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Pancreatic Neoplasms: HELP
Articles by Andrew R. Hart
Based on 11 articles published since 2010
(Why 11 articles?)
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Between 2010 and 2020, A. Hart wrote the following 11 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Bridging clinic: The initial medical management of patients with newly diagnosed pancreatic cancer. 2019

Sreedharan, Loveena / Kumar, Bhaskar / Jewell, Anna / Banim, Paul / Koulouris, Andreas / Hart, Andrew R. ·ST Upper GI Surgery, East of England Deanery, UK. · Upper GI Surgery, Norfolk and Norwich Hospital, Norwich, UK. · Pancreatic Cancer UK, London, UK. · James Paget University Hospitals, Great Yarmouth, Norfolk, UK. · Academic Clinical Fellow in Gastroenterology, Norfolk and Norwich Hospital, Norwich, UK. · Gastroenterology, Norfolk and Norwich Hospital, Norwich, UK. ·Frontline Gastroenterol · Pubmed #31288251.

ABSTRACT: Pancreatic cancer is the 11th most common cancer in the UK and has the worst prognosis of any tumour with minimal improvements in survival over recent decades. As most patients are either ineligible for surgery or may decline chemotherapy, the emphasis is on control of symptoms and management of complications such as poor nutritional status. The time period between informing the patient of their diagnosis and commencing cancer treatments presents a valuable opportunity to proactively identify and treat symptoms to optimise patients' overall well-being. The 'bridging clinic', delivered by a range of healthcare professionals from gastroenterologists to nurse practitioners, can provide this interface where patients are first informed of their diagnosis and second supportive therapies offered. In this article, we provide a structure for instituting such supportive therapies at the bridging clinic. The components of the clinic are summarised using the mnemonic INDASH (Information/Nutrition/Diabetes and Depression/Analgesia/Stenting/Hereditary) and each is discussed in detail below.

2 Review Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use. 2018

Broadhurst, Philip J / Hart, Andrew R. ·Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK. P.Broadhurst@uea.ac.uk. · Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK. · Norfolk and Norwich University Hospital NHS Trust, University of East Anglia, Norwich, NR4 7TJ, UK. ·Dig Dis Sci · Pubmed #30159732.

ABSTRACT: Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely laboratory, pharmacoepidemiological, experimental medicine and clinical trial evidence for investigating metformin in patients with pancreatic ductal adenocarcinoma. Laboratory evidence shows metformin inhibits mitochondrial ATP synthesis which directly and indirectly inhibits carcinogenesis. Drug-drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma. To date, most cohort studies have demonstrated a positive association with metformin on survival in pancreatic ductal adenocarcinoma, although there are many methodological limitations with such study designs. From experimental medicine studies, there are sparse data in humans. The current trials of metformin have methodological limitations. Two small randomized controlled trials (RCTs) reported null findings, but there were potential inequalities in cancer staging between groups and poor compliance with the intervention. Proof of concept data, predominantly from laboratory work, supports assessing metformin as an adjunct for pancreatic ductal adenocarcinoma in RCTs. Ideally, more experimental medicine studies are needed for proof of concept. However, many feasibility criteria need to be answered before such trials can progress.

3 Review Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments. 2017

Koulouris, Andreas I / Banim, Paul / Hart, Andrew R. ·Norwich Medical School, University of East Anglia, Bob Champion Research Center, Norwich Research Park, Norfolk, NR4 7TJ, UK. a.koulouris@uea.ac.uk. · Norfolk and Norwich University Hospital, Gastroenterology, Colney Lane, Norwich, NR4 7UY, UK. a.koulouris@uea.ac.uk. · Norwich Medical School, University of East Anglia, Bob Champion Research Center, Norwich Research Park, Norfolk, NR4 7TJ, UK. · James Paget University Hospital, Lowestoft Rd, Gorleston-on-Sea, Great Yarmouth, NR31 6LA, UK. · Norfolk and Norwich University Hospital, Gastroenterology, Colney Lane, Norwich, NR4 7UY, UK. ·Dig Dis Sci · Pubmed #28229252.

ABSTRACT: Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

4 Article An observational study to justify and plan a future phase III randomized controlled trial of metformin in improving overall survival in patients with inoperable pancreatic cancer without liver metastases. 2020

Broadhurst, Philip J / Hart, Andrew R. ·Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK. pbroadhurst@doctors.org.uk. · Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK. · Norfolk and Norwich University Hospital NHS Trust, Norwich, NR4 7TJ, UK. ·J Cancer Res Clin Oncol · Pubmed #32157435.

ABSTRACT: PURPOSE: Metformin has plausible direct and indirect anti-cancer properties against pancreatic adenocarcinoma cells. However, metformin may only be efficacious in patients with inoperable pancreatic ductal adenocarcinoma (PDAC) without liver metastases. Absorption may be decreased by gastrointestinal symptoms and proton pump inhibitors (PPIs). We aimed to justify and inform a future phase III trial of metformin versus placebo on survival in inoperable PDAC by documenting prevalence of patients meeting eligibility criteria, gastrointestinal symptoms and PPI use. METHODS: Patient notes with PDAC were reviewed at a large teaching hospital over 2 years. Study variables were obtained from multiple sources of information. RESULTS: 141 participants were identified (51.8% female), of which 37.6% were not prescribed metformin at diagnosis and had no radiological hepatic metastases. Characteristics were similar between non-metformin and metformin users. In eligible patients, 65.2% reported nausea and vomiting and 46.2% were prescribed PPIs. CONCLUSION: Approximately, a third of all patients with inoperable PDAC are eligible for a future trial of metformin, allowing an estimate of the number of hospitals required for recruitment. Nausea and vomiting are common and should be managed effectively to prevent trial dropouts. PPI use is frequent and their influence on metformin's pharmacodynamic actions needs to be clarified.

5 Article Dietary Fiber and the Risk of Pancreatic Cancer. 2019

Koulouris, Andreas I / Luben, Robert / Banim, Paul / Hart, Andrew R. ·Institute of Public Health, University of Cambridge, Cambridge. · Department of Gastroenterology, James Paget University Hospital, Great Yarmouth, United Kingdom. ·Pancreas · Pubmed #30489447.

ABSTRACT: OBJECTIVES: High dietary fiber may protect against pancreatic ductal adenocarcinoma (PDAC). We investigated associations between fiber intake and the risk of PDAC using for the first time 7-day food diaries. METHODS: Participants in the European Prospective Investigation Into Cancer-Norfolk completed the 7-day food diaries at recruitment. The cohort was followed up for 17 years to identify those who developed PDAC. Participants were divided into quintiles of fiber intake, and hazard ratios (HR) were estimated with their 95% confidence intervals (CIs). Fiber was tested for effect modification of high red and processed meat intake and smoking and the risk of PDAC. RESULTS: No significant associations for any quintiles of intake (HR Q5 vs Q1, 1.08; 95% CI, 0.56-2.08) were detected with no trend across quintiles. A high-fiber diet modified positive associations between red and processed meats with the development of PDAC (HR trends, 0.89 [95% CI, 0.47-1.69] and 1.02 [95% CI, 0.55-1.88], respectively) but not those with lower fiber intake. Fiber intake did not modify the risk of PDAC in past and current smokers. CONCLUSION: The findings do not suggest that fiber protects against PDAC, although it may decrease potential deleterious effects of meats.

6 Article Dietary oleic acid is inversely associated with pancreatic cancer - Data from food diaries in a cohort study. 2018

Banim, Paul Jr / Luben, Robert / Khaw, Kay-Tee / Hart, Andrew R. ·James Paget University Hospital, Great Yarmouth, Norfolk, UK. Electronic address: paul.banim@jpaget.nhs.uk. · Institute of Public Health, University of Cambridge, UK. · Norwich Medical School, University of East Anglia, Norwich, UK. ·Pancreatology · Pubmed #30031691.

