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Does anything work in acute pancreatitis? A complete systematic review on treatment modalities in the disease
e4
Abstracts / Pancreatology 12 (2012) e1–e8
Take-home message: Distal bile duct adenocarcinoma is a rare malignancy with not well known prognostic factors. In this large DBDA series has been shown that younger patients with well differentiated DBDA and 2 or less involved LNs have longer survival post radical resection.
2.2. Nrf2 target gene expression through the panin progression in pancreatic oncogenesis A.J. Hayes 1, B. Haugk 2, F. Oakley 1, M. Walsh 1, D.A. Mann 1, R.M. Charnley 3 Newcastle University, Newcastle-upon-Tyne, UK, 2 Dept of Cellular Pathology, Newcastle Hospitals Trust, UK, 3 Dept of HPB Surgery, Newcastle Hospitals Trust, UK
1
to assess the mortality risk. Results 16% of tumours had no COX-2 expression, while 84% had a degree of COX-2 cytoplasm expression of which 18% had high COX-2 expression. High tumour stage, perineural invasion, and large tumours were proportionally more likely to express COX-2 (P¼0.02). In univariate analysis, high COX-2 expression was associated with significantly reduced median overall survival (9.0months [95%CI:7.9–10.2]) compared to patients with low expression (17.1months [95%CI:13.6–20.5]) or no expression (39.6months [95%CI:19.6–59.6, P¼0.001]). Most importantly, in a multivariate analysis, high COX-2 expression remained an independent predictor of poor survival (P¼0.005). Furthermore we investigated the relationship between COX-2 and Lkb1 expression in PDAC, as well as markers of angiogenesis. Discussion COX-2 expression indicates a poor prognosis for patients with resectable PDAC, particularly in larger tumours. Take-home message: COX-2 is associated with multiple tumourigenic effects. We have shown that expression in PDAC is independently associated with poor prognosis.
Category: Malignant Abstract: Pancreatic intraepithelial neoplasias (PanINs) are precursors to pancreatic ductal adenocarcinoma (PDAC). Nrf2, a master transcription factor which can up-regulate cytoprotective genes, is over-expressed in PDAC but has not been evaluated in human precursors. The Nrf2 pathway has been implicated as a mediator of pancreatic oncogenesis. We are conducting an immunohistochemistry study to detect expression of Nrf2 target-genes, including tumour marker aldo-ketoreductase 1B10, through the PanIN progression. Methods: Pancreatectomy blocks were identified by a pancreatic histopathologist comprising 4 sections of normal pancreas and 19 lesions: PanIN 1A+1B, n¼8; PanIN 2+3, n¼7, PDAC, n¼4. Citrate antigen retrieval was used before probing with antibodies, DAB staining and counterstaining. Expression was scored using an Aperio Spectrum? positive pixel count algorithm. Results: Preliminary results showed mean (SEM) AKR1B10 expression was increased in low grade PanINs at 64.0% (4.8%), compared to normal ducts, 42.0% (6.2%) [p¼0.049]. Expression then decreased through the progression with high grade PanINs at 53.6% (12.6%) and 20.3% (2.2%) in PDAC, a significant reduction [p¼0.006]. Conclusions: AKR1B10 seems to have a strong expression in low grade PanINs before progressive reduction. Additional PanIN lesions are currently undergoing immunohistochemistry to further investigate a likely association between Nrf2 activity and PanIN progression. Take-home message: NRF2 target genes, including AKR1B10, may offer a biomarker for PanIN progression or a drug target to reduce the risk of developing pancreatic cancer amongst high-risk patients.
2.3. Tumour cox-2 expression correlates with poor prognosis in patients with resectable pancreatic ductal adenocarcinoma Nigel B. Jamieson 1, Karin A. Oien 2, Euan J. Dickson 1, C.Ross Carter 1, Colin J. McKay 1 1
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, U.K., 2 Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, G61 1BD, U.K.
2.4. A review of care received by patients diagnosed with stage iii/iv pancreatic cancer at a tertiary hepatobiliary centre S. De Vos 1,2, K. Badgery 1, S. Noble 1, M. Metcalfe 1, W. Steward 1, C. Cooke 1, 2 1 University Hospitals of Leicester (UHL), UK, 2 LOROS Hospice, Leicester, UK
Category: Malignant Introduction: Life expectancy for those presenting with advanced pancreatic cancer is a few months, irrespective of treatment. Quality of life and patient care experience are therefore paramount. This retrospective study examined elements of care at a tertiary centre to assess how the service might be improved. Method: The Hepatobiliary MDT identified 80 patients who died between July and December 2010. Data was collated from hospital and hospice notes. Results: Mean survival time from diagnosis was 6.6 months. 54 patients were referred to oncology; 29 received chemotherapy. Only 8 completed the planned course. 46 patients had jaundice; 40 underwent biliary drainage procedures. Few were successful at first attempt; repeated attempts prolonged admission and sometimes contributed to patients dying in hospital rather than elsewhere. 79% were referred to hospital palliative care teams, frequently near end of life. Prognosis was discussed with 50%. There was little end of life care planning. DNA-CPR forms were completed in 43%, often within days/hours of death. 30% died in hospital. Conclusions: Patients with advanced disease were often unfit for chemotherapy. Whilst biliary drainage may improve symptoms, patients needed complicated procedures, prolonging hospital admissions at a time when they were deteriorating. There was little advance care planning. Take-home message: Palliative chemotherapy and procedures to relieve biliary obstruction in advanced pancreatic cancer should be planned realistically with patients, in accordance with their wishes and priorities. Early discussion and planning for end of life care would improve the quality of care, patient and carer satisfaction and cost effectiveness of the service.
Category: Benign & Inflammatory 2.5. Abstract: Introduction As patient outcome in pancreatic ductal adenocarcinoma (PDAC) is not reliably predicted using pathological factors alone, markers of tumour behaviour are required. There is strong epidemiological and experimental evidence to support the role of COX-2 in the development and progression of PDAC. Methods Immunohistochemical staining for COX-2 was assessed in a tissue microarray cohort of 118 patients undergoing pancreaticoduodenectomy for PDAC with full clinicopathological data. KaplanMeier analysis and Cox proportional hazards regression modeling were used
Does anything work in acute pancreatitis? A complete systematic review on treatment modalities in the disease K. Altaf 1, M.A. Javed 1, D. Lythgoe 2, F. Wright 2, A. Sultana 1, R. Sutton 1 1
Liverpool NIHR Pancreas Biomedical Research Unit, Royal Liverpool and Broadgreen University Hospitals, NHS Trust, UK, 2 CRUK Cancer Research Centre, University of Liverpool, UK
Abstracts / Pancreatology 12 (2012) e1–e8
e5
Category: Malignant 3.1. Background: Acute pancreatitis (AP) has high morbidity and mortality. Currently there is no specific pharmacotherapy for AP and treatment remains predominantly supportive. We have assessed the impact of trialled treatment options on mortality from AP. Methods: MEDLINE, EMBASE and Cochrane Library were searched by two independent reviewers to identify all RCTs that tested treatments to reduce mortality in AP. Data were extracted for Jadad scoring, grouping of RCTs by therapeutic mechanism and separate meta-analysis of each group. Results: 62 high quality trials (Jadad3) were identified. Enteral nutrition [Trials(T)-6,patients(P)-224,RR-0.311,95%CI–0.118-0.816] was associated with significantly reduced mortality when compared with total parenteral nutrition, whereas immunonutrition (T-10,P-651,RR-0.771,CI0.351-1.693), antibiotics (T-10,P-650,RR 0.805,CI 0.503-1.289), endoscopic sphincterotomy (T-3,P-366,RR-1.914,CI-0.865-4.235), secretion inhibitors (T-13,P-1000,RR-0.832,CI-0.597-1.16), protease inhibitors (T-10,P-956,RR0.875,CI-0.616-1.243), lexifapant (T-3,P-423,RR-0.698,CI-0.413-1.181), fresh frozen plasma therapy(T-2,P-267,RR-0.994,CI-0.51-1.94) and antioxidants (T-5,P-181,RR-0.868,CI-0.283-2.66) did not reduce mortality compared to control. Peritoneal lavage (T-2,P-130,RR-7.373,CI 1.73531.376) was associated with adverse effects and no difference was found when lavage was compared to pancreatic resection (T-2, P-56,RR-0.654,CI0.265-1.613). Conclusion: Potential benefit from enteral over parenteral nutrition in AP should be assessed in large, highly powered studies. There is a dire need for new, effective treatments to reduce mortality from AP. Take-home message: There is currently no treatment for acute pancreatitis, despite several randomised controlled trials. There is an urgent need of finding an effective treatment for the disease
