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Introduction Recent years have seen a dramatic shift to more conservative management of the axilla and the presence of a positive sentinel lymph node biopsy does not now automatically mandate an axillary clearance. This is based largely on data from the American College of Surgeons Oncology Group (ACOSOG) Z11 study, which failed to demonstrate a difference in local recurrence or overall survival when an axillary clearance was omitted in a highly selective group of patients with a positive sentinel lymph node. However, the presence of a positive pre-operative ultrasound guided axillary FNAC(Fine Needle Aspiration Cytology) may be representative of a higher burden of axillary disease. Aim Therefore, the aims of this study were firstly to quantify the actual nodal burden in breast cancer patients with a positive pre-operative ultrasound guided axillary FNAC and secondly to identify the number of patients who may have been spared an axillary clearance based on Z11 eligibility criteria. Methods A retrospective review of a prospectively maintained database within a tertiary breast cancer referral centre was performed. All patients with a positive pre-operative axillary FNAC were identified within a five year period (2007 – 2011). Demographic, tumour and biological characteristics and final nodal status were analysed. Eligibility for randomisation according to the Z11 criteria was assessed based on the final pathology and the number of patients who could have been spared an axillary clearance was identified. Results A total of 360 patients were identified with a positive axillary ultrasound guided FNAC. Sixty-three patients had no axillary surgery and three patients had recurrent disease, leaving a total of 294 for analysis. The mean age was 56 years (range 22 – 87). The mean size of the tumour was 31.3mm (range 4mm – 132mm) and the majority were an invasive grade 3 (57%) ductal carcinoma (84%). Luminal A (63%) was the commonest sub-type. The mean number of nodes removed at axillary clearance was 24 (range 7 – 58) while the mean number of positive nodes excised was 6 (range 0 – 47). Of these, the mean number of level I positive nodes was 4, level II was 1 and level III nodes was Overall a total of 78 patients had less than three positive nodes identified in the axilla and potentially may have been eligible for the Z11 study. However, when patients who had a mastectomy, neo-adjuvant chemotherapy were excluded and the presence of extra-capsular nodal involvement was accounted for only 19 (6.4%) patients may have been spared an axillary clearance. Conclusions The presence of nodal positivity on a pre-operative FNAC is associated with a higher burden of axillary disease. Only a minority of these patients would be able to avoid an axillary clearance in the setting of the recent Z11 study. Performing an axillary ultrasound and FNAC of suspicious nodes allows patients to avoid an unnecessary sentinel lymph node biopsy and proceed directly to an axillary clearance. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-05.

The 2nd International Consensus Conference for Breast Cancer in Young Women (BCY2) took place in November 2014, in Dublin, Ireland organized by the European School of Oncology (ESO). Consensus recommendations for the management of breast cancer in young women (BCYW) were updated from BCY1 with incorporation of new evidence to inform the guidelines, and areas of research priorities were identified. This manuscript summarizes these international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

The objective of this study was to make an assessment of the utility of fine needle aspiration cytology (FNAC), in a “one-stop” symptomatic breast triple assessment clinic. Controversy surrounds the optimal tissue biopsy methodology in the diagnosis of symptomatic breast cancer and the identification of benign disease. FNAC in the context of a Rapid Assessment Breast Clinic (RABC) allows the same day diagnosis and early treatment of breast cancer, with the immediate reassurance and discharge of those with benign disease. We analyzed prospective data accrued at a RABC, over a 4-year period from 2004 to 2007. All patients were triple assessed, with FNACs performed on site by two consultant cytopathologists. Investigations were reported immediately, and clinical data were captured via a database using compulsory data field entry. There were 4487 attendances at our RABC, with 1572 FNACs were performed. The positive predictive value of FNAC with a C5 cancer diagnosis was 100%, 95.6% for a C4 report, with a complete sensitivity of 94%. The full specificity of correctly identified benign lesions was 77.4%, with a false negative rate of 3.85%. This enabled 66% of patients attending the RABC to receive a same day diagnosis of benign disease and discharge. FNAC is highly accurate in the diagnosis of symptomatic breast cancer in an RABC. FNAC allows accurate diagnosis of benign disease and immediate discharge of the majority of patients. In this era, when a large majority of patients have benign disease, we believe that FNAC provides an equivalent, if not better, method of evaluation of patients in a triple assessment RABC.

Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15-20% of women who develop breast cancer have a family history and 5-10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score >or=16. BRCA1/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management

© 2015 FEBS. The majority of women diagnosed with lymph node-negative breast cancer are unnecessarily treated with damaging chemotherapeutics after surgical resection. This highlights the importance of understanding and more accurately predicting patient prognosis. In the present study, we define the transcriptional networks regulating well-established prognostic gene expression signatures. We find that the same set of transcriptional regulators consistently lie upstream of both 'prognosis' and 'proliferation' gene signatures, suggesting that a central transcriptional network underpins a shared phenotype within these signatures. Strikingly, the master transcriptional regulators within this network predict recurrence risk for lymph node-negative breast cancer better than currently used multigene prognostic assays, particularly in estrogen receptor-positive patients. Simultaneous examination of p16INK4Aexpression, which predicts tumours that have bypassed cellular senescence, revealed that intermediate levels of p16INK4A correlate with an intact pRB pathway and improved survival. A combination of these master transcriptional regulators and p16INK4A, termed the OncoMasTR score, stratifies tumours based on their proliferative and senescence capacity, facilitating a clearer delineation of lymph node-negative breast cancer patients at high risk of recurrence, and thus requiring chemotherapy. Furthermore, OncoMasTR accurately classifies over 60% of patients as 'low risk', an improvement on existing prognostic assays, which has the potential to reduce overtreatment in early-stage patients. Taken together, the present study provides new insights into the transcriptional regulation of cellular proliferation in breast cancer and provides an opportunity to enhance and streamline methods of predicting breast cancer prognosis.

Background The majority of women with breast cancer present with localized disease. The optimal strategy for identifying patients with metastatic disease at diagnosis remains unclear. The aim of this study was to evaluate the additional diagnostic yield from isotope bone scanning when added to CT staging of the thorax, abdomen and pelvis (CT-TAP) in patients with newly diagnosed breast cancer. Methods All patients diagnosed with breast cancer who underwent staging CT-TAP and bone scan between 2011 and 2013 were identified from a prospective database of a tertiary referral breast cancer centre that provides a symptomatic and population-based screening breast service. Criteria for staging included: biopsy-proven axillary nodal metastases; planned neoadjuvant chemotherapy or mastectomy; locally advanced or inflammatory breast cancer and symptoms suggestive of metastases. Results A total of 631 patients underwent staging by CT-TAP and bone scan. Of these, 69 patients (10·9 per cent) had distant metastasis at presentation, with disease confined to a single organ in 49 patients (71 per cent) and 20 (29 per cent) having metastatic deposits in multiple organs. Bone metastasis was the most common site; 39 of 49 patients had bone metastasis alone and 12 had a single isolated metastatic deposit. All but two of these were to the axial skeleton. No preoperative histological factors identified a cohort of patients at risk of metastatic disease. Omission of the bone scan in systemic staging would have resulted in a false-negative rate of 0·8 per cent. Conclusion For patients diagnosed with breast cancer, CT-TAP is a satisfactory stand-alone investigation for systemic staging.

Sentinel lymph node biopsy (SLNB) has become the gold standard for axillary staging. Debate remains as to the optimal method of SLN detection.Determine whether patients undergoing an SLNB required the addition of isosulfan blue dye to radioisotope when an SLN was identified on a preoperative lymphoscintigram.A prospective randomized controlled trial comparing the combination of radioisotope and blue dye versus radioisotope alone was performed between March 2010 and September 2012. The trial protocol was registered with Current Controlled Trials. Women with clinically and radiologically node-negative breast cancer with a positive preoperative lymphoscintigram were eligible for inclusion.A total of 667 patients were included in the analysis with 342 patients receiving the combination (blue dye and radioisotope) and 325 patients receiving radioisotope alone. The groups were evenly matched both demographically and pathologically. The mean age was 48 years (48.3 vs 47.7 years; P = 0.47), the mean tumour size was 24.2 mm (24.3 mm vs 24.1 mm; P = 0.7) and there was no statistically significant difference in the grade of the tumors between the 2 groups (P = 0.58). There was no difference in the identification rate, nor was that in the number of nodes retrieved between the 2 groups (P = 0.30). There was no difference in the number of positive lymph nodes that were identified between the 2 groups (23.8% vs 22.1%; P = 0.64).This study failed to demonstrate an advantage with the addition of isosulfan blue dye to radioisotope in the identification of the SLN in the presence of a positive preoperative lymphoscintigram.

This observational, cohort study aimed to examine the potential utility of Rapid Assessment Breast Clinics (RABC) beyond cancer detection at presentation. One thousand four hundred and twenty nine women were studied over an 18 month period. 154 (10.7%) had breast cancer - 87.7% of whom were seen expediently with 92.9% being diagnosed at one attendance. One hundred and forty three (10%) of those with a benign diagnosis were found by routine questioning to have significant familial risk separate to their reason for referral. Despite careful triage, considerable contamination of appointment allotment occurred with many who were correctly triaged as non-urgent being seen 'urgently'. One hundred and seventy six attendees (12.3%) had neither the symptom that triggered referral, nor breast lump, nipple discharge nor family history of breast cancer, while 283 (19.8%) had no objective clinical or radiological abnormality. Although RABC reliably categorise malignant versus non-malignant diagnoses despite cluttering by low risk women, a significant proportion of non-cancer patients still require address of future risk rather than reassurance of their present status alone.

