Multistate Model of the Natural History of Inflammatory Pancreatic Diseases: A Nationwide Population-based Cohort Study.

BACKGROUND & AIMS: Understanding the nature of inflammatory pancreatic diseases is essential for planning health care system requirements and interventions. The aim of this study was to quantify the trajectories of inflammatory pancreatic diseases and their association with pancreatic cancer in a population-based setting. METHODS: National health registries were used to identify all Danish residents (18 years or older) in the period from 2000 through 2018 with incident cases of acute pancreatitis (AP), recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. We used a multistate model to examine transitions from a healthy state to intermediate states of acute pancreatic inflammation (AP and RAP) to chronic states (CP and pancreatic cancer) and, ultimately, death. Results were reported as transition incidence rates per 1000 person-years with 95% CIs. RESULTS: There were 4,663,864 individuals included (mean age, 46 years; 51% were women). During a mean follow-up of 16.8 years, 31,396 individuals were diagnosed with incident AP, 5546 with RAP, 8898 with CP, and 18,182 with pancreatic cancer. The cumulative incidence of pancreatitis (acute and chronic) during the study period was 0.80% (95% CI, 0.79%-0.80%). The transition incidence rates to CP were 12.1 (95% CI, 8.1-18.1) from AP, 46.8 (95% CI, 31.6-69.3) from RAP, and 0.07 (95% CI, 0.04-0.13) from a healthy state. Similar patterns were observed for transitions to pancreatic cancer. Most patients diagnosed with CP (64.2%) and pancreatic cancer (96.4%) transitioned directly from a healthy state. Among patients with pancreatitis, 41.0% (95% CI, 40.5%-41.5%) died during follow-up. CONCLUSIONS: The study findings revealed an increased risk of CP and pancreatic cancer in patients with a history of AP. However, most patients with CP and pancreatic cancer transitioned directly from a healthy state.

Metabolic Sequelae and All-Cause Mortality in Chronic Pancreatitis With and Without Prior Acute Pancreatitis: A Nationwide Population-Based Cohort Study.

INTRODUCTION: The purpose of this study was to investigate the risk of metabolic sequelae and all-cause mortality in a population-based cohort of chronic pancreatitis (CP) patients with and without prior acute pancreatitis (AP). METHODS: We used nationwide health registries to identify all Danish residents (18 years and older) with incident CP from 2000 to 2018. Information on AP/CP diagnoses, metabolic sequelae (post-pancreatitis diabetes mellitus [PPDM], exocrine pancreatic dysfunction, and osteoporosis), and all-cause mortality were obtained from Danish national health registries. CP cases were stratified based on the presence of AP before CP diagnosis. The risk of metabolic sequelae and all-cause mortality was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), calculated using multivariate Cox proportional hazards models. RESULTS: A total of 9,655 patients with CP were included. Among patients with CP, 3,913 (40.5%) had a prior AP diagnosis. Compared with patients without a history of AP, patients with prior AP had a decreased risk of death (HR 0.79, 95% CI 0.74-0.84), which was largely confined to the initial period after CP diagnosis. Patients with prior AP had an increased risk of PPDM (HR 1.53, 95% CI 1.38-1.69), which persisted for up to a decade after CP diagnosis. No overall differences in risk were observed for exocrine pancreatic dysfunction (HR 0.97, 95% CI 0.87-1.07) and osteoporosis (HR 0.87, 95% CI 0.74-1.02). DISCUSSION: This nationwide study revealed that most of the patients with CP have no prior episode(s) of AP, indicating that an attack of AP sensitizing the pancreas is not essential for CP development. CP patients with and without prior AP have different risk profiles of PPDM and all-cause mortality.

