Back to the future: breast surgery with tumescent local anesthesia (TLA)?

PURPOSE: Breast surgery is usually performed under general anesthesia. Tumescent local anesthesia (TLA) offers the possibility to anesthetize large areas with highly diluted local anesthetic. METHODS: In this paper, the implementation, and experiences with TLA in the field of breast surgery are discussed. CONCLUSION: For carefully selected indications, breast surgery in TLA represents an alternative to ITN.

Lysine-urethane-based tissue adhesion for mastectomy-an approach to reducing the seroma rate?

PURPOSE: Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu® without drainage is equal/ non-inferior to standard mastecomy with drainage. METHODS: The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu® without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups. RESULTS: Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu® group than in the drainage group, especially aspirations of clinically relevant seromas (p = 0.014). The TissuGlu® group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu® group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu® compared to standard drainage couldn't be reached. DISCUSSION: The present evaluation shows no advantage of the tissue adhesive TissuGlu® in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life.

Iatrogenic endometriosis harbors somatic cancer-driver mutations.

STUDY QUESTION: Does incisional endometriosis (IE) harbor somatic cancer-driver mutations? SUMMARY ANSWER: We found that approximately one-quarter of IE cases harbor somatic-cancer mutations, which commonly affect components of the MAPK/RAS or PI3K-Akt-mTor signaling pathways. WHAT IS KNOWN ALREADY: Despite the classification of endometriosis as a benign gynecological disease, it shares key features with cancers such as resistance to apoptosis and stimulation of angiogenesis and is well-established as the precursor of clear cell and endometrioid ovarian carcinomas. Our group has recently shown that deep infiltrating endometriosis (DE), a form of endometriosis that rarely undergoes malignant transformation, harbors recurrent somatic mutations. STUDY DESIGN, SIZE, DURATION: In a retrospective study comparing iatrogenically induced and endogenously occurring forms of endometriosis unlikely to progress to cancer, we examined endometriosis specimens from 40 women with IE and 36 women with DE. Specimens were collected between 2004 and 2017 from five hospital sites in either Canada, Germany or the Netherlands. IE and DE cohorts were age-matched and all women presented with histologically typical endometriosis without known history of malignancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Archival tissue specimens containing endometriotic lesions were macrodissected and/or laser-capture microdissected to enrich endometriotic stroma and epithelium and a hypersensitive cancer hotspot sequencing panel was used to assess for presence of somatic mutations. Mutations were subsequently validated using droplet digital PCR. PTEN and ARID1A immunohistochemistry (IHC) were performed as surrogates for somatic events resulting in functional loss of respective proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, we detected somatic cancer-driver events in 11 of 40 (27.5%) IE cases and 13 of 36 (36.1%) DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA and CTNNB1. Heterogeneous PTEN loss occurred at similar rates in IE and DE (7/40 vs 5/36, respectively), whereas ARID1A loss only occurred in a single case of DE. While rates of detectable somatic cancer-driver events between IE and DE are not statistically significant (P > 0.05), KRAS activating mutations were more prevalent in DE. LIMITATIONS, REASONS FOR CAUTION: Detection of somatic cancer-driver events were limited to hotspots analyzed in our panel-based sequencing assay and loss of protein expression by IHC from archival tissue. Whole genome or exome sequencing, or epigenetic analysis may uncover additional somatic alterations. Moreover, because of the descriptive nature of this study, the functional roles of identified mutations within the context of endometriosis remain unclear and causality cannot be established. WIDER IMPLICATIONS OF THE FINDINGS: The alterations we report may be important in driving the growth and survival of endometriosis in ectopic regions of the body. Given the frequency of mutation in surgically displaced endometrium (IE), examination of similar somatic events in eutopic endometrium, as well as clinically annotated cases of other forms of endometriosis, in particular endometriomas that are most commonly linked to malignancy, is warranted. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a Canadian Cancer Society Impact Grant [701603, PI Huntsman], Canadian Institutes of Health Research Transitional Open Operating Grant [MOP-142273, PI Yong], the Canadian Institutes of Health Research Foundation Grant [FDN-154290, PI Huntsman], the Canadian Institutes of Health Research Project Grant [PJT-156084, PIs Yong and Anglesio], and the Janet D. Cottrelle Foundation through the BC Cancer Foundation [PI Huntsman]. D.G. Huntsman is a co-founder and shareholder of Contextual Genomics Inc., a for profit company that provides clinical reporting to assist in cancer patient treatment. R. Aguirre-Hernandez, J. Khattra and L.M. Prentice have a patent MOLECULAR QUALITY ASSURANCE METHODS FOR USE IN SEQUENCING pending and are current (or former) employees of Contextual Genomics Inc. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Hyperthermic chest wall re-irradiation in recurrent breast cancer: a prospective observational study.

