Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Eribulin as first-line treatment in older patients with advanced breast cancer: A multicenter phase II trial [SAKK 25/14].

INTRODUCTION: Standard-dose eribulin mesylate (1.4 mg/m2 d1 + 8) achieves clinical benefit rates of 26%-52% in patients with metastatic breast cancer (mBC). <10% of patients in the registration trial were ≥ 70 years old; dose reductions were common in these older patients. MATERIALS AND METHODS: This single-arm phase II trial explored the efficacy of reduced starting dosing of first-line eribulin at 1 mg/m2 d1 + 8 q3 weeks in patients with mBC aged ≥70 years. The primary endpoint was a disease control rate (DCR) ≥55%. The secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), and patient-reported neurotoxicity. RESULTS: Overall, 77 patients were accrued; their median age was 76 years and Eastern Cooperative Oncology Group performance status was 0-1 in 90%. The DCR was 40% (90% confidence interval [CI]: 31-50); therefore, the primary endpoint was not reached. The overall response rate was 22% (95%CI: 13-33), median PFS 5.4 months (95%CI: 4.5-7.7), and median OS 16.1 months (95%CI: 13.5-26.9). Dose modifications were necessary in 35% of patients. In nine patients, more than fifteen cycles were given; 48 patients (62%) experienced at least one grade 3 toxicity. Median patient-reported neurotoxicity scores remained stable for at least fifteen cycles. The main reason for treatment discontinuation was disease progression (57%). DISCUSSION: We report the first prospective data on first-line eribulin in older patients. The reduced starting dose of 1.1 mg/m2 was safe, with prolonged treatment and DC achieved in a considerable proportion of patients (but less than the 55% assumed), without cumulative neurotoxicity. The reduced dose was apparently within the range of the minimal effective dose, as shown by the efficacy lack in patients requiring further dose reductions. Thus, our results do not support the approach of a reduced starting dose for older patients.

SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients.

Objective: CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibiting and androgen receptor (AR)-modulating properties (IC504.4 nM) with antitumor effects against AR-positive tumor cells in vitro. This trial investigated the efficacy and safety of CR1447 for patients with metastatic estrogen receptor-positive (A) and AR-positive triple-negative breast cancers (B). Design and methods: (A) included patients with at most one prior endocrine therapy line without progression ≥6 months, whereas (B) included patients with ≤2 prior chemotherapy lines, all displaying advanced signs of disease. The primary endpoint was disease control at week 24 (DC24). The null hypothesis was DC24 ≤30% (A) and ≤15% (B). Thirty-seven patients were recruited (29 in (A) and 8 in (B)); accrual was stopped following an interim analysis demonstrating futility in (A) and slow accrual in (B). Results: DC24 was attained in 5/21 (95% CI: 8.2-47.2) patients in (A) and none in (B). The median progression-free survival was 5.1 months (95% CI: 2.5-5.6) in (A) and 2.5 months (95% CI: 0.7-2.6) in (B). The median overall survival was 24.6 months (95% CI: 22.9-not applicable) in (A) and 10.8 months (95% CI: 3.3-10.9) in (B). CR1447 had a favorable safety profile without treatment-related grade 3-5 toxicities in (A). Especially no side effects linked to androgenic effects were observed. Conclusions: Despite this trial being negative, the 24% DC24 rate in a second-line setting, and the prolonged partial response experienced by a patient, indicate activity. Further evaluation of CR1447 in endocrine-sensitive patients or combination trials appears warranted.

Retrospective, Multicenter Analysis Comparing Conventional with Oncoplastic Breast Conserving Surgery: Oncological and Surgical Outcomes in Women with High-Risk Breast Cancer from the OPBC-01/iTOP2 Study.

INTRODUCTION: Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). METHODS: Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. RESULTS: A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 ("ink on tumor") in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. CONCLUSIONS: Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI.

Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

AIM: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. METHODS: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. RESULTS: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. CONCLUSIONS: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

Prepectoral versus subpectoral implant-based breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02/ PREPEC): a pragmatic, multicentre, randomised, superiority trial.

INTRODUCTION: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients' own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions. METHODS AND ANALYSIS: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm). ETHICS AND DISSEMINATION: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator's site by the Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles. TRIAL REGISTRATION NUMBER: NCT04293146.

Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers.

