Effects of different regions of the developing gut on the migration of enteric neural crest-derived cells: A role for Sema3A, but not Sema3F

AbstractThe enteric nervous system arises from vagal (caudal hindbrain) and sacral level neural crest-derived cells that migrate into and along the developing gut. Data from previous studies have suggested that (i) there may be gradients along the gut that induce the caudally directed migration of vagal enteric neural precursors (ENPs), (ii) exposure to the caecum might alter the migratory ability of vagal ENPs and (iii) Sema3A might regulate the entry into the hindgut of ENPs derived from sacral neural crest. Using co-cultures we show that there is no detectable gradient of chemoattractive molecules along the pre-caecal gut that specifically promotes the caudally directed migration of vagal ENPs, although vagal ENPs migrate faster caudally than rostrally along explants of hindgut. Exposure to the caecum did not alter the rate at which ENPs colonized explants of hindgut, but it did alter the ability of ENPs to colonize the midgut. The co-cultures also revealed that there is localized expression of a repulsive cue in the distal hindgut, which might delay the entry of sacral ENPs. We show that Sema3A is expressed by the hindgut mesenchyme and its receptor, neuropilin-1, is expressed by migrating ENPs. Furthermore, there is premature entry of sacral ENPs and extrinsic axons into the distal hindgut of fetal mice lacking Sema3A. These data show that Sema3A expressed by the distal hindgut regulates the entry of sacral ENPs and extrinsic axons into the hindgut. ENPs did not express neuropilin-2 and there was no detectable change in the timetable by which ENPs colonize the gut in mice lacking neuropilin-2

Breast cancer screening in women with extremely dense breasts recommendations of the European Society of Breast Imaging (EUSOBI)

Breast density is an independent risk factor for the development of breast cancer and also decreases the sensitivity of mammography for screening. Consequently, women with extremely dense breasts face an increased risk of late diagnosis of breast cancer. These women are, therefore, underserved with current mammographic screening programs. The results of recent studies reporting on contrast-enhanced breast MRI as a screening method in women with extremely dense breasts provide compelling evidence that this approach can enable an important reduction in breast cancer mortality for these women and is cost-effective. Because there is now a valid option to improve breast cancer screening, the European Society of Breast Imaging (EUSOBI) recommends that women should be informed about their breast density. EUSOBI thus calls on all providers of mammography screening to share density information with the women being screened. In light of the available evidence, in women aged 50 to 70 years with extremely dense breasts, the EUSOBI now recommends offering screening breast MRI every 2 to 4 years. The EUSOBI acknowledges that it may currently not be possible to offer breast MRI immediately and everywhere and underscores that quality assurance procedures need to be established, but urges radiological societies and policymakers to act on this now. Since the wishes and values of individual women differ, in screening the principles of shared decision-making should be embraced. In particular, women should be counselled on the benefits and risks of mammography and MRI-based screening, so that they are capable of making an informed choice about their preferred screening method

FDG-PET-CT in the early response evaluation for primary systemic therapy of breast cancer

Primary systemic therapy (PST) is a standard treatment for patients with locally advanced breast cancer. We report one of our patients to demonstrate the optimal use of FDG-PET-CT in the routine clinical workup during PST, especially when clinicians face contradictory clinical and pathological findings, and to show the advantages of this imaging modality in the decision-making process about the initial treatment choice. By reviewing the literature we would also like to confirm that FDG-PET-CT is highly sensitive in the measurement of the early therapeutic response and the prediction of the complete pathological remission, as early as after the first cycle of chemotherapy is administered. © 2014 Versita and Springer-Verlag

Axillary lymphadenopathy at the time of COVID-19 vaccination: ten recommendations from the European Society of Breast Imaging (EUSOBI).

