Introduction: Ultrasound guided localisation is established practice in the management of breast pathology. A safe and simple technique, it is increasing being used in the management of lesions in the head and neck region.

Background:NabP+GEM chemotherapy improves survival as treatment for mPDAC, compared with GEM alone. The UK randomised phase 2 SIEGE trial showed that sequential (SEQ) delivery of nabP+GEM (with nabP given 24 hours before GEM) trended towards improved efficacy compared with standard concomitant (CON) delivery. Preclinical models suggest that nabP potentiates GEM activity by either impacting on stroma or reducing CDA levels. Methods: 146 pts were randomised to receive CON or SEQ nabP+GEM. Baseline whole blood (wb) CDA activity was measured using an endpoint read, spectrometric, plate based assay. Baseline tumour IHC assessed stromal content (H&E), CDA (ab137605) and nucleoside transporter protein, hENT1 (Ventana SP120) expression. Results: 6-month (m) progression-free survival (PFS, primary end point) by SEQ and CON arms was 47% and 33%; median PFS was 5.8 and 4.1m (HR 0.68, 95%CI 0.48-0.97); median overall survival (OS) was 10.1 and 7.9m, respectively. Baseline wb CDA activity correlated only with ANC (R2 0.70, p<.0001) after adjustment for other baseline factors including KPS, disease burden, CRP and did not predict for PFS, OS or toxicity. Of 105 tumours evaluable by IHC, 34 had diffuse strong (ds) CDA staining which predicted for improved PFS with SEQ therapy (HR 0.43, 95%CI 0.20-0.91); this was not evident for other staining patterns or ds-CDA staining for pts on CON therapy. Ds-CDA staining trended towards improved OS with SEQ compared with CON therapy (HR 0.73, 95%CI 0.35-1.52). On disease progression, 34 pts (13 SEQ, 21 CON) received further anti-cancer treatment. Stroma or hENT1 expression did not predict for PFS or OS with SEQ or CON therapy. Tumour stroma staining, but not CDA or hENT1, was an independent prognostic factor for improved OS (moderate/extensive vs none/little, HR 0.55, 95%CI 0.37-0.84). Conclusions: Whole blood CDA activity was not a useful predictive biomarker, due to the dominant neutrophil effect. Instead, strong tumour CDA expression predicted for pts most likely to have a survival benefit from SEQ therapy and warrants further exploration. Clinical trial identification: EudraCT Nr: 2013-001868-40 Sponsors Protocol ID: AX-PANC-PI-0101 ISRCTN: ISRCTN71070888 Legal entity responsible for the study: Cambridge University Hospitals NHS Foundation Trust Funding: Celgene UK Disclosure: P. Corrie: Funding for the SIEGE clinical trial from Celgene Advisory boards in the last 2 years for BMS, Novartis, MSD, Pierre Fabre, Baxalta. J.W. Valle: Speakers' Bureau, Travel, acommodations and expenses from Celgene. B. Basu: Research funding and provision of trial drug from Celgene. Travel, accommodation and registration expenses for ASCO and ESMO Congresses from Bayer. Consulting and advisory role with Baxter Healthcare, Astex, Celgene, Nordic. Honararium from BTG Itrnl. H. Wasan: Honoraria, Speakers bureau and research funding from Celgene and Merck KGA. D. Palmer: Honoraria from Celgene, Nucana, BMS, Sirtex, Bayer. J. Wadsley: Honoraria from Celgene for participation in advisory boards, financial support Celgene to attend conferences. D. Jodrell: Receipt of grants/research supports: Support for Educational Symposium (Celgene) Receipt of honoraria or consultation fees: Support for Scientific Meeting attendance (Celgene). All other authors have declared no conflicts of interest.

