David Bunting

Long term follow-up and risk of breast cancer after a radial scar or complex sclerosing lesion has been identified in a benign open breast biopsy

AIMS Radial scars (RS)/complex sclerosing lesions (CSL) are rare, benign breast lesions of unknown aetiology. Associations with breast cancer have been suggested particularly with larger lesions. This study aims to identify the risk of developing subsequent breast cancer after excision of a benign RS/CSL with respect to lesion size and compared to expected rates in the normal UK population. METHODS A prospective cohort analysis was performed on patients diagnosed with RS/CSL in benign, open breast biopsy specimens over a 20-year period. The rate of subsequent breast cancer development was compared to expected rates in the normal UK population. Subjects were divided into two groups according to lesion size and the rates of subsequent breast cancer compared. RESULTS 149 women without proliferative breast disease were followed for an average of 68 months. Five women developed subsequent cancer, equating to a rate of 0.84% per year. This compares to 0.32% per year in the normal population (RR 2.6, 95% CI 0.86-6.0). There were two subsequent cancers in the RS group and three subsequent cancers in the CSL group, P = 0.64. CONCLUSIONS The study finds no evidence to suggest that lesions greater than 10 mm (CSL) have any greater risk of developing cancer after excision than those below 10 mm (RS). Women treated for RS/CSL do not need any additional follow-up beyond routine mammographic breast screening. Additional surveillance should only be performed if there is associated pathology indicating an increased risk of subsequent malignancy.

Laparoscopic Distal Pancreatectomy Using the Modified Prolonged Prefiring Compression Technique Reduces Pancreatic Fistula

BACKGROUND Pancreatic fistula (PF) is a common postoperative complication following distal pancreatectomy. The prolonged prefiring compression (PFC) technique to reduce PF has been described by Nakamura and colleagues in Japan. The present study assessed if this technique can be applied to the United Kingdom patient population in a tertiary referral center and replicate the low incidence of PF after the laparoscopic approach to distal pancreatectomy (Lap-DP). MATERIALS AND METHODS This is a retrospective study of all patients who underwent Lap-DP using the modified PFC technique by the senior author between June 2011 and July 2014. The modified PFC technique involved compression of the pancreatic parenchyma with an endo-stapler for a 3-minute period prior to firing and further 1-minute compression after firing prior to removal of the stapler, which is a small variant to the original technique of maintaining a 2-minute compression post firing. RESULTS Twenty patients (15 females; median age, 66 [range, 25-77] years) underwent Lap-DP using the PFC technique during the study period. Six patients had splenic-preserving Lap-DP. Median operating time was 240 minutes (range, 150-420 minutes) with a median length of hospital stay of 6 days (range, 3-22 days). Six patients (30%) developed Type A (biochemically noted as high drain fluid amylase) PF, and none of the patients had Type B/C PF. In the splenic preservation group, 1 patient had complete splenic infarction requiring laparoscopic splenectomy on Day 3, and 1 patient had partial infarction requiring prolonged hospital stay for pain relief. One patient required prolonged respiratory support due to severe preexisting lung disease. Overall mortality was zero. CONCLUSIONS Our data confirm that the PFC technique is safe, feasible, and effective in reducing clinically significant PF post-Lap-DP in the United Kingdom patient population.

Prospective cohort study of neoadjuvant therapy toxicity in the treatment of oesophageal adenocarcinoma

BACKGROUND Early studies investigating the benefits of neoadjuvant therapy in oesophageal cancer showed conflicting results, taking many years before a survival advantage was demonstrated in randomised trials. Gains are modest, limited by progressive disease and toxicity. This study aimed to investigate the relationship between neoadjuvant therapy-associated toxicity and clinical outcomes including survival in patients with potentially curable oesophageal adenocarcinoma. MATERIALS AND METHODS A cohort of 286 patients undergoing neoadjuvant therapy followed by surgical resection at a single institution was identified from a prospective database. Adverse events from neoadjuvant therapy were recorded and graded. Patients were divided into two groups according to whether they suffered toxicity or not. Clinical outcomes including whether patients completed the neoadjuvant course, whether they proceeded to resection and overall survival, were compared between the groups. RESULTS Neoadjuvant therapy-related toxicity was identified in 67/286 patients. 46 patients suffered severe, life-threatening or fatal adverse events. In patients with toxicity, 47% did not complete the chemotherapy course compared to 17% without toxicity, RR 2.7 (95%CI 1.7-4.4), (P < 0.001). In patients suffering toxicity, 17.9% failed to proceed to resection compared with 7.8% in those without toxicity, RR 2.3 (95%CI 1.2-4.6) P = 0.02. Median overall survival was shorter in patients suffering toxicity (20.7 months) compared to those without toxicity (37.8 months), P = 0.008. When patients failing to proceed to resection were excluded, median overall survival was shorter in patients suffering toxicity (26.2 months) compared with those without toxicity (47.8), P = 0.039. CONCLUSION Neoadjuvant therapy-related toxicity is common and can have serious consequences including failure to complete chemotherapy cycles, a higher risk of not proceeding to surgical resection and poorer overall survival. Efforts should be made to reduce toxicity and research should aim to identify responders and factors predictive of toxicity.

