Interventions for Pancreatitis-New Approaches, Knowledge Gaps, and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

ABSTRACT: There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.

Surgery versus Endoscopy for the Management of Painful Chronic Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Debate exists regarding the optimal treatment for painful chronic pancreatitis (CP). This meta-analysis aims to determine the outcomes of surgical intervention as compared to endoscopy in patients with painful CP. METHODS: A systematic review and meta-analysis including studies from PubMed, Embase, Web of Science, and Cochrane Databases (1995 onwards) was done by two independent reviewers using PRISMA guidelines. Primary outcome was pain relief. RESULTS: Among 8,479 studies, three were randomized trials, comprising a total of 199 patients. Compared with endoscopy, surgery was associated with a lower Izbicki score, both at medium term (mean difference (MD) 21.46, 95% confidence interval (CI) 13.48-29.43, p < 0.00001) and long term (MD: 17.80, 95% CI: 8.36-27.23, p = 0.0002). A higher proportion of surgical patients had some sort of pain relief compared with those who had endoscopy, both at medium term (72% vs. 46%, RR: 1.51, 95% CI: 1.19-1.90, p = 0.0006) and long term (73% vs. 47%, RR: 1.50, 95% CI: 1.19-1.89, p = 0.0007). Complete pain relief was more common in the surgical group compared to the endoscopy group, both at medium term (33% vs. 17%, RR: 1.97, 95% CI: 1.16-3.36, p = 0.01) and long term (35% vs. 18%, RR: 1.92, 95% CI: 1.15-3.20, p = 0.01). The pooled crossover rate from endoscopy to surgery was 22% (22/99). CONCLUSIONS: Surgical treatment in patients with painful CP leads to better pain control, requiring fewer interventions as compared to endoscopic treatment.

Prevalence of Osteopathy in Chronic Pancreatitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Individuals with chronic pancreatitis (CP) are at increased risk for nutritional complications during their clinical course. We appraised the literature to provide updated estimates of the prevalence and predictors of osteoporosis, osteopenia, and osteopathy in CP using a systematic review and meta-analysis. METHODS: Search strategies were developed for major databases from inception through October 2021. Outcomes of interest included rates of osteopenia and osteoporosis based on dual-energy X-ray absorptiometry scans and risk factors. A random-effects model was used for analysis, and results were expressed as pooled cumulative rates along with 95% confidence interval (CI). RESULTS: From an initial total of 1,704 identified articles, we ultimately selected 17 studies that involved 1,659 subjects (n = 1,067 men) with CP. The pooled rate of osteopathy was 58% (95% CI: 49%-67%; P < 0.001; I 2 = 91.8%). The pooled rate of osteoporosis was 18% (95% CI: 12%-23%; P < 0.001; I 2 = 86.3%), and the pooled rate of osteopenia was 39% (95% CI: 31%-48%; P < 0.001; I 2 = 91.53%). In the systematic review, factors associated with decreased bone mineral density included smoking, alcohol consumption, older age, female sex, low body mass index, decreased vitamins D and K, and fecal elastase levels. DISCUSSION: Patients with CP have high rates of osteopathy when assessed with dual-energy X-ray absorptiometry imaging. Additional studies with longitudinal follow-up are needed to understand the observed heterogeneity, the cumulative burden of disease, and rate of bone loss in CP.

Recent Advances in Pancreatic Ductal Adenocarcinoma: Strategies to Optimise the Perioperative Nutritional Status in Pancreatoduodenectomy Patients.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy for which the mainstay of treatment is surgical resection, followed by adjuvant chemotherapy. Patients with PDAC are disproportionately affected by malnutrition, which increases the rate of perioperative morbidity and mortality, as well as reducing the chance of completing adjuvant chemotherapy. This review presents the current evidence for pre-, intra-, and post-operative strategies to improve the nutritional status of PDAC patients. Such preoperative strategies include accurate assessment of nutritional status, diagnosis and appropriate treatment of pancreatic exocrine insufficiency, and prehabilitation. Postoperative interventions include accurate monitoring of nutritional intake and proactive use of supplementary feeding methods, as required. There is early evidence to suggest that perioperative supplementation with immunonutrition and probiotics may be beneficial, but further study and understanding of the underlying mechanism of action are required.