Background Although breast conservation surgery, when combined with radiotherapy, has been shown to provide excellent locoregional control for breast cancer, approximately one third of women with breast cancer require mastectomy. Many of these women are offered immediate reconstruction. Postmastectomy radiotherapy (PMRT) is indicated in some cases, but is associated with side-effects, including its impact on the reconstructed breast. Objective To review the pertinent issues surrounding PMRT, including patient selection for radiotherapy and the effect of radiotherapy on reconstructive decisions. Methods A literature review was performed using the Medline database. Conclusions PMRT is indicated in patients who are deemed to have a high risk of loco-regional recurrence. Although PMRT is strongly recommended for patients with four or more positive lymphnodes, other indications for PMRT remain controversial. Immediate reconstruction post mastectomy has been shown to have favorable outcomes. However, PMRT may increase the need for revision surgery post immediate reconstruction. There are few randomized trials looking at these key issues, and the evidence is largely derived from observational retrospective studies. Patients should be carefully counseled before a decision is made to proceed with immediate reconstruction, where there is a high chance that PMRT may be indicated.

In recent times there have been many important changes in the surgical management of rectal cancer. The general thrust of these changes has been towards a less invasive approach with preservation of intestinal continuity and avoidance of the psychological sequelae of a stoma. It is also becoming increasingly apparent that profound sexual and autonomic dysfunction can be associated with abdominoperineal resection. This paper highlights these issues and the conflict between performing an adequate oncological procedure and reducing the incidence of postoperative psychological morbidity. It outlines the great changes there have been in surgical technique and their relevance to psychological problems after surgery for rectal cancer. The need for auditing psychological morbidity when assessing the outcome of surgical series is emphasised, as is the importance of involving the patient in the medical decision making.

Radioimmunoguided surgery is a technique that aims to delineate the extent of epithelial neoplasms (primary/recurrent) and their spread (local, regional, and distant) which are not adequately visualized by conventional imaging techniques. The target lesion binds radiolabelled, tumour-associated monoclonal antibodies which are administered in the days before surgery and which bind to the target lesion. The radiotracer is detected intraoperatively using a hand-held gamma detecting probe. This identifies the extent of the tumour, involvement of lymph nodes or other organs and may allow a more complete surgical clearance of the tumour. This article provides a basic understanding of the RIGS (radioimmunoguided surgery) technique, the monoclonal antibodies which are used and outlines the advantages and limitations of this technique.

Pancreatic adenocarcinoma is a relatively common malignancy and its incidence is increasing. Prognosis in these patients is poor, and surgery, the only effective treatment, saves only a minority of patients. The number in this small group of patients might be increased by early detection of pancreatic tumours. This review examines the current status of pancreatic tumour associated proteins in the detection of pancreatic cancer. As well as existing markers, the review also reports on newer markers that may offer advantages over existing ones in the detection of pancreatic adenocarcinoma. This is particularly important because recent studies have identified high-risk groups susceptible to pancreatic cancer. Future research in pancreatic cancer should be directed at earlier detection, and tumour markers may play an important role in this process.

1. We have examined the effects of pre-hepatic portal hypertension on the responsiveness of rat small mesenteric arteries and aorta. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham-operated. 2. In rat mesenteric arteries, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of noradrenaline (NA), but the maximum contractile responses to NA, U46619 and KCl were significantly increased in vessels from portal hypertensive animals. This altered maximum contractile response was not due to alterations in smooth muscle mass. 3. In rat mesenteric arteries, there were no significant differences between portal hypertensive and sham-operated animals in endothelium-dependent relaxations to acetylcholine (ACh). The difference between portal hypertensive and sham-operated rats in the maximum response to U46619 was maintained following a combination of methylene blue (1 microM) and NG-monomethyl-L-arginine (100 microM), suggesting that any differences in endothelial function do not explain differences in the response to vasoconstrictors. 4. In rat aorta, there were no significant differences between portal hypertensive and sham-operated animals in the contractile response to NA or KCl or in the endothelium-dependent relaxations to ACh. 5. In pithed rats, there was no difference between portal hypertensive and sham-operated animals in the pressor potency of NA. 6. It is concluded that portal hypertension produces an increase in the contractile response to the vasoconstrictors NA, U46619 and KCl in rat mesenteric arteries but not in the aorta. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle.