International Careers: Training and Working Abroad

One of the highlights of being a medical student is the opportunity to travel abroad on an elective. This is often an inspiration for future work abroad. In this chapter we will provide an overview of electives with a surgical focus, as well as discussing the most common English-speaking destinations for British graduates, including the USA, Canada, Australia, New Zealand, the Republic of Ireland and developing countries.

Loco-regional staging accuracy in oesophageal cancer—How good are we in the modern era?

INTRODUCTION Accuracy of locoregional staging in patients with oesophageal cancer is critical in determining operability and the need for neoadjuvant treatment. Imaging technology has advanced significantly in recent years but it is not known whether this translates to improved staging accuracy. This study investigates staging accuracy in relation to CT, EUS, PET-CT and final pre-operative stage. It specifically addresses the accuracy of staging with respect to the threshold for administering neoadjuvant therapies. MATERIALS AND METHODS Pre-operative staging according to CT, EUS, PET-CT and final pre-operative stage were compared to the postoperative histological staging in 133 patients undergoing potentially curative surgery (without neoadjuvant therapy) for oesophageal cancer between January 2010 and January 2015. T and N stage accuracies were reported separately for each imaging modality. Patients were also divided into two groups depending on whether the final pre-operative stage was below (≤T2, N0, early tumours) or above (≥T3 and/or ≥N1, locally advanced tumours) the threshold for offering neoadjuvant therapy. Accuracy of pre-operative staging was then analysed with respect to identification of patients below/above this threshold. The additional benefit offered by EUS for this purpose was investigated. RESULTS T stage accuracies were 72.6%, 76.7% and 79.3% for CT, EUS and final pre-operative stage respectively. N stage accuracies were 75.6%, 77.2%, 74.5% and 78.6% for CT, EUS, PET-CT and final pre-operative stage respectively. Staging accuracy with respect to threshold for neoadjuvant treatment showed 62.0% early tumours were correctly staged and 80.5% advanced tumours were correctly staged. Whether or not patients underwent EUS did not affect the staging accuracy with respect to neoadjuvant treatment threshold. CONCLUSIONS Staging accuracy with respect to the threshold for treatment with neoadjuvant therapy is poor, leading to potential over/under treatment. Predicting individual response to neoadjuvant therapy would provide a better way to determine which patients should receive this additional treatment.

PTU-140 Neoadjuvant therapy toxicity and efficacy in oesophago-gastric cancer

Introduction The advantages of neoadjuvant therapy (NAT) in oesophago-gastric (OG) cancer have been proven in randomised trials. Benefits are modest and likely to be restricted to patients who respond well to therapy. The risks may outweigh benefits in earlier stages of disease. This study explores the risks associated with NAT, analyses which patients benefit and investigates whether there is a need for a change in NAT treatment strategy. Method All patients planned for surgical resection of OG cancer in this unit between 01/2010 and 12/2014 were identified. Part a) patients were divided according to pre-operative stage. Within each stage, survival was compared in patients undergoing NAT and those undergoing surgery alone. Similar comparisons were made with the NAT group further divided into histological responders and non-responders. Part b) from the cohort, patients undergoing NAT were identified. Adverse effects (AE) were recorded and graded according to the Common Terminology Criteria for Adverse Events v3.0. The relationships between the presence of AE and a range of variables were investigated along with survival. Survival analyses were undertaken by plotting Kaplan-Meier curves. Groups were compared using the Log Rank (Mantel-Cox) test. Results 587 patients were identified from the database. Part a) only stage III patients had improved survival with NAT vs. surgery alone (P = 0.02). Those in stage II with a histological response to treatment showed a trend towards better survival vs. surgery alone (P = 0.058). In all patients above the threshold for offering NAT (≥stage II), survival was no different in non-responders vs. those having surgery alone. Age and performance status were lower in the NAT group vs. the surgery only group and were both associated inversely with survival. This could mean NAT effects are overestimated and true survival in non-responders to NAT may be poorer than in patients having surgery alone. Part b) 376 patients received NAT and 88 (23.4%) suffered AE. 69% of these were severe, life-threatening or fatal. NAT course completion rate was lower in patients suffering AE vs. those not (P = 0.003). 20.5% patients with AE did not proceed to resection vs. 6.4% without AE (P = 0.001). Survival was better in patients without AE vs. with AE (P = 0.02) and was better in those undergoing resection (P < 0.001) but was no different in patients completing the course vs. not completing (P = 0.861). Conclusion Efficacy of NAT is dependent on cancer stage and histological response to NAT. AE are common, often severe and associated with a reduced resection rate and survival. Identifying a means of predicting response to NAT is of great importance and should be used to guide treatment alongside/instead of disease stage. Disclosure of interest None Declared.