Development of a clinical score to estimate pancreatitis-related hospital admissions in patients with a new diagnosis of chronic pancreatitis: the trinity score.

BACKGROUND: The clinical course of chronic pancreatitis is unpredictable and there is no globally accepted score to predict the disease course. We developed a clinical score to estimate pancreatitis-related hospitalisation in patients with newly diagnosed chronic pancreatitis. METHODS: We conducted a retrospective cohort study using two clinical chronic pancreatitis databases held in tertiary referral centres in Dublin, Ireland, and in Tarragona, Spain. Individuals diagnosed with chronic pancreatitis between 2007 and 2014 were eligible for inclusion. Candidate predictors included aetiology, body mass index, exocrine dysfunction, smoking and alcohol history. We used multivariable logistic regression to develop the model. RESULTS: We analysed data from 154 patients with newly diagnosed chronic pancreatitis. Of these, 105 patients (68%) had at least one hospital admission for pancreatitis-related reasons in the 6 years following diagnosis. Aetiology of chronic pancreatitis, body mass index, use of pain medications and gender were found to be predictive of more pancreatic-related hospital admissions. These predictors were used to develop a clinical score which showed acceptable discrimination (area under the ROC curve = 0.70). DISCUSSION: We developed a clinical score based on easily accessible clinical parameters to predict pancreatitis-related hospitalisation in patients with newly diagnosed chronic pancreatitis.

Significantly Lower Physical Activity Participation in Individuals with Chronic Pancreatitis Compared to Controls: An Exploratory Study of Objectively Assessed Physical Activity Levels.

INTRODUCTION: The beneficial effects of exercise and physical activity (PA) have been demonstrated in many chronic inflammatory diseases. Knowledge on PA levels is unknown in the chronic pancreatitis population, and there are currently no specific PA recommendations for this condition. METHODS: PA was measured objectively over a 7-day period in 17 individuals with chronic pancreatitis using an accelerometer (ActiGraph) and in 15 controls, matched for age, sex, and body mass index. RESULTS: Participants with chronic pancreatitis spent a significantly lower amount of time in moderate, light, and moderate/vigorous activity compared to the healthy control group. Mean time in light activity in the chronic pancreatitis group was 825.4 ± 972 (standard deviation [SD]) compared to 1,500 ± 958 (SD) in the healthy control group. Moderate activity mean minutes were 61.6 ± 85 in the chronic pancreatitis group compared to 161.4 ± 131.2 in the healthy control group. Moderate/vigorous mean minutes were 62.1 ± 86 (SD) in the chronic pancreatitis group compared to 164.3 ± 132 (SD) in the healthy control group. There was no significant difference found between the groups for either vigorous activity or time spent sedentary. CONCLUSION: This exploratory study offers early objective evidence that activity levels in the chronic pancreatic group are not meeting current international recommendations. Further investigation of this chronic illness population is strongly recommended.

Measurement of Body Composition in Pancreatic Cancer: A Systematic Review, Meta-Analysis, and Recommendations for Future Study Design.

BACKGROUND/OBJECTIVES: Sarcopenia in pancreatic cancer may increase the risk of chemotherapy-related toxicity and post-operative morbidity. This systematic review and meta-analysis aimed to quantify the prevalence of sarcopenia in early stage pancreatic cancer. METHODS: Relevant studies were identified using Ovid Medline and Elsevier Embase. Pooled estimates of prevalence rates (percentages) and corresponding 95% confidence interval (CI) were computed using a random-effects model to allow for heterogeneity between studies. RESULTS: The majority of the 33 studies (n = 5,593 patients) included in this meta-analysis utilized computed tomography (CT)-derived measures for body composition assessment in patients undergoing pancreatic resection. Reported prevalence of sarcopenia varied between 14 and 74%, and the pooled prevalence was 39% (95% CI: 38-40%) Heterogeneity was considerable, however, (I2 = 93%) and did not improve significantly when controlling for assessment method, and use of pre-defined cut-offs for sarcopenia, limiting potential to evaluate the true impact of sarcopenia. CONCLUSION: The ready availability of sequential CT offers a valuable opportunity for body composition assessment, but the quality of assessment and interpretation must improve before the impact of body composition on treatment-related outcomes and survival can be assessed. We suggest recommendations for the assessment of body composition for the design of future studies.

