Consensus Review of Discordant Imaging Findings after the Introduction of Digital Screening Mammography: Irish National Breast Cancer Screening Program Experience.

Background When there are discordant results between individual readers interpreting screening mammograms, consensus by independent readers may reduce unnecessary recalls for further work-up. Few studies have looked at consensus outcomes following the introduction of full-field digital mammography (FFDM). Purpose To determine outcomes of women discussed at consensus meetings during a 5-year period after introduction of FFDM, including recall rates, cancer detection, and interval cancers. Materials and Methods In this retrospective study from January 2010 to December 2014, the authors reviewed all screening mammograms from a single unit of a biennial Irish national breast screening program after the introduction of FFDM. Screening mammograms were double reported. Abnormalities detected at discordant screening mammography readings were discussed at biweekly consensus meetings. Outcomes of consensus meetings were reviewed in terms of referral for assessment, biopsy rates, cancer detection, and outcomes from later rounds of screening. Statistical analysis was performed by using a χ2 test to compare recall rate and cancer detection rates between FFDM and screen-film mammography based on a previously published study from the authors' institution. Results A total of 2565 women (age range, 50-64 years) with discordant mammographic findings were discussed at consensus meetings. Of these 2565 women, 1037 (40%) were referred for further assessment; 108 cancers were detected in these women. Of the 1285 women who returned to biennial screening, malignancy was detected at the site of original concern in 12 women at a further round of screening. Three true interval cancers were identified. Sensitivity (88.5% [108 of 122]; 95% confidence interval [CI]: 81.5%, 93.6%) and negative predictive value (99.1% [1528 of 1542]; 95% CI: 98.5%, 99.4%) of consensus review remained stable after the introduction of FFDM. Specificity of consensus review increased from 57.6% (729 of 1264; 95% CI: 54.9%, 60.4%) to 62.2% (1528 of 2457; 95% CI: 60.2%, 64.1%) (P = .008). Conclusion Consensus review of discordant mammographic screening-detected abnormalities remains a valuable tool after introduction of full-field digital mammography as it reduces recall for assessment and demonstrates persistently high sensitivity and negative predictive values. © RSNA, 2020 See also the editorial by Hofvind and Lee in this issue.

The paradox of MRI for breast cancer screening: high-risk and dense breasts-available evidence and current practice.

In the mid-1990s, the identification of BRCA1/2 genes for breast cancer susceptibility led to testing breast MRI accuracy in screening women at increased risk. From 2000 onwards, ten intraindividual comparative studies showed the marked superiority of MRI: the sensitivity ranged 25-58% for mammography, 33-52% for ultrasound, 48-67% for mammography plus ultrasound, and 71-100% for MRI; specificity 93-100%, 91-98%, 89-98%, and 81-98%, respectively. Based on the available evidence, in 2006-2007, the UK National Institute for Clinical Excellence and the American Cancer Society recommended MRI screening of high-risk women, followed by other international guidelines. Despite evidence-based medicine ideally requiring randomised controlled trials (RCTs) for policy changes regarding screening procedures, breast MRI for high-risk screening was adopted in many countries worldwide. In 2019, the results of the "DENSE" RCT were published in favour of breast MRI screening of women with extremely dense breasts compared to mammography alone, showing a reduction of more than 80% of the interval cancer rate in women who attended MRI screening. Even though international recommendations in favour of this practice were issued, substantial obstacles still prevent health systems from adopting breast MRI for screening women with extremely dense breasts. A paradox is evident: we adopted a screening procedure without evidence from RCTs, and now that we have this level-1 evidence for the same procedure, we fail to do so. This critical review tries to explain the differences between the two cases, as examples of the complex pathways of translating radiological research into everyday practice.Critical relevance statement The high-level evidence in favour of breast MRI screening of women with extremely dense breasts is failing to persuade policy makers to translate this into clinical practice.Key points• Breast MRI screening of high-risk women was adopted on basis of the evidence provided by test accuracy comparative studies showing an MRI performance greatly superior to that of mammography.• Breast MRI screening of women with extremely dense breasts has not been adopted although the evidence of a large reduction in interval cancer rate from a RCT.• We illustrate the differences between the two cases, as an example of the complex ways of translation of radiological research in clinical practice according to the EBM theory.

A review of expression profiling of circulating microRNAs in men with prostate cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in gene regulation and expression. These molecules have been implicated in the pathogenesis of several malignancies. MiRNAs have the potential to be both a tissue- and blood-based biomarker for cancer diagnosis, classification, prognosis and response to treatment. The levels of dysregulated miRNAs in the circulation of individuals make miRNAs an ideal biomarker for the detection of prostate cancer. The present study provides a comprehensive review of the expression profiling of miRNAs in the circulation of men with prostate cancer. Further research is necessary to identify if circulating miRNAs have the potential to be a biomarker for prostate cancer in clinical practice.

