Management of vagus nerve stimulation therapy in the peri-operative period: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists.

Vagus nerve stimulation is a well-established treatment option for patients with drug-resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri-operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services.

The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer.

BACKGROUND: Oestrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of progesterone receptor (PgR) status is less certain. The aim of this study was to describe clinicopathological features of ER-positive (ER+)/PgR-negative (PgR-) BC and to determine the effect of PgR negativity in ER+ disease. METHODS: Consecutive female patients with ER+ BC from a single institution were included. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analysis. RESULTS: In total, 2660 patients were included with a mean(s.d.) age of 59.6(13.3) years (range 21-99 years). Median follow-up was 97.2 months (range 3.0-181.2). Some 2208 cases were PgR+ (83.0 per cent) and 452 were PgR- (17.0 per cent). Being postmenopausal (odds ratio (OR) 1.66, 95 per cent c.i. 1.25 to 2.20, P < 0.001), presenting with symptoms (OR 1.71, 95 per cent c.i. 1.30 to 2.25, P < 0.001), ductal subtype (OR 1.51, 95 per cent c.i. 1.17 to 1.97, P = 0.002) and grade 3 tumours (OR 2.20, 95 per cent c.i. 1.68 to 2.87, P < 0.001) were all associated with PgR negativity. In those receiving neoadjuvant chemotherapy (308 patients), pathological complete response rates were 10.1 per cent (25 of 247 patients) in patients with PgR+ disease versus 18.0 per cent in PgR- disease (11 of 61) (P = 0.050). PgR negativity independently predicted worse disease-free (hazard ratio (HR) 1.632, 95 per cent c.i. 1.209 to 2.204, P = 0.001) and overall survival (HR 1.774, 95 per cent c.i. 1.324 to 2.375, P < 0.001), as well as worse overall survival in ER+/HER2- disease (P = 0.004). CONCLUSIONS: In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.

Disease recurrence and oncological outcome of patients treated surgically with curative intent for estrogen receptor positive, lymph node negative breast cancer.

BACKGROUND: The molecular era has identified four breast cancer subtypes. Luminal A breast cancer (LABC) is defined by estrogen-receptor positive (ER+), progesterone-receptor positive (PgR+) and human epidermal growth factor receptor-2 negative (HER2-) tumours; these cancers are the most common and carry favourable prognoses. AIMS: To describe clinicopathologic features, oncological outcome and relapse patterns in LABC. METHODS: Consecutive female patients diagnosed with ER/PgR+/HER2-, lymph node negative (LN-) breast cancer between 2005 and 2015 were included. Clinicopathological and recurrence data was recorded using descriptive statistics. Oncological outcome was determined using Kaplan-Meier and Cox-regression analyses. RESULTS: Analysis was performed for 849 patients with median follow-up of 102.1 months. Mean disease-free (DFS) and overall survival (OS) were 85.8% and 91.8%. Seventy patients died during this study (8.2%), while 58 patients had recurrence; 7 had local recurrence (0.8%) and 51 had distant recurrence (DDR) (6.0%). Patients developing DDR were likely to be postmenopausal (P = 0.028), present symptomatically (P < 0.001) and have larger tumours (P < 0.001). The mean time to DDR was 65.7 months, with fatal recurrence occurring in 66.6% of patients with DDR (34/51). Systemic chemotherapy prescription did not influence DDR (P = 0.053). Age >65 (hazards ratio (HR):1.66, 95% Confidence Interval (CI):1.07-2.55, P = 0.022), presenting symptomatically (HR:2.28, 95%CI:1.21-4.29, P = 0.011) and tumour size >20 mm (HR:1.81, 95%CI:1.25-2.62, P = 0.002) predicted DFS, while age>65 (HR:2.60, 95%CI:1.49-4.53, P = 0.001) and being postmenopausal at diagnosis (HR:3.13, 95%CI:1.19-8.22, P = 0.020) predicted OS. CONCLUSION: Our series demonstrated excellent survival outcomes for patients diagnosed with LN- LABC after almost a decade of follow-up. However, following DDR, fatal progression is often imminent.

Does Mode of Surgical Intervention Based on Oncotype DX Score Influence Disease Recurrence in Early Breast Cancer?

Introduction Routine utilization of multigene assays to inform operative decision-making in early breast cancer (EBC) treatment is yet to be established. In this pilot study, we sought to establish the potential benefits of surgical intervention in EBC based on recurrence risk quantification using the Oncotype DX (ODX) assay. Materials and Methods Consecutive ODX tests performed over a 9-year period from October 2007 to May 2016 were evaluated. Oncotype scores were classified into high (≥31), medium (18-30), or low-risk (0-17) groups. The primary outcome was breast cancer recurrence. Subgroup analysis offered assessment of the recurrence effect of mode of surgical intervention for patient groups as defined by the oncotype score. Results In total 361 patients underwent ODX testing. The mean age and follow-up were 55.25 (± 10.58) years and 38.59 (± 29.1) months, respectively. The majority of patients underwent wide local excision (86.7%) with 8.9 and 4.4% patients having a mastectomy or wide local excision with completion mastectomy, respectively. Fifty-one percent of patients fell into the low risk ODX category with a further 40.2 and 8.5% deemed to be of intermediate and high risk. Five patients (1.38%) had disease recurrence. Comparative analysis of operative groups in each oncotype group revealed no difference in recurrence scores in the low- ( p = 0.84) and high-risk groups ( p = 0.92) with a statistically significant difference identified in the intermediate risk group ( p = 0.002). Conclusion To date we have been unable to definitively identify a role for ODX in guiding surgical approach in EBC. There is, however, a need for larger studies to examine this hypothesis.

Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER-/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER-/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER-/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER-/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER-/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER-/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER-/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER-/PR- None of the cases were confirmed to be ER-/PR+. The ER-/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.

Influence of complications following immediate breast reconstruction on breast cancer recurrence rates.

BACKGROUND: The rate of immediate breast reconstruction is rising. Postoperative infections are more frequent in patients who undergo reconstruction. The inflammatory response to a postoperative infection can increase the risk of tumour recurrence in other forms of cancer through the release of proinflammatory mediators. The aim of this study was to assess the relationship between complications and breast cancer recurrence in patients undergoing immediate reconstruction. METHODS: This was a review of a prospectively maintained database of all patients who had immediate breast reconstruction between 2004 and 2009 at Galway University Hospital, a tertiary breast cancer referral centre serving the west of Ireland. All patients had a minimum follow-up of 5 years. Outcomes assessed included the development of wound complications and breast cancer recurrence. The data were evaluated by univariable and multivariable Cox regression analysis. RESULTS: A total of 229 patients who underwent immediate reconstruction were identified. The overall 5-year recurrence-free survival rate was 85·6 per cent. Fifty-three patients (23·1 per cent) had wound complications, of whom 44 (19·2 per cent) developed a wound infection. There was a significantly greater risk of developing systemic recurrence among patients who experienced a postoperative wound complication compared with those without a complication (hazard ratio 4·94, 95 per cent c.i. 2·72 to 8·95; P < 0·001). This remained significant after adjusting for Nottingham Prognostic Index group in the multivariable analysis. The 5-year recurrence-free survival rate for patients who had a wound complication was 64 per cent, compared with 89·2 per cent in patients without a complication (P < 0·001). CONCLUSION: This study has demonstrated that wound complications after immediate breast reconstructive surgery have significant implications for patients with breast cancer. Strategies are required to minimize the risk of postoperative wound complications in patients with breast cancer undergoing immediate reconstruction.

A qualitative analysis of the attitudes of Irish patients towards participation in genetic-based research.

BACKGROUND: Progress in diagnostic and therapeutic strategies in medicine is dependent upon high-quality biomedical research. Technological advances have facilitated improved understanding of disease aetiology, and rapidly emerging data promises further progress. Translating this potential into the clinic depends on patient participation in innovative clinical trials. We investigated attitudes to genetic research in Ireland, particularly with respect to commercial and financial implications. METHODS: A multi-centre, cross-sectional survey study was performed. Consecutive out-patients attending four clinics were asked to complete paper-based questionnaires. The same questionnaire was publicly available in electronic format on www.surveymonkey.com for 72 h. Data were analysed using SPSS. RESULTS: 351 questionnaires were completed (99 paper, 252 electronic). The majority of respondents were female (n = 288, 82 %), and highly educated, with 244 (70 %) attending college/university. Most participants supported genetic research (267, 76 %), more frequently for common diseases (274, 78 %) than rare disorders (204, 58 %, p < 0.001, χ 2). 103 (29 %) had participated in scientific research, and 57 (16 %) had donated material to a bio-bank. The majority (n = 213, 61 %) would not support research with potential financial/commercial gain. 106 (30 %) would decline to participate in research if researchers would benefit financially, compared to 49 (14 %) if the research was supported by a pharmaceutical company (p < 0.001, χ 2). Respondents would provide buccal samples (258, 74 %) more readily than tissue (225, 64 %) or blood (222, 63 %). CONCLUSIONS: A high level of support for genetic research exists among the Irish population, but active participation is dependent upon a number of factors, notably, type of biological material required, frequency of the disease in question, and commercial interest of the researchers.

The future of UK/Irish surgery: A European solution.

The United Kingdom (UK) and Republic of Ireland (ROI) hospital systems are dependent on junior doctors for their functionality however it is increasingly difficult to recruit UK/ROI trained doctors to fill these posts. Directive 2005/36/EC, which came into force in 2007, is the principal European legislation on the recognition of equivalence of professional qualifications across Europe. European trained doctors are therefore attractive candidates for junior doctor posts. However, although their training is recognised as equivalent by the Irish Medical Council (IMC) and General Medical Council (GMC) they are not being appointed to equivalent posts by the Health Service Executive (HSE) or National Health Service (NHS). With the influence of European Union (EU) centralisation, modification of UK/ROI consultant grade is imminent, possibly to pyramidal structure of the Continental European model with clearer lines of corporate responsibility.

Analysis of subsequent publication and impact of abstracts presented at the Sir Peter Freyer Surgical Symposium: Focus on the Plenary Session.

BACKGROUND: The quality of abstracts presented at a conference reflects the academic activity and research productivity of the surgical/scientific association concerned. The abstract to publication rate (44.5 % internationally), is an important indicator of the quality of presented research. AIM: To evaluate the publication rate and impact of abstracts presented at the plenary session of the Sir Peter Freyer Surgical Symposium over a 25-year period (1989-2014), and identify factors influencing publication. METHODS: Plenary abstracts were identified from abstract books of the Symposium from 1989-2014. The authors, institution, subspecialty and research subject were recorded. A Medline search with name of the first and last author, key words and content of all abstracts was conducted to identify related publications. The impact factor (IF) of the journal and the time to publication was recorded. RESULTS: 298 presented abstracts resulted in 168 publications (publication rate: 56 %). Basic Science research accounted for 80 % (n = 237) of the total number of presentations with the remaining 20 % (n = 61) being categorised as clinical research. Overall, cancer research accounted for 48 % of presented work. The average time to publication was 2 ± 7 years, while 11 % of all published studies achieved publication in the year of the symposium. The median impact factor for published research was 3.558 (IF range 0-39). CONCLUSION: These results indicate that the quality of papers presented at the Sir Peter Freyer Surgical Symposium compares favourably with international equivalents, making this meeting an important forum for Irish Academic Surgery.

Familial breast cancer genetic testing in the West of Ireland.

AIMS: The majority of hereditary breast and ovarian cancers are associated with highly penetrant mutations in two genes: BRCA 1 and 2. Our aim was to investigate the prevalence and types of BRCA mutations in patients from the West of Ireland. METHODS: A retrospective cohort study was undertaken that included all patients from the counties, Mayo, Sligo, Galway, Roscommon, and Clare, who were referred to the National Centre for Medical Genetics (NCMG) for testing for mutations in BRCA 1 or 2 between 2000 and 2010. Data including age, symptoms, family history, Manchester score, and test results were recorded and analysed using SPSS. RESULTS: The NCMG received 380 referrals from the Western seaboard, including 148 for diagnostic testing and 232 for predictive evaluation. Sixty-five patients did not attend for assessment. Two hundred and fifty-six patients fulfilled criteria for genetic counselling, which was accepted by 184, of whom 127 proceeded to testing. Predictive tests were more often declined than diagnostic [41 (46 %) vs. 16 (17 %)]. Ten mutations in BRCA 1 were identified in 20 patients (15 families), including Exon 1-23del (3 families); Exon 14-20del (2 families) and E143X (2 families). Six mutations in BRCA 2 were identified in 15 patients (12 families) including 8525delC (n = 2 families) and 8205-1G>C (n = 3 families). Patients with positive results had significantly higher Manchester scores than those with negative tests [median 25.5 (12-48) vs. 20 (8-37), p = 0.042, Mann-Whitney U test]. CONCLUSION: To identify patients with highly penetrant variants, referrals should be made with strict adherence to guidelines. Counselling should be individualised to counteract intrinsic psychological barriers to testing.

Intracystic papillary carcinoma of the male breast: a case report and review of the literature.

INTRODUCTION: Carcinoma of the male breast is an infrequent and poorly understood disease (Sinha et al. in Ann R Coll Surg Engl 88(5):W3-W5, 2006). It differs from female breast cancer in both demographic and histopathological characteristics. MATERIALS AND METHODS: Herein we describe a case of intracystic papillary carcinoma in situ in a male breast with a review of the literature. CONCLUSION: Although rare, in situ carcinoma constitutes a larger proportion of male than female breast cancer in a non-screened population. It is characteristically of the papillary and micropapillary subtype. Intracystic papillary carcinoma is a noncomedo intraductal carcinoma constituting about 0.5% of female breast cancers and is associated with a slightly inferior prognosis than other noncomedo intraductal carcinomas (Lefkowitz et al. in Hum Pathol 25:802-809, 1994).

Quality of life after immediate breast reconstruction and skin-sparing mastectomy - a comparison with patients undergoing breast conserving surgery.

BACKGROUND: Historically breast cancer surgery was associated with significant psychosocial morbidity and suboptimal cosmetic outcome. Recent emphasis on women's quality of life following breast cancer treatment has drawn attention to the importance of aesthetic outcome and potential benefits of immediate breast reconstruction (IBR). Our primary aim was to assess patient's quality of life after IBR, compared to a matched group undergoing breast conservation. We also investigated the oncological safety and morbidity associated with immediate reconstruction. METHODS: A prospectively collected database of all breast cancer patients who underwent IBR at a tertiary referral breast unit was reviewed. Patients were reviewed clinically, and administered two validated quality of life questionnaires, at least one year after completing their treatment. RESULTS: 255 patients underwent IBR following mastectomy over a 55 month period. Reconstruction with ipsilateral latissimus dorsi flap was most commonly performed (88%). After mean follow-up of 36 months, IBR patients' quality of life was comparable to a group of age-matched women (n = 160) who underwent breast conserving surgery (p = 0.89). No patient experienced local recurrence (0%), distant metastases developed in 4.8% and disease related mortality was 2.2%. Post-operative morbidities included wound infection (11.8%), chronic pain (2.0%), capsular contracture (11%; 36% of whom had radiotherapy) and fat necrosis (14.1%). No patient experienced flap loss. CONCLUSIONS: IBR is a highly acceptable form of treatment for women requiring mastectomy. With high rates of patient satisfaction, low associated morbidity, and proven oncological safety, it is an appropriate recommendation for all women requiring mastectomy.

NCCP breast cancer referral guidelines--are breast cancer patients prioritised?

Following centralisation of breast cancer services, the National Cancer Control Programme (NCCP) introduced referral guidelines indicating which patients require urgent, early and routine review. This study prospectively analysed referrals to a symptomatic breast unit over 3 months to measure Primary Care Physician (GP) uptake of the NCCP referral guidelines, compare triage patterns of GP and consultant breast surgeon and evaluate the efficacy of the guidelines at identifying patients with breast cancer. 1044 consecutive referrals were categorised according to NCCP guidelines. 637 (61%) were referred using the NCCP form. GP referrals correlated well with consultant breast surgeon for patients requiring urgent review (r = 0.71, p < 0.001; Pearson). Patients categorised as "urgent" were more likely to have a breast biopsy compared to those categorised as "routine" (p < 0.0001; Chi2). The overall cancer incidence was 34 (3.3%) and significantly higher in the "urgent" group at 10.5%. NCCP guidelines were 91% sensitive for triaging breast cancer patients into the correct (urgent) category. The NCCP guidelines are accurate and should be considered the gold-standard for referral to the symptomatic breast service. Consideration should be given to a GP-delivered service to patients outside the "urgent" category.

The h index and the identification of global benchmarks for breast cancer research output.

