic in estrogen receptor (ER) positive breast cancer.

INTRODUCTION: Overexpression of Topoisomerase II alpha (TOP2A) has been implicated with gene amplification of the 17q21 amplicon and consecutively with ErbB2 overexpression and amplification. However, gene amplification does not necessarily correlate with RNA and protein expression. There is growing evidence that TOP2A protein expression is a strong prognostic and TOP2A gene amplification might be a predictive marker (particularly for the use of anthracyclines). METHODS: Large scale analysis was performed using Affymetrix microarray data from n = 1,681 breast cancer patients to evaluate TOP2A expression. RESULTS: TOP2A expression showed a strong correlation with tumor size (chi(2)-test, P < 0.001), grading (P < 0.001), ErbB2 (P < 0.001) and Ki67 expression (P < 0.001) as well as nodal status (P = 0.042). Survival analysis revealed a significant prognostic value in ER positive (n = 994; log rank P < 0.001), but not in ER negative breast cancer patients (n = 369, P = 0.35). The prognostic impact of TOP2A expression was independent of Ki67 expression in ER positive tumors (P = 0.002 and P = 0.007 for high and low Ki67, respectively). Moreover a worse prognosis of high TOP2A expressing tumors was found in the subgroup of ErbB2 negative tumors (P < 0.001) and a trend among ErbB2 positive tumors (P = 0.11). The prognostic value of TOP2A was independent of whether the patients were untreated or had received adjuvant therapy. In multivariate Cox regression analysis including standard parameters TOP2A emerged to be the top prognostic marker (HR 2.40, 95% CI 1.68-3.43, P < 0.001). CONCLUSION: TOP2A expression is an independent prognostic factor in ER positive breast cancer and could be helpful for risk assessment in ER positive breast cancer patients.

Acid ceramidase 1 expression correlates with a better prognosis in ER-positive breast cancer.

OBJECTIVES: Ceramide and sphingosine mediate response to cancer therapy, inhibit cell growth and induce apoptosis in vitro. Only a few clinical data about the impact of ceramide and sphingosine iny vivo are available. We investigated the relevance of ceramide- and sphingosine-generating enzymes in breast cancer (acid ceramidase 1 (ASAH1), ceramide synthases 4 (LASS4) and 6 (LASS6)) by means of gene expression analysis. METHODS: We analyzed differences in ASAH1, LASS4 and LASS6 on mRNA level between breast cancer subgroups using microarray data from 1581 tumor samples. RESULTS: High ASAH1, LASS4 and LASS6 expression correlates with pathohistological grading (p < 0.001) and estrogen receptor (ER) status (p < 0.001). High ASAH1 expression was associated with a larger tumor size >2 cm (p = 0.003), while high LASS6 expression was correlated with ErbB2 negativity (p < 0.001). In survival analysis, we detected a significant better prognosis of patients with higher ASAH1 expression (p = 0.002) in the ER-positive subgroup. In contrast, expression of LASS4 or LASS6 did not show any prognostic impact. In the multivariate analysis, only ASAH1 expression (p = 0.002), tumor size (p < 0.0001) and ErbB2 positivity (p = 0.041) remained significant. CONCLUSION: ASAH1 is an estrogen-dependent member of the sphingolipid metabolism, which might provide further prognostic information in ER-positive breast cancers.

Management of venous port systems in oncology: a review of current evidence.

BACKGROUND: Over the last decades, many changes have occurred in oncology with new chemotherapy combinations and more complex application schemes becoming available. Central venous catheters and implantable venous port systems have become widely used and have facilitated the problem of vascular access. However, important complications are associated with permanent central venous catheters. MATERIAL AND METHODS: This review summarizes evidence on venous port system use published in Medline up to February 2007. Moreover, recent guidelines for the prevention and management of catheter-related infections issued by the Infectious Diseases Society of America, the American College of Critical Care Medicine, the Society for Healthcare Epidemiology of America, the Center for Disease Control and Prevention, Atlanta, and the Infectious Diseases Working Party of the German Society of Hematology and Oncology are included. RESULTS: Sterile precautions are essential when implanting and accessing port systems. Infections must be treated with adequate antimicrobial therapy. Catheter-related thromboembolic complications were found at a rate of 12-64% in retrospective studies. Five current clinical trials investigated the effect of prophylactic anticoagulation with either low molecular weight heparin or warfarin in cancer patients with central venous devices. On the basis of these results, routine anticoagulation cannot be recommended. CONCLUSIONS: This article reviews the current literature on long-term complications of venous port systems, focusing on infection and thrombosis. In addition, it summarizes the evidence regarding routine maintenance of port systems in follow-up care.

"Stem cell like" breast cancers-a model for the identification of new prognostic/predictive markers in endocrine responsive breast cancer exemplified by Plexin B1.

The identification of new biological markers for breast cancer has adopted a new dimension by the use of novel techniques such as global gene expression profiling. While important results have been achieved by these methods not all hopes for a more precise assessment of patients' prognosis have yet been accomplished and validation of prognostic or predictive gene signatures is still often difficult. Several recent approaches suggest that comparisons of differential gene expression could be more instructive if prior classifications of tumors based on molecular or biological characteristics were applied. We previously reported a subtype of breast cancer by using a cluster of coordinately expressed genes many of which has been associated with the mammary epithelial stem cells. While a stringent inverse link of ER status and proliferation of the tumor was observed among those "stem cell like" (SCL) tumors, this link was "uncoupled" in about half of the Non-"stem cell like" (Non-SCL) tumors. This subgroup of SCL tumors can be used as a reference system to analyze changes in the ER pathway by comparing the expression of genes dependent on the ER status. By using this strategy we identified Plexin B1, a cell-surface receptor for the semaphorin Sema4D, whose expression is reduced in the group of "uncoupled" tumors. Loss of Plexin B1 is associated with a poor prognosis in both univariate (all patients: p=0.0062; ER positive: p=0.0107) and multivariate analyses (all patients: p=0.032; ER positive: p=0.022). In conclusion those strategies of gene expression analysis in a context of biological meaningful classifications could be helpful to reveal new prognostic/predictive markers.