No Effect of Methylnaltrexone on Acute Pancreatitis Severity: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia. METHODS: This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers. Patients were randomized to receive 5 days of continuous intravenous methylnaltrexone (0.15 mg/kg/d) or placebo added to the standard of care. The primary end point was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality. RESULTS: In total, 105 patients (54% men) were randomized to methylnaltrexone (n = 51) or placebo (n = 54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference 3.8, 95% confidence interval [CI] -40.1 to 47.6; P = 0.87). At 48 hours, we found no differences between the groups in pain severity (0.0, 95% CI -0.8 to 0.9; P = 0.94), pain interference (-0.3, 95% CI -1.4 to 0.8; P = 0.55), and morphine equivalent doses (6.5 mg, 95% CI -2.1 to 15.2; P = 0.14). Methylnaltrexone also did not affect the risk of severe disease (8%, 95% CI -11 to 28; P = 0.38) and mortality (6%, 95% CI -1 to 12; P = 0.11). The medication was well tolerated. DISCUSSION: Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of AP.

Co-existence of hepatic and pancreatic fibrosis in chronic pancreatitis patients including associated risk factors: a magnetic resonance elastography study.

OBJECTIVES: To investigate the co-existence of hepatic and pancreatic fibrosis using magnetic resonance elastography (MRE) in chronic pancreatitis (CP), including the association between hepatic and pancreatic MRE-derived stiffness and exploration of potential etiological risk factors. MATERIALS AND METHODS: Fifty-four CP patients and 35 healthy controls underwent hepatic and pancreatic MRE with measurements of tissue stiffness. Clinical parameters including stage (probable or definite CP), etiology of CP, the presence of diabetes or exocrine insufficiency, and previous history of common bile duct stenosis were assessed. Uni- and multivariate regression models were used to investigate risk factors associated with hepatic fibrosis/stiffness in CP patients. RESULTS: Fifteen percent of CP patients and none of the controls had abnormal liver stiffness (>2.5 kPa), p = 0.02. 5.6% of CP patients had liver stiffness indicating F1 fibrosis (>2.93 kPa). However, hepatic stiffness was not higher in patients than in healthy controls (2.20 ± 0.41 vs 2.08 ± 0.21 kPa, p = 0.10). In patients, a positive association was seen between hepatic and pancreatic stiffness (r = 0.270, p = 0.048). In the multivariate analysis (adjusted for age, gender and BMI), liver stiffness was significantly associated with alcoholic etiology of CP (p = 0.029). In contrast, stage of CP, history of common bile duct stenosis, and the presence of diabetes or exocrine insufficiency were not associated with liver stiffness (all p > 0.14). CONCLUSIONS: Only a modest co-existence of hepatic and pancreatic fibrosis was observed in CP. However, the positive association between hepatic and pancreatic stiffness indicates some level of common pathophysiology. Especially, alcoholic etiology of CP was related to increased hepatic stiffness.

Intra-pancreatic fat deposition and its relation to obesity: a magnetic resonance imaging study.

OBJECTIVES: Intra-pancreatic fat deposition (IPFD) is suspected to be associated with various medical conditions. This study aimed to assess pancreatic fat content in lean and obese individuals, characterize obese individuals with and without IPFD, and explore the underlying mechanisms. MATERIALS AND METHODS: Sixty-two obese individuals without diabetes and 35 lean controls underwent magnetic resonance imaging (MRI) using proton density fat fraction (PDFF) maps to evaluate pancreatic and hepatic fat content, and visceral adipose tissue (VAT) content. Pancreatic fibrosis was explored by T1 relaxation time and MR elastography (MRE) measurements. Associations between pancreatic fat, measures of obesity and metabolic syndrome were examined using uni- and multivariate regression analyses. RESULTS: Pancreatic PDFF was higher in obese than in lean controls (median 8.0%, interquartile range (6.1;13.3) % vs 2.6(1.7;3.9)%, p < 0.001). Obese individuals with IPFD (PDFF ≥6.2%) had higher waist circumference (114.0 ± 12.5 cm vs 105.2 ± 8.7 cm, p = 0.007) and VAT (224.9(142.1; 316.1) cm2 vs 168.2(103.4; 195.3) cm2, p < 0.001) than those without. In univariate analysis, pancreatic PDFF in obese individuals correlated with BMI (r = 0.27, p = 0.03), waist circumference (r = 0.44, p < 0.001), VAT (r = 0.37, p = 0.004), hepatic PDFF (r = 0.25, p = 0.046) and diastolic blood pressure (r = 0.32, p = 0.01). However, in multivariate analysis, only VAT was associated to pancreatic fat content. MRI measures of pancreatic fibrosis indicated no evident fibrosis in relation to increased pancreatic fat content. CONCLUSIONS: Pancreatic fat content was increased in obese individuals compared with lean controls and predominantly correlated with the amount of visceral adipose tissue. Pancreatic fat content was not clearly linked to measures of pancreatic fibrosis.