S S19 seen in women over 70. It has been suggested that case mix may partly explain this variation in practice. Methods: Data from two UK regional cancer registry offices were analysed to identify whether variation in treatment observed between 2002 and 2010 at hospital and clinician level persisted following adjustment for case mix. Expected case-mix adjusted surgery rates were derived by logistic regression using the variables age, proxy Charlson Co-morbidity Score, deprivation quintile, method of cancer detection, tumour size, stage, grade and nodal status. Results: Data on 17154 women over 70 with ER+ operable breast cancer were analysed using control charts. There was considerable variation in surgery rates at hospital and clinician level, with 39/68 (57.4%) of hospitals and 73/167 (43.7%) of clinicians falling outside the 95% limits. High variation remained after adjustment for case mix at hospital level (30/68; 44.1% remaining outside of the 95% limits), but was substantially reduced at clinician level (17/167; 10% remaining outside of the 95% limits). Conclusion: This study demonstrates variation in selection criteria for operative treatment of older women with early breast cancer, which may result in underor over-treatment. It emphasises the urgent need for evidence based guidelines for treatment selection criteria in older women with breast cancer. http://dx.doi.org/10.1016/j.ejso.2015.03.007 7. Positive pre-operative axillary ultrasound guided fine needle aspiration cytology is associated with higher axillary disease burden in breast cancer patients compared with those detected by sentinel lymph node biopsy Roisin Ni Chearbhaill, Michael R. Boland, Denis Evoy, James Geraghty, Jane Rothwell, Cecily Quinn, Ann O’Doherty, Enda W. McDermott, Ruth S. Prichard 1 Dept. of Breast Surgery, St Vincents University Hospital, Dublin, Ireland Dept. of Pathology, St Vincents University Hospital, Dublin, Ireland Dept. of Radiology, St Vincents University Hospital, Dublin, Ireland Introduction: Recent evidence indicates that breast cancer (BC) patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Whether such an approach could be applied to patients with axillary metastases on ultrasound-guided fine needle aspiration cytology (FNAC) is uncertain. The aim of this study was to determine nodal burden in patients with positive axillary FNAC compared with those with a positive SLNB. Methods: A retrospective study was performed involving patients with BC between 2007e2013 who had either ultrasound-guided FNAC or SLNB. Patient, tumour characteristics and nodal burden were examined in all patients who underwent AC. Results: 784 patients were eligible for analysis. 348 (44%) had positive FNAC and 436 (56%) had a positive SLNB. FNAC-positive patients were more likely to undergo mastectomy (Chi Square test; p < 0.001), have lymphovascular invasion (p 1⁄4 0.007), a negative ER status (p < 0.001) and positive HER2 status (p < 0.001). Median total lymph nodes (LNs) excised was 23 in both groups. Median involved LNs was 4 (range 1e47) in FNAC-positive patients vs. 2 (range 1e37) in SLN-positive patients (Unpaired t-test; p < 0.0001). Median involved LNs in level 1 was 3 in FNACpositive patients vs. 1 in SLNB-positive patients (p< 0.0001). 49% of SLNpositive patients had 1 involved LN, 28% had 2, and 23% had 3. 13% of FNAC-positive patients had 1 involved LN, 12% had 2 and 74% had 3. Conclusion: FNAC positive patients have higher axillary burden than patients with a positive SLNB. 75% of SLN positive patients may fulfill ACOSOG Z0011 criteria and not require further surgery. http://dx.doi.org/10.1016/j.ejso.2015.03.008 8. Multisite breast tumours: Management and outcome Joshka Nel, LindaWilliams,Monika Brzezinzka, Teresa Fernandez, Matthew Barber 1 Edinburgh Breast Unit, Edinburgh, UK University of Edinburgh, Edinburgh, UK Introduction: Mastectomy has been regarded as the standard surgical management of multifocal, multicentric and multiple tumours. Recently, breast conservation has been employed as an alternative although the outcome of this approach is not clear. The aim of this study was to assess the management and outcome of patients diagnosed with multisite tumours. Methods: Three separate cohorts (2007, 2010, 2013) of patients with invasive breast cancer were analyzed retrospectively. Characteristics of those with multisite disease identified pre-operatively, as well as post-operatively, were recorded. Results: A total of 200 patients were diagnosed with multisite tumours: 63/673 in 2007, 66/681 in 2010 and 71/763 in 2013.In 22 patients at least one focus of disease was due to DCIS. The proportion of patients identified pre-operatively as having multisite disease increased significantly over time (62% in 2007, 79% in 2013; p 1⁄4 0.03). The proportion diagnosed pre-operatively (with multisite disease) who had been managed with breast conservation, also increased over time (12.8% in 2007, 55.4% in 2013; p < 0.0001). Local recurrence rate for all multisite cancer patients treated with breast conservation was 3% and with mastectomy, 5% (p 1⁄4 0.72). Survival outcome was poorer for those patients treated with mastectomy (79% vs 94% for breast conservation; p 1⁄4 0.0023) likely due to higher risk disease at presentation. Conclusion: Breast conservation is often feasible in patients with multisite tumours. This approach appears to be a safe alternative to mastectomy in selected patients http://dx.doi.org/10.1016/j.ejso.2015.03.009 Monday 15th June 2015, Session 4: BJS Papers. 11:00 to 13:00 9. Global abnormalities in lymphatic function occur following systemic therapy in breast cancer patients Salena Bains, Mike Peters, Charles Zammit, Nicola Ryan, James Ballinger, Daphne Glass, Sarah Allen, Anthony Stanton, Peter Mortimer, Arnie Purushotham 1 King’s College London, London, UK Guy’s & St Thomas’ NHS Foundation Trust, London, UK Brighton and Sussex University Hospitals NHS Trust, Brighton, UK Harley Street Clinic, London, UK 5 St George’s, University of London, London, UK Introduction: Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and not simply a ‘stopcock’ effect resulting from removal of axillary lymph nodes. The aim is to test the hypothesis that there is a constitutional ‘global’ lymphatic dysfunction in patients developing BCRL. Methods: Lower limb lymphoscintigraphy was performed in women who had axillary nodal clearance at least 3 years previously: 15 patients with BCRL and 15 without. None had clinical abnormalities of the lower limbs. The control group comprised 24 women with no history of cancer or lower limb lymphoedema. Tc-Nanocoll was injected subcutaneously

