Nodal positivity in patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy: multicentre collaborative study.

BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.

Initial experience of magnetic seed localization for impalpable breast lesion excision: First 100 cases performed in a single Irish tertiary referral centre.

INTRODUCTION: Wire guided localization has been widely utilized as the standard method of pre-operative localization of breast lesions. Magnetic seeds were developed to counter some of the disadvantages associated with wires. This aim of this study was to assess outcomes following the introduction of magnetic seeds at a tertiary specialist breast centre. METHODS: A retrospective review of a prospective database of the first 100 patients who underwent magnetic seed (Magseed) guided breast surgery between November 2018 and November 2019. Data was collected from 17 wire guided cases completed during the trial phase for comparison. The primary outcome measures were successful excision of index lesion and retrieval of the magnetic seed. Secondary outcomes analyzed included time ready for theatre, post-operative complications and breast margin re-excision rate. RESULTS: Of these 100 cases, 85 patients underwent Magseed guided wide local excision for invasive or in-situ carcinoma and 15 underwent Magseed guided diagnostic excision. The primary lesion was excised, and Magseed was retrieved in all 100 cases. 54% of patients were ready to proceed as the first scheduled theatre case of the day, compared to 0% of wire-guided cases. Amongst therapeutic Magseed guided cases, the re-excision rate for margin clearance was 9.4%. CONCLUSION: Magseed guided breast excision is a new technology that has been implemented with relative ease in our unit. We have shown that magnetic seed guided surgery reliably localizes lesions, is associated with low re-excision rates without an increase in patient morbidity or mortality and results in improvements in theatre planning and efficiency.

Benign breast papilloma: Is surgical excision necessary?

In many centers internationally, current standard of care is to excise all papillomas of the breast, despite recently reported low rates of upgrade to malignancy on final excision. The objective of this study was to determine the upgrade rate to malignancy in patients with papilloma without atypia. A retrospective review of a prospectively maintained database of all cases of benign intraductal papilloma in a tertiary referral symptomatic breast unit between July 2008 and July 2018 was performed. Patients with evidence of malignancy or atypia on core biopsy and those with a history of breast cancer or genetic mutations predisposing to breast cancer were excluded. One hundred and seventy-three cases of benign papilloma diagnosed on core biopsy were identified. Following exclusions, the final cohort comprised of 138 patients. Mean age at presentation was 51. Mean follow-up time was 9.6 months. The most common symptom was a lump (40%). Of the 124 patients who underwent excision, three had ductal carcinoma in situ and there were no cases of invasive disease, giving an upgrade rate to malignancy of 2.4%. Upgrade to other high-risk lesions (atypical lobular and ductal hyperplasia and lobular carcinoma in situ) was demonstrated in 15 cases (12.1%). Benign papilloma was confirmed in 100 cases (81.5%), and 6 (4.8%) had no residual papilloma found on final excision. Twelve patients (8.7%) were managed conservatively. Of those, one later went on to develop malignancy. Patients with a diagnosis of benign papilloma without atypia on core biopsy have a low risk of upgrade to malignancy on final pathology, suggesting that observation may be a safe alternative to surgical excision. Further research is warranted to determine which patients can be safely managed conservatively.

Lobular intraepithelial neoplasia: Outcomes and optimal management.