Physical activity for chronic pancreatitis: a systematic review.

BACKGROUND: Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. Sarcopenia is a degenerative loss of skeletal muscle mass, quality, and strength and is commonly associated with chronic pancreatitis. Regular physical activity and adequate functional fitness have been found to ameliorate the risk and effects of sarcopenia in other chronic diseases. The objective of this systematic review was to collate all the published evidence which has examined any type of physical activity as an intervention in the chronic pancreatitis patient population. METHODS: This systematic review was conducted in accordance with the PRISMA guidelines. The search strategy was designed by the medical librarian (DM) for Embase and then modified for the other search platforms. Two of the researchers (BM) and (AM) then performed the literature search using the databases Embase, Medline, CINAHL, and Web of Science. RESULTS: An electronic identified a total of 571 references imported to Covidence as 420 when the duplicates (151) were removed. 420 titles were screened and 390 were removed as not relevant from their titles. 30 full text papers were selected and from these, only one full text paper was deemed suitable for inclusion. CONCLUSIONS: There is currently insufficient evidence to advise physical activity in the chronic pancreatitis population. However, given the evidence to support physical activity in many other chronic diseases this review highlights the need for urgent investigation of physical activity as an intervention on this specific patient population.

Dietary intake in patients with chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND: A progressive reduction in the secretion of pancreatic enzymes in patients with chronic pancreatitis (CP) results in malabsorption and ultimate malnutrition. However, the pathogenesis of malnutrition is multifactorial and other factors such as chronic inflammation, alcohol excess and poor dietary intake all contribute. Patients may restrict their dietary intake due to poor appetite or to avoid gastrointestinal symptoms and abdominal pain. Whilst up to half of patients with chronic pancreatitis are reportedly malnourished, the dietary intake of patients with CP is relatively understudied and has not been systematically reviewed to date. AIM: To perform a systematic review and meta-analysis of the dietary intakes of patients with CP compared to healthy controls, and to compare the dietary intake of patients with alcohol-related CP and non-alcohol-related CP. METHODS: A systematic literature search was performed using EMBASE, MEDLINE, and Cochrane review on studies published between 1946 and August 30th, 2019. Adult subjects with a diagnosis of CP who had undergone dietary assessment were included in the systematic review (qualitative analysis). Studies on patients with other pancreatic diseases or who had undergone pancreatic surgery were not included. Studies comparing the dietary intake of patients with CP to that of healthy controls were included in the meta-analysis (quantitative analysis). Meta-analysis was performed using Review Manager 5.3. Newcastle Ottawa Scale (NOS) was used to assess quality of studies. RESULTS: Of 6715 studies retrieved in the search, 23 were eligible for qualitative analysis while 12 were eligible for quantitative analysis. In the meta-analysis, the total energy (calorie) intake of patients with CP was similar to that of healthy controls [mean difference (MD): 171.3; 95% confidence interval (CI): -226.01, 568.5; P = 0.4], however patients with CP consumed significantly fewer non-alcohol calories than controls [MD: -694.1; 95%CI: -1256.1, (-132.1); P = 0.02]. CP patients consumed more protein, but carbohydrate and fat intakes did not differ significantly. Those with alcohol-related CP consumed more mean (standard deviation) calories than CP patients with a non-alcohol aetiology [2642 (1090) kcal and 1372 (394) kcal, respectively, P = 0.046], as well as more protein, fat, but not carbohydrate. CONCLUSION: Although patients with CP had similar calorie intake to controls, studies that analysed the contribution of alcohol to energy intake showed that patients with CP consumed fewer non-alcohol calories than healthy controls. A high calorie intake, made up to a large degree by alcohol, may in part contribute to poor nutritional status in CP.

Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines.

INTRODUCTION: Pancreatic exocrine insufficiency is a finding in many conditions, predominantly affecting those with chronic pancreatitis, pancreatic cancer and acute necrotising pancreatitis. Patients with pancreatic exocrine insufficiency can experience gastrointestinal symptoms, maldigestion, malnutrition and adverse effects on quality of life and even survival.There is a need for readily accessible, pragmatic advice for healthcare professionals on the management of pancreatic exocrine insufficiency. METHODS AND ANALYSIS: A review of the literature was conducted by a multidisciplinary panel of experts in pancreatology, and recommendations for clinical practice were produced and the strength of the evidence graded. Consensus voting by 48 pancreatic specialists from across the UK took place at the 2019 Annual Meeting of the Pancreatic Society of Great Britain and Ireland annual scientific meeting. RESULTS: Recommendations for clinical practice in the diagnosis, initial management, patient education and long term follow up were developed. All recommendations achieved over 85% consensus and are included within these comprehensive guidelines.

A high prevalence of genetic polymorphisms in idiopathic and alcohol-associated chronic pancreatitis patients in Ireland.

BACKGROUND: Individual genetic architecture is considered central to susceptibility and progression of disease in chronic pancreatitis. The study aimed to evaluate the presence of common pancreatic gene mutations in a defined cohort of idiopathic and alcohol-induced chronic pancreatitis patients in Ireland. METHODS: The study comprised patients with idiopathic and alcohol-induced chronic pancreatitis and historic controls. Variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, cationic trypsinogen (PRSS1) gene and serine protease inhibitor kazal type-1 (SPINK1) gene, were assessed by Taqman© genotyping assay. RESULTS: Of n = 126 patients and n = 167 controls, mutations were detected in 23 (20%) and in 10 (6%) respectively (P < 0.001). The majority of mutations found were in the SPINK1 gene variant N34S (13%) which increased disease risk almost six-fold (OR 5.9). Neither CFTR severe mutation (F508del) (P = 0.649) nor mild variant (R117H) (P = 0.327) were over-represented amongst patients compared to control subjects. PRSS1 variants were not detected in either patient or control subjects. CONCLUSION: There was a significant prevalence of chronic pancreatitis-associated gene mutations in this well-phenotyped cohort. In patients with alcohol-related or idiopathic chronic pancreatitis, the possibility of genetic mutations in the SPINK 1 gene should be considered as a contributing aetiology factor.

Metabolic dysfunction and diabetes mellitus during long-term follow-up of severe acute pancreatitis: A case-matched study.

BACKGROUND/OBJECTIVES: Endocrine insufficiency following severe acute pancreatitis (SAP) leads to diabetes of the exocrine pancreas, (type 3c diabetes mellitus), however it is not known how this metabolic phenotype differs from that of type 2 diabetes, or how the two subtypes can be differentiated. We sought to determine the prevalence of diabetes following SAP, and to analyse the behaviour of glucose and pancreatic hormones across a 2-h oral glucose tolerance test (OGTT). METHODS: Twenty-six patients following SAP (mean (range) duration of first SAP episode to study time of 119.3 (14.8-208.9) months) along with 26 matched controls underwent an OGTT with measurement of glucose, insulin, c-peptide, glucagon and pancreatic polypeptide (PP) at fasting/15/90/120min. Beta-cell area was estimated using the 15min c-peptide/glucose ratio, and insulin resistance (IR) using homeostasis model assessment (HOMA) and oral glucose insulin sensitivity (OGIS) models. RESULTS: The prevalence of diabetes/prediabetes was 54% following SAP (38.5% newly-diagnosed compared to 19.2% newly-diagnosed controls). Estimated beta-cell area and IR did not differ between groups. AUC c-peptide was lower in SAP versus controls. AUC insulin and AUC c-peptide were lower in SAP patients with diabetes versus controls with diabetes; between-group differences were observed at the 90 and 120 min time-points only. Half of new diabetes cases in SAP patients were only identified at the 120min timepoint. CONCLUSIONS: Diabetes and pre-diabetes occur frequently following SAP and are difficult to distinguish from type 2 diabetes in controls but are characterised by reduced insulin and c-peptide at later stages of an OGTT. Consistent with this observation, most new post SAP diabetes cases were diagnosed by 2-h glucose levels only.