OBJECTIVE: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice. METHODS: Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy. RESULTS: One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) ≥ 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI ≥ 12 months, CR and normalization of CA-125. CONCLUSIONS: Platinum-free interval ≥ 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy.

Predictors of a Successful Bipolar Radiofrequency Endometrial Ablation.

Introduction The study's objectives were to determine the success rate following radiofrequency endometrial ablation to treat abnormal menstrual bleeding and to assess risk factors for failure of the method. Materials and Methods 195 women who were treated with bipolar radiofrequency endometrial ablation between 01/2009 and 06/2016 were included in this prospective cohort study. Postoperative data from 187 women were collected at a median of 17.5 months (IQR 4.5-34.9; 1-82). Multivariate analyses of risk factors were performed. Success was defined as amenorrhoea or spotting. Results Patient characteristics were as follows: mean age 44 years (SD ± 5), median parity 2 (IQR 2-3), median hysterometer 8.7 cm (SD ± 1.1), and median BMI 23.5 kg/m 2 (IQR 21-27). 30 patients (19.5%) had intramural masses that could be measured with ultrasound. Postoperative success rate was 86.1%. 10 patients (5%) had a hysterectomy postoperatively - 6 for heavy bleeding, 3 due to prolapse, and 1 due to dysmenorrhoea. Multivariate analyses showed the presence of intramural masses in women < 45 years was a significant risk factor for therapeutic failure (p = 0.033; 95% CI 1.08-12.57), with an increased risk of hysterectomy (OR 7.9, 95% CI 1.2-52.7, p = 0.033). Conclusion Bipolar radio frequency endometrial ablation was highly successful in the absence of an intramural mass (88%). Even smaller intramural fibroids (DD: adenomyomas of a median of 15 mm) reduce the success rate (76%), which is why preoperative ultrasound is recommended. In the presence of intramural masses, the risk of a hysterectomy for women < 45 years increases eightfold.

Prevention of Cervical Cancer: Guideline of the DGGG and the DKG (S3 Level, AWMF Register Number 015/027OL, December 2017) - Part 1 with Introduction, Screening and the Pathology of Cervical Dysplasia.

Aims Annual opportunistic screening for cervical carcinoma has been carried out in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as the guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The first part of this short summary presents the pathological basis and considers various questions related to screening for cervical cancer. As also reported in earlier reviews, the meta-analysis by Kleijnen Systematic Reviews showed that HPV-based screening offers better protection against invasive cervical cancer compared to cytology-based screening. The authors of this guideline therefore recommend - in accordance with the guideline of the Joint National Committee of Germany (Gemeinsamer Bundesauschuss, G-BA) - that women aged 35 and above should be examined at regular intervals (at least every 3 years) and undergo HPV-based screening. Co-testing can also be carried out. Women between the ages of 20 and 35 should have cytological screening every 2 years.

Prevention of Cervical Cancer: Guideline of the DGGG and the DKG (S3 Level, AWMF Register Number 015/027OL, December 2017) - Part 2 on Triage, Treatment and Follow-up.

Aims Annual opportunistic screening for cervical carcinoma has been done in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as this guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The second part of this short summary deals with the triage, treatment and follow-up care of cervical dysplasia. With regard to those women who do not participate in screening, the guideline authors recommend sending out repeat invitation letters or an HPV self-collection kit. Colposcopy should be carried out for further investigation if cytology findings are Pap II-p and HPV test results are positive or if the results of an HPV 16 or HPV 18 screening test are positive. A single abnormal Pap smear should be triaged and investigated using HPV testing or p16/Ki67 dual staining.

Subcutaneous botulinum toxin type A injections for provoked vestibulodynia: a randomized placebo-controlled trial and exploratory subanalysis.