INTRODUCTION: Lobular neoplasia is a term encompassing both atypical lobular hyperplasia and lobular carcinoma in situ. These pathological findings are of uncertain malignant potential and predispose to a higher lifetime risk of breast cancer. Debate surrounds the management of such lesions, with the rationale for diagnostic excision based on the possibility of upgrading to malignancy. In this study, we report the upgrade rate of these lesions and risk of subsequent development of breast cancer. METHODS: This is a retrospective review of a prospectively maintained data base of all biopsies of breast screening-detected abnormalities in a single Irish breast-screening unit. We included all patients with lobular neoplasia on core needle biopsy who underwent diagnostic excision from 2005 to 2012. We excluded those who had concurrent high-risk lesions on biopsy. End points included upgrade rate and subsequent diagnosis of malignancy on follow-up. RESULTS: During the study period, 66 patients met criteria for inclusion, with a mean age of 53.74 years. Upgrade rate following excision was 13.64% (n = 9/66). Of those not upgraded, 7.02% (n = 4/57) were subsequently diagnosed with malignancy. Median time to diagnosis was 59.61 months (range = 10.5-124.4). CONCLUSION: There is a significant rate of upgrade following diagnostic excision of lobular neoplasia, supporting the practice of diagnostic excision. There is an increased lifetime risk of breast cancer for women with a diagnosis of lobular neoplasia, with many of these cancers occurring outside the standard five-year monitoring period, suggesting a potential benefit in extending surveillance.

Cowden Syndrome: Serendipitous Diagnosis in Patients with Significant Breast Disease. Case Series and Literature Review.

Cowden syndrome (CS) is a multi-system disease that carries an increased lifetime risk of developing certain cancers as well as benign neoplasms. The presence of features of CS in the general unaffected population results in difficulties in the recognition and diagnosis of this condition. Early diagnosis is essential to prevent the development of malignant neoplasms, yet despite the introduction of diagnostic criteria and risk calculators, accurate diagnosis remains a challenge. We identified three patients who presented to the symptomatic breast unit of a University Teaching Hospital over a period of 12 weeks who subsequently were diagnosed with CS. In this article, we discuss their clinical presentations as well as their path to diagnosis. The short timeframe between the presentations of these patients undoubtedly expedited their diagnosis. Upon application of internationally recognized diagnostic criteria, only two out of our three patients were accurately diagnosed. The risk of breast cancer in CS is comparable with that found in Hereditary Breast and Ovarian Cancer Syndrome and while a protocol for breast screening in these patients exists in most centres, no such protocol exists for patients with CS in our institution. The recommended cancer surveillance programs for patients with CS have not been found to prolong survival, however. CS consists of a vast array of diseases that span the various specialties and the subsequent varied phenotypic presentation poses diagnostic difficulties for clinicians as emphasized in our series. Continued research is required to improve recognition and diagnosis and will hopefully result in the emergence of life prolonging strategies.

Impact of Simulation Training on Core Skill Competency of Undergraduate Medical Students.

INTRODUCTION: Simulation based medical training (SBMT) is gaining traction for undergraduate learning and development. We designed, implemented, and independently assessed the impact of an SBMT programme on competency in surgical history taking and clinical examination for senior clinical students. METHODS: With institutional ethical approval and initial pilot study of student volunteers that ensured format appropriateness, we implemented an SBMT programme weekly for ten weeks during the core surgery module of our Medicine degree programme. Groups of 5 students collaboratively undertook an observed focused history and physical examination while simultaneously directing care on a simulated surgical patient (actor) with acute abdominal pain. This was conducted in a nonclinical, standardised, tutor-supervised environment and followed by a group debriefing led by both the simulated patient and tutor discussing student interaction and competency. All students undertook Southampton Medical Assessment Tool (SMAT) on a surgical inpatient prior to (baseline) and within 2 weeks after SBMT. Students without simulation training functioned as a control group and randomized cluster sampling was utilised for group selection. Second assessments were by independent surgical academics blinded to student group. Feedback was collected via anonymous questionnaire from those who undertook SBMT. RESULTS: One hundred students took part, fifty of whom undertook SBMT. Global mean SMAT scores were similar between the control and intervention group at baseline (p > 0.05). Scores on the second assessment were significantly higher (p = 0.0006) for those who had undertaken SBMT vs. controls; 94% of students taking SBMT reported benefit via questionnaire with 85% stating increased confidence in history-taking and 78% reporting improved abdominal examination. CONCLUSIONS: Undergraduate simulation training at scale is feasible and positively impacts undergraduate student core task competency.

Implementation of an on-site simulation programme during COVID-19 and the assessment of its impact on medical students' competence.