Unilateral axillary lymphadenopathy is a frequent mild side effect of COVID-19 vaccination. European Society of Breast Imaging (EUSOBI) proposes ten recommendations to standardise its management and reduce unnecessary additional imaging and invasive procedures: (1) in patients with previous history of breast cancer, vaccination should be performed in the contralateral arm or in the thigh; (2) collect vaccination data for all patients referred to breast imaging services, including patients undergoing breast cancer staging and follow-up imaging examinations; (3) perform breast imaging examinations preferentially before vaccination or at least 12 weeks after the last vaccine dose; (4) in patients with newly diagnosed breast cancer, apply standard imaging protocols regardless of vaccination status; (5) in any case of symptomatic or imaging-detected axillary lymphadenopathy before vaccination or at least 12 weeks after, examine with appropriate imaging the contralateral axilla and both breasts to exclude malignancy; (6) in case of axillary lymphadenopathy contralateral to the vaccination side, perform standard work-up; (7) in patients without breast cancer history and no suspicious breast imaging findings, lymphadenopathy only ipsilateral to the vaccination side within 12 weeks after vaccination can be considered benign or probably-benign, depending on clinical context; (8) in patients without breast cancer history, post-vaccination lymphadenopathy coupled with suspicious breast finding requires standard work-up, including biopsy when appropriate; (9) in patients with breast cancer history, interpret and manage post-vaccination lymphadenopathy considering the timeframe from vaccination and overall nodal metastatic risk; (10) complex or unclear cases should be managed by the multidisciplinary team

A survey by the European Society of Breast Imaging on the utilisation of breast MRI in clinical practice

Objectives: While magnetic resonance imaging (MRI) is considered a helpful diagnostic tool in breast imaging, discussions are ongoing about appropriate protocols and indications. The European Society of Breast Imaging (EUSOBI) launched a survey to evaluate the utilisation of breast MRI in clinical practice. Methods: An online survey reviewed by the EUSOBI board and committees was distributed amongst members. The questions encompassed: training and experience; annual breast MRI and MRI-guided-intervention workload; examination protocols; indications; reporting habits and preferences. Data were summarised and subgroups compared using \u3c72test. Results: Of 647 EUSOBI members, 177 (27.4%) answered the survey. The majority were radiologists (90.5%), half of them based in academic centres (51.9%). Common indications for MRI included cancer staging, treatment monitoring, high-risk screening and problem-solving, and differed significantly between countries (p 640.03). Structured reporting and BI-RADS were mostly used. Breast radiologists with 6410 years of experience preferred inclusion of additional techniques, such as T2/STIR (p=0.03) and DWI (p=0.08) in the scan protocol. MRI-guided interventions were performed by a minority of participants (35.4%). Conclusions: The utilisation of breast MRI in clinical practice is generally in line with international recommendations. There are substantial differences between countries. MRI-guided interventions and functional MRI parameters are not widely available. Key points: \u2022 MRI is commonly used for the detection and characterisation of breast lesions. \u2022 Clinical practice standards are generally in line with current recommendations. \u2022 Standardised criteria and diagnostic categories (mainly BI-RADS) are widely adopted. \u2022 Younger radiologists value additional techniques, such as T2/STIR and DWI. \u2022 MRI-guided breast biopsy is not widely available

The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma

Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been reported to promote proliferation and survival of Hodgkin and Reed–Sternberg cells of Hodgkin lymphoma (HL). We investigated the activity of the JAK inhibitor AZD1480 in HL-derived cell lines and determined its mechanisms of action. AZD1480 at low doses (0.1–1 μ) potently inhibited STATs phosphorylation, but did not predictably result in antiproliferative effects, as it activated a negative-feedback loop causing phosphorylation of JAK2 and extracellular signal-regulated kinases 1 and 2 (ERK1/2), and increased IP-10, RANTES and interleukin (IL)-8 concentrations in the supernatants. Inhibition of the ERK activity by mitogen-activated extracellular signal regulated kinase (MEK) inhibitors (UO126 and PD98059) enhanced the cytotoxic activity of AZD1480. Interestingly, submicromolar concentrations of AZD1480 demonstrated significant immunoregulatory effects by downregulating T-helper 2 cytokines and chemokines, including IL-13 and thymus- and activation-regulated chemokine, and the surface expression of the immunosuppressive programmed death ligands 1 and 2. Higher concentrations of AZD1480 (5 μ) induced G2/M arrest and cell death by inhibiting Aurora kinases. Our study demonstrates that AZD1480 regulates proliferation and immunity in HL cell lines and provides mechanistic rationale for evaluating AZD1480 alone or in combination with MEK inhibitors in HL

Breast MRI: EUSOBI recommendations for women's information.

