Akt pathway is involved in colon cancer cell migration

Akt pathway is involved in colon cancer cell migration

1128 to 18.5 months), the local recurrence rate was 29% (6/21), and the median survival from recurrence was 14 months (IQR 8.25 to 26.25 months). Conc...

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1128 to 18.5 months), the local recurrence rate was 29% (6/21), and the median survival from recurrence was 14 months (IQR 8.25 to 26.25 months). Conclusions: This series of patients with RPS, who are under ongoing follow up, currently have a rate of relapse well in keeping with published figures, and good survival even after detection of recurrence. P81. Enhanced Recovery Programme for Colorectal Surgery: Four Year Experience Philip Pastides, V. Kosmoliaptsis, J. Cushion, A. Oshowo, H. Mukhtar The Whittington Hospital, Magdala Avenue, London, N19 5NF Background: The Enhanced Recovery programme was introduced to improve post operative patient outcomes. It has been successfully adopted in several institutions with good results1,2 Methods and Results: All consecutive patients undergoing elective colorectal resections and large hernia repairs within a 3-year period (2006-2008) were included (n¼169) in the study. A standard enhanced recovery protocol was followed2. Mean length of stay was reduced from 8 to 6.5 days, mortality from 2.11% to 0.72% and short-term morbidity from 1.88% to 1.55% (p<0.05 for all variables). Since 2008 a specialist enhanced recovery nurse was appointed to oversee the programme and participant education was vigorously instigated. A hospital booklet was produced for the duration of treatment clearly stipulating daily goals. Outcomes were re-audited in a second cohort of 179 patients over an 18 month period (2008-2009). Significantly, mean length of stay decreased further to 5.6 days. Protocol parameters were achieved in more than 90% of cases and no adverse effects associated with the programme were observed. Conclusions: Implementation of enhanced recovery programmes using a multidisciplinary approach can lead to significant improvements in patient outcomes. Based on this experience, further expansion of the programme to include other complex procedures may be advantageous. References 1 Fearon KC, Ljungqvist O, Von Meyenfeldt M, Revhaug A, Dejong CH, Lassen K, Nygren J, Hausel J, Soop M, Andersen J, Kehlet (2005), ‘Enhanced recovery after surgery: consensus review of clinical care for patients undergoing colonic resection’,Clin Nutr,24(3):466-77 2 Kehlet H, Wilmore DW(2002), ‘Multimodal strategies to improve surgical outcome’,Am J Surg, 183(6):630-41 P82. Physiological effect of adjuvant pre-operative chemotherapy and/ or radiotherapy (APT) on patients undergoing colorectal cancer resection Samir Rahmani, S. Turvill, S. Howell, D. Burke Leeds Teaching Hospitals NHS Trust, John Goligher Colorectal Department, Leeds General Infirmary, Great George Street, Leeds, LS1 3EX Introduction and aim: Adjuvant pre-operative therapy (APT) in patients with colorectal cancer offers better control of local disease, sphincter preservation and an increase in survival. However, both chemotherapy and radiotherapy may affect a patient’s wellbeing and so influence the outcome of surgery. The physiological effects of APT are still unknown. Our primary aim is to assess the cardiopulmonary reserve before and after the administration of APT. Methods: A prospective pilot study was performed to measure physiological variables before, and 2 weeks after, the administration of APT. These variables assessed were: cardiopulmonary exercise test (CPEX), anthropometric measurements (weight, height, body mass index, mid-arm circumference, triceps skin fold, hand-grip strength), Bio-electrical impedance analysis (intra and extra cellular water with their resistance, total body water, fat free mass) and quality of life questionnaires (EORTC QLQ-C30 and PG-SGA). Results: A significant decline in the maximum oxygen consumption (VO2max) has been demonstrated along with a drop in the anaerobic