BACKGROUND: COVID-19 has greatly impacted medical students' clinical education. This study evaluates the usefulness of a rapidly implemented on-site simulation programme deployed to supplement our disrupted curriculum. METHODS: Students on surgical rotations received 4-hour tutor-led simulated patient sessions (involving mannikins with remote audio-visual observation) respecting hospital and public health protocols. Attitudes were questionnaire-assessed before and after. Independent, blinded, nonacademic clinicians scored students' clinical competencies by observing real patient interactions using the surgical ward assessment tool in a representative sample versus those completing same duration medicine clinical rotations without simulation (Mann-Whitney U testing, p < 0.05 denoting significance) with all students receiving the same surgical e-learning resources and didactic teaching. RESULTS: A total of 220 students underwent simulation training, comprising 96 hours of scheduled direct teaching. Prior to commencement, 15 students (7% of 191 completing the survey) admitted anxiety, mainly due to clinical inexperience, with only two (1%) anxious re on-site spreading/contracting of COVID-19. A total of 66 students (30%, 38 females and 29 graduate entrants) underwent formal competency assessment by clinicians from ten specialties at two clinical sites. Those who received simulation training (n = 35) were judged significantly better at history taking (p = 0.004) and test ordering (p = 0.01) but not clinical examination, patient drug chart assessment, or differential diagnosis formulation. Of 75 students providing subsequent feedback, 88% stated simulation beneficial (notably for history taking and physical examination skills in 63%) with 83% advocating for more. CONCLUSION: Our rapidly implemented simulation programme for undergraduate medical students helped mitigate pandemic restrictions, enabling improved competence despite necessarily reduced clinical activity encouraging further development.

Upgrade rates and outcomes of screen-detected atypical intraductal epithelial proliferation (AIDEP) diagnosed on core needle biopsy.

INTRODUCTION: Atypical intraductal epithelial proliferation (AIDEP) is a breast lesion categorised as "indeterminate" if identified on core needle biopsy (CNB). The rate at which these lesions are upgraded following diagnostic excision varies in the literature. Women diagnosed with AIDEP are thought to be at increased risk of breast cancer. Our aim was to identify the rate of upgrade to invasive or in situ carcinoma in a group of patients diagnosed with AIDEP on screening mammography and to quantify their risk of subsequent breast cancer. METHODS: We conducted a retrospective review of a prospectively maintained database containing all patients diagnosed with AIDEP on CNB between 2005 and 2012 in an Irish breast screening centre. Basic demographic data was collected along with details of the original CNB result, rate of upgrade to carcinoma and details of any subsequent cancer diagnoses. RESULTS: In total 113 patients were diagnosed with AIDEP on CNB during the study period. The upgrade rate on diagnostic excision was 28.3% (n = 32). 6.2% (n = 7) were upgraded to invasive cancer and 22.1% (n = 25) to DCIS. 81 patients were not upgraded on diagnostic excision and were offered 5 years of annual mammographic surveillance. 9.88% (8/81) of these patients went on to receive a subsequent diagnosis of malignancy. The mean time to diagnosis of these subsequent cancers was 65.41 months (range 20.18-145.21). CONCLUSION: Our data showing an upgrade rate of 28% to carcinoma reflects recently published data and we believe it supports the continued practice of excising AIDEP to exclude co-existing carcinoma.

Management and outcomes of phyllodes tumours - 10 year experience.