EndoFLIP evaluation of the pylorus during minimal invasive Ivor-Levis esophagectomy.

BACKGROUND/AIMS: During esophagectomy for malignancy, the anterior and posterior branches of the vagus nerve are transected in order to achieve surgical radicality. This leads to loss of central nervous system-control of the pylorus which may lead to delayed gastric emptying. We aimed to investigate the feasibility of the EndoFLIP technique for assessment of pyloric biomechanical properties in patients undergoing esophagectomy. METHODS: A feasibility study in six patients undergoing surgery was conducted. EndoFLIP measurements were carried out preoperative (Pre-op), after surgical resection (Post-op) and following prophylactic balloon dilatation of the pylorus (Post-dil). By measuring the cross-sectional area and pressure of the pylorus the pyloric compliance and the incremental pressure-strain elastic modulus (Ep) were calculated. RESULTS: Placing the catheter in the pyloric region was successfully achieved in all six patients. No complications were observed. Resection of the esophagus increased the incremental pyloric elastic modulus (Ep) from 0.59 ± 0.18 kPa to 0.99 ± 0.34 kPa (p = 0.03). After dilatation, the Ep was reduced to 0.53 ± 0.23 kPa (p = 0.04), which was close to Pre-op (p = 0.62). The pyloric compliance showed a similar pattern as that found for Ep. CONCLUSION: The EndoFLIP system holds promise for assessment of biomechanics of the pyloric region in patients undergoing esophagectomy for cancer.

Opium tincture has anti-propulsive effects in patients with chronic diarrhea: a randomized, placebo-controlled, and cross-over trial.

OBJECTIVE: Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. MATERIALS AND METHODS: The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. RESULTS: Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. CONCLUSION: Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found.Trial Registration Number: NCT05690321 (registered 2023-01-10).

Diarrhoea of unknown cause: medical treatment in a stepwise mannerManagement of Idiopathic Diarrhoea Based on Experience of Step-Up Medical Treatment.

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.

Chronic diarrhoea without an established cause is common.There are a small number of clinical trials, often with a limited number of patients or healthy volunteers.Treatment is often carried out on a trial-and-error basis, with considerable variation in the choice of treatment.There is a paucity of guidelines, and there is a gap in knowledge concerning treatment goals, such as the frequency, consistency and form of stool.The stepwise approach to the treatment of chronic idiopathic diarrhoea described in this article is based on clinical knowledge and experience.

Social disparity is associated with an increased risk of acute and chronic pancreatitis.

AIM: To study social disparity in acute pancreatitis (AP) and chronic pancreatitis (CP).We also aimed at exploring whether an interaction exists between alcohol intake and socioeconomic factors. METHODS: Prospective cohort study based on data from 271 696 men and women participating in the Danish National Health Surveys 2010, and 2013. Information on alcohol and smoking parameters, body mass index (BMI), diet, and education, were self-reported and information on family income was obtained from administrative registers. Outcome variables (acute and chronic pancreatitis) were obtained from national health registers. RESULTS: The incidence rate ratio (IRR) of developing AP and CP increased with decreasing family income. Compared to participants in the highest income quintile, participants in the lowest income quintile had 43 (95% CI: 14-80%), 99 (95% CI: 26-214%), and 56% (95% CI: 26-94%) higher incidence rates of AP, CP, and all pancreatitis, respectively. The associations persisted after adjustment for alcohol intake, smoking, BMI, and diet.Likewise, participants with only primary school education had an IRR for an AP of 1.30 (95% CI: 1.06-1.59) compared to those with higher education after adjustment for baseline year, age, and sex. We found no interactions between alcohol intake and income or between alcohol intake and education in relation to neither AP, CP, nor all pancreatitis. CONCLUSION: This large prospective population study showed a significant social disparity in incidence rates of pancreatitis by family income, with higher rates among those with the lowest income and education independent of risk factors such as alcohol intake, smoking, BMI, and diet.