ABSTRACTS threshold (AT). There was more extracelluar water found in the patients post APT, which may indicate post-therapy oedema. Fat free mass was reduced after treatment with a correlating reduction in the BMI. There was an overall reduction in quality of life after both radiotherapy and chemoradiotherapy. Discussion: APT for colorectal cancer has an impact on patients’ physiological reserve which may increase the risk of peri-operative complications. A period of optimisation between the end of APT and the colorectal resection may improve the patients’ function and so improve outcome. P83. Feasibility of laparoscopic colorectal cancer resection in elderly patients; single centre experience Harminder Sra, V. Kosmoliaptsis, J. Hon, P. Pastides, A. Oshowo, H. Mukhtar The Whittington Hospital, Magdala Avenue, London, N19 5NF Introduction: There is currently limited evidence to support decisionmaking with regards to the benefits of laparoscopic colorectal cancer surgery for elderly patients. The purpose of this study was to determine the outcomes in unselected elderly patients undergoing elective laparoscopic cancer surgery in a District General Hospital. Methods: We studied 37 consecutive patients (age 75-95 years) who underwent elective curative-intent laparoscopic colorectal cancer operations in our centre from 2007-2009, retrieving data from a prospective computerised database. Statistical analyses were performed using SPSS v16. Results: The overall 30-day mortality rate was 11% (4/37) with no additional mortality within 1 year post-operatively. Three out of 4 patients died of immediate post-operative cardiac events whereas 1 death was due to anastomotic leak. Male gender was a significant risk factor of mortality (p¼0.046). The majority of patients had distal resections (65%) and classified as high-risk (51% ASA grade 3) but these were not predictors of adverse outcomes. Conversion to open operation was 24% and median length of stay was 8 days (3-20). All-cause morbidity was 41% but only 3 patients underwent successful re-operation for surgical complications. Conclusion: Laparoscopic colorectal cancer resection can be offered to elderly, high-risk patients with acceptable short and long-term outcomes. P84. Akt pathway is involved in colon cancer cell migration Anur Miah, S. Yang, M. Winslet Division of Surgery and Interventional Sciences, UCL, University Department of Surgery, UCL, Rowland Hill Street, London, NW3 2PF

Introduction: Colorectal cancer (CRC) is the third most common malignancy worldwide. At diagnosis, 57% of patients have metastatic disease which accounts for more than 90% of CRC patient deaths. CRC cell migration is an early essential step in the process of metastasis. Inhibition of cancer cell migration could prevent CRC metastasis. Akt has been proven to be a key regulator of cell proliferation, apoptosis, glucose metabolism, ribosomal function, transcription and angiogenesis. Its dysregulation has been a prevalent finding in many human malignancies including colorectal cancers. Method: Metastatic CRC cells were treated with different doses of a variety of Akt inhibitors (Akt inhibitor IV and XII). The cell death and viability was assessed following 24 and 48 hours of treatment. Expression of a variety of migration related proteins was examined and quantified following treatment. The ability of metastatic CRC cell migration after Akt inhibition was also investigated. Results: Inhibition of Akt significantly decreased metastatic CRC cell viability and increased cell death (P<0.01) by ANOVA Multiple Comparison analysis. The cell migration rate and expression of a variety of migration related proteins were also affected by both the Akt inhibitors. This

ABSTRACTS suggests that in addition to cellular proliferation and apoptosis, the Akt pathway may be involved with cancer cell migration. Conclusion: Inhibition of Akt markedly induced metastatic CRC cell death, and interfered with cell migratory processes indicating Akt pathway has a significant role in the development of CRC metastasis. Targeting Akt may provide a rationale for new treatment options for metastatic CRC patients. P85. Short-term outcomes for patients undergoing surgery for colorectal cancer employing three different treatment approaches (laparoscopic vs open vs robotic). Emilio Bertani, A. Chiappa, R. Biffi, P. Bianchi, V. Branchi, B. Andreoni Department of Surgery, European Institute of Oncology, Via Ripamonti, 435-20141-Milan, Italy Background: During last years, colorectal cancer surgical therapy could benefit from new techniques like laparoscopy and robotic surgery. However, many treatment disparities exist among different centers for patients affected by the same kind of tumours. Methods: One hundred and ninety-nine patients were enrolled during a 15 months period. Thirty (28%) laparoscopic vs 45 (41%) open vs 34 (31%) robotic assisted colectomies and 34 (40%) open vs 52 (60%) robotic rectal resections were compared. Those cases presenting clear contraindications for minimally invasive surgery were excluded from the analysis. Results: Overall complication rates were 15%, 24% and 19% for laparoscopic, open and robotic colectomies respectively (p¼NS) and 36% vs 33% for open and robotic rectal resections (p¼NS). Postoperative mortality was nil. Mean time (days) to first bowel movement to gas was 2.3 vs 3.3 vs 2.6 respectively for laparoscopic, open and robotic colectomies (open vs robotic, p¼0.003; open vs laparoscopic, p<0.001) and 3.2 vs 2.0 for open vs robotic rectal resections (p¼0.003). Postoperative hospital stay (days) was 5.3 vs 7.4 vs 6.0 for laparoscopic, open and robotic colectomies respectively (open vs robotic, p¼0.002; laparoscopic vs open, p<0.001) and 8.7 vs 7.9 for open and robotic rectal resections respectively (p¼0.004). Among several EORTC QLQ-C30 functional scales considered only physical functioning was significantly different at 30 days for robotic vs open colectomies (93.6 robotic vs 85.5 open;p¼0.01) Conclusions: Laparoscopic and robotic colorectal surgery for cancer could present some advantages in comparison to open procedures in terms of faster recovery and quality of life issues. P86. Systematic review: The Use of Ablative Techniques for the Treatment of Unresectable Colorectal Liver Metastases (CRLM) Samir Pathaka, J. Tangb, R. Jonesa, H. Malika, S. Fenwicka, G. Postona a University Hospital Aintree, Department of Surgery, Lower Lane, Liverpool, L7 9AL b Department of Surgery and Oncology, Royal Liverpool University Hospital, Liverpool, L69 3GA Background: The gold-standard treatment for CRLM is surgical resection. Unfortunately, only 20-30% of patients are surgically resectable. Furthermore, high local recurrence rates (53-68%) mean that novel strategies for re-intervention are required. One such strategy is ablative therapy, which may be deployed either to treat unresectable CRLM or to extend the margins of resectability. The current study aims to assess the longterm outcomes and complication rates of ablative techniques in the management of CRLM Methods: A literature search with parameters of Jan 1994 to Jan 2010 was performed on electronic databases including Medline, Cochrane Collaboration Library, ClinicalTrials.gov, and NLM. Inclusion criteria: original articles or RCTs, >1yr follow-up, ablation via open, percutaneous or laparoscopic methods, survival and/or recurrence data and >10 patients with CRLM.