The h index is used to assess an individual's contribution to the literature. This metric should not be employed to compare individuals across research areas; rather each subject should have its own baseline and standard. This work aimed to identify global bibliometric benchmarks for those involved in breast cancer research, and specifically, to describe the bibliographic characteristics of breast surgeons in the UK and Ireland. Authorship data was extracted from breast cancer related output from 1945 to 2008, as indexed in the Web of Science. Authors' publications, citations and h indexes were identified. The breast-related output of 277 UK and Irish breast surgeons was evaluated, and a citation report generated for each. Strong correlation was noted between the h index and number of publications (r = 0.642, P < 0.001) and number of total citations (r = -0.922, P < 0.001). The author with the highest h index is B Fisher (h index = 80). 23.0% of surgeons had not published original research pertaining to the breast; the remainder had together produced 2,060 articles, accounting for 59,002 citations. The top quartile was responsible for 83% of output; the 90th percentile was 20 publications. The range of h index values for the surgeons was 0-50, with a median h index returned of 3 (IQR 1-6); the 90th percentile was 13.5. This work has identified bibliometric benchmarks to which those involved in breast cancer research might aspire. Our findings suggest that there is need for wider involvement of surgeons in the research process and raises questions regarding the future of scientific breast surgery.

A study of pre-operative type and screen in breast surgery: improved efficiency and cost saving.

INTRODUCTION: Patients undergoing major breast surgery have an almost negligible need for blood transfusions. However, type and screen requests are still routinely performed. This represents an inefficient utilization of resources and unnecessary workload for laboratory staff. The aim of this study was to ascertain whether pre-operative blood typing is justified in patients undergoing surgical procedures with an intermediate transfusion probability. METHODS: A retrospective analysis of all patients undergoing a mastectomy and axillary clearance, with or without breast reconstruction in the last 2 years was undertaken. The number of group and hold and cross-match samples that were performed were identified and compared to the number of patients requiring a blood transfusion. The overall cost of routine pre-operative blood typing was analysed. RESULTS: A total of 229 patients were identified. Of these, a group and hold was performed on 192 (83.8%) patients. Cross-matching was undertaken in thirty-one patients (13.5%). In total, five patients (2.1%) required transfusion. No patient was transfused intra-operatively. The overall cost of routine group and hold blood requests was 1,920 euros and of pre-operative cross-matching was 465 euros. Forty-seven units of blood was returned unused to the blood transfusion service at an estimated cost of 23,500 euros. CONCLUSION: The need for routine group and hold blood requests is not justified for patients undergoing elective breast surgery and represents a waste of clinical resources. A more targeted approach will not only reduce the demand on blood products but also reduce the associated costs to blood transfusion services.

Asymptomatic primary fallopian tube cancer: an unusual cause of axillary lymphadenopathy.

Primary Fallopian tube malignancy is considered a rare disease and is often mistaken histologically and clinically for ovarian cancer. The etiology is poorly understood, and it typically presents at an advanced disease stage, as symptoms are often absent in the initial period. As a result, primary fallopian tube cancer is generally associated with a poor prognosis. We present the case of a 45-year-old female who presents with a 5-day history of left axillary swelling and a normal breast examination. Mammogram and biopsy of a lesion in the left breast revealed a fibroadenoma but no other abnormalities. Initial sampling of the axillary node was suspicious for a primary breast malignancy, but histology of the excised node refuted this. PET-CT showed an area of high uptake in the right pelvis, and a laparoscopy identified a tumor of the left fallopian tube which was subsequently excised and confirmed as a serous adenocarcinoma.

Authorship trends in the surgical literature.

BACKGROUND: Authorship is increasingly influential in career progression and academic promotion. This study aimed to examine authorship trends in surgical titles between 1998 and 2008, and to compare these trends with those in general medicine publications. METHODS: Clinical trials published in high-impact medical and surgical titles were identified. The number of authors associated with these studies and trends over time were analysed using PubReMiner. Trends were then compared between titles with and without author contribution forms (ACFs). Author numbers in top-cited articles were correlated with citation rates. RESULTS: Some 6290 trials involving 54,120 different authorships were identified. A significant difference was found between authorship numbers associated with clinical trials in medicine versus those in surgery (P = 0.003). Introduction of ACFs did not influence the number of authors per trial (P = 0.670). The top 100 most highly cited articles accounted for 114,935 citations; author number correlated with subsequent citation rate (r = 0.26, P = 0.011). CONCLUSION: Author numbers have increased in the past decade, in both medical and surgical journals. Although medical output is associated with significantly higher levels of authorship, the difference cannot be explained by complexity of research alone.