Introduction: Breast magnetic resonance imaging (MRI) is highly sensitive in detecting invasive lobular carcinoma (ILC) of the breast. We investigate the use of breast MRI in ILC and in what proportion of patients it influences a change in the management. Methods: A prospective cohort study over a 58-months period, including all consecutive patients with ILC having breast MRI scans. Results: A total of 334 bilateral breast MRI scans were performed. 72 (21.5%) of these were for the assessment of histologically confirmed ILC and were eligible for evaluation. All these MRI scans were carried out within 2 week of patients given the diagnosis (median 5.5 days). Age range of these patients was 24e83 (median 56.5) years. 19 out of 72 patients in ILC group (26.4%) had change in their planned operation from wide local excision (WLE) to a different operation based on the MRI. This included 7 patients with multifocal cancers, 10 patients with significantly larger size of the cancer shown on the MRI than mammogram/ ultrasound and 2 patients with contralateral malignancy. Instead of simple WLE, different operations in these 19 patients included 15 mastectomies, 1 double wire guided WLE, 1 therapeutic mammoplasty and 2 bilateral operations. With regards to the size of cancers, MRI (median 25mm) correlated significantly better with histopathology (median 23mm) than mammogram (median 17mm) and ultrasound scans (median 14.5mm). Over a median 37 months follow up (range 20e78), 2.7% mortality rate (2/72) was observed with no loco-regional recurrence or distant metastases. Conclusions: One out of every four patients (26.4%) with ILC had a change in planned operation, including 20.8% needing mastectomies instead of planned WLE due to MRI findings, hence proving its usefulness in ILC.

Solid tumours contain regions of hypoxia, which may be a prognostic indicator and determinant of malignant progression, metastatic development and chemoradio-resistance. The degree of intra-tumoural hypoxia has been shown to be positively correlated with the expression of the transcription factor hypoxia-inducible factor 1. HIF-1 is composed of 2 sub-units, namely HIF-1alpha and HIF-1beta. The production of hypoxia inducible factor 1-alpha has been identified as a key element in allowing cells to adapt and survive in a hostile hypoxic environment via a variety of pathways. HIF-1alpha is stabilised by hypoxia at the protein level, and also by the oncogenes HER2neu, v-src and ras. There are over 60 target genes for HIF-1, many of which are activated in cancers in comparison to equivalent normal tissues. Chemotherapeutic modulation of HIF-1 pathways has shown promise for patients with chemo-radio resistant or recurrent tumours in Phase II clinical trials. We herein review the existing literature on hypoxia inducible factor-1alpha, particularly its role in carcinogenesis and clinical implications of its over-expression.