Does pre-operative breast MRI have an impact on surgical outcomes in high-grade DCIS?

OBJECTIVES: High-grade DCIS (HG DCIS) is associated with upgrade to invasive disease but few studies evaluate the role of MRI in this subset of DCIS. This study compared surgical outcomes of females with HG DCIS on biopsy who had pre-operative MRI with those that proceeded directly to surgery. METHODS: This single-centre retrospective, observational study identified patients with pure HG DCIS on pre-operative biopsy from the pathology database. Surgical outcomes, clinicopathological and radiological features were obtained for all patients. RESULTS: From August 2015 to February 2020, 217 patients had HG DCIS on biopsy. Pre-operative MRI was performed in 40 (MRI group) and not in 88 (No MRI group) patients. Initial mastectomy was performed in 25/40 (63%) women in the MRI group and 20/88 (23%) women in the no MRI group (p < 0.0001). No difference was observed in re-operation rate between the two groups, 15% in MRI group vs 22% in No MRI group (p = 0.4749). Mean tumour size on histology was larger in mastectomy cases in the MRI group (73.4 mm, range 6-140 mm), than the total MRI group, (58.3 mm, range 0-140 mm) or no MRI group (30.7 mm, range 0-130 mm) (p < 0.0001). CONCLUSIONS: Pre-operative MRI in HG DCIS is associated with higher mastectomy rates, possibly due to patient selection for MRI, as tumours on final histology were significantly larger. Fewer re-operations were observed in the MRI group although this was not significant. ADVANCES IN KNOWLEDGE: Breast MRI performed pre-operatively in HG DCIS is associated with higher mastectomy rates and fewer re-operation rates.

Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers--role of estrogen receptor and HER2 reactivation.

INTRODUCTION: The human epidermal growth factor receptor 2 (HER2)-targeted therapies trastuzumab (T) and lapatinib (L) show high efficacy in patients with HER2-positive breast cancer, but resistance is prevalent. Here we investigate resistance mechanisms to each drug alone, or to their combination using a large panel of HER2-positive cell lines made resistant to these drugs. METHODS: Response to L + T treatment was characterized in a panel of 13 HER2-positive cell lines to identify lines that were de novo resistant. Acquired resistant lines were then established by long-term exposure to increasing drug concentrations. Levels and activity of HER2 and estrogen receptor (ER) pathways were determined by qRT-PCR, immunohistochemistry, and immunoblotting assays. Cell growth, proliferation, and apoptosis in parental cells and resistant derivatives were assessed in response to inhibition of HER or ER pathways, either pharmacologically (L, T, L + T, or fulvestrant) or by using siRNAs. Efficacy of combined endocrine and anti-HER2 therapies was studied in vivo using UACC-812 xenografts. RESULTS: ER or its downstream products increased in four out of the five ER+/HER2+ lines, and was evident in one of the two intrinsically resistant lines. In UACC-812 and BT474 parental and resistant derivatives, HER2 inhibition by T reactivated HER network activity to promote resistance. T-resistant lines remained sensitive to HER2 inhibition by either L or HER2 siRNA. With more complete HER2 blockade, resistance to L-containing regimens required the activation of a redundant survival pathway, ER, which was up-regulated and promoted survival via various Bcl2 family members. These L- and L + T-resistant lines were responsive to fulvestrant and to ER siRNA. However, after prolonged treatment with L, but not L + T, BT474 cells switched from depending on ER as a survival pathway, to relying again on the HER network (increased HER2, HER3, and receptor ligands) to overcome L's effects. The combination of endocrine and L + T HER2-targeted therapies achieved complete tumor regression and prevented development of resistance in UACC-812 xenografts. CONCLUSIONS: Combined L + T treatment provides a more complete and stable inhibition of the HER network. With sustained HER2 inhibition, ER functions as a key escape/survival pathway in ER-positive/HER2-positive cells. Complete blockade of the HER network, together with ER inhibition, may provide optimal therapy in selected patients.

Role of early post-operative breast MRI: how helpful is it in deciding the next step for women who may have residual disease?

OBJECTIVES: Positive resection margins following breast conserving surgery are a risk factor for local disease recurrence. Subsequent management of patients is often not straightforward, with post-operative breast MRI increasingly used to aid decision-making. Interpretation of MRI after surgery can prove challenging due to local inflammatory enhancement. We reviewed our experience of post-operative breast MRIs to determine their ability to detect residual disease and to evaluate how they changed initial patient management from re-excision to an alternative. METHODS: A search of breast MRIs performed from August 2014 to December 2019 was undertaken, to identify those performed post-operatively within 4 months of breast conserving surgery. Electronic patient records and imaging were evaluated to determine additional work-up, pathology and surgical outcomes. RESULTS: Of the 2274 breast MRIs during the study period, 44 (2%) were performed post-operatively to evaluate 47 breasts. MRI was normal in 20 cases (43%), suspicious findings at surgical cavity only in 13 (28%), suspicious ipsilateral distant breast findings only in 6 (13%), and both cavity and distant findings in 7 cases (15%). Contralateral abnormalities were identified in 3 cases. Following MRI, mastectomy was performed in 11 cases, re-excision in 25, with 2 subsequent mastectomies, and multidisciplinary team accepted margins in 11 cases, 10 of whom underwent post-operative radiotherapy. MRI altered initial patient management from re-excision to an alternative in 25 cases (45%). CONCLUSION: Post-operative breast MRI, although potentially challenging to interpret, can prove useful in planning the next step in patient management, particularly in its ability to evaluate the whole breast. ADVANCES IN KNOWLEDGE: Post-operative breast MRI is increasingly requested at multidisciplinary team following breast conserving surgery with positive surgical margins on histology, however interpretation is challenging. The value of these studies lie in assessment of the distant breast rather than the surgical resection cavity and can alter patient management guiding the most appropriate next step for definitive treatment.

Breast microcalcifications: the UK RCR 5-point breast imaging system or BI-RADS; which is the better predictor of malignancy?

OBJECTIVE: In the UK RCR 5-point breast imaging system (UKS), radiologists grade mammograms from 1 to 5 according to suspicion for malignancy, however unlike BI-RADS, no lexicon of descriptors is published. The aim of this study was to determine whether strict categorisation of microcalcifications (MCC) according to BI-RADS was a better predictor of malignancy than the UKS and whether these descriptors could be used within the UKS. METHODS: A retrospective review of 241 cases, with MCC on mammography, who underwent biopsy was performed. Morphology, distribution, extent, UKS score, BI-RADS category and pathology were recorded. The positive predictive value (PPV) of each classification system for malignancy was calculated. RESULTS: 28.6% were diagnosed with DCIS/IDC. The PPV for malignancy using the UKS was 18.9%, 69.4%, 100% for M3-5 respectively (p < 0.001) and using ΒI-RADS morphology was amorphous: 7.1%, coarse heterogeneous: 33.3%, fine pleomorphic: 48.1% and fine linear/fine linear branching: 85.2% (p < 0.001). The PPV based on distribution was grouped: 14.2%, regional: 32.3%, diffuse: 33.3% and linear/segmental: 77.8% (p < 0.001). Combining all cases of benign-appearing, amorphous and grouped coarse heterogenous and grouped fine pleomorphic MCC gave a PPV of 12.8%. Combining regional, linear or segmental coarse heterogenous and fine pleomorphic and all fine linear/branching MCC resulted in a PPV of 83.3% for malignancy. CONCLUSION: Combining morphology and distribution of MCC is accurate in malignancy prediction. Use of BI-RADS descriptors could help standardise reporting within the UKS and an algorithm using these within the UKS is proposed. Better prediction would enable more appropriate counselling and help to identify discrepancies. ADVANCES IN KNOWLEDGE: No guidance exists on scoring of suspicious MCC in the UK breast imaging system. Use of BI-RADS morphologic/distribution descriptors can aid malignancy prediction. Findings other than morphology of MCC are important in malignancy prediction. An algorithm for use by the UK radiologist when evaluating MCC is provided.

Treatment of hepatic metastases from medullary thyroid cancer with transarterial embolisation.

Transarterial chemoembolisation (TACE) is well established in the treatment of primary hepatocellular carcinoma and of metastatic disease from colorectal and neuroendocrine tumours. There are few published studies on the effectiveness of treating hepatic metastases from medullary thyroid carcinoma with chemoembolisation and none to our knowledge utilising bland particle transarterial embolisation (TAE). Here we describe the management of multifocal hepatic metastases from medullary thyroid cancer in a 39-year-old woman who underwent bland particle TAE with a biochemical and radiological response and discuss the potential for a wider scope of clinical application for bland TAE in hepatic metastases.

Role models and mentors in surgery.