INTRODUCTION: Phyllodes tumours represent 0.3-1% of breast tumours, typically presenting in women aged 35-55 years. They are classified into benign, borderline and malignant grades and exhibit a spectrum of features. There is significant debate surrounding the optimal management of phyllodes tumour, particularly regarding appropriate margins. METHODS: This is a retrospective review of a prospectively maintained database of patients who underwent surgical management for phyllodes tumours in a single tertiary referral centre from 2007-2017. Patient demographics, tumour characteristics, surgical treatment and follow-up data were analysed. Tumour margins were classified as positive (0 mm), close (≤2 mm) and clear (>2 mm). RESULTS: A total of 57 patients underwent surgical excision of a phyllodes tumour. The Mean age was 37.7 years (range: ages 14-91) with mean follow-up of 38.5 months (range: 0.5-133 months). There were 44 (77%) benign, 4 (7%) borderline and 9 (16%) malignant phyllodes cases. 54 patients had breast conserving surgery (BCS) and 3 underwent mastectomy. 30 (53%) patients underwent re-excision of margins. The final margin status was clear in 32 (56%), close in 13 (23%) and positive in 12 (21%). During follow-up, 4 patients were diagnosed with local recurrence (2 malignant, 1 borderline and 1 benign pathology on recurrence samples). CONCLUSION: There are no clear guidelines for the surgical management and follow-up of phyllodes tumours. This study suggests that patients with malignant phyllodes and positive margins are more likely to develop local recurrence. There is a need for large prospective studies to guide the development of future guidelines.

Nipple discharge and the efficacy of duct cytology in evaluating breast cancer risk.

BACKGROUND: Nipple discharge accounts for up to 5% of referrals to breast surgical services. With the vast majority of breast carcinomas originating in the ductal system, symptomatic dysfunction of this system often raises disproportionate clinical concern. The aim of this study is firstly, to evaluate the clinical importance of nipple discharge as an indicator of underlying malignancy and secondly, to assess the diagnostic application of duct cytology in patients presenting with nipple discharge. STUDY DESIGN: We performed a retrospective analysis of all patients presenting with nipple discharge as their primary symptom to the symptomatic breast unit at a tertiary referral center over a 30-month period (n = 313). The Hospital Inpatient Enquiry (HIPE) System and BreastHealth database were used to identify our study cohort. Parameters evaluated included patient demographics, clinical presentation, clinical evaluation, radiological assessment and histological/cytological analysis. RESULTS: Three-hundred and thirteen patients presented with nipple discharge as their primary complaint. Invasive breast carcinoma was diagnosed by Triple Assessment in 5% of patients. 24% of patients presenting with nipple discharge underwent nipple aspiration and cytological analysis. Duct cytology was diagnostic of the underlying breast carcinoma in 50% of triple assessment diagnosed carcinoma. Four risk factors were identified as having a significant association with breast carcinoma, these included (a) age >50 years (p < 0.0001), (b) bloody nipple discharge (p < 0.008), (c) presence of a breast lump (p < 0.0001) and (d) single duct discharge (p < 0.006). CONCLUSIONS: Nipple discharge is a poor indicator of an underlying malignancy. Use of nipple aspiration and duct cytology for the assessment of nipple discharge is of limited diagnostic benefit. However, by utilizing the systematic, gold standard approach of Triple Assessment (clinical, radiological and cytological evaluation), the risk of underlying carcinoma can be accurately defined.

Removal of a sex toy under general anaesthesia using a bimanual-technique and Magill's forceps: A case report.

INTRODUCTION: Phallic objects may cause large bowel obstruction if not promptly removed. A bi-manual technique with the aid of a Magill's forceps is presented here. PRESENTATION OF CASE: A 68-year-old man presented to the emergency department with severe lower abdominal discomfort, distension and inability to pass urine, flatus or bowel motions. He had inserted a phallic object in the rectum 10 hours prior to presentation and had been unable to remove same. Abdominal examination was remarkable for distension with tenderness also elicited suprapubically and in the left iliac fossa. The foreign body was barely palpable per rectum. Plain radiographs showed prominent left-sided colonic segments. Following the trial of a manual attempt at removal in the emergency department, a decision was made to remove this under anaesthesia due to worsening symptoms. The phallic object was successfully removed under general anaesthesia using bi-manual manipulation assisted by a pair of Magill's forceps. DISCUSSION: The method of removal of phallic objects varies from one individual case to another. In the presence of obstruction, a quick decision must be made for removal under general anaesthesia and the patient will also need to be consented for laparotomy. Previous literature described a "cork-in-bottle" technique using myomectomy screws as well as use of single-incision laparoscopic surgery (SILS) ports for removal of phallic objects. CONCLUSION: Extraction of phallic objects requires ingenuity. We describe another minimally invasive technique of removal that adds to the literature, thereby limiting the need for laparotomy and open removal of foreign bodies.