Quality assurance is the process by which quality care can be assessed. The general principles include setting a standard with the aim of achieving particular outcomes, followed by the evaluation of parameters that allow for quality assessment. Locoregional and survival outcomes are the major parameters but require years to evaluate and have other limitations. Other parameters therefore may assist in evaluation, such as the availability of the structures and processes required to achieve desired outcomes. Unlike chemotherapy and radiotherapy the quality of surgery is difficult to quantify, yet it is central to the issue of locoregional control and survival. In breast cancer surgery, quality control starts at the diagnostic service; from referral by the family practitioner to the appropriate triage of patients thereby preventing diagnostic delays. The surgical oncologist is pivotal in the multidisciplinary input necessary with both radiologists and pathologists in achieving the correct preoperative diagnoses of symptomatic and screen detected lesions as specified by many of the guidelines. Quality control of the operative surgery addresses issues such as training, volume and life audit of the surgeon. Standardisation of operative technique, pathology reporting with emphasis on specimen orientation and margins, management of the axilla and how it impacts on adjuvant treatment are other important issues. More recently, the availability of breast reconstruction services and the development of the oncoplastic surgeon is becoming an important quality issue. Finally, the quality of the follow up process provides the tools to assess the outcome of both the patient and the service.

Preface: Introduction * 1.Historical Overview * 2. Pathology & Staging * 3. Screening, Genetics & Chemoprevention * 4. The Role of Imaging in Diagnosis & Staging * 5. Neoadjuvant Treatments * 6. Restorative Procedures * 7. Abdominoperineal Resection * 8. Total Mesorectal Excision * 9. Laparoscopic Surgery * 10. Minimal Access Surgery for Rectal Cancer * 11. Postoperative Chemo-Radiation * 12. Follow Up * 13. Surgical Approach to Recurrent Disease * 14. Metastatic Rectal Cancer * 15. Rare Histotypes * 16. Quality of Life * 17. Cost Analysis.

Introduction The advent of multimodal and targeted breast cancer treatment has seen a radical shift from aggressive surgical intervention to a more minimalist approach, both within the breast and axilla. Primary among these changes is the utilisation of the sentinel lymph node biopsy (SLNB) to detect disease within the axilla and a move away from an obligatory axillary clearance when the sentinel node is positive. This depends on the accurate identification of the SLN and initial studies describe a higher identification rate and a lower false negative rate with a dual tracer identification technique. This encompasses a combination of a blue / green dye and radio-labelled isotope. The use of blue dye has been, of itself, associated with significant morbidity and therefore many clinicians may opt for single tracer identification. Aims The aim of the current study was to determine whether the addition of blue dye to radio-isotope increased the positive SLN detection rate, where the SLN was identified pre-operatively on a lymphoscintigram. Methods A prospective randomised controlled trial comparing the combined techniques of isosulphan blue dye and isotope scanning versus isotope scanning alone was performed at a single tertiary referral centre. Ethical approval was obtained prior to commencing the study from the hospital ethics committee. Enrolment commenced in March 2010 and ceased in September 2012. The study design was a randomised open label controlled parallel group trial. The primary outcome measure was the effect of the omission of the blue dye on the identification of SLN if the lymphoscintigram was positive (1 -3 nodes identified). Results A total of 673 patients were included in the final analysis with 344 patients receiving the combination (blue dye and radio-isotope) and 329 patients who received radio-isotope scanning alone. The groups were evenly matched both demographically and pathologically. The mean age was 48 years (48.3 versus 47.7 years; P = 0.47), the mean tumour size was 23.1mm (23.2mm versus 23.0mm; p = 0.89) and there was no statistically significant difference in the grade of the tumours between the two groups (p = 0.58). Overall, there was no difference in the number of nodes retrieved between the two groups (563 versus 523; p = 0.30). Similarly, there was no difference in the number of positive lymph nodes that were identified between the two groups (107 versus 98; 23.8% versus 22%; p = 0.65). Conclusions The addition of isosulphan blue dye does not aid in the identification of the SLN in patients who have a positive lymphoscintigram when radioisotope colloid is used. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-01.

Surgical resection is presently the only therapeutic option that provides patients with liver neoplasms a chance of cure. Nonetheless, at the time of diagnosis, the majority of patients with liver tumours present with unresectable hepatic disease.1 The need for new forms of treatment aimed at improving survival in patients with liver neoplasms while preserving quality of life is thus quite apparent.

The selective recognition of tumour cells by monoclonal antibodies, labelled with radioactive isotopes, for use in diagnosis and treatment, forms the basis of immunoscintigraphy, radio-immunoguided surgery and radio-immunotherapy. Research into the application of these systems has encountered multiple difficulties, most notably a low tumour to non-tumour ratio of radioactivity. The development of pretargeting systems, separating the individual steps of tumour cell targeting and the introduction of the radioactive label, have led to significant increments in tumour to non-tumour ratios and an improvement in diagnostic accuracy. Before pretargeting strategies are applied clinically, a thorough understanding of these systems is required and forms the backbone of this report. Clinical examples of early trials have already confirmed many of the theoretical advantages of pretargeting systems and new protocols are already being investigated.