Has the Incidence of Inflammatory Bowel Disease Peaked? Evidence From the Population-Based NorDIBD Cohort 1978-2020.

INTRODUCTION: While the incidence of inflammatory bowel disease (IBD) is rising globally, it has been suggested to stabilize in westernized countries, but this has not yet been shown in exhaustive and large cohorts. We generated an IBD cohort in North Denmark (NorDIBD) of 6,158 patients with IBD diagnosed from 1978 to 2020, based on all recorded and verified IBD diagnoses in the region. While describing the establishment of this cohort, we aimed to present the accurate incidence and prevalence of IBD over 4 decades. METHODS: The NorDIBD cohort covered all pediatric and adult patients with an IBD diagnosis dated between January 1, 1978, and December 31, 2020, and living in North Denmark, hence forming an unselected population-based patient cohort. IBD incidence rates between 1978 and 2020 and IBD point prevalences between 2003 and 2020 were calculated. RESULTS: We observed a 4-fold increase in the incidence of IBD from 11.5 per 100,000 persons (95% confidence interval [CI] 8.4-14.6) in the year 1978 to 51.3/100,000 (95% CI 45.5-57.1) in the year 2014, whereas in 2020, this rate stabilized. The overall prevalence of IBD more than doubled from 2003 to 2020, from 424 (95% CI 407-443) in 2003 to 872 (95% CI 849-896) IBD cases per 100,000 persons in 2020. DISCUSSION: Our population-based NorDIBD cohort suggests stabilizing of the incidence of IBD in Denmark, whereas the prevalence continues to rise. Because the data represent a 10% sample of the entire Danish IBD population, we believe that data can be extrapolated to the IBD population in general and used for healthcare planning.

Risk of pancreatic cancer in people with new-onset diabetes: A Danish nationwide population-based cohort study.

BACKGROUND: New onset diabetes (NOD) in people 50 years or older may indicate underlying pancreatic ductal adenocarcinoma (PDAC). The cumulative incidence of PDAC among people with NOD remains uncertain on a population-based level. METHODS: This was a nationwide population-based retrospective cohort study based on the Danish national health registries. We investigated the 3-year cumulative incidence of PDAC in people 50 years or older with NOD. We further characterised people with pancreatic cancer-related diabetes (PCRD) in relation to demographic and clinical characteristics, including trajectories of routine biochemical parameters, using people with type 2 diabetes (T2D) as a comparator group. RESULTS: During a 21-year observation period, we identified 353,970 people with NOD. Among them, 2105 people were subsequently diagnosed with pancreatic cancer within 3 years (0.59%, 95% CI [0.57-0.62%]). People with PCRD were older than people with T2D at diabetes diagnosis (median age 70.9 vs. 66.0 years (P < 0.001) and had a higher burden of comorbidities (P = 0.007) and more prescriptions of medications used to treat cardiovascular diseases (all P < 0.001). Distinct trajectories of HbA1c and plasma triglycerides were observed in PCRD vs. T2D, with group differences observed for up to three years prior to NOD diagnosis for HbA1c and up to two years for plasma triglyceride levels. CONCLUSIONS: The 3-year cumulative incidence of PDAC is approximately 0.6% among people 50 years or older with NOD in a nationwide population-based setting. Compared to T2D, people with PCRD are characterised by distinct demographic and clinical profiles, including distinctive trajectories of plasma HbA1c and triglyceride levels.

Position statement on the definition, incidence, diagnosis and outcome of acute on chronic pancreatitis.