UNLABELLED: This paper summarizes information about breast MRI to be provided to women and referring physicians. After listing contraindications, procedure details are described, stressing the need for correct scheduling and not moving during the examination. The structured report including BI-RADS® categories and further actions after a breast MRI examination are discussed. Breast MRI is a very sensitive modality, significantly improving screening in high-risk women. It also has a role in clinical diagnosis, problem solving, and staging, impacting on patient management. However, it is not a perfect test, and occasionally breast cancers can be missed. Therefore, clinical and other imaging findings (from mammography/ultrasound) should also be considered. Conversely, MRI may detect lesions not visible on other imaging modalities turning out to be benign (false positives). These risks should be discussed with women before a breast MRI is requested/performed. Because breast MRI drawbacks depend upon the indication for the examination, basic information for the most important breast MRI indications is presented. Seventeen notes and five frequently asked questions formulated for use as direct communication to women are provided. The text was reviewed by Europa Donna-The European Breast Cancer Coalition to ensure that it can be easily understood by women undergoing MRI. KEY POINTS: • Information on breast MRI concerns advantages/disadvantages and preparation to the examination • Claustrophobia, implantable devices, allergic predisposition, and renal function should be checked • Before menopause, scheduling on day 7-14 of the cycle is preferred • During the examination, it is highly important that the patient keeps still • Availability of prior examinations improves accuracy of breast MRI interpretation.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00330-015-3807-

Breast ultrasound: recommendations for information to women and referring physicians by the European Society of Breast Imaging

Abstract This article summarises the information that should be provided to women and referring physicians about breast ultrasound (US). After explaining the physical principles, technical procedure and safety of US, information is given about its ability to make a correct diagnosis, depending on the setting in which it is applied. The following definite indications for breast US in female subjects are proposed: palpable lump; axillary adenopathy; first diagnostic approach for clinical abnormalities under 40 and in pregnant or lactating women; suspicious abnormalities at mammography or magnetic resonance imaging (MRI); suspicious nipple discharge; recent nipple inversion; skin retraction; breast inflammation; abnormalities in the area of the surgical scar after breast conserving surgery or mastectomy; abnormalities in the presence of breast implants; screening high-risk women, especially when MRI is not performed; loco-regional staging of a known breast cancer, when MRI is not performed; guidance for percutaneous interventions (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring patients with breast cancer receiving neo-adjuvant therapy, when MRI is not performed. Possible indications such as supplemental screening after mammography for women aged 40–74 with dense breasts are also listed. Moreover, inappropriate indications include screening for breast cancer as a stand-alone alternative to mammography. The structure and organisation of the breast US report and of classification systems such as the BI-RADS and consequent management recommendations are illustrated. Information about additional or new US technologies (colour-Doppler, elastography, and automated whole breast US) is also provided. Finally, five frequently asked questions are answered. Teaching Points • US is an established tool for suspected cancers at all ages and also the method of choice under 40. • For US-visible suspicious lesions, US-guided biopsy is preferred, even for palpable findings. • High-risk women can be screened with US, especially when MRI cannot be performed. • Supplemental US increases cancer detection but also false positives, biopsy rate and follow-up exams. • Breast US is inappropriate as a stand-alone screening method

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study

Objectives: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. Methods: The MIPA observational study enrolled women aged 18–80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. Results: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. Conclusions: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. Key Points: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups