Joe Geraghty - Academia.edu (original) (raw)

Papers by Joe Geraghty

Experimental in vitro models that accurately capture pathophysiological characteristics of human ... more Experimental in vitro models that accurately capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix, specifically designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from murine genetically engineered models and human patients, essential adhesive cues were empirically defined and incorporated into the hydrogel scaffold, revealing a functional role of laminin – integrin a3/a6 signalling in adhesion and survival of pancreatic organoids. Altered tissue stiffness — a hallmark of pancreatic cancer — was recapitulated in culture by adjusting the hydrogel properties to engage mechano-signalling and alter organoid growth. Pancreatic stromal cells were readily incorporated and replicated phenotypic traits characteristic of the tumour environment in vivo. This model ther...

Medical Education, 2009

on a 5-point scale; P < 0.001), more confident about assessing their patients' physical safety at... more on a 5-point scale; P < 0.001), more confident about assessing their patients' physical safety at home (pre = 2.3, post = 4.0; P < 0.001) and less concerned about the time investment involved in making home visits. In all 17 visits, new and important clinical information was uncovered. It appears a focused, patient-centred experiential curriculum that improved residents' skills as well as their confidence and comfort in conducting patient home visits, all of which should help primary care doctors to make home visits clinically meaningful, particularly in terms of preventing future physical injuries in patients at risk.

Gastrointestinal Endoscopy, 2011

Gastrointestinal Endoscopy, 2011

We read with great interest the study by Gonzalez et al, 1 in which the role and the diagnostic v... more We read with great interest the study by Gonzalez et al, 1 in which the role and the diagnostic value of duodenal bulb biopsies in the management and diagnosis of celiac disease were investigated. The authors conclude that the diagnostic yield, because of the patchy damage of the celiac disease enteropathy, is increased by performing duodenal bulb biopsies. The study investigates an interesting topic, but we think that some methodological points need to be clarified. First, it is unusual that in a tertiary referral hospital, only 319 of 1079 biopsy samples (30%) were well oriented, and consequently there was an unacceptable loss of approximately 37% of the patients. Orientation of the duodenal specimens is a determinant for a correct diagnosis, and well-known techniques to obtain adequate samples are available in the literature. 2,3 Second, from their Tables 4 and 5, it appears that 50% of the samples from duodenal bulb were inadequate and only 1 patient had 4 adequate biopsy samples from the distal duodenum, as required by international standards 4 ; thus, it is very difficult to derive conclusions about the concordance of bulb and D2 lesions and, moreover, to define true negative subjects. In conclusion, these results should be interpreted with caution and, by our own experience, the main message is that in a center devoted to celiac disease diagnosis and management, strict collaboration among gastroenterologists, endoscopists, and pathologists is essential.

European Journal of Gastroenterology & Hepatology, 2012

Background Emergency readmission after elective procedures is a quality indicator of healthcare d... more Background Emergency readmission after elective procedures is a quality indicator of healthcare delivery, but data for endoscopy are limited. Objectives Using hospital episode statistics (HES) registration systems and a multicentre audit to describe outcomes of emergency readmission following elective endoscopy. Methods Emergency readmissions (April 2008-2009) within 6 days of an elective day-case upper-GI endoscopy (UE) and lower GI endoscopy (LE) were subjected to a multicentre retrospective audit (north-west of England) following the identification of cases from routinely coded hospital administrative data from HES. Results Of 29 868 day cases, there were 235 readmissions, of which 147 (63%) were endoscopy related. The overall endoscopy readmission rate was 0.5% and the highest for therapeutic UE (1.74%; P = 0.0001). The rates for therapeutic LE, diagnostic UE and LE were 0.6, 0.5 and 0.4%, respectively. The incidence of readmission was 0.2% because of cardiorespiratory event, 0.14% for symptoms and 0.08, 0.03, 0.02 and 0.016%, respectively, for bleeding, perforation, obstruction and nonrespiratory sepsis. Management was simple observation in 84.4%, intravenous antibiotics in 7.5%, surgery in 4.8% and repeat endoscopy in 2.7%. Although 24.5% were short-stay discharges, the mean hospital stay was 8.2 days. All-cause 30-day mortality was low at 0.06%, but was considerably higher in readmitted patients at 6.8% (P = 0.0001). Conclusion Novel insights into readmission rates can be gained following endoscopy using a combination of commercial analytical tools to examine HES data to identify eligible readmitted cases; multicentred patient-level audit readmission rates varied predictably across procedure types with cardiorespiratory events, the major cause. The risk of mortality in readmitted patients was significant. Eur

Colorectal Disease, 2014

Aim UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy ... more Aim UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS). Considerable variation in practice exists due to a lack of expertise, technical difficulties and other, as yet ill-defined features. This retrospective multi-centre study aims to determine the outcome following colonic stenting for large bowel obstruction and identify factors associated with successful intervention. Method A regional programme of colonic stenting for large bowel obstruction, in five UK centres from 2005 to 2010 was evaluated for outcome including technical and clinical success, survival, complications and reoperation. Results A SEMS was inserted in 334 patients, including 264 (79.0%) for palliation and 52 (15.6%) as a bridge to surgery. Technical success was achieved in 292 (87.4%) patients, with 46 (13.8%) experiencing a complication or technical failure. Reoperation was required in 39 (14.8%) patients stented for palliation of colorectal cancer of whom 16 (6.1%) subsequently required a colostomy. A one-stage primary anastomosis was achieved in 35 (67.3%) of the 52 patients undergoing stenting as a bridge to resection. Technical success did not vary by indication or site of obstruction (P = 0.60) but was higher for operators who had performed more than 10 procedures (OR 3.34, P = 0.001). ASA grade ≥3 predicted a worse clinical outcome (OR 0.43, P = 0.04). The through-the-scope (TTS) endoscopy technique was more successful than radiological placement alone (90.3% vs 74.8%, P < 0.001). Conclusion Experienced operators using a TTS technique achieved a better outcome for the emergency management of large bowel obstruction. Older, sicker patients and those with extracolonic and benign strictures fared less well.

Colonic stenting is part of the UK service provision guidelines for colorectal cancer. However, t... more Colonic stenting is part of the UK service provision guidelines for colorectal cancer. However, there are issues about availability and expertise within the UK, and controversies remain regarding various clinical and technical aspects of the technique. Based on the current evidence, this article will provide a practical update on the indications, the clinical and technical considerations and the remaining unanswered questions regarding colonic stenting.

Hepatobiliary & Pancreatic Diseases International

Liver Cancer International

Journal of Gastrointestinal Cancer

Background Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In th... more Background Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions. Methods Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented. Results The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented. C...

Gastrointestinal Endoscopy

BACKGROUND AND AIMS Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDD) with an electro... more BACKGROUND AND AIMS Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDD) with an electrocautery enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with MDBO. Our aim was to assess the efficacy, safety, and outcomes in patients with malignant distal biliary obstruction (MDBO), who underwent EUS-CDD with EC-LAMS. METHODS A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMS at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 to November 2020 was undertaken. RESULTS One hundred twenty patients (55% male) with a median age of 73 years (IQR 17, range 43 - 94) were included. The median follow-up period in 117 patients was 70 days (IQR 169, range 3 - 869) and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to ≤50% of original value within 14 days) was achieved in 94.8% (92/97 patients). The adverse event (AE) rate was 17.5% (n=21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). CONCLUSION EUS-CDD with EC-LAMS at tertiary institutions within a regional HPB network for treatment of MDBO is effective in those where ERCP was not possible or unsuccessful. When technical failures or adverse events occur, the majority can be managed with conservative or endoscopic therapy.

Posters

number of diagnoses in the 2020 cohort compared with the 2019 cohort. The mean time from diagnosi... more number of diagnoses in the 2020 cohort compared with the 2019 cohort. The mean time from diagnosis to discussion at the MDT meetings was reduced in the 2020 cohort (20.8 vs 11.2 days) and the mean time to first treatment was also reduced (93.2 vs 53.8 days). There was no evidence of patients presenting at a more advanced stage in 2020. Data used in the BCLC staging criteria was used as a marker of disease progression. There was no significant difference in the size of lesions (p=0.39) or the number of lesions (p=0.94) in the 2 cohorts. Conclusion During the COVID-19 pandemic there was a 40% reduction in HCC diagnoses referred to the WOS MDT, compared with 2019. However there is no evidence that patients have presented with more advanced disease. Additionally, we have demonstrated a reduction in the referral to treatment time where active treatment was indicated. Given that the incidence of chronic liver disease has continued to rise in our population, we would expect an increased number of patients to present with more advance stage HCC over the coming months.

Nature Materials

Experimental in vitro models that capture pathophysiological characteristics of human tumours are... more Experimental in vitro models that capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from genetically engineered murine models and human patients, essential adhesive cues were empirically defined and replicated in the hydrogel scaffold, revealing a functional role of laminin–integrin α3/α6 signalling in establishment and survival of pancreatic organoids. Altered tissue stiffness—a hallmark of pancreatic cancer—was recapitulated in culture by adjusting the hydrogel properties to engage mechano-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro. A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin–integrin interactions in their growth.

Posters

information concerning number per year, patient age and sex at referral, cyst size, cyst site, ab... more information concerning number per year, patient age and sex at referral, cyst size, cyst site, ability to give a cytological diagnosis, surgical resection and malignant surgical resection pathology were recorded. Kendall's tau test (continuous data) or the Chi squared (categorical data) for trend test was used to determine significant changes over time. Results 417 patients (mean age 64.3 years, 163 males) underwent EUS in our unit for the assessment of cystic lesions over the study period. There was no significant difference in patient age or sex at referral over the study period. There was a significant increase in the number of procedures per year from 2003 (n=11) to 2012 (n=74)(tau 0.556, p=0.032) but a significant decrease in cyst size from 4.75cm in 2003 to 2.2cm in 2012 (tau-0.112, p=0.001). There was a significant change in the cyst site over time mainly due to an increase in the proportion of cysts found in the body of pancreas (p for trend<0.0001). Inability to give a cytological diagnosis rates fell significantly from 45.5% in 2003 to 21.6% in 2012 (p for trend=0.0048) and surgical resection rates fell from 36.4% to 17.6% (tau-0.112, p=0.0006). The number of malignant cysts (resected or not) also decreased significantly from 11.4% to 4.1% (p for trend=0.0097). Conclusions Cyst referrals for EUS have increased significantly but cysts are smaller, less likely to undergo resection, have a lower rate of malignancy and more likely to be in the body. Inability to give a cytological diagnosis rates also reduced significantly which may be due to improved laboratory techniques or a learning curve effect.

Objective Developments in advanced polypectomy technique provide an alternative to surgery in the... more Objective Developments in advanced polypectomy technique provide an alternative to surgery in the management of large and complex colorectal polyps. These endoscopic techniques require expertise and can potentially incur high complication rates. This survey evaluates current UK practice, attitudes and training in advanced polypectomy. Design Anonymous online questionnaire. Setting Colonoscopists within the UK were asked about their approach to large polyps (>2 cm). Results Among the 268 respondents (64% of whom were BCSP accredited), 86% were confident in removing lesions >2 cm by endoscopic mucosal resection (EMR). Of these, 27% were classed as low volume operators (<10 lesions resected/annum) and 14% as high volume operators (>50/annum). By comparison, only 3% currently performed endoscopic submucosal dissection (ESD). Referring one or more benign polyps for surgery a year was common among responders of all levels (11–68%). Training deficiencies were common: only 21% o...

Gut

We examined whether roll out of the bowel cancer screening programme (BCSP) across England was as... more We examined whether roll out of the bowel cancer screening programme (BCSP) across England was associated with a reduced risk of emergency hospital admission for people presenting with colorectal cancer (CRC) during this period.

Experimental in vitro models that accurately capture pathophysiological characteristics of human ... more Experimental in vitro models that accurately capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix, specifically designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from murine genetically engineered models and human patients, essential adhesive cues were empirically defined and incorporated into the hydrogel scaffold, revealing a functional role of laminin – integrin a3/a6 signalling in adhesion and survival of pancreatic organoids. Altered tissue stiffness — a hallmark of pancreatic cancer — was recapitulated in culture by adjusting the hydrogel properties to engage mechano-signalling and alter organoid growth. Pancreatic stromal cells were readily incorporated and replicated phenotypic traits characteristic of the tumour environment in vivo. This model ther...

Medical Education, 2009

on a 5-point scale; P < 0.001), more confident about assessing their patients' physical safety at... more on a 5-point scale; P < 0.001), more confident about assessing their patients' physical safety at home (pre = 2.3, post = 4.0; P < 0.001) and less concerned about the time investment involved in making home visits. In all 17 visits, new and important clinical information was uncovered. It appears a focused, patient-centred experiential curriculum that improved residents' skills as well as their confidence and comfort in conducting patient home visits, all of which should help primary care doctors to make home visits clinically meaningful, particularly in terms of preventing future physical injuries in patients at risk.

Gastrointestinal Endoscopy, 2011

Gastrointestinal Endoscopy, 2011

We read with great interest the study by Gonzalez et al, 1 in which the role and the diagnostic v... more We read with great interest the study by Gonzalez et al, 1 in which the role and the diagnostic value of duodenal bulb biopsies in the management and diagnosis of celiac disease were investigated. The authors conclude that the diagnostic yield, because of the patchy damage of the celiac disease enteropathy, is increased by performing duodenal bulb biopsies. The study investigates an interesting topic, but we think that some methodological points need to be clarified. First, it is unusual that in a tertiary referral hospital, only 319 of 1079 biopsy samples (30%) were well oriented, and consequently there was an unacceptable loss of approximately 37% of the patients. Orientation of the duodenal specimens is a determinant for a correct diagnosis, and well-known techniques to obtain adequate samples are available in the literature. 2,3 Second, from their Tables 4 and 5, it appears that 50% of the samples from duodenal bulb were inadequate and only 1 patient had 4 adequate biopsy samples from the distal duodenum, as required by international standards 4 ; thus, it is very difficult to derive conclusions about the concordance of bulb and D2 lesions and, moreover, to define true negative subjects. In conclusion, these results should be interpreted with caution and, by our own experience, the main message is that in a center devoted to celiac disease diagnosis and management, strict collaboration among gastroenterologists, endoscopists, and pathologists is essential.

European Journal of Gastroenterology & Hepatology, 2012

Background Emergency readmission after elective procedures is a quality indicator of healthcare d... more Background Emergency readmission after elective procedures is a quality indicator of healthcare delivery, but data for endoscopy are limited. Objectives Using hospital episode statistics (HES) registration systems and a multicentre audit to describe outcomes of emergency readmission following elective endoscopy. Methods Emergency readmissions (April 2008-2009) within 6 days of an elective day-case upper-GI endoscopy (UE) and lower GI endoscopy (LE) were subjected to a multicentre retrospective audit (north-west of England) following the identification of cases from routinely coded hospital administrative data from HES. Results Of 29 868 day cases, there were 235 readmissions, of which 147 (63%) were endoscopy related. The overall endoscopy readmission rate was 0.5% and the highest for therapeutic UE (1.74%; P = 0.0001). The rates for therapeutic LE, diagnostic UE and LE were 0.6, 0.5 and 0.4%, respectively. The incidence of readmission was 0.2% because of cardiorespiratory event, 0.14% for symptoms and 0.08, 0.03, 0.02 and 0.016%, respectively, for bleeding, perforation, obstruction and nonrespiratory sepsis. Management was simple observation in 84.4%, intravenous antibiotics in 7.5%, surgery in 4.8% and repeat endoscopy in 2.7%. Although 24.5% were short-stay discharges, the mean hospital stay was 8.2 days. All-cause 30-day mortality was low at 0.06%, but was considerably higher in readmitted patients at 6.8% (P = 0.0001). Conclusion Novel insights into readmission rates can be gained following endoscopy using a combination of commercial analytical tools to examine HES data to identify eligible readmitted cases; multicentred patient-level audit readmission rates varied predictably across procedure types with cardiorespiratory events, the major cause. The risk of mortality in readmitted patients was significant. Eur

Colorectal Disease, 2014

Aim UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy ... more Aim UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS). Considerable variation in practice exists due to a lack of expertise, technical difficulties and other, as yet ill-defined features. This retrospective multi-centre study aims to determine the outcome following colonic stenting for large bowel obstruction and identify factors associated with successful intervention. Method A regional programme of colonic stenting for large bowel obstruction, in five UK centres from 2005 to 2010 was evaluated for outcome including technical and clinical success, survival, complications and reoperation. Results A SEMS was inserted in 334 patients, including 264 (79.0%) for palliation and 52 (15.6%) as a bridge to surgery. Technical success was achieved in 292 (87.4%) patients, with 46 (13.8%) experiencing a complication or technical failure. Reoperation was required in 39 (14.8%) patients stented for palliation of colorectal cancer of whom 16 (6.1%) subsequently required a colostomy. A one-stage primary anastomosis was achieved in 35 (67.3%) of the 52 patients undergoing stenting as a bridge to resection. Technical success did not vary by indication or site of obstruction (P = 0.60) but was higher for operators who had performed more than 10 procedures (OR 3.34, P = 0.001). ASA grade ≥3 predicted a worse clinical outcome (OR 0.43, P = 0.04). The through-the-scope (TTS) endoscopy technique was more successful than radiological placement alone (90.3% vs 74.8%, P < 0.001). Conclusion Experienced operators using a TTS technique achieved a better outcome for the emergency management of large bowel obstruction. Older, sicker patients and those with extracolonic and benign strictures fared less well.

Colonic stenting is part of the UK service provision guidelines for colorectal cancer. However, t... more Colonic stenting is part of the UK service provision guidelines for colorectal cancer. However, there are issues about availability and expertise within the UK, and controversies remain regarding various clinical and technical aspects of the technique. Based on the current evidence, this article will provide a practical update on the indications, the clinical and technical considerations and the remaining unanswered questions regarding colonic stenting.

Hepatobiliary & Pancreatic Diseases International

Liver Cancer International

Journal of Gastrointestinal Cancer

Background Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In th... more Background Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions. Methods Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented. Results The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented. C...

Gastrointestinal Endoscopy

BACKGROUND AND AIMS Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDD) with an electro... more BACKGROUND AND AIMS Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDD) with an electrocautery enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with MDBO. Our aim was to assess the efficacy, safety, and outcomes in patients with malignant distal biliary obstruction (MDBO), who underwent EUS-CDD with EC-LAMS. METHODS A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMS at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 to November 2020 was undertaken. RESULTS One hundred twenty patients (55% male) with a median age of 73 years (IQR 17, range 43 - 94) were included. The median follow-up period in 117 patients was 70 days (IQR 169, range 3 - 869) and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to ≤50% of original value within 14 days) was achieved in 94.8% (92/97 patients). The adverse event (AE) rate was 17.5% (n=21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). CONCLUSION EUS-CDD with EC-LAMS at tertiary institutions within a regional HPB network for treatment of MDBO is effective in those where ERCP was not possible or unsuccessful. When technical failures or adverse events occur, the majority can be managed with conservative or endoscopic therapy.