BACKGROUND: Acute on chronic pancreatitis (ACP) is a relatively common condition, but there are significant gaps in our knowledge on the definition, incidence, diagnosis, treatment and prognosis. METHODS: A systematic review that followed PICO (Population; Intervention; Comparator; Outcome) recommendation for quantitative questions and PICo (Population, Phenomenon of Interest, Context) for qualitative research was done to answer 10 of the most relevant questions about ACP. Quality of evidence was judged by the GRADE criteria (Grades of Recommendation, Assessment, Development and Evaluation). The manuscript was sent for review to 12 international experts from various disciplines and continents using a Delphi process. RESULTS: The quality of evidence, for most statements, was low to very low, which means that the recommendations in general are only conditional. Despite that, it was possible to reach strong levels of agreement by the expert panel for all 10 questions. A new consensus definition of ACP was reached. Although common, the real incidence of ACP is not known, with alcohol as a major risk factor. Although pain dominates, other non-specific symptoms and signs can be present. Serum levels of pancreatic enzymes may be less than 3 times the upper limit of normal and cross-sectional imaging is considered more accurate for the diagnosis in many cases. It appears that it is less severe and with a lower mortality risk than acute pancreatitis. CONCLUSIONS: Although the evidence base is poor, this position statement provides a foundation from which to advance management of ACP.

Prospective evaluation of bowel function and quality of life after colon cancer surgery - is it time for routine screening for late sequelae?

AIM: Bowel dysfunction after colon cancer (CC) surgery is widely neglected in current follow up programmes. This study explored changes in bowel function and quality of life (QoL) from three (3 m) to twelve months (12 m) after surgery in CC patients undergoing right- or left-sided colon resection (RightSCR/LeftSCR) and investigated differences between the two groups 12 m after surgery. METHOD: CC patients undergoing surgical resection in 2018-2020 at five surgical departments were included in this population-based prospective cohort study. Included patients completed electronic surveys consisting of a collection of validated scores 3 m and 12 m after surgery. RESULTS: A total of 708 CC patients (423 RightSCR, 285 LeftSCR) were included. In RightSCR, no improvement was observed from 3 m to 12 m in most scores/items, on the contrary, symptom worsening in flatus- and faecal incontinence and urgency was observed (p < 0.05). Also, the proportion of patients rating their bowel function as very good/good decreased (p < 0.05) in this group. In LeftSCR improvement was found in flatus and faecal incontinence, urgency and night-time defaecation (p < 0.02), while no improvement was observed in the remaining scores/items. At 12 m, higher proportions of RightSCR than LeftSCR reported loose stools, incontinence and urgency (all p < 0.001), whereas LeftSCR more often reported hard stools and flatus incontinence (p < 0.05). Among all CC patients 18.3% reported bowel-related impairment of QoL at 12 m with no differences between the two groups. CONCLUSION: From 3 m to 12 m no significant change was observed in the majority of bowel function and QoL scores/items, however, some symptoms worsened in RightSCR, while a few improved in LeftSCR. Bowel dysfunction and impaired QoL were still common in both groups at 12 m, although the symptom pattern differed between the groups. These findings call for a systematic screening for bowel dysfunction to ensure early treatment of symptoms.

Chronic loose stools following right-sided hemicolectomy for colon cancer and the association with bile acid malabsorption and small intestinal bacterial overgrowth.

AIM: Patients treated with right-sided hemicolectomy for colon cancer may suffer from long-term bowel dysfunction, including loose stools, urgency and faecal incontinence. The underlying causes are poorly understood. The aim of this case-control study was to investigate the aetiology of chronic loose stools among patients with right-sided hemicolectomy curatively operated for cancer. METHOD: Cases with chronic loose stools (Bristol stool type 6-7) after right-sided hemicolectomy were compared with a control group of patients with right-sided hemicolectomy without loose stools. All patients underwent a selenium-75 homocholic acid taurine (SeHCAT) scan to diagnose bile acid malabsorption (BAM) and a glucose breath test to diagnose small intestinal bacterial overgrowth (SIBO). Gastrointestinal transit time (GITT) was assessed with radiopaque markers. In a subgroup of patients, fibroblast growth factor 19 (FGF19) was measured in fasting blood. SIBO was treated with antibiotics and BAM was treated with bile acid sequestrants. RESULTS: We included 45 cases and 19 controls. In the case group, 82% (n = 36) had BAM compared with 37% (n = 7) in the control group, p < 0.001. SIBO was diagnosed in 73% (n = 33) of cases with chronic loose stools and in 74% (n = 14) of controls, p = 0.977. No association between BAM and SIBO was observed. GITT was similar in cases and controls. No difference in median FGF19 was observed between cases and controls (p = 0.894), and no correlation was seen between FGF19 and SeHCAT retention (rs 0.20, p = 0.294). Bowel symptoms among cases were reduced after treatment. CONCLUSION: BAM and SIBO are common in patients having undergone right-sided hemicolectomy for cancer. Chronic loose stools were associated with BAM but not with SIBO.