2.6. Neutrophil to lymphocyte ratio: Predictor of poor outcome in acute pancreatitis Aravind Suppiah, Deep J. Malde, Tameem Arab, Andrew M. Smith, Gareth Morris-Stiff The HPB Unit, St James University Hospital, Leeds, UK Category: Benign & Inflammatory Background: Current scoring systems in acute pancreatitis pancreatic (AP) are cumbersome and require multiple investigations and delay in scoring. Early deterioration in AP is associated with marked inflammatory response. Method: Neutrophil to lymphocyte ratio (NLR) was calculated on Day 1, 2 and 3 of admission and correlated with outcome. Poor outcome was defined as intensive care admission, need for nutritional support, complications directly associated with pancreatitis, pancreatic necrosis or death. Results: 146 consecutive patients (January-December 2010) were included with 29 having poor outcome. NLR in the poor prognosis group was significantly higher than in the favourable prognosis group on all 3 days (Day 1: 17.4 vs. 13.3; Day 2: 16.2 vs. 10.2; Day 3:14.6 vs. 7.2). The optimal cut-of calculated from a ROC curve was 3.5 giving a sensitivity (Sn) and Specificity (Sp) of 93% and 15% (Day 1); 96%(Sn) and 26%(Sp) Day 2; 93%(Sn) and 37%(Sp) Day 3. The Positive and Negative values of poor outcome were 28% and 90% on Day 1, 30% and 95% on Day 2 and 30% and 94% on Day 3. Conclusion: Admission and early NLR is significantly higher in patients with poor outcome and is an independent predictor of poor prognosis. Take-home message: Neutrophil to lymphocyte ration is an independent indicator of poor prognosis in acute pancreatitis
Loss of e-cadherin and b-catenin expression correlate with poor prognosis in patients with resectable pancreatic ductal adenocarcinoma Nigel B. Jamieson 1, Karin A. Oien 2, Euan J. Dickson 1, Colin J. McKay 1, C. Ross Carter 1 1
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, U.K., 2 Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, G61 1BD, U.K. Category: Malignant Introduction. The 5-yr survival for pancreatic ductal adenocarcinoma (PDAC) remains poor and there remains a need for prognostic markers. bcatenin/ E-cadherin interactions are important for the maintenance of cellto-cell adhesion. We sought to determine the prognostic influence of these cell-adhesion markers. Methods. Immunohistochemical staining patterns for E-cadherin and b-catenin were evaluated in a tissue microarray cohort of 118 patients undergoing pancreaticoduodenectomy for PDAC with full clinicopathological data. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk. Results. High tumour grade was significantly associated with lower Ecadherin and b-catenin expression levels (P<0.001). In univariate analysis, preserved E-cadherin expression resulted in a prolonged survival of 19.6months (95%CI:15.6–23.6) versus low expression of 10.3months (95% CI:7.3–13.2, P¼0.002). For b-catenin preserved membranous expression resulted in a prolonged median overall survival of 25.7months (95% CI:17.1–34.3) versus medium expression, of 18.4months (95%CI:14.3– 22.5); and low expression of 13.1months (95%CI:10.5–15.5, P¼0.006). Multivariate analysis indicated that, high E-cadherin (HR:0.31, 95%CI:0.180.53, P<0.0001) and high b-catenin expression (HR:0.54, 95%CI:0.35-0.84, P¼0.005) remained independent predictors of good prognosis. Additionally we investigated the relationship between b-catenin and other aberrant PDAC pathways. Discussion. Among patients undergoing resection for PDAC loss of both E-cadherin and b-catenin expression correlated with a poor prognosis independent of other pathological factors. Take-home message: E-cadherin and b-catenin are easily assessed markers that have integral roles in PDAC biology. Loss of expression were strongly and independently associated with poor prognosis.
3.2. Do statins prevent the development of pancreatic cancer in the general population and in patients with type 2 diabetes? Preliminary results from a case-control study in two centres in the UK F.J. Carey 1, M.W. Little 1, T.F.G. Pugh 1, R. Ndokera 2, H. Ing 2, A. Clark 1, A. Dennison 2, M.S. Metcalfe 2, R.J. Robinson 2, A.R. Hart 1 1 Norwich Medical School, University of East Anglia, UK, 2 Leicester General Hospital, University Hospitals of Leicester, UK
Category: Benign & Inflammatory Introduction: There are plausible biological mechanisms for how statins may prevent pancreatic cancer. The evidence from epidemiological studies in the general population is conflicting and their role in patients with type 2 diabetes is unknown. This study aimed to clarify the associations in these two groups. Methods: A case-control study was conducted in patients diagnosed with pancreatic cancer and dermatology controls of similar ages and gender, treated for basal cell carcinoma. The medical records were
Abstracts / Pancreatology 12 (2012) e1–e8
Take-home message: Distal bile duct adenocarcinoma is a rare malignancy with not well known prognostic factors. In this large DBDA series has been shown that younger patients with well differentiated DBDA and 2 or less involved LNs have longer survival post radical resection.