ABSTRACT: BACKGROUND: Dietary oleic acid may prevent pancreatic ductal adenocarcinoma (PDA) by reducing hyperinsulinaemia which can otherwise promote DNA damage and tumour growth. Results from previous epidemiological studies investigating oleic acid are inconsistent. This study aims to clarify the relationship between dietary oleic acid intake and the risk of developing PDA using nutritional information from food diaries plus published serum biomarker data from HbA1c. METHODS: 23,658 participants, aged 40-74 years, were recruited into EPIC-Norfolk and completed 7-day food diaries which recorded; foods, brands and portion sizes to calculate nutrient intakes. Serum HbA1c was measured at recruitment in 11,147 participants (48.7% of cohort). Hazard ratios (HRs) for quintiles of dietary oleic acid intake and serum HbA1c were estimated using Cox regression. Additional analyses were made according to whether body mass index (BMI) was greater or less than 25 kg/m RESULTS: 88 participants (55% women) developed PDA after a mean follow-up of 8.4 years (SD = 3.9) (mean age at diagnosis = 72.6 years, SD = 8.8). A decreased risk of PDA was associated with increased dietary oleic acid intake (highest vs lowest quintile, HR = 0.29, 95% CI = 0.10-0.81, P trend across quintiles = 0.011), with statistical significance maintained when BMI>25 kg/m CONCLUSIONS: The data supports a protective role of oleic acid against development of PDA in those with higher BMIs possibly through influencing hyperinsulinaemia. Oleic acid intake should be accurately measured in future aetiological studies.

7 Article Higher Meat Intake Is Positively Associated With Higher Risk of Developing Pancreatic Cancer in an Age-Dependent Manner and Are Modified by Plasma Antioxidants: A Prospective Cohort Study (EPIC-Norfolk) Using Data From Food Diaries. 2017

Beaney, Alec J / Banim, Paul J R / Luben, Robert / Lentjes, Marleen A H / Khaw, Kay-Tee / Hart, Andrew R. ·From the *Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Norwich; †Department of Gastroenterology, James Paget University Hospital, Great Yarmouth, Norfolk; ‡Department of Public Health & Primary Care, University of Cambridge, Cambridge, Cambridgeshire; and §Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom. ·Pancreas · Pubmed #28375948.

ABSTRACT: OBJECTIVE: Carcinogens in meat may be involved in pancreatic carcinogenesis. Meat intake was investigated using 7-day food diaries and according to factors potentially influencing carcinogenesis: age, cooking method, and antioxidants. METHODS: Twenty-three thousand one hundred thirty-three participants in the European Prospective Investigation of Cancer-Norfolk cohort study completed 7-day food diaries and were followed up. Meat intakes were compared with controls and hazard ratios (HRs) calculated. RESULTS: Eighty-six participants developed pancreatic cancer. If younger than 60 years at recruitment, all quintiles of red meat (Q1 vs Q5; HR, 4.62; 95% confidence interval [CI], 0.96-22.30; P = 0.06) and processed meat (Q1 vs Q5; HR, 3.73; 95% CI, 0.95-14.66; P = 0.06) were nonsignificantly positively associated, with significant trends across quintiles (HRtrend, 1.33; 95% CI, 1.01-1.77 and HRtrend, 1.37; 95% CI, 1.04-1.82, respectively). Red meat's effect was attenuated by higher, but not lower, plasma vitamin C (HR, 1.06; 95% CI, 0.69-1.63 vs HR, 1.84; 95% CI, 1.09-3.14) and for processed meat (HR, 1.07; 95% CI, 0.71-1.63 vs HR, 1.80; 95% CI, 1.10-2.96). A nonstatistically significant risk was observed for high-temperature cooking methods in younger people (HR, 4.68; 95% CI, 0.63-34.70; P = 0.13). CONCLUSIONS: Red and processed meats may be involved in pancreatic carcinogenesis.