43 Background: Predicting the risk of tumour recurrence, and thus the need for chemotherapy, for lymph node-negative breast cancer patients is a significant problem for clinicians and patients. Methods: We have identified a ‘core proliferation signature,’ which is consistently high in proliferating primary cultures, and is downregulated during cellular senescence. Using a reverse engineering approach on a breast cancer-specific regulatory network, and confirmed by ChIP-seq analysis, we have identified a hierarchy of several highly interconnected Master Transcriptional Regulators upstream of these core proliferation genes. Results: Further analysis of the expression of these factors in breast cancer cohorts at the mRNA and protein levels reveals a remarkable ability to reliably predict recurrence risk for early-stage breast cancer. Strikingly, in our analyses, a combination of just two of these factors outperforms the currently used clinical biomarkers for breast cancer recurrence risk, as well as recently developed multi-gene prognostic assays. Moreover, the addition of the senescence regulator p16INK4A to this panel further increases its prognostic capability. Conclusions: We propose that this novel approach has succeeded in identifying ‘drivers’ of breast cancer proliferation which, when combined with a marker of senescence such as p16INK4A, successfully identify actively proliferating tumours with an impaired senescence response pathway. Furthermore, we suggest that this gene combination has the potential to become an improved prognostic assay for early-stage breast cancer.

See page 433 Advances in molecular biological techniques in recent years have greatly increased our level of understanding about the mechanisms underlying carcinogenesis. Such advances have also enabled identification of genetic mutations associated with specific cancers. It is accepted that this recent acceleration in the discovery of genetic mutations linked to tumour type will have a great impact on clinical practice. However, the translation of such scientific knowledge into patient benefit is by no means clear cut in many instances, and the marriage between new discoveries in basic science and clinical practice— “translational medicine”—is a tremendous challenge. The paper by Vasen and colleagues in this issue of The Lancet provides a clear example of how translational medicine can influence clinical practice. It addresses the long-existing surgical dilemma of the choice between restorative proctocolectomy or colectomy and ileorectal anastomosis in the management of familial adenomatous polyposis, an autosomal dominant disease due to a mutation in the adenomatous polyposis coli (APC) gene. Proctocolectomy is the more acceptable option from the oncological standpoint but it carries a higher morbidity than do colectomy and ileorectal anastomosis. By contrast, ileorectal anastomosis is associated with a risk of developing rectal cancer of 10–55% over 20 years. 1,2 To resolve this dilemma, the authors investigate the possibility that the site of the mutation in the APC gene may assist in the choice of surgical procedure. Their study shows that further surgery, needed for recurrent polyps or rectal cancer, was greater in patients with mutations in the region after codon 1250 than in those with mutations before this codon. The take-home clinical message from the molecular genetic studies in this paper is that ileorectal anastomosis should be the preferred surgical option for polyposis in patients with mutations before codon 1250 and restorative protocolectomy in those with mutations after this codon. Although we await confirmation of the results of this study, other studies have shown a definite correlation between the site of mutation and phenotype of the disease. Mutations between codons 1250–1464 in exon 15, for example, have been reported to be associated with extensive polyposis (over 5000) and an early age of onset, whereas those outside this region have been associated with fewer polyps and an older age of onset of symptoms. 3

A European Conference on Continuing Medical Education (CME) in Oncology was designed and organised in Dublin (Ireland), on 12th and 13th October 1995 by the European School of Oncology in collaboration with University College Dublin and with the financial support of the European Commission (Europe Against Cancer Programme). Two experts were invited from each Member State and all attended the Conference with the sole exception of the representatives of Luxembourg, who did not attend due to unexpected important commitments. Observers were invited to contribute to the discussion as representatives of organisations that were involved either directly or indirectly in CME. The Conference took the format of a plenary session coupled with the identification of five discussion groups formed to debate key areas in CME at a European level in oncology (Table 1). As a result of these discussions and subsequent consultations, an agreement was reached on the following statements: 1. (a) Continuing Medical Education (CME) is an ethical duty and an individual responsibility for each doctor. Although CME should remain voluntary at the present time, it is nevertheless a professional obligation since almost 50% of medical knowledge becomes obsolete after ten years. It should be organised with clear guidelines for medical personnel working in hospitals, in primary health care and in private practice. 2. (b) The CME system within the European Union (EU) should remain self-directed without the necessity for interval examinations: it should be interdisciplinary and must be driven and controlled by the profession itself. 3. (c) A common concept and system within a CME framework may have a considerable impact on EU integration. It should certainly be developed, maintained and monitored at national level but on the basis of a common European model to ensure scientific and cultural interchange among Member States. 4. (d) It was agreed that a credit system is needed to help doctors keep track of their CME activities: the system should be based on the accumulation of credit points (one credit equalling one hour of continuing medical education) and monitored at a national level. Credit transfer among Member States is vital to facilitate exchange between Member States. 5. (e) Oncology provides a very useful model of CME within which guidelines can be proposed and tested. Harmonisation of CME systems among the different European cancer organisations and scientific societies within this model system may represent a useful basis that other specialities can follow.