PURPOSE: To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC). METHODS: Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50-50.4 Gy, with a boost up to 60-60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40-42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated. RESULTS: 20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy. CONCLUSION: Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up.

Unexpected malignant uterine pathology: Incidence, characteristics and outcome in a large single-center series of hysterectomies for presumed benign uterine disease.

OBJECTIVE: Hysterectomy is a frequently used therapeutic option for benign gynecological conditions. The purpose of this study was to investigate the incidence and characteristics of unforeseen malignant pathologies of the uterine corpus in a large population-based, single center cohort. METHODS: Patients who underwent hysterectomy for presumed benign conditions between 2003 and 2016 were identified. In cases of unexpected malignancies of the uterine corpus (UUM), available tissue samples were collected and a specialized gynecopathological review was performed. RESULTS: A total of 10,756 patients underwent hysterectomy for benign indications. After chart and gynecopathological review, 45/10,756 (0.42%) cases of unexpected uterine malignancies were confirmed. 33/45 (73.3%) were endometrial carcinomas (UEC) and 12/45 (26.7%) were uterine sarcomas (UUS). 27/33 (81.8%) UEC were FIGO IA, 5/33 (15.2%) FIGO IB and 1/33 (3%) FIGO stage II disease. Endometrioid and serous histotype were present in 31/33 (93.9%) and in 2/33 (6.1%) cases, respectively. 8/12 (66.7%) USS were early stage (FIGO IA or IB); only 3/12 (25.0%) were diagnosed at an advanced stage (≥FIGO II). Fatal outcome was observed in 1 patient diagnosed with UEC and 3 patients diagnosed with UUS. CONCLUSION: Our study shows that diagnosis of UUM is rare (0.42%). The majority of UUM tend to be early stage, making preoperative diagnosis difficult. In case of UEC, patient outcome is generally favorable. Nevertheless, the appropriate surgical approach for hysterectomy for a benign indication should be chosen carefully, taking all preoperative findings into account. Patients should always be informed about the residual risk of UUM.

Neovagina creation methods and their potential impact on subsequent uterus transplantation: a review.

Congenital uterovaginal aplasia commonly occurs in Mayer-Rokitansky-Küster-Hauser syndrome. Various methods of neovagina creation exist, including nonsurgical self-dilation, surgical dilation, and surgical procedures involving skin or intestinal transplants. Subsequent uterus transplantation is necessary to enable pregnancy. We review the main characteristics, advantages, and disadvantages of established neovagina creation methods and discuss their suitability regarding subsequent uterus transplantation. Suitability criteria include sufficient vaginal length, absence of previous major intra-abdominal surgery, a natural vaginal axis, and a natural vaginal epithelium. In conclusion, Vecchietti-based laparoscopically assisted neovagina creation provides ideal functional conditions for uterus transplantation. Nonsurgical self-dilation and Wharton-Sheares-George vaginoplasty may also be suitable. TWEETABLE ABSTRACT: This review discusses the main advantages and disadvantages of neovagina creation methods with regard to subsequent uterus transplantation.

Vaginal prevalence of human papillomavirus infections in women with uterovaginal aplasia before and after laparoscopically assisted creation of a neovagina: a prospective epidemiological observational study.

OBJECTIVE: To study vaginal as opposed to cervical human papillomavirus (HPV) acquisition with regard to true prevalence, HPV types, and the role of co-factors in virgins and after their sexual debut. DESIGN: Prospective epidemiological observational study. SETTING: University hospital specialised in genital malformations. POPULATION: Women diagnosed with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) and undergoing neovaginoplasty between November 2011 and July 2017. METHODS: This is a prospective study including 186 women with MRKHS before and after sexual debut. MAIN OUTCOME MEASURES: Conventional vaginal cytology and different HPV tests were performed at surgery and during routine gynaecological follow-up 1, 3, 6 and ≥ 11 months after surgery and risk factors were documented. RESULTS: The mean age of all women at surgery was 20.1 years (SD 5.4), mean body mass index (BMI) was 22.1 kg/m2 (SD 4.6). In 83 vaginal samples from 41 different women at least one of the HPV tests was positive. Thirty-three different HPV types were detected. The prevalence of 41/186 = 22.0% as well as type distribution are comparable with those found in a young German female population. The overall rate of acquisition was clearly associated with sexual activity and smoking habits. Out of 367 Papanicolaou smears only six were abnormal with Pap IIID (MN II) and no obvious vaginal lesion was detected. CONCLUSIONS: Vaginal HPV prevalence and HPV types in previously virgin women after creation of a neovagina are not different from the acquisition of cervical infections in the general population and is clearly associated with sexual activity and with smoking habits. However, abnormal Papanicolaou smears are rarely seen. TWEETABLE ABSTRACT: Vaginal HPV prevalence after creation of a neovagina is similar to that on the cervix in the general population.

Prevention of maternal-fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration.

OBJECTIVE: To examine the efficacy of biweekly hyperimmunoglobulin (HIG) administration to prevent maternal-fetal transmission of cytomegalovirus (CMV) in women with primary first-trimester CMV infection. METHODS: This was a prospective observational study of women with confirmed primary CMV infection in the first trimester who had the first HIG administration at or before 14 weeks' gestation. All women had biweekly HIG treatment until 20 weeks' gestation at a dose of 200 IU/kg of maternal body weight. Each subject underwent amniocentesis at least 6 weeks after first presentation at about 20 weeks. Primary outcome was maternal-fetal transmission at the time of amniocentesis, and secondary outcome was the frequency of congenital CMV infection at birth. The results were compared with a historic cohort of women with first-trimester CMV infection who did not undergo HIG treatment and who had amniocentesis at about 20 weeks. RESULTS: Subjects were 40 pregnant women with a primary CMV infection, with a median gestational age at first presentation of 9.6 (range, 5.1-14.3) weeks. On average, HIG administration started at 11.1 weeks and continued until 16.6 weeks. Within this interval, HIG was administered between two and six times in each patient. While CMV immunoglobulin-G (IgG) monitoring showed periodic fluctuations during biweekly HIG administration cycles, high CMV-IgG avidity indices remained stable over the whole treatment period. Maternal-fetal transmission before amniocentesis occurred in only one of the 40 cases (2.5% (95% CI, 0-13.2%)). At delivery, two additional subjects were found to have had late-gestation transmission. Considering all three cases with maternal-fetal transmission, the transmission rate was 7.5% (95% CI, 1.6-20.4%) in our 40 cases. All infected neonates were asymptomatic at birth. The matched historical control group consisted of 108 pregnancies. Thirty-eight transmissions (35.2% (95% CI, 26.2-45.0%)) occurred in the control group, which was significantly higher (P < 0.0001) than the transmission rate in the HIG treatment group. CONCLUSION: After a primary maternal CMV infection in the first trimester, biweekly HIG administration at a dose of 200 IU/kg prevents maternal-fetal transmission up to 20 weeks' gestation. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Difficulties in diagnosis of a minimal deviation adenocarcinoma of uterine cervix diagnosed postoperatively: brief communication and literature review.

PURPOSE: Rare minimal deviation adenocarcinoma (MDA) diagnosed postoperatively as incidental finding of a suspicious cervical lesion at laparoscopy, emphasizing it represents a diagnostic challenge mimicking both benign and malignant cervical lesions with often overlapping imaging characteristics-case report and literature review. CASE PRESENTATION: 35-year-old Gravida with primary infertility presented with a suspicious cervical lesion and complained about menorrhagia, hyper-/dysmenorrhea. Clinical examination was unremarkable, transvaginal scan presented a 42 × 38 × 28 mm sized cervical lesion (i.e. fibroid) without hypervascularization. Unexpectedly, the diagnosis of minimal deviation adenocarcinoma in tissue sample taken from suspicious cervical lesion at laparoscopy was revealed in final pathological report. According to suspected early stage of MDA a radical abdominal hysterectomy (PIVER III/IV), bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymphadenectomy was scheduled. Final histology report confirmed: "MDA", G2, FIGO pT1b1, pN0 (0/23 LN) L0 V0 Pn0 R0. RESULTS: Ultrasonography may indicate MDA throughout the examination of vascularization/echogenicity with possibility of mimicking benign lesions with similar characteristics. Magnetic resonance imaging shows no pathognomonic signs for MDA. Subsequently, a review of literature was conducted and main factors affecting the prognosis of MDA considering diagnostic tools, clinical stage, histopathological results and surgical protocols were analyzed. CONCLUSIONS: Minimal deviation adenocarcinoma represents one of rare cervical adenocarcinomas without HPV-association. While it is crucial to differentiate benign from malignant lesions in this subtype, imaging characteristics often overlap and may not provide a specific diagnosis. Therefore, it should be considered in suspicious multicystic cervical lesions and inconclusive PAP-smear. Definitive diagnosis of this subtype should be based on cervical biopsy.

Thermal effects of a novel electrosurgical device for focused preparation in breast surgery tested in a specified porcine tissue ex vivo breast model using infrared measurement.

PURPOSE: This article investigates the qualities and thermal effects of a novel electrosurgical device (PT) which has been designed by ERBE Elektromedizin GmbH, Germany, for the preparation of critical locations such as in skin-sparing or nipple-sparing techniques and compares it to a standard device (SD) in a porcine ex vivo breast model using an heat map generated by infrared thermography. METHODS: In total, 42 abdominal wall specimens of porcine tissue consisting of the skin and the underlying subcutaneous and muscle layer were alternately dissected using one of the devices and pre-settings. During the preparation with the two devices, the epicutaneous temperature was measured by an infrared camera (VarioCam, Jenoptik, Germany) and the maximum temperature as well as the slope of the temperature rise was analysed. RESULTS: The use of PT shows significantly lower values for [Formula: see text] compared to SD. This effect was independent from the chosen mode. Using the same instrument in different modes, the use of AutoCut mode showed a significant reduction of [Formula: see text] at all indicated time points (SD: p < 0.0001 and PT: p < 0.0001). In summary, the combination of AutoCut + PT showed the lowest rise in temperature, whereas the combination of DryCut + SD led to the highest rise in temperature. The temperature difference between these two settings was 13.84 °C, which means a possible temperature reduction of 67% can be achieved by the right choice of device and its tailored mode. CONCLUSIONS: The novel PT shows a significant reduction in epicutaneous temperature and a significant reduction of the slope of temperature rise most probably by a more focused application of energy compared to SD.

Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series.

Background: We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methods: We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Results: Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P = 0.001) and disease-specific (P = 0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, κ 0.88. Discussion: We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Pregnancy after vasectomy: surgical reversal or assisted reproduction?