8 Article Investigating Physical Activity in the Etiology of Pancreatic Cancer: The Age at Which This Is Measured Is Important and Is Independent of Body Mass Index. 2016

Noor, Nurulamin M / Banim, Paul J R / Luben, Robert N / Khaw, Kay-Tee / Hart, Andrew R. ·From the *Department of Medicine, University of Cambridge, Cambridge, United Kingdom; †Department of Gastroenterology, James Paget University Hospital, Great Yarmouth, United Kingdom; ‡Institute of Public Health, University of Cambridge, Cambridge, United Kingdom; and §Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. ·Pancreas · Pubmed #26390426.

ABSTRACT: OBJECTIVES: There are plausible biological mechanisms for how increased physical activity (PA) may prevent pancreatic cancer, although findings from epidemiological studies are inconsistent. We investigated whether the risk is dependent on the age at which PA is measured and if independent of body mass index (BMI). METHODS: A total of 23,639 participants, aged 40 to 74 years, were recruited into the EPIC-Norfolk (European Prospective Investigation of Cancer) cohort study between 1993 and 1997 and completed validated questionnaires on PA. The cohort was monitored for pancreatic cancer development, and hazard ratios (HRs) were estimated and adjusted for covariates. RESULTS: Within 17 years, 88 participants developed pancreatic cancer (55% female). There was no association between PA and risk in the cohort (HR trend, 1.06; 95% confidence interval [CI], 0.86-1.29). However, in participants younger than 60 years, higher PA was associated with decreased risk (highest vs lowest category HR, 0.27; 95% CI, 0.07-0.99). Higher PA was not inversely associated when older than 60 years (HR trend, 1.23; 95% CI, 0.96-1.57). Including BMI in all models produced similar estimates. CONCLUSIONS: The reasons why PA in younger, but not older, people may prevent pancreatic cancer need to be investigated. Physical activity may operate through mechanisms independent of BMI. If this association is causal, 1 in 6 cases might be prevented by encouraging more PA.

9 Article The differential effects of statins on the risk of developing pancreatic cancer: a case-control study in two centres in the United Kingdom. 2013

Carey, F J / Little, M W / Pugh, T F G / Ndokera, R / Ing, H / Clark, A / Dennison, A / Metcalfe, M S / Robinson, R J / Hart, A R. ·Norfolk and Norwich University Hospital, Norwich, UK, f.carey@uea.ac.uk. ·Dig Dis Sci · Pubmed #23864194.

ABSTRACT: INTRODUCTION: There are plausible biological mechanisms for how statins may prevent pancreatic cancer, although the evidence from epidemiological studies in the general population is conflicting. This study aims to clarify whether statins exert their effects in specific sub-groups, namely, gender, smoking status and diabetes. METHODS: A matched case-control study was conducted in patients diagnosed with pancreatic cancer, and a group of dermatology patients of similar ages and gender, diagnosed with basal cell carcinoma. Participants' medical records were reviewed for information on statin use prior to diagnosis. Odds ratios and 95 % CIs for the development of pancreatic cancer were estimated using conditional logistic regression. Subgroup analysis was performed in men, women, smokers and those with type 2 diabetes. RESULTS: Two hundred fifty-two cases (median age 71 years, range 48-73 years, 51 % women) and 504 controls were identified, of which 23 % of cases were regular statin users versus 21 % of controls. In the general study population there was no association between pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53-1.23, p = 0.33). However, in male smokers, regular statin use was associated with significantly reduced odds of pancreatic cancer compared to male smokers not prescribed a statin (OR 0.11, 95 % CI 0.01-0.96, p = 0.05). In patients with type 2 diabetes statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35-2.45, p = 0.80), with no gender effects. CONCLUSIONS: In male smokers, statins may reduce the odds of pancreatic cancer. Statin use should be measured in aetiological studies of pancreatic cancer but analysed in specific sub-groups. Future work should investigate statins as chemopreventative agents in this high risk sub-group.

10 Article Dietary antioxidants and the aetiology of pancreatic cancer: a cohort study using data from food diaries and biomarkers. 2013

Banim, Paul J R / Luben, Robert / McTaggart, Alison / Welch, Ailsa / Wareham, Nicholas / Khaw, Kay-Tee / Hart, Andrew R. ·Department of Medicine, University of East Anglia, Norwich, UK. ·Gut · Pubmed #22826513.