Alcohol Drinking Patterns and Risk of Developing Acute and Chronic Pancreatitis.

AIM: The aim was to analyze the effects of drinking pattern and type of alcohol on risk of acute and chronic pancreatitis. METHODS: Prospective cohort study based on data from 316,751 men and women participating in the Danish National Health Surveys 2010 and 2013. Self-reported questionnaire-based alcohol parameters and information on pancreatitis was obtained from national health registers. Cox regression models were used adjusting for baseline year, gender, age, smoking, Body Mass Index, diet and education. RESULTS: Development of acute and chronic pancreatitis increased with alcohol intake with a significant increase among abstainers and those drinking >14 drinks per week compared with individuals drinking 1-7 drinks per week. Frequent binge drinking and frequent drinking (every day) was associated with increased development of acute and chronic pancreatitis compared with those drinking 2-4 days per week. Problematic alcohol use according to the CAGE-C questionnaire was associated with increased development of acute and chronic pancreatitis.Intake of more than 14 drinks of spirits per week was associated with increased development of acute and chronic pancreatitis, and more than 14 drinks of beer per week were associated with increased development of chronic pancreatitis, whereas drinking wine was not associated with development of pancreatitis. CONCLUSION: This large prospective population study showed a J-shaped association between alcohol intake and development of pancreatitis. Drinking every day, frequent binge drinking and problematic alcohol use were associated with increased development of pancreatitis and drinking large amounts of beer and spirits might be more harmful than drinking wine.

Quantification of parenchymal fibrosis in chronic pancreatitis: relation to atrophy and pancreatic function.

BACKGROUND: Non-invasive modalities for assessing chronic pancreatitis (CP) are needed in clinical practice. PURPOSE: To investigate the correlation between magnetic resonance elastography (MRE)-derived stiffness and T1 relaxation times (as proxies of fibrosis) and explore their relationships to gland volume and pancreatic functions in patients with CP and healthy controls (HCs). MATERIAL AND METHODS: In 49 patients with CP and 35 HCs, pancreatic stiffness, T1 relaxation times, and gland volume were assessed. Fecal elastase and the presence of diabetes were used to evaluate pancreatic exocrine and endocrine functions. Uni- and multivariable linear regression models were used to analyze correlations between imaging parameters. RESULTS: There was a positive correlation between MRE-derived stiffness and T1 relaxation times in patients with CP (R2 = 0.42; P < 0.001) and HCs (R2 = 0.14; P = 0.028). There was no correlation between MRE-derived stiffness and gland volume in patients (R2 = 0.007; P = 0.065) or HCs (R2 = 0.010; P = 0.57). T1 relaxation time was correlated to gland volume (R2 = 0.19; P = 0.002) in patients with CP but not in the HCs (P = 0.056). Severity of pancreatic functional impairment was reflected by increased fibrosis-related parameters in patients without functional impairment, followed by a further increase in fibrosis-related parameters and reduction in gland volume in patients with pancreatic functional impairments. CONCLUSION: Pancreatic MRE-derived stiffness and T1 relaxation times might reflect early pathophysiological changes in CP. The dynamic correlation with pancreatic function suggests that these parameters may be useful for the non-invasive and early identification of CP.

Development of the Comprehensive Pain Assessment Tool Short Form for Chronic Pancreatitis: Validity and Reliability Testing.