Abstract Capecitabine (CAP) is an oral fluoropyrimidine, converted sequentially and selectively to 5-FU at the tumour site. It is used in the treatment of a number of cancers as a single agent and in patients with pancreatic cancer, in combination with gemcitabine. However, pre-clinical data in pancreatic cancer models are limited. In this study, we investigated the pharmacokinetics (PK) and efficacy of CAP in a GEMM of spontaneous pancreatic adenocarcinoma (PDA) occurring in KrasG12D; p53R172H; Pdx1-Cre (KPC) mice, compared to an allograft model of a cell line isolated from a PDA arising in the KPC mice. In the PK study, tumour was collected 2 hours after CAP treatment (755 mg/kg by oral gavage), homogenates were analysed using an LC-MS/MS assay developed to simultaneously detect capecitabine and its 3 metabolites DFCR, DFUR and 5-FU (modified from S.M.Guichard, et al., J. Chrom. B. 2005). Data were compared to our previously reported studies in an allograft model (Proc. AACR 2011 a 5446). After a QDx7 treatment, 5-FU concentrations of 27 ± 13 μM were achieved (compared to 23.0 ± 8.1 μM and 22.7 ± 7.7 μM in allograft tumours after 1 and 5 consecutive doses respectively), confirming adequate drug delivery to the in situ tumour following oral administration of CAP. Therefore we proceeded to efficacy studies in this model. In the allograft model we had identified a significant reduction of the tumour doubling time with 755 mg/kg CAP (5 days/week, 3 weeks), compared to control (7.5 ± 3.0 vs 3.5 ± 0.5 days; P<0.001). In in situ tumours, a short term study over 7 days showed a reduction in tumour growth in CAP-treated KPC PDA tumours compared to control (199% ± 22% vs 121% ± 10%; P<0.01). In a survival study in KPC mice, CAP (755 mg/kg, 5 days/week) was compared to the standard treatment for advanced pancreatic cancer, gemcitabine (GEM, 100 mg/kg, Q3D), and there was no difference in the median survival of mice with spontaneous PDA tumours (P=0.61) suggesting a similar efficacy of CAP to GEM. There is conflicting evidence regarding the utility of the combination of GEM and CAP in this disease, so we also investigated the combination in mice bearing allograft PDA tumours. Full doses of both drugs were not tolerated, but the combination of GEM (75 mg/kg Q3D, 2 weeks) plus CAP (539 mg/kg, 5 days/week, 2 weeks) was feasible. This regimen was associated with significant growth inhibition, but this was not superior to GEM alone (75 mg/kg) at the same dose (tumour doubling time: 8.6 ± 10.8 vs 7.2 ± 2.8 days respectively). In summary, orally administered CAP achieves active concentrations of 5-FU in PDA tumours. Similar effects on survival compared to GEM are seen in PDA tumours. Growth inhibition data in allograft tumours did not show any additional benefit for the GEMCAP combination, when compared to GEM alone. CAP could be considered as an alternative to GEM in future, rationally designed, combination treatment strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3771. doi:1538-7445.AM2012-3771

Today we stand on the threshold of a new medical paradigm. The post-1948 consensus has broken down, and medicine in the United Kingdom embarks on a journey into the unknown. Aneurin Bevan famously complained that in order to bring the effectively private sector consultants on board the new NHS in 1948 he had “to stuff their mouths with gold.” Training as I did in the 1970s I met many consultants who fondly remembered this era and for whom practising in a large teaching hospital was a salaried hobby, with the right to see and treat private patients as and when they chose. As one of my bosses said, “I am a consultant. I am not here to do anything; I am here to be consulted.” Not for him the tyranny of job plans and planned activities—just the certainty that he was valued for his expertise. Not all was well in the medical world then. As juniors we really did work one in twos and three in fives. One contract I had was for 128 hours a week, leaving just 40 hours free for everything else: social life, shopping, arranging the next job, and, oh yes, sleeping. Mind you, we covered fewer patients, the inpatients were generally less sick, and the very sick, very elderly patients were given tender loving care in a side room instead of heroic medicine and surgery and a long stay bed in the high dependency unit. There were compensations. Doctors, however junior, had the respect of society. Hospitals had doctors' car parks. There was a doctors' dining room; and in many a doctors' mess there was a cleaner or housekeeper to cook a breakfast and mother young doctors who had been working continuously for 48 or 72 hours every weekend. All that has gone. We learnt by apprenticeship, we knew our patients, and we had pride in our firm. Even when we got annoyed at not seeing “the boss” for weeks on end, at least we knew that one day we too would be consultants with our own junior staff, our own right to private practice where and when we chose, and, above all, the unflagging respect of society. That's all gone too.​too. Figure 1 Pride in the firm: but are today's doctors in danger of losing power and society's respect? Credit: WELLCOME LIBRARY, LONDON Today most of us are just about to sign a time sensitive contract. This would have been an anathema to our forebears, proud as they were of their commitment to continuity of care. Where once we worked for local hospitals with their own idiosyncratic logos and quaint traditions, now the ubiquitous, uniform blue and white banner of the NHS covers all. Some would argue that medicine retains its power through medical management, in the person of clinical and medical directors. I would argue, however, that medical managers are marginalised in the lower tiers of the organisation, while real power emanates from politicians and the Department of Health directly to chief executives of the trusts and health authorities. This year's fashion is for shorter training of doctors to increase their numbers. From a human resources point of view this must weaken the position of doctors, as the bargaining power of any individual decreases. A shorter training period will decrease the expertise of the people trained, and as a consequence they will lose expert power and society's respect. It is not a coincidence that the margins between medicine and the paramedics are being blurred by the transfer of duties formerly undertaken only by doctors. The other fashion of the day is for plurality of provision—shorthand for the first steps to privatisation. What then is the new medical paradigm? Perhaps the future of British doctors is no more than as interchangeable medico-surgical units working out a portfolio career for a series of American and South African multinationals. Surely we can do better than this?