ABSTRACT: OBJECTIVE: To investigate whether the dietary antioxidants vitamins C and E, selenium and zinc decrease the risk of developing pancreatic cancer, for the first time using 7-day food diaries, the most accurate dietary methodology in prospective work. DESIGN: 23,658 participants, aged 40-74 years, recruited into the EPIC-Norfolk Study completed 7-day food diaries which recorded foods, brands and portion sizes. Nutrient intakes were calculated in those later diagnosed with pancreatic cancer and in 3970 controls, using a computer program with information on 11,000 foods. Vitamin C was measured in serum samples. The HRs of developing pancreatic cancer were estimated across quartiles of intake and thresholds of the lowest quartile (Q1) against a summation of the three highest (Q2-4). RESULTS: Within 10 years, 49 participants (55% men), developed pancreatic cancer. Those eating a combination of the highest three quartiles of all of vitamins C and E and selenium had a decreased risk (HR=0.33, 95% CI 0.13 to 0.84, p<0.05). There were threshold effects (Q2-4 vs Q1) for selenium (HR=0.49, 95% CI 0.26 to 0.93, p<0.05) and vitamin E (HR=0.57, 95% CI 0.29 to 1.09, p<0.10). The HRs of quartiles for antioxidants, apart from zinc, were <1, but not statistically significant. For vitamin C, there was an inverse association with serum measurements (HR trend=0.67, 95% CI 0.49 to 0.91, p=0.01), but the threshold effect from diaries was not significant (HR=0.68, 95% CI 0.37 to 1.26). CONCLUSION: The results support measuring antioxidants in studies investigating the aetiology of pancreatic cancer. If the association is causal, 1 in 12 cancers might be prevented by avoiding the lowest intakes.

11 Unspecified The Practical Management of Chronic Pancreatitis: A Multidisciplinary Symposium Held at the Annual Meeting of the Pancreatic Society of Great Britain and Ireland, Manchester 2016. 2019

Jegatheeswaran, Santhalingam / Puleston, Joanne M / Duggan, Sinead / Hart, Andrew / Conlon, Kevin C / Siriwardena, Ajith K. ·Hepato-Pancreato-Biliary Unit, Manchester, United Kingdom. · Department of Gastroenterology Manchester Royal Infirmary, Manchester, United Kingdom. · Department of Surgery, Trinity College, Dublin, Ireland. · Department of Gastroenterology, Norfolk and Norwich University Hospital and University of East Anglia, Dublin, Ireland. · Hepato-Pancreato-Biliary Unit, Manchester, United Kingdomajith.siriwardena@cmft.nhs.uk. ·Dig Surg · Pubmed #29339657.

ABSTRACT: AIM: This study is about a questionnaire survey of delegates attending the chronic pancreatitis symposium at the 2016 meeting of the Pancreatic Society of Great Britain and Ireland and seeks a multidisciplinary "snapshot" overview of practice. METHODS: A questionnaire was developed with multidisciplinary input. Questions on access to specialist care, methods of diagnosis and treatment including specific scenarios were incorporated. Eighty-three (66%) of 125 delegates effectively participated in this survey. RESULTS: Twenty-four (29%) had neither a chronic pancreatitis MDT in their hospital nor a chronic pancreatitis referral MDT. Most frequently utilised diagnostic modalities were CT, MR and EUS with no respondents utilising duodenal intubation tests. Initial treatment was provided through non-opiate analgesia by 69 (93%), through the use of opiates by 56 (76%) and through the use of co-analgesics by 49 (66%). Fifty two (68%) routinely referred patients with alcohol-related disease for counselling. Preferred treatment for large duct disease without mass was endoscopic therapy. In older patients with a mass, pancreaticoduodenectomy was preferred. CONCLUSION: This is a small study likely to be skewed by sampling bias but is thought to be the first multidisciplinary survey of the management of chronic pancreatitis in the United Kingdom and Ireland. The results show a need for comprehensive access to specialist pancreatitis MDT care and there remains substantial variation in management.