BACKGROUND: A number of studies have highlighted the importance of positive role models and mentors in influencing medical students' ultimate career decisions. This article sought to review the relevant literature in relation to mentors and role models in surgery. DATA SOURCES: A comprehensive PubMed search of the literature on the subject of role models and mentors was performed using the following keywords: "Mentors," "Mentorship," and "Role Models" alone and in conjunction with the words "medicine" and "surgery." CONCLUSIONS: This article defines the terms role model and mentor and highlights the differences between these. It identifies the importance of early intervention in medical students' careers by surgeons and the possibility of junior doctors acting as mentors. Formal mentoring programs appear to be associated with greater satisfaction among surgical trainees regarding mentorship. In addition, this review serves to show the potential approaches to developing mentorship and role models in surgery.

Surgical mentors and role models: prevalence, importance and associated traits.

BACKGROUND: Role models and mentors play an important part in attracting undergraduates into various medical specialties. However, little is known about the part played by role models and mentors in the context of surgery. The aim of this survey was to elucidate medical students' and surgical trainees' experiences of role models and to determine how mentoring works in practice. We also set out to identify traits associated with successful role models and mentors. METHODS: A questionnaire was distributed to senior undergraduate medical students in 1 medical school, and postgraduate surgical trainees (members of the Association of Surgeons in Training (ASIT) in the UK and Ireland. The survey included questions about the availability of mentors and role models and explored mentorship process. RESULTS: A total of 163 medical students and 216 surgical trainees completed the questionnaire. While most medical students did not have a mentor, 52% (n = 104) of trainees reported having a surgical mentor. In both cases, mentoring was ill-structured and informal. While most medical students expressed a preference for a formal mentoring program, only 38% of surgical trainees expressed a preference for a more formal approach. Experiences of negative surgical role models were a pervasive feature for both medical student and surgical trainee respondents. DISCUSSION: This survey highlights a lack of a deliberate approach to mentoring in surgery and the presence of an excess of negative role models. It is, therefore, time for surgeons to pay much more attention to their roles as professional exemplars and mentors.

Modern management of pyogenic hepatic abscess: a case series and review of the literature.

BACKGROUND: Pyogenic hepatic abscesses are relatively rare, though untreated are uniformly fatal. A recent paradigm shift in the management of liver abscesses, facilitated by advances in diagnostic and interventional radiology, has decreased mortality rates. The aim of this study was to review our experience in managing pyogenic liver abscess, review the literature in this field, and propose guidelines to aid in the current management of this complex disease. METHODS: Demographic and clinical details of all patients admitted to a single institution with liver abscess over a 5 year period were reviewed. Clinical presentation, aetiology, diagnostic work-up, treatment, morbidity and mortality data were collated. RESULTS: Over a 5 year period 11 patients presented to a single institution with pyogenic hepatic abscess (55% males, mean age 60.3 years). Common clinical features at presentation were non-specific constitutional symptoms and signs. Aetiology was predominantly gallstones (45%) or diverticular disease (27%). In addition to empiric antimicrobial therapy, all patients underwent radiologically guided percutaneous drainage of the liver abscess at diagnosis and only 2 patients required surgical intervention, including one 16-year old female who underwent hemi-hepatectomy for a complex and rare Actinomycotic abscess. There were no mortalities after minimum follow-up of one year. CONCLUSIONS: Pyogenic liver abscesses are uncommon, and mortality has decreased over the last two decades. Antimicrobial therapy and radiological intervention form the mainstay of modern treatment. Surgical intervention should be considered for patients with large, complex, septated or multiple abscesses, underlying disease or in whom percutaneous drainage has failed.

Primary splenic lymphoma presenting with ascites.

An 84 year-old gentleman presented with abdominal distension, anorexia and occasional epigastric pain over a four-week period. Blood parameters revealed a hypochromic microcytic anaemia. Both CT and US scan identified ascites and a mass in the left upper quadrant. An ascitic tap was performed identifying bloody ascites and the presence of reactive mesothelial cells on cytology. A subsequent laparotomy and splenectomy was performed. Histology of the resected spleen revealed a Grade 2 follicular lymphoma (Figure 2). The patient had an uneventful postoperative recovery and was well at 6 months follow up. The spleen is an organ with an important immunological function. Primary splenic involvement occurs in less than 1% of non-hodgkin's lymphoma. Symptoms of primary splenic lymphoma (PSL) include pyrexia, weight-loss, night sweats, generalised weakness and left upper quadrant pain secondary to spleno - megaly. Ascites is a rare presenting feature of PSL. This report illustrates a case of primary splenic lymphoma which poses diagnostic challenges for the pathologist and clinician and ultimately requires definitive splenectomy to confirm a diagnosis.Figure 2Photograph of histology slide displaying the lymphoma at 10× magnification.