The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis.

BACKGROUND: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis. PATIENTS AND METHODS: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists. RESULTS: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd. CONCLUSIONS: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.

Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatments received, and outcomes of HER2-low breast cancer.

BACKGROUND: Approximately 80% of all breast cancers (BCs) are currently categorized as human epidermal growth factor receptor 2 (HER2)-negative [immunohistochemistry (IHC) 0, 1+, or 2+/in situ hybridization (ISH) negative]; approximately 60% of BCs traditionally categorized as HER2-negative express low levels of HER2. HER2-low (IHC 1+ or IHC 2+/ISH-) status became clinically actionable with approval of trastuzumab deruxtecan to treat unresectable/metastatic HER2-low BC. Greater understanding of patients with HER2-low disease is urgently needed. PATIENTS AND METHODS: This global, multicenter, retrospective study (NCT04807595) included tissue samples from patients with confirmed HER2-negative unresectable/metastatic BC [any hormone receptor (HR) status] diagnosed from 2014 to 2017. Pathologists rescored HER2 IHC-stained slides as HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 IHC 0 after training on low-end expression scoring using Ventana 4B5 and other assays at local laboratories (13 sites; 10 countries) blinded to historical scores. HER2-low prevalence and concordance between historical scores and rescores were assessed. Demographics, clinicopathological characteristics, treatments, and outcomes were examined. RESULTS: In rescored samples from 789 patients with HER2-negative unresectable/metastatic BC, the overall HER2-low prevalence was 67.2% (HR positive, 71.1%; HR negative, 52.8%). Concordance was moderate between historical and rescored HER2 statuses (81.3%; κ = 0.583); positive agreement was numerically higher for HER2-low (87.5%) than HER2 IHC 0 (69.9%). More than 30% of historical IHC 0 cases were rescored as HER2-low overall (all assays) and using Ventana 4B5. There were no notable differences between HER2-low and HER2 IHC 0 in patient characteristics, treatments received, or clinical outcomes. CONCLUSIONS: Approximately two-thirds of patients with historically HER2-negative unresectable/metastatic BC may benefit from HER2-low-directed treatments. Our data suggest that HER2 reassessment in patients with historical IHC 0 scores may be considered to help optimize selection of patients for treatment. Further, accurate identification of patients with HER2-low BC may be achieved with standardized pathologist training.

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.

Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers.

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR-negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time.This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails.

[Organoids for the advancement of intraoperative diagnostic procedures]. / Organoide zur Weiterentwicklung der intraoperativen Diagnostik.

In the context of cancer surgery, there is always a trade-off between oncological safety and preservation of function. This is especially true in pelvic surgery due to the close relationship to the pelvic floor muscles, blood supply and nerves. Currently, risk models, preoperative imaging, the surgeon's assessment, and the intraoperative frozen section serve as the basis for decision-making. New imaging techniques and standardization in frozen section have significantly improved this in recent years. However, limitations remain due to time delays as well as more difficult correct anatomical assignment in the follow-up. Alternative intraoperative techniques may overcome this limitation in the future. Patient-derived organoids have emerged as an important new research vehicle in recent years. They are based on tumor stem cells that, under special culture conditions, form three-dimensional replicas of the original tissue. This makes them ideally suited for testing individual system therapies but also as a validation technique for new intraoperative diagnostic procedures. The Research Training Group 2543/I, which is funded by the German Research Foundation, is researching the potential of new diagnostic methods in an interdisciplinary team regarding validation in addition to intraoperative frozen sections.

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.

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.

Experiences of a multistep process with medical and psychological interventions for patients with congenital uterine aplasia to achieve motherhood: the Gothenburg-Tübingen collaboration.

Congenital uterine aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a condition associated to a non-functional uterus in the presence of functional ovaries. In a setting where surrogacy is illegal (or not accepted) and adoption is the only alternative, neovaginoplasty and subsequent uterus transplantation (UTx) can provide a route to motherhood for women with MRKHS. This review article describes a multistep process by which patients with MRKHS can achieve motherhood with their own biological child. This process involving a careful clinical diagnosis, psychological counselling, assessment of eligibility for neovagina creation and UTx, the surgical treatment, fertility treatment, and long-term follow-up was developed at the Tübingen University Hospital and in close collaboration with Sahlgrenska Academy, University of Gothenburg, Sweden, where the basic experimental and clinical groundwork for UTx was laid and the first-ever UTx procedure was performed.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.