PTU-139 Re-defining response to neoadjuvant therapy in patients with oesophago-gastric cancer

Introduction Response to neoadjuvant therapy in oesophago-gastric (OG) cancer can be measured using a range of radiological and histological measures. However, there is no agreed definition of what constitutes a beneficial response. An accurate definition is critical for standardisation of outcome reporting and will be necessary if predicting response can be used to provide personalised treatment. This study re-defines response to neoadjuvant therapy in OG cancer. Method A literature search was performed to identify potential measures for accurately defining response the neoadjuvant therapy. All patients undergoing surgical resection for OG cancer at this Unit between January 2010 and December 2014 were identified from a database. Part a) Patients meeting the threshold for offering neoadjuvant therapy (≥T3 and/or ≥N1) were identified and divided according to whether they were TRG responders, non-responders or had surgery only. These groups were then compared with respect to the apparent T- and N-down-staging (defined as a reduction in stage between pre-operative staging and post-operative pathological staging) in order to assess the validity of down-staging for use in defining response. Part b) Patients undergoing neoadjuvant therapy were identified and potentially valid measures of response were then analysed with respect to overall survival in order to determine and validate a definition of response. Results The literature review identified methods using histopathological regression as the most promising measures of response with the Becker and Mandard scoring systems validated for use in OG cancer. T and N down-staging offer the potential to identify partial responders. 587 patients were identified from the database. Part a) In 419 patients above the neoadjuvant therapy threshold, the rate of apparent T down-staging was 62.8% in TRG responders, 15.7% in non-responders and 21.4% in the surgery only patients. The rate of apparent N down-staging was 35.9% in responders, 13.0% in non-responders and 12.9% in the surgery only patients. Part b) In 376 patients undergoing neoadjuvant therapy, patients with a Mandard TRG score of 1–3 had longer survival than those with TRG 4–5, mean survival 49.5 months vs. 35.7 months respectively (P = 0.001, Log Rank Mantel-Cox). Conclusion Histopathological regression scores correlate well with survival and represent the most accurate measure of response to neoadjuvant therapy in OG cancer. Survival in TRG1–3 patients (Mandard Score) is better than in TRG 4–5 patients. Apparent T and N down-staging were no higher in the TRG non-responder group than the surgery only group suggesting this represents clinical over-estimation of stage rather than a true therapy effect and is not valid for use in the definition of response to therapy. Disclosure of interest None Declared.

PTU-141 Circulating biomarkers for predicting the response to neoadjuvant therapy in oesophago-gastric cancer

Introduction Neoadjuvant therapy is used to improve survival in OG cancer, however, only 1 in 4 patients respond sufficiently to gain any benefit. Non-responders are exposed to the toxic effects of therapy and a delay to surgery. Predicting the response to neoadjuvant therapy could lead to more individualised patient care and better outcomes. Pre-therapy biomarkers have shown the most promise. Serum/plasma markers are not reliant on invasive tests, are repeatable and can often be measured using basic, widely available laboratory techniques. Method A systematic search of the MEDLINE, Embase, and Cinharl databases was performed combining the terms “(o)esophageal cancer” or “gastric cancer” and “therapy”, “chemotherapy” or “chemoradiotherapy” and “predict” and “response”. Additional studies were identified through reference lists, and the PubMed search/related articles features. Only clinical studies and those using neoadjuvant therapies were included. Results 542 articles were identified from the search, of which 28 met all criteria for inclusion in the analysis. Pre-therapy biomarkers predictive of response are presented in the table divided into groups according to marker function/pathway involved. The relationship between marker levels and outcome are detailed along with P- value, study size and author/publication year.Abstract PTU-141 Table 1 Conclusion A number of circulating biomarkers show potential for predicting response to neoadjuvant therapy and serial measurements may be able to monitor response in vivo. These markers need to be validated in larger, prospective studies before being adopted into randomised studies designed to investigate their potential clinical benefit. Disclosure of interest None Declared.