2.2. Nrf2 target gene expression through the panin progression in pancreatic oncogenesis A.J. Hayes 1, B. Haugk 2, F. Oakley 1, M. Walsh 1, D.A. Mann 1, R.M. Charnley 3 Newcastle University, Newcastle-upon-Tyne, UK, 2 Dept of Cellular Pathology, Newcastle Hospitals Trust, UK, 3 Dept of HPB Surgery, Newcastle Hospitals Trust, UK
1
to assess the mortality risk. Results 16% of tumours had no COX-2 expression, while 84% had a degree of COX-2 cytoplasm expression of which 18% had high COX-2 expression. High tumour stage, perineural invasion, and large tumours were proportionally more likely to express COX-2 (P¼0.02). In univariate analysis, high COX-2 expression was associated with significantly reduced median overall survival (9.0months [95%CI:7.9–10.2]) compared to patients with low expression (17.1months [95%CI:13.6–20.5]) or no expression (39.6months [95%CI:19.6–59.6, P¼0.001]). Most importantly, in a multivariate analysis, high COX-2 expression remained an independent predictor of poor survival (P¼0.005). Furthermore we investigated the relationship between COX-2 and Lkb1 expression in PDAC, as well as markers of angiogenesis. Discussion COX-2 expression indicates a poor prognosis for patients with resectable PDAC, particularly in larger tumours. Take-home message: COX-2 is associated with multiple tumourigenic effects. We have shown that expression in PDAC is independently associated with poor prognosis.
Category: Malignant Abstract: Pancreatic intraepithelial neoplasias (PanINs) are precursors to pancreatic ductal adenocarcinoma (PDAC). Nrf2, a master transcription factor which can up-regulate cytoprotective genes, is over-expressed in PDAC but has not been evaluated in human precursors. The Nrf2 pathway has been implicated as a mediator of pancreatic oncogenesis. We are conducting an immunohistochemistry study to detect expression of Nrf2 target-genes, including tumour marker aldo-ketoreductase 1B10, through the PanIN progression. Methods: Pancreatectomy blocks were identified by a pancreatic histopathologist comprising 4 sections of normal pancreas and 19 lesions: PanIN 1A+1B, n¼8; PanIN 2+3, n¼7, PDAC, n¼4. Citrate antigen retrieval was used before probing with antibodies, DAB staining and counterstaining. Expression was scored using an Aperio Spectrum? positive pixel count algorithm. Results: Preliminary results showed mean (SEM) AKR1B10 expression was increased in low grade PanINs at 64.0% (4.8%), compared to normal ducts, 42.0% (6.2%) [p¼0.049]. Expression then decreased through the progression with high grade PanINs at 53.6% (12.6%) and 20.3% (2.2%) in PDAC, a significant reduction [p¼0.006]. Conclusions: AKR1B10 seems to have a strong expression in low grade PanINs before progressive reduction. Additional PanIN lesions are currently undergoing immunohistochemistry to further investigate a likely association between Nrf2 activity and PanIN progression. Take-home message: NRF2 target genes, including AKR1B10, may offer a biomarker for PanIN progression or a drug target to reduce the risk of developing pancreatic cancer amongst high-risk patients.
2.3. Tumour cox-2 expression correlates with poor prognosis in patients with resectable pancreatic ductal adenocarcinoma Nigel B. Jamieson 1, Karin A. Oien 2, Euan J. Dickson 1, C.Ross Carter 1, Colin J. McKay 1 1
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, U.K., 2 Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, G61 1BD, U.K.