1129 Results:

Ablative Technique

Cryotherapy Ethanol Microwave ablation Radiofrequency ablation Edge Cryotherapy RFA+ Resection

Recurrence (range)

Survival (Year, %)

Local (%)

Overall (%)

1

12e39 e 5e13

78e88 e 50e78

84 37 17 29 e e e 5 73 30 16 7

10e31

47e86

85 36 24 6

7e19 6e31

42e83 58e84

85 51 30 39 92 43 0 19

3

Complications (%)

5

Conclusions: Ablative therapies offer significantly improved survival rates (with acceptable complication rates) compared to palliative chemotherapy alone. We therefore recommend the use of either RFA or MCT to improve survival in selected patients with unresectable CRLM. Furthermore, ablative techniques may be used as an adjunct to surgery to extend the boundaries of resectability. Nevertheless, further studies focusing on long-term outcomes are required to confirm this. P87. Comparative Quality of Life in patients following Low Anterior Resection and Abdominoperineal Excision for Low Rectal Cancer: Preliminary Results from a Prospective Multicentre Study Peter Howa, K. Chandrakumaranb, G. Brownc, B. Healda, B. Moranb a Pelican Cancer Foundation, The Ark, Dinwoodie Drive, Basingstoke, RG24 9NA b North Hampshire Hospital c Royal Marsden Hospital Introduction: It is widely believed that quality of life (QOL) is worse after abdominoperineal excision (APE) than after low anterior resection (LAR). However, this view is not supported unequivocally. This study compared QOL in patients one year following LAR and APE for low rectal cancer. Methods: Data was prospectively collected on 27 patients undergoing LAR (n¼14) or APE (n¼13) for low rectal adenocarcinoma (within 6cm of the anal verge). Patients with metastatic disease were excluded. QOL was assessed using EORTC QLQ-C30 and QLQ-CR38 questionnaires. QOL in patients who had LAR was compared with those who had APE both preoperatively and 1 year following surgery. Results: Patients undergoing LAR were younger (median age 56 versus 63, p ¼ 0.04) with higher tumours (4.3cm versus 2.5 from the anal verge, p ¼ 0.002) and less likely to receive preoperative radiotherapy (36% versus 62%). Preoperative QOL scores were similar. Similarly at one year post-operatively, no significant differences were observed. LAR patients tended to report better body image (p ¼ 0.21) and future perspective (p ¼ 0.05). Some degree of post-operative faecal incontinence (FI) was reported in 54.5% of LAR patients. Conclusion: QOL following APE is comparable to that for LAR, despite a high incidence of FI in those who had LAR. Longer follow up and larger numbers of patients are being evaluated to further assess these findings. P88. The value of extended lateral pelvic lymphadenectomy in recurrent and locally advanced primary rectal cancer Panagiotis A. Georgiou, S. Ali, G. Brown, A. Antoniou, R. Nicholls, P. Tekkis The Royal Marsden NHS Foundation Trust, Department of Colorectal Surgery, Fulham Road, SW3 6JJ