STUDY QUESTION: Should we opt for surgical vasovasostomy or IVF/ICSI after a vasectomy? SUMMARY ANSWER: Both options reveal acceptable pregnancy rates though the time to pregnancy was significantly lower in the immediate IVF/ICSI group. WHAT IS KNOWN ALREADY: About 7.4% of men regret their vasectomy and express a renewed child wish. The choice between surgical vasectomy reversal or ICSI remains difficult for patients and their fertility specialist. STUDY DESIGN, SIZE, DURATION: This study was a retrospective single-center cohort analysis of all males with a vasectomy in the past seeking treatment between 2006 and 2011 (n = 163). One group of patients opted for a reanastomosis procedure while the others opted for an immediate IVF/ICSI treatment. This included 99 males who underwent reanastomosis and 64 couples who immediately underwent ICSI treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: All reanastomosis procedures were done by the same surgeon. ICSI was used in all cases where testicular sperm were extracted by fine needle aspiration (FNA) or testicular sperm extraction (TESE). MAIN RESULTS AND THE ROLE OF CHANCE: The mean male age at vasectomy was 35.5 years and 44.4 years at reanastomosis. The mean (range) obstructive interval was 9.53 years (1-27). No significant differences were found between the two groups in female patient characteristics, such as age and parity. In the reversal group, the crude cumulative delivery rate (CDR) was 49.5%. However, in the 45 patients of this group who attempted to conceive spontaneously ('primary reanastomosis' pathway), the crude CDR was 40.0%. The remaining 54 patients (the 'switchers' pathway) who underwent a reversal procedure and later switched to ART, had a crude CDR of 57.4%. Of these, four patients opted for insemination, including two who later decided to switch to IVF/ICSI. The 64 patients who immediately underwent IVF/ICSI ('primary IVF/ICSI' pathway) had a crude CDR of 43.8% and an expected CDR of 51.6%. The difference in delivery rates between the primary reanastomosis group (40.0%) and the primary IVF/ICSI group (43.8%) was not statistically significant. Time to pregnancy was significantly shorter in the primary IVF/ICSI pathway, at 8.2 versus 16.3 months in the reanastomosis group. LIMITATIONS, REASONS FOR CAUTION: The study population was rather small. Furthermore, the study may be limited by the fact that the reason for the renewed child wish in most cases was a new relationship with another woman, a factor which may also play a role in the cause of infertility. WIDER IMPLICATIONS OF THE FINDINGS: Recanalisation of the vas seems to be a reasonable alternative for patients who do not wish to undergo immediate IVF/ICSI. In those who opt for ART immediately, the cumulative pregnancy rates seem comparable but the pregnancies occurred earlier. STUDY FUNDING, COMPETING INTEREST(S): No funding was used for this study. There is no conflict of interest for this study. TRIAL REGISTRATION NUMBER: N/A.

First-trimester risk assessment based on ultrasound and cell-free DNA vs combined screening: a randomized controlled trial.

OBJECTIVE: This was a randomized controlled trial to compare risk assessment by first-trimester combined screening (FTCS) with an approach that combines a detailed ultrasound examination at 11-13 weeks' gestation and cell-free DNA (cfDNA) analysis. METHODS: Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (fetal nuchal translucency (NT) ≤ 3.5 mm and no fetal defects) were randomized into one of two groups. In the first group, risk of aneuploidy was assessed using FTCS based on the most recent UK Fetal Medicine Foundation algorithm. In the second group, risk assessment was based on ultrasound findings and cfDNA analysis. An additional tube of blood was collected for FTCS in case the cfDNA analysis was uninformative. Primary outcome was false-positive rate in screening for trisomy 21. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was >1:100, irrespective of the method of risk calculation. Results were compared using 95% CIs using the Clopper-Pearson method. RESULTS: Between October 2015 and December 2016, 1518 women with singleton pregnancy underwent first-trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (> 3.5 mm) and/or fetal defect. After exclusion of women who declined randomization (n = 87) and cases of fetal death and loss to follow-up (n = 24), 688 pregnancies were randomized into the FTCS arm and 688 into the ultrasound + cfDNA analysis arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, use of assisted reproduction and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10 000. None of the cases had a risk above 1: 100 (95% CI, 0.0-0.5%). In the FTCS arm, the median risk for trisomy 21 was 1 in 3787 and in 17 cases, the risk was higher than 1:100, which corresponds to 2.5% (95% CI, 1.5-3.9%) of the FTCS study-arm population. CONCLUSION: Our study has shown that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

High intensity focused ultrasound (HIFU) for the treatment of symptomatic breast fibroadenoma.

PURPOSE: The aim of the study was to evaluate the efficacy of high intensity focused ultrasound (HIFU) in the treatment of symptomatic breast fibroadenomas (FA) after 6 and 12 months. MATERIALS AND METHODS: Between December 2013 and November 2014, 27 patients with histologically confirmed FA received one application of HIFU under local anesthesia (NCT02011919). Follow-up visits occurred after 6 and 12 months measuring the FA volume and clinical symptoms. A volume reduction of more than 65% was defined as success. Core needle biopsy (CNB) was offered after 12 months if indistinct residuals were visible on ultrasound (US). RESULTS: A successful reduction in FA volume after 12 months was achieved in 24/27 patients (89%). At baseline 16 patients (59%) had pain, which was resolved in 63% (10/16). All patients were satisfied with the cosmetic related outcome. Twenty-four patients (89%) would repeat the procedure. After 12 months 21 patients with sonographically indistinct residuals underwent a CNB. There were no vital cells in 86%. Three cases showed vital cells of FA. Retrospectively possible reasons in these three cases were an insufficient treatment due to bad visibility and insufficient fixation of the FA during HIFU and/or a too short follow-up time. CONCLUSION: US-guided HIFU is an effective procedure and a minimally invasive alternative for the treatment of breast FA.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.

Virucide properties of cold atmospheric plasma for future clinical applications.

Cold atmospheric plasma (CAP) has been repeatedly identified to bear powerful microbicidal efficacy on bacteria including multidrug resistant organisms and fungi on non-living surfaces, in biofilms as well as on contaminated and infected tissues. CAP furthermore was found to stimulate wound healing in chronic wounds and exerted anti-neoplastic effects on numerous tumor entities. Thus, CAP represents a promising medical tool for many clinical and therapeutic issues. Studies about CAP effects on virus particles recently were in arrears, but to date increasingly move into the focus of interest. Apparently, CAP treatment is followed by a promising virus inactivation and contributes to tissue regeneration. Here we review the current state of science concerning the so far investigated CAP effects on different virus species and virus-associated disorders. J. Med. Virol. 89:952-959, 2017. © 2017 Wiley Periodicals, Inc.

Gestational diabetes alters the fetal heart rate variability during an oral glucose tolerance test: a fetal magnetocardiography study.

OBJECTIVE: Gestational diabetes mellitus (GDM) potentially harms the child before birth. We previously found GDM to be associated with developmental changes in the central nervous system. We now hypothesise that GDM may also impact on the fetal autonomic nervous system under metabolic stress like an oral glucose tolerance test (OGTT). DESIGN: We measured heart rate variability (HRV) of mothers and fetuses during a three-point OGTT using fetal magnetocardiography (fMCG). SETTING: Measurements were performed in the fMEG Centre in Tübingen. POPULATION: After exclusion of 23 participants, 13 pregnant women with GDM and 36 pregnant women with normal glucose tolerance were examined. METHODS: All women underwent the same examination setting with OGTT during which fMCG was recorded three times. MAIN OUTCOME MEASURE(S): Parameters of heart rate variability were measured. RESULTS: Compared with mothers with normal glucose regulation, mothers with GDM showed increased heart rate but no significant differences of maternal HRV. In contrast, HRV in fetuses of mothers with GDM differed from those in the metabolically healthy group regarding standard deviation normal to normal beat (SDNN) (P = 0.012), low-frequency band (P = 0.008) and high-frequency band (P = 0.031). These HRV parameters exhibit a decrease only in GDM fetuses during the second hour of the OGTT. CONCLUSIONS: These results show an altered response of the fetal autonomic nervous system to metabolic stress in GDM-complicated pregnancies. Hence, disturbances in maternal glucose metabolism might not only impact on the central nervous system of the fetus but may also affect the fetal autonomic nervous system. TWEETABLE ABSTRACT: Metabolic stress reveals a different response of fetal autonomic nervous system in GDM-complicated pregnancies.

The pattern of lipids and lipoproteins during the menopausal transition in Chinese women.

Objective To investigate changes in levels of lipids and lipoproteins in Chinese women during perimenopause and postmenopause as primary study endpoints, for the first time including lipoprotein(a). Methods The retrospective study was performed in 1015 women without hormone therapy aged 34-76 years from 20 provinces of China who visited the Beijing Obstetrics & Gynecology hospital. Menopausal status was defined by the criteria of the 2011 Stages of Reproductive Aging Workshop. Results Levels of total cholesterol, triglycerides and low density lipoprotein (LDL) cholesterol increased and that of high density lipoprotein (HDL) cholesterol decreased in the postmenopausal compared to the perimenopausal group. In the women with body mass index (BMI) ≥ 25 kg/m(2), total cholesterol and LDL cholesterol increased, HDL cholesterol decreased and changes in triglyceride levels were not significant. In the women with BMI < 25 kg/m(2), the increase in triglyceride levels during the transition was significant. Changes in lipoprotein(a), apolipoprotein A1 and apolipoprotein B were not significant. Comparing the groups with BMI ≥ 25 kg/m(2) vs. BMI < 25 kg/m(2), only the differences for apolipoprotein A1 and for triglycerides were significant. Triglycerides correlated positively with follicle stimulating hormone and BMI, and total cholesterol correlated positively with follicle stimulating hormone and age (all p < 0.05). Conclusions Some changes in lipids can be related to menopausal status, some to increasing age, some to both; especially triglycerides and apolipoprotein A1 were found also to be related to BMI. Surprisingly lipoprotein(a) did not change either with increasing age or during the transition despite known possible interference with estrogenic status.

[Why Strive after Clinical Social Medicine? From Epidemiological Association to Personalized Social Medicine: a Case of Breast Cancer Care]. / Klinische Sozialmedizin - Warum? Von der epidemiologischen Assoziation zur personalisierten Sozialmedizin am Beispiel der Versorgung bei Mammakarzinom.

Advances in biomedicine, especially molecular biology and genetics, gave rise to the concept of personalized medicine targeting the patient's individual characteristics and needs to ensure the best possible therapy and healthcare. This concept, however, can be successfully implemented only if due consideration is given to (psycho-)social factors, as is shown for instance by considerably reduced post-therapy survival rates among cancer patients in regions with lower socioeconomic status, How breast cancer patients, for instance, find their way back to daily life and work after initial treatment at a breast center is substantially determined by multiple factors going beyond pure medical care. These factors critically affect health status and therapy outcomes, but are missing in current research agenda. A profound expertise in social medicine is required to respond in ways tailored to the individual's healthcare needs that go beyond just medical therapy. This expertise comprises, in particular, knowledge of inequality of access to healthcare due to varying health competence that in turn, results in inequality of health outcome and care. Competence in social medicine both in the clinic and outpatient care can help to individually target negative factors that originate from the social environment as well as from deficits in communication and coordination in the healthcare system and have an effect on the health status of patients..This, however, requires institutionalization of (clinical) social medicine and in particular, better opportunities for advanced training in social medicine in clinical departments and outpatient units.