BACKGROUND: Previous studies using botulinum toxin type A (BT) to treat provoked vestibulodynia (PVD) reported conflicting findings, possibly attributable to singular injections or low doses. We assessed PVD treatment effectiveness with high-dose single injections of BT (50 or 100 units) versus placebo, and then repeat BT 100 U injections over 6 months. METHODS: This was a randomized, double-blind, three-arm, placebo-controlled study with 33 PVD patients. BT 50 U (arm A), 100 U (arm B) or saline (arm C) were injected subcutaneously into the dorsal vulvar vestibulum and pain was assessed after 3 months. The investigation proceeded as an unblinded exploratory analysis, in which symptomatic patients received a BT 100 U injection. Symptomatic patients in arm C received a second BT 100 U injection at the 6-month visit. Symptoms were measured at 3-month cycles using: (1) cotton swab-provoked visual analogue scale (VAS), (2) von Frey filaments, and (3) Marinoff dyspareunia scale. RESULTS: The three groups were comparable in terms of demographics and baseline clinical characteristics. Three months after the initial injection, no significant differences in pain were observed among the study arms, yet significant improvements occurred within all groups using the von Frey filaments test. Results from the exploratory analyses showed repeat injections of 100 U BT over 6 months led to significant pain reduction (VAS and von Frey filaments). Fifty-eight percent (7/12) of patients assessable after repeat injections were symptom-free or had ≥ 2 VAS reduction. Adverse events were minor and no serious adverse events occurred during the RCT or exploratory analysis. CONCLUSIONS: PVD symptoms after one subcutaneous injection of BT (50 or 100 units) did not significantly differ compared to placebo, yet all three study arms experienced a reduction in pain 3 months after a single injection. Exploratory analyses indicated that repeat high-dose BT injections may significantly reduce pain over 6 months. TRIAL REGISTRATION: This trial was registered with the Swiss Medical Agency (reference number: 2007DR2102) in 2007.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III Trial.

BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. METHODS: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. RESULTS: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]. CONCLUSIONS: TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

Role of intrinsic sphincter deficiency with and without urethral hypomobility on the outcome of tape insertion.

AIMS: Intrinsic sphincter deficiency (ISD) is a known risk factor for therapy failure after tension-free vaginal tape (TVT) insertion. The purpose of this study was to investigate if the severity of ISD alone or other factors such as urethral mobility and tape localization influence outcomes. METHODS: One hundred and nine women with urodynamically determined ISD, a TVT insertion, and a 6-month follow-up visit were included. Urethral length, mobility, and tape localization were evaluated by pelvic floor sonography. Patients were classified into three urethral mobility groups (hypomobile, normomobile, hypermobile). Surgical outcome was assessed by a combination of objective and subjective criteria. RESULTS: Therapeutic success rate after TVT insertion was 81.6%. The severity of ISD did not associate with therapy failure. But urethral mobility (P < 0.0001), relative tape position (P = 0.0003), and tape-urethra distance (P < 0.0001) differed between cured and not cured patient groups. Patients with a relative tape position toward 1/2 of urethral length had a higher cure rate. Significantly different cure rates (P = 0.0003) were found for hypomobile (67%), normomobile (76%), and hypermobile (100%) urethras. For ISD patients with a hypomobile urethra, highest cure rates were obtained for tape-urethra distances between 2.5 and 3.5 mm. CONCLUSIONS: The reduced cure rate for ISD patients was due to the subgroup with a hypomobile urethra. A prospective study is needed to confirm that slightly shorter tape-urethra distances and a relative tape position more toward the mid-urethra will lead to better outcomes for this patient group.

Sensory Hyperinnervation Distinguishes Bladder Pain Syndrome/Interstitial Cystitis from Overactive Bladder Syndrome.

PURPOSE: Pain is the key symptom that distinguishes bladder pain syndrome/interstitial cystitis from overactive bladder syndrome but overlap occurs. To find a discriminating marker for these bladder diseases we examined sensory hyperinnervation and neurotrophin receptor expression in bladder biopsies as well as nerve growth factor levels in urine. MATERIALS AND METHODS: Bladder biopsies from patients with bladder pain syndrome/interstitial cystitis, including 12 with and 19 without Hunner lesions, 13 with overactive bladder syndrome and 12 healthy controls, were analyzed by immunohistochemistry with antibodies to the nerve cell marker PGP9.5 (neuron-specific protein gene product 9.5), p75NTR (p75 neurotrophin receptor), the B-lymphocyte marker CD20 and mast cell tryptase. Urinary nerve growth factor was quantified by enzyme-linked immunosorbent assay. RESULTS: Subepithelial sensory hyperinnervation on PGP9.5 staining had 97% sensitivity and 76% specificity, increased lymphocytic infiltration had 90% sensitivity and 80% specificity, and urothelial defects had 97% sensitivity and 76% specificity to distinguish bladder pain syndrome/interstitial cystitis with and without Hunner lesions from overactive bladder syndrome and healthy controls. Increased sensory innervation was associated with submucosal mast cell localization. Staining of p75NTR in basal urothelial cells was indicative of bladder pain syndrome/interstitial cystitis. Urinary nerve growth factor levels were below the detection level and did not differentiate bladder diseases from healthy controls. CONCLUSIONS: Sensory hyperinnervation and basal urothelial p75NTR staining together with assessment of inflammatory lymphocytes and urothelial integrity allow for the differentiation of bladder pain syndrome/interstitial cystitis and overactive bladder syndrome even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligosymptomatic/asymptomatic cases and may permit timely treatment to prevent disease progress.