Clinical Classification and Severity Scoring Systems in Chronic Pancreatitis: A Systematic Review.

INTRODUCTION: Chronic pancreatitis (CP) is characterised by pain, functional deficits, nutritional and mechanical complications. Frequently managed in out-patient settings, the clinical course is unpredictable and requires multi-disciplinary care. There remains substantial variation in management. In contrast to acute pancreatitis, there are no globally accepted classification or severity scores to predict the disease course or compare interventions. We conducted a systematic review to determine the scope and clinical use of existing scoring systems. METHODS: A systematic search was developed with a medical librarian using the Embase, Medline and Cochrane databases. Original articles and conference abstracts describing an original or modified classification or scoring system in CP that stratified patients into clinical and/or severity categories were included. To assess clinical application/validation, studies using all or part of a score as a stratification tool to measure another parameter or outcome were selected. Studies reporting on diagnosis or aetiology only were excluded. Four authors performed the search in independent pairs and conflicts were resolved by a fifth author using CovidenceTM systematic review software. RESULTS: Following screening 6,652 titles and 235 full-text reviews, 48 papers were analysed. Eleven described original scores and 6 described modifications of published scores. Many were comprehensive but limited in capturing the full spectrum of disease. In 31 studies, a score was used to categorise patients to compare or correlate various outcome measures. Exocrine and endocrine dysfunction and pain were included in 6, 5, and 4 scoring systems, respectively. No score included other nutrition parameters, such as bone health, malnutrition, or nutrient deficiency. Only one score has been objectively validated prospectively and independently for monitoring clinical progression and prognosis, but this had been applied to an in-patient population. CONCLUSION: Available systems and scores do not reflect recent advances and guidelines in CP and are not commonly used. A practical clinical classification and scoring system, validated prospectively for prognostication would be useful for the meaningful analysis in observational and interventional studies in CP.

Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer.

BACKGROUND: Pancreatic Cancer remains a lethal disease for the majority of patients. New chemotherapy agents such as Folfirinox offer therapeutic potential for patients who present with Borderline Resectable disease (BRPC). However, results to date are inconsistent, with factors such as malnutrition limiting successful drug delivery. We sought to determine the prevalence of sarcopenia in BRPC patients at diagnosis, and to quantify body composition change during chemotherapy. METHODS: The diagnostic/restaging CT scans of BRPC patients were analysed. Body composition was measured at L3 using Tomovision Slice-O-Matic™. Total muscle and adipose tissue mass were estimated using validated regression equations. Sarcopenia was defined as per gender- and body mass index (BMI)-specific lumbar skeletal muscle index (LSMI) and muscle attenuation reference values. RESULTS: Seventy-eight patients received neo-adjuvant chemotherapy, and 67 patients underwent restaging CT, at which point a third were deemed resectable. Half were sarcopenic at diagnosis, and sarcopenia was equally prevalent across all BMI categories.. Skeletal muscle and adipose tissue (intra-muscular, visceral and sub-cutaneous) area decreased during chemotherapy (p < 0.0001). Low muscle attenuation was observed in half of patients at diagnosis, and was associated with increased mortality risk. Loss of lean tissue parameters during chemotherapy was associated with an increased mortality risk; specifically fat-free mass, HR 1.1 (95% CI 1.03-1.17, p = 0.003) and skeletal muscle mass, HR 1.21 (95%CI 1.08-1.35, p = 0.001). CONCLUSIONS: Sarcopenia was prevalent in half of patients at the time of diagnosis with BRPC. Low muscle attenuation at diagnosis, coupled with lean tissue loss during chemotherapy, independently increased mortality risk.

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.

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.

Systematic review and meta-analysis on the effect of obesity on recurrence after laparoscopic anti-reflux surgery.