Posters

number of diagnoses in the 2020 cohort compared with the 2019 cohort. The mean time from diagnosi... more number of diagnoses in the 2020 cohort compared with the 2019 cohort. The mean time from diagnosis to discussion at the MDT meetings was reduced in the 2020 cohort (20.8 vs 11.2 days) and the mean time to first treatment was also reduced (93.2 vs 53.8 days). There was no evidence of patients presenting at a more advanced stage in 2020. Data used in the BCLC staging criteria was used as a marker of disease progression. There was no significant difference in the size of lesions (p=0.39) or the number of lesions (p=0.94) in the 2 cohorts. Conclusion During the COVID-19 pandemic there was a 40% reduction in HCC diagnoses referred to the WOS MDT, compared with 2019. However there is no evidence that patients have presented with more advanced disease. Additionally, we have demonstrated a reduction in the referral to treatment time where active treatment was indicated. Given that the incidence of chronic liver disease has continued to rise in our population, we would expect an increased number of patients to present with more advance stage HCC over the coming months.

Nature Materials

Experimental in vitro models that capture pathophysiological characteristics of human tumours are... more Experimental in vitro models that capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from genetically engineered murine models and human patients, essential adhesive cues were empirically defined and replicated in the hydrogel scaffold, revealing a functional role of laminin–integrin α3/α6 signalling in establishment and survival of pancreatic organoids. Altered tissue stiffness—a hallmark of pancreatic cancer—was recapitulated in culture by adjusting the hydrogel properties to engage mechano-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro. A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin–integrin interactions in their growth.

Posters

information concerning number per year, patient age and sex at referral, cyst size, cyst site, ab... more information concerning number per year, patient age and sex at referral, cyst size, cyst site, ability to give a cytological diagnosis, surgical resection and malignant surgical resection pathology were recorded. Kendall's tau test (continuous data) or the Chi squared (categorical data) for trend test was used to determine significant changes over time. Results 417 patients (mean age 64.3 years, 163 males) underwent EUS in our unit for the assessment of cystic lesions over the study period. There was no significant difference in patient age or sex at referral over the study period. There was a significant increase in the number of procedures per year from 2003 (n=11) to 2012 (n=74)(tau 0.556, p=0.032) but a significant decrease in cyst size from 4.75cm in 2003 to 2.2cm in 2012 (tau-0.112, p=0.001). There was a significant change in the cyst site over time mainly due to an increase in the proportion of cysts found in the body of pancreas (p for trend<0.0001). Inability to give a cytological diagnosis rates fell significantly from 45.5% in 2003 to 21.6% in 2012 (p for trend=0.0048) and surgical resection rates fell from 36.4% to 17.6% (tau-0.112, p=0.0006). The number of malignant cysts (resected or not) also decreased significantly from 11.4% to 4.1% (p for trend=0.0097). Conclusions Cyst referrals for EUS have increased significantly but cysts are smaller, less likely to undergo resection, have a lower rate of malignancy and more likely to be in the body. Inability to give a cytological diagnosis rates also reduced significantly which may be due to improved laboratory techniques or a learning curve effect.

Objective Developments in advanced polypectomy technique provide an alternative to surgery in the... more Objective Developments in advanced polypectomy technique provide an alternative to surgery in the management of large and complex colorectal polyps. These endoscopic techniques require expertise and can potentially incur high complication rates. This survey evaluates current UK practice, attitudes and training in advanced polypectomy. Design Anonymous online questionnaire. Setting Colonoscopists within the UK were asked about their approach to large polyps (>2 cm). Results Among the 268 respondents (64% of whom were BCSP accredited), 86% were confident in removing lesions >2 cm by endoscopic mucosal resection (EMR). Of these, 27% were classed as low volume operators (<10 lesions resected/annum) and 14% as high volume operators (>50/annum). By comparison, only 3% currently performed endoscopic submucosal dissection (ESD). Referring one or more benign polyps for surgery a year was common among responders of all levels (11–68%). Training deficiencies were common: only 21% o...

Gut

We examined whether roll out of the bowel cancer screening programme (BCSP) across England was as... more We examined whether roll out of the bowel cancer screening programme (BCSP) across England was associated with a reduced risk of emergency hospital admission for people presenting with colorectal cancer (CRC) during this period.