There were no differences between mesenteric arteries from sham or 14-day portal hypertensive (PH) rats in the potency of or maximum endothelium-dependent relaxations (EDR) to acetylcholine. There were no differences between sham-operated and PH rats in the effects of the combination of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (100 mumol/l) and methylene blue (10 mumol/l) in causing a significant reduction in the EDR to acetylcholine. The degree of portal-systemic shunting, as measured by 57Co-labeled microspheres, was unaffected by acute administration of NG-monomethyl-L-arginine (50 mg/kg) or methylene blue (5 mg/kg). In conclusion, nitric oxide is the main mediator of EDR in rat mesenteric artery, and no evidence was found for an increased role for endothelial-derived nitric oxide in PH rats.

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.

There is no consensus on the management of cancer in elderly patients and age per se should not be the sole factor in the decision-making process. We present a case of regional metastatic melanoma in an 83-year-old patient who received either untested or inadequate treatments. The general condition and stage of the disease, rather than chronological age alone, should be the determinant factor.

Summary Background Axillary lymph-node dissection is an important staging procedure in the surgical treatment of breast cancer. However, early diagnosis has led to increasing numbers of dissections in which axillary nodes are free of disease. This raises questions about the need for the procedure. We carried out a study to assess, first, whether a single axillary lymph node (sentinel node) initially receives malignant cells from a breast carcinoma and, second, whether a clear sentinel node reliably forecasts a disease-free axilla. Methods In a consecutive series of 163 women with operable breast carcinoma, we injected microcolloidal particles of human serum albumin labelled with technetium-99m. This tracer was injected subdermally, close to the tumour site, on the day before surgery, and scintigraphic images of the axilla and breast were taken 10 min, 30 min, and 3 h later. A mark was placed on the skin over the site of the radioactive node (sentinel node). During breast surgery, a hand-held γ-ray detector probe was used to locate the sentinel node, and make possible its separate removal via a small axillary incision. Complete axillary lymphadenectomy was then done. The sentinel node was tagged separately from other nodes. Permanent sections of all removed nodes were prepared for pathological examination. Findings From the sentinel node, we could accurately predict axillary lymph-node status in 156 (97·5%) of the 160 patients in whom a sentinel node was identified, and in all cases (45 patients) with tumours less than 1·5 cm in diameter. In 32 (38%) of the 85 cases with metastatic axillary nodes, the only positive node was the sentinel node. Interpretation In the large majority of patients with breast cancer, lymphoscintigraphy and γ-probe-guided surgery can be used to locate the sentinel node in the axilla, and thereby provide important information about the status of axillary nodes. Patients without clinical involvement of the axilla should undergo sentinel-node biopsy routinely, and may be spared complete axillary dissection when the sentinel node is disease-free.

Background. Axillary lymph-node dissection is an important staging procedure in the surgical treatment of breast cancer. However, early diagnosis has led to increasing numbers of dissections in which axillary nodes are free of disease. This raises first, questions about the need for the procedure. We carried out a study to assess, first, whether a single axillary lymph node (sentinel node) initially receives malignant cells from a breast carcinoma and, second, whether a clear sentinel node reliably forecasts a disease-free axilla. Methods. In a consecutive series of 163 women with operable breast carcinoma, we injected microcolloidal particles of human serum albumin labelled with technetium-99m. This tracer was injected subdermally, close to the tumor site, on the day before surgery, and scintigraphic images of the axilla and breast were taken 10 min, 30 min, and 3 h later. A mark was placed on the skin over the site of the radioactive node (sentinel node). During breast surgery, a hand-held γ-ray det$ector probe was used to locate the sentinel node, and make possible its separate removal via a small axillary incision. Complete axillary lymphadenectomy was then done. The sentinel node was tagged separately from other nodes. Permanent sections of all removed nodes were prepared for pathological examination. Findings. From the sentinel node, we could accurately predict axillary lymph-node status in 156 (97.5%) of the 160 patients in whom a sentinel node was identified, and in all cases (45 patients) with tumours less than 1.5 cm in diameter. In 32 (38%) of the 85 cases with metastatic axillary nodes, the only positive node was the sentinel node. Interpretation. In the large majority of patients with breast cancer, lymphoscintigraphy and γ-probe-guided surgery can be used to locate the sentinel node in the axilla, and thereby provide important information about the status of axillary nodes. Patients without clinical involvement of the axilla should undergo sentinel-node biopsy routinely, and may be spared complete axillary dissection when the sentinel node is disease-free.