BACKGROUND & AIMS: Laparoscopic anti-reflux surgery (LARS) aims to provide relief from gastroesophageal reflux disease (GORD). With increase in the prevalence of obesity, there is a concurrent increase in obese patients requiring LARS. In addition to being a more technically difficult procedure, there is conflicting evidence regarding the effectiveness of LARS in obese patients. We performed a systematic review and meta-analysis to compare the outcomes of LARS in obese versus non-obese patients. METHODS: Articles on the effects of obesity on LARS were identified from Ovid Medline, EMBASE and the Cochrane Library databases up to 30th of November 2016. Two independent searches were conducted. Data were extracted independently by two researchers. The primary outcome was recurrence, whilst the secondary outcome was operative time. Pooled data were statistically analysed using forest and funnel plots. RESULTS: Twelve studies (3346 patients) met the inclusion criteria, with 923 patients in the obese group and 2423 patients in the non-obese group. Based on a random effects model, there was a risk ratio of 1.36 (95% CI 1.08-1.72, p = 0.009), if studies reporting recurrence objectively are analysed risk ratio of 1.53 (95% CI 1.01-2.32, p = 0.05) showing 53% increased risk of recurrence for obese patients. Using a random effects model, the difference in operative time was 13.94 min (95% confidence interval (CI) 9.33-18.55, p < 0.0001), showing an increased operative time for obese patients. CONCLUSION: A meta-analysis of 12 studies showed that there was greater recurrence of GORD symptoms and longer operative time relating to LARS in obese patients compared to non-obese patients.

The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI).

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls. METHODS: Thirty-five patients and 31 age-, gender- and smoking status-matched healthy controls were evaluated for SIBO by means of a fasting glucose hydrogen breath test (GHBT). The relationship between SIBO and clinical symptoms in chronic pancreatitis was evaluated. RESULTS: SIBO was present in 15% of chronic pancreatitis patients, while no healthy controls tested positive (P = 0.029). SIBO was more prevalent in those taking pancreatic enzyme replacement therapy (PERT) (P = 0.016), with proton pump inhibitor use (PPI) (P = 0.022) and in those with alcohol aetiology (P = 0.023). Patients with concurrent diabetes were more often SIBO-positive and this was statistically significant (P = 0.009). There were no statistically significant differences in reported symptoms between patients with and without SIBO, with the exception of 'weight loss', with patients reporting weight loss more likely to have SIBO (P = 0.047). CONCLUSION: The prevalence of SIBO in this study was almost 15% and consistent with other studies of SIBO in non-surgical chronic pancreatitis patients. These data support the testing of patients with clinically-relevant PEI unresolved by adequate doses of PERT, particularly in those patients with concurrent diabetes. SIBO can be easily diagnosed therefore allowing more specific and more targeted symptom treatment.

The potential role of gut microbiota in pancreatic disease: A systematic review.

BACKGROUND: Several studies have suggested a link between microbiota imbalance and some gastrointestinal, inflammatory and neoplastic diseases. However, the role in pancreatic diseases remain unclear. To evaluate the available evidence for pancreatic diseases, we undertook a systematic review. METHODS: OVID Medline (1946-2017), EMBASE (1980-2017) and the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2017) were searched for studies on microbiota in pancreatic disease. We also searched the reference lists of retrieved papers, and conference proceedings. We excluded animal studies, reviews, and case reports. RESULTS: A total of 2833 articles were retrieved. After screening and applying the exclusion criteria, 10 studies were included. Three studies showed lower levels of Bifidobacterium or Lactobacillus and higher levels of Enterobacteriaceae in chronic pancreatitis. Two of these studies were uncontrolled, and the third (controlled) study which compared patients with endocrine and exocrine insufficiency, reported that Bacteroidetes levels were lower in those patients without diabetes, while Bifidobacteria levels were higher in those without exocrine insufficiency. Only one study investigated acute pancreatitis, showing higher levels of Enterococcus and lower levels of Bifidobacterium versus healthy participants. There was an overall association between pancreatic cancer and lower levels of Neisseria elongate, Streptococcus mitis and higher levels of Porphyromonas gingivalis and Granulicatella adiacens. CONCLUSIONS: Current evidence suggests a possible link between microbiota imbalance and pancreatic cancer. Regarding acute and chronic pancreatitis, data are scarce, dysbiosis appears to be present in both conditions. However, further investigation is required to confirm these findings and to explore therapeutic possibilities.