Effect of anaesthetic technique on immune cell infiltration in breast cancer: a follow-up pilot analysis of a prospective, randomised, investigator-masked study.

BACKGROUND: Live animal studies using an inoculation model of breast cancer indicate that anaesthetic drugs and techniques differentially affect cancer metastasis, inversely related to Natural Killer (NK) cell and T lymphocyte levels. Clinical histological studies demonstrate that the distribution of these immune cells and macrophages in intra-tumoral cancer tissue can predict prognosis and response to therapy. No study has evaluated whether the anaesthetic technique influences human breast cancer immune cell infiltration. MATERIALS AND METHODS: Excised breast cancer specimens from patients previously enrolled in an ongoing, prospective, randomised trial (NCT00418457) investigating the effect of anaesthetic technique on long-term breast cancer outcome were immunohistochemically stained to enable a colour deconvolution technique to summate marked immune cell infiltration: CD56 (NK cells), CD4 (T helper cells), CD8 (T suppressor cells) and CD68 (macrophages). Patients were randomised to receive either a propofol-paravertebral anaesthetic with continuing analgesia (PPA, n=12) or a balanced general anaesthesia with opioid analgesia (GA, n=16) for 24 h postoperatively. Investigators were masked to group allocation. RESULTS: Normalised positive intensity values, (median (interquartile range (IQR)), for CD56 were lower in GA121 (116-134) versus 136 (132-142), p=0.015. CD4 was also lower in GA10.9 (5.5-27.8) versus PPA 19.7 (14.4-83.5), p=0.03 but CD8 5.5 (4.0-9.75) versus 13.0 (5.0-14.5) respectively, p=0.24 and CD 68 infiltration 5.8 (3.25-8.75) versus 8.0 (3.0-8.75), p=0.74 were not significantly different. CONCLUSION: PPA induces increased levels of NK and T helper cell infiltration into breast cancer tissue compared with GA but not T suppressor cells or macro phages. This is consistent with the hypothesis that the anaesthetic technique may affect perioperative immune function conducive to resisting breast cancer recurrence and metastasis.

Digital mammography in a screening programme and its implications for pathology: a comparative study.

AIMS: Most studies comparing full-field digital mammography (FFDM) with conventional screen-film mammography (SFM) have been radiology-based. The pathological implications of FFDM have received little attention in the literature, especially in the context of screening programmes. The primary objective of this retrospective study is to compare FFDM with SFM in a population-based screening programme with regard to a number of pathological parameters. METHODS: During the study period, 107 818 women underwent screening mammograms with almost equal numbers obtained with each technique (49.9% with SFM vs 50.1% with FFDM). We compared SFM with FFDM using the following parameters: recall rate, diagnostic core biopsy rate, cancer detection rates, B3 rate, B4 rate, preoperative diagnostic rate for malignancy, positive predictive values and tumour characteristics. RESULTS: The recall rate was significantly higher with FFDM (4.21% vs 3.52%, p<0.0001). The overall cancer detection rate of 7.2 per 1000 women screened with FFDM was also significantly higher than the rate of 6.2 per 1000 women screened with SFM (p=0.04). The B3 rate in the SFM group was 1.3 per 1000 women screened versus 2.5 per 1000 women screened in the FFDM group (p<0.001). The recall rate and cancer detection rates (overall, invasive and pure ductal carcinoma in situ) were all significantly higher with FFDM for lesions presenting as microcalcifications. CONCLUSIONS: The higher cancer detection rate with FFDM in this study was due to improved detection of microcalcifications. However, this was achieved at the cost of a higher recall rate and a higher B3 rate, indicating that overtreatment may be problematic with digital mammography.

An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

BACKGROUND: Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. METHODS: Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. RESULTS: Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumorigenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. CONCLUSIONS: Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.