2.4. A review of care received by patients diagnosed with stage iii/iv pancreatic cancer at a tertiary hepatobiliary centre S. De Vos 1,2, K. Badgery 1, S. Noble 1, M. Metcalfe 1, W. Steward 1, C. Cooke 1, 2 1 University Hospitals of Leicester (UHL), UK, 2 LOROS Hospice, Leicester, UK
Category: Malignant Introduction: Life expectancy for those presenting with advanced pancreatic cancer is a few months, irrespective of treatment. Quality of life and patient care experience are therefore paramount. This retrospective study examined elements of care at a tertiary centre to assess how the service might be improved. Method: The Hepatobiliary MDT identified 80 patients who died between July and December 2010. Data was collated from hospital and hospice notes. Results: Mean survival time from diagnosis was 6.6 months. 54 patients were referred to oncology; 29 received chemotherapy. Only 8 completed the planned course. 46 patients had jaundice; 40 underwent biliary drainage procedures. Few were successful at first attempt; repeated attempts prolonged admission and sometimes contributed to patients dying in hospital rather than elsewhere. 79% were referred to hospital palliative care teams, frequently near end of life. Prognosis was discussed with 50%. There was little end of life care planning. DNA-CPR forms were completed in 43%, often within days/hours of death. 30% died in hospital. Conclusions: Patients with advanced disease were often unfit for chemotherapy. Whilst biliary drainage may improve symptoms, patients needed complicated procedures, prolonging hospital admissions at a time when they were deteriorating. There was little advance care planning. Take-home message: Palliative chemotherapy and procedures to relieve biliary obstruction in advanced pancreatic cancer should be planned realistically with patients, in accordance with their wishes and priorities. Early discussion and planning for end of life care would improve the quality of care, patient and carer satisfaction and cost effectiveness of the service.
Category: Benign & Inflammatory 2.5. Abstract: Introduction As patient outcome in pancreatic ductal adenocarcinoma (PDAC) is not reliably predicted using pathological factors alone, markers of tumour behaviour are required. There is strong epidemiological and experimental evidence to support the role of COX-2 in the development and progression of PDAC. Methods Immunohistochemical staining for COX-2 was assessed in a tissue microarray cohort of 118 patients undergoing pancreaticoduodenectomy for PDAC with full clinicopathological data. KaplanMeier analysis and Cox proportional hazards regression modeling were used
Does anything work in acute pancreatitis? A complete systematic review on treatment modalities in the disease K. Altaf 1, M.A. Javed 1, D. Lythgoe 2, F. Wright 2, A. Sultana 1, R. Sutton 1 1
Liverpool NIHR Pancreas Biomedical Research Unit, Royal Liverpool and Broadgreen University Hospitals, NHS Trust, UK, 2 CRUK Cancer Research Centre, University of Liverpool, UK
Abstracts / Pancreatology 12 (2012) e1–e8
e5
Category: Malignant 3.1. Background: Acute pancreatitis (AP) has high morbidity and mortality. Currently there is no specific pharmacotherapy for AP and treatment remains predominantly supportive. We have assessed the impact of trialled treatment options on mortality from AP. Methods: MEDLINE, EMBASE and Cochrane Library were searched by two independent reviewers to identify all RCTs that tested treatments to reduce mortality in AP. Data were extracted for Jadad scoring, grouping of RCTs by therapeutic mechanism and separate meta-analysis of each group. Results: 62 high quality trials (Jadad3) were identified. Enteral nutrition [Trials(T)-6,patients(P)-224,RR-0.311,95%CI–0.118-0.816] was associated with significantly reduced mortality when compared with total parenteral nutrition, whereas immunonutrition (T-10,P-651,RR-0.771,CI0.351-1.693), antibiotics (T-10,P-650,RR 0.805,CI 0.503-1.289), endoscopic sphincterotomy (T-3,P-366,RR-1.914,CI-0.865-4.235), secretion inhibitors (T-13,P-1000,RR-0.832,CI-0.597-1.16), protease inhibitors (T-10,P-956,RR0.875,CI-0.616-1.243), lexifapant (T-3,P-423,RR-0.698,CI-0.413-1.181), fresh frozen plasma therapy(T-2,P-267,RR-0.994,CI-0.51-1.94) and antioxidants (T-5,P-181,RR-0.868,CI-0.283-2.66) did not reduce mortality compared to control. Peritoneal lavage (T-2,P-130,RR-7.373,CI 1.73531.376) was associated with adverse effects and no difference was found when lavage was compared to pancreatic resection (T-2, P-56,RR-0.654,CI0.265-1.613). Conclusion: Potential benefit from enteral over parenteral nutrition in AP should be assessed in large, highly powered studies. There is a dire need for new, effective treatments to reduce mortality from AP. Take-home message: There is currently no treatment for acute pancreatitis, despite several randomised controlled trials. There is an urgent need of finding an effective treatment for the disease