Risk factors for emergency caesarean section in planned vaginal breech delivery.

PURPOSE: To identify risk factors for emergency caesarean section in women attempting a vaginal breech delivery at term. METHODS: Data from 1092 breech deliveries performed between 1998 and 2013 at a Swiss cantonal hospital were extracted from an electronic database. Of the 866 women with a singleton, full term pregnancy, 464 planned a vaginal breech delivery. Fifty-seven percent (265/464) were successful in delivering vaginally. Multivariate regression analyses of risk factors were performed, and neonatal and maternal complications were compared. RESULTS: Risk factors for failed vaginal delivery were peridural anaesthesia (OR 2.05; 95 % CI 1.09-3.84; p = 0.025), nulliparity (OR 2.82; 95 % CI 1.87-4.25; p < 0.001), high birth weight (OR 1.17; 95 % CI 1.04-1.30; p = 0.006) and induction of labour (OR 1.56; 95 % CI 1.003-2.44; p = 0.048). Maternal age, height and weight; gestational age; or newborn length and head circumference were not associated with an unplanned caesarean section. The rate of successful vaginal delivery in the low risk sub-group (multiparous women without induction of labour) was 58-83 %, depending on birth weight category. The likelihood of success for the high risk sub-group (nulliparous women with induction of labour) fell below a third at neonatal birth weights >3250 g. Complication rates were low in the cohort. CONCLUSIONS: Use of peridural anaesthesia, nulliparity, high birth weight and induction of labour were risk factors for unsuccessful vaginal breech delivery requiring an unplanned caesarean section. Awareness of these risk factors is useful when counselling women who are considering a vaginal breech delivery.

Hysterectomy for Benign Uterine Disease.

BACKGROUND: Hysterectomy is the second most common operation in obstetrics and gynecology after Cesarean section. Until now, there has not been any German clinical guideline with recommendations concerning the indications for hysterectomy for benign uterine conditions, in consideration of the available uterus-preserving alternative treatments. METHODS: We systematically searched the Medline database in 2013, in 2014, and in December 2015, focusing on aggregate evidence, and assessed the retrieved literature. The guideline recommendations were developed by a consensus process with structured independent moderation. RESULTS: 30 systematic reviews and 8 randomized controlled trials were analyzed. Among the study patients treated with either hysterectomy (by any technique) or an organ-preserving alternative, at least 75-94% were satisfied with their treatment. Vaginal hysterectomy was associated with lower complication rates, shorter procedure duration, and more rapid recovery than abdominal hysterectomy and is therefore the preferred technique. If vaginal hysterectomy is not possible, a laparoscopic approach should be considered. Abdominal hysterectomy should be reserved for special indications. In 2012, the frequency of abdominal hysterectomy in Germany, Austria, and Switzerland was lower than elsewhere in the world, at 15.7% , 28.0% , and 23.9% , respectively. Uterus-preserving techniques were associated with higher reintervention rates compared to hysterectomy (11-36% vs 4-10% ). CONCLUSION: The main objective is to reduce the frequency of abdominal hysterectomy. Patients should be counseled and made aware of uterus-sparing alternatives to hysterectomy so that they are able to make informed decisions.

European Network of Gynaecological Oncological Trial Groups' Requirements for Trials Between Academic Groups and Industry Partners--First Update 2015.

The first version of ENGOT's Requirements for Trials Between Academic Groups and Industry Partners in Europe was published 2010. This first update integrates the experiences made by the ENGOT network and the cooperative group studies while performing, analyzing, and publishing -among others - three large phase III trials. Furthermore, progress in European legislation and its impact on clinical studies in Europe have been considered in this update process.