Negotiating the complexities of exocrine and endocrine dysfunction in chronic pancreatitis.

Chronic pancreatitis is a chronic inflammatory disease of the pancreas characterised by irreversible morphological change and typically causing pain and/or permanent loss of function. This progressive, irreversible disease results in destruction of healthy pancreatic tissue and the development of fibrous scar tissue. Gradual loss of exocrine and endocrine function follows, along with clinical manifestations such as steatorrhoea, abdominal pain and diabetes. Nutrition in chronic pancreatitis has been described as a problem area and, until recently, there was little research on the topic. It is often asserted that >90 % of the pancreas must be damaged before exocrine insufficiency occurs; however, an exploration of the original studies from the 1970s found that the data do not support this assertion. The management of steatorrhoea with pancreatic enzyme replacement therapy is the mainstay of nutritional management, and early identification and treatment is a key. The presence of steatorrhoea, coupled with poor dietary intake (due to intractable abdominal pain, gastrointestinal side effects and often alcoholism) renders the chronic pancreatitis patients at considerable risk for undernutrition, muscle depletion and fat-soluble vitamin deficiency. Premature osteoporosis/osteopenia afflicts two-thirds of patients as a consequence of poor dietary intake of calcium and vitamin D, low physical activity, low sunlight exposure, heavy smoking, as well as chronic low-grade inflammation. Bone metabolism studies show increased bone formation as well as bone resorption in chronic pancreatitis, indicating that bone turnover is abnormally high. Loss of the pancreatic islet cells occurs later in the disease process as the endocrine cells are diffusely distributed throughout the pancreatic parenchyma. Patients may develop type 3c (pancreatogenic) diabetes, which is complicated by concurrent decreased glucagon secretion, and hence an increased risk of hypoglycaemia. Diabetes control is further complicated by poor diet, malabsorption and (for some) alcoholism, and therefore those with type 3c diabetes have clinical characteristics and therapeutic goals that are different from that of type 1 and type 2 diabetes patients. This review describes emerging research and clinical guidelines for nutrition in chronic pancreatitis.

Hospital discharges and patient activity associated with chronic pancreatitis in Ireland 2009-2013.

OBJECTIVE: To investigate trends in acute public hospital patient discharges in Ireland, to analyse hospital discharge activity for geographical variations, aetiological differences, and to estimate a national prevalence for chronic pancreatitis. METHOD: We performed a nationwide retrospective study of all in-patient discharges from acute public hospitals in Ireland, participating in the Hospital In-Patient Enquiry (HIPE) reporting system. We searched for International Classification of Disease, Tenth Revision, Australian Modification (ICD-10-AM) codes K86.0 alcohol-induced chronic pancreatitis, and K86.1 other chronic pancreatitis, and data were extracted for the years 2009-2013. RESULTS: There were 4098 emergency admissions for any aetiology chronic pancreatitis during the 5 year study period. Total discharges ranged from 753 in 2009 to 999 in 2013. Total patients ranged from 530 in 2009 to 601 in 2013. Prevalence of chronic pancreatitis is estimated at 11.6 per 100,000 to 13.0 per 100,000 over the five years. 'Other aetiology chronic pancreatitis' discharges were almost double that of 'alcohol chronic pancreatitis'. We found notable geographical variation in hospital discharge activity for chronic pancreatitis. CONCLUSIONS: We report a prevalence which is similar to those worldwide studies who adopted a similar methodology utilising exact counts of patients. Our data are an underestimated as they are based on in-patient discharges only, excluding those attending primary care, outpatient or emergency room visits without admission. Despite studying this disease in a population with high per capita alcohol consumption, we report almost twice as many discharges for non-alcohol aetiology chronic pancreatitis.