2.6. Neutrophil to lymphocyte ratio: Predictor of poor outcome in acute pancreatitis Aravind Suppiah, Deep J. Malde, Tameem Arab, Andrew M. Smith, Gareth Morris-Stiff The HPB Unit, St James University Hospital, Leeds, UK Category: Benign & Inflammatory Background: Current scoring systems in acute pancreatitis pancreatic (AP) are cumbersome and require multiple investigations and delay in scoring. Early deterioration in AP is associated with marked inflammatory response. Method: Neutrophil to lymphocyte ratio (NLR) was calculated on Day 1, 2 and 3 of admission and correlated with outcome. Poor outcome was defined as intensive care admission, need for nutritional support, complications directly associated with pancreatitis, pancreatic necrosis or death. Results: 146 consecutive patients (January-December 2010) were included with 29 having poor outcome. NLR in the poor prognosis group was significantly higher than in the favourable prognosis group on all 3 days (Day 1: 17.4 vs. 13.3; Day 2: 16.2 vs. 10.2; Day 3:14.6 vs. 7.2). The optimal cut-of calculated from a ROC curve was 3.5 giving a sensitivity (Sn) and Specificity (Sp) of 93% and 15% (Day 1); 96%(Sn) and 26%(Sp) Day 2; 93%(Sn) and 37%(Sp) Day 3. The Positive and Negative values of poor outcome were 28% and 90% on Day 1, 30% and 95% on Day 2 and 30% and 94% on Day 3. Conclusion: Admission and early NLR is significantly higher in patients with poor outcome and is an independent predictor of poor prognosis. Take-home message: Neutrophil to lymphocyte ration is an independent indicator of poor prognosis in acute pancreatitis
Loss of e-cadherin and b-catenin expression correlate with poor prognosis in patients with resectable pancreatic ductal adenocarcinoma Nigel B. Jamieson 1, Karin A. Oien 2, Euan J. Dickson 1, Colin J. McKay 1, C. Ross Carter 1 1
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, U.K., 2 Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, G61 1BD, U.K. Category: Malignant Introduction. The 5-yr survival for pancreatic ductal adenocarcinoma (PDAC) remains poor and there remains a need for prognostic markers. bcatenin/ E-cadherin interactions are important for the maintenance of cellto-cell adhesion. We sought to determine the prognostic influence of these cell-adhesion markers. Methods. Immunohistochemical staining patterns for E-cadherin and b-catenin were evaluated in a tissue microarray cohort of 118 patients undergoing pancreaticoduodenectomy for PDAC with full clinicopathological data. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk. Results. High tumour grade was significantly associated with lower Ecadherin and b-catenin expression levels (P<0.001). In univariate analysis, preserved E-cadherin expression resulted in a prolonged survival of 19.6months (95%CI:15.6–23.6) versus low expression of 10.3months (95% CI:7.3–13.2, P¼0.002). For b-catenin preserved membranous expression resulted in a prolonged median overall survival of 25.7months (95% CI:17.1–34.3) versus medium expression, of 18.4months (95%CI:14.3– 22.5); and low expression of 13.1months (95%CI:10.5–15.5, P¼0.006). Multivariate analysis indicated that, high E-cadherin (HR:0.31, 95%CI:0.180.53, P<0.0001) and high b-catenin expression (HR:0.54, 95%CI:0.35-0.84, P¼0.005) remained independent predictors of good prognosis. Additionally we investigated the relationship between b-catenin and other aberrant PDAC pathways. Discussion. Among patients undergoing resection for PDAC loss of both E-cadherin and b-catenin expression correlated with a poor prognosis independent of other pathological factors. Take-home message: E-cadherin and b-catenin are easily assessed markers that have integral roles in PDAC biology. Loss of expression were strongly and independently associated with poor prognosis.
3.2. Do statins prevent the development of pancreatic cancer in the general population and in patients with type 2 diabetes? Preliminary results from a case-control study in two centres in the UK F.J. Carey 1, M.W. Little 1, T.F.G. Pugh 1, R. Ndokera 2, H. Ing 2, A. Clark 1, A. Dennison 2, M.S. Metcalfe 2, R.J. Robinson 2, A.R. Hart 1 1 Norwich Medical School, University of East Anglia, UK, 2 Leicester General Hospital, University Hospitals of Leicester, UK
Category: Benign & Inflammatory Introduction: There are plausible biological mechanisms for how statins may prevent pancreatic cancer. The evidence from epidemiological studies in the general population is conflicting and their role in patients with type 2 diabetes is unknown. This study aimed to clarify the associations in these two groups. Methods: A case-control study was conducted in patients diagnosed with pancreatic cancer and dermatology controls of similar ages and gender, treated for basal cell carcinoma. The medical records were