BACKGROUND & AIMS: Pain is the foremost complication to chronic pancreatitis (CP), but no validated questionnaires for assessment exist. The COMPAT questionnaire includes all relevant pain dimensions in CP, but a short form is needed to make it usable in clinical practice. METHODS: The full COMPAT questionnaire was completed by 91 patients and systematically reduced to 6 questions. Pain severity and analgesic use were merged, leaving 5 pain dimensions. The pain dimension ratings were normalized to a 0-100 scale, and the weighted total score was calculated, where 3 dimensions were weighted double. Reliability of the short form was tested in a test-retest study in 76 patients, and concurrent validity tested against the Brief Pain Inventory and Izbicki pain questionnaire. Convergent validity was verified using confirmatory factor analysis, and criterion validity tested against quality-of-life and hospitalization rates. RESULTS: The COMPAT-SF questionnaire consisted of the following pain dimensions: a) pain severity, b) pain pattern, c) factors provoking pain, d) widespread pain, and e) a qualitative pain-describing dimension. Quality of life correlated with the total score and all pain dimensions (P <.05). The total score, pain severity, pain pattern, and factors provoking pain were correlated with hospitalization rates (P <.05). The total score correlated with the Izbicki and Brief Pain Inventory scores (P <.0001). The reliability of the questionnaire in patients in a stable phase was good with an interclass correlation coefficient of 0.89. CONCLUSION: The COMPAT-SF questionnaire includes the most relevant aspects of pain in CP and is a feasible, reliable, and valid pain assessment instrument recommended to be used in future trials.

Gastrointestinal function in diabetes is affected regardless of asymptomatic appearance.

BACKGROUND: Gastrointestinal dysmotility may exist without concomitant symptoms. We hypothesize that asymptomatic individuals with diabetes have altered gastrointestinal function associated with age, cardiac vagal tone and glycaemic control. METHODS: One hundred fifty-four asymptomatic participants (61 with type 1 diabetes (T1D), 70 type 2 diabetes (T2D) and 23 healthy volunteers (HV)) underwent wireless motility capsule investigation. Transit times, motility indices and pH were retrieved. Age, cardiac vagal tone, glucose and haemoglobin A1c levels were collected. RESULTS: In T1D, prolongation of colonic (p = 0.03) and whole-gut transit times (p = 0.04) were shown. Transpyloric pH rise was decreased in T1D (p = 0.001) and T2D (p = 0.007) and was associated with cardiac vagal tone (p = 0.03) or glucose (p = 0.04) and haemoglobin A1c (p = 0.005). Ileocaecal pH fall was decreased in T2D (p < 0.001). CONCLUSIONS: Gastrointestinal function was altered in asymptomatic individuals with diabetes. These findings call for further investigations of gastrointestinal function in order to identify risk factors or even predictors for diabetic enteropathy, particularly when glycaemic control is impaired.

White matter brain changes in chronic pancreatitis: A 7-year longitudinal follow-up study.

BACKGROUND/OBJECTIVES: The progression of cerebral white matter changes over time has not been explored in chronic pancreatitis (CP). We aimed to characterize such alterations in individuals with CP at baseline and after 7-years as compared with controls and to explore associations to risk factors and clinical parameters. METHODS: Diffusion tensor imaging was used to evaluate 20 individuals with CP and 13 healthy controls at baseline and after 7-years (CP: n = 9, controls: n = 11). Tract-based spatial statistics were used to assess whole-brain white matter structure, extract significant fractional anisotropy (FA) clusters between groups, mean FA skeleton, mean FA and mean diffusivity (MD). FA of the extracted significant clusters between groups were used for regression analyses with risk factors and clinical parameters, including duration of CP, smoking, and diabetes. RESULTS: At baseline, widespread reductions in FA were found in CP compared to controls involving corpus callosum, the anterior, posterior thalamic radiation, and superior and posterior corona radiata (cluster volume: 49,431 mm3, all P < 0.05). At baseline, also the mean FA (P = 0.004) and FA skeleton (P = 0.002) were reduced in CP compared to controls. FA of the extracted significant cluster was associated with the daily tobacco use (P = 0.001) and duration of CP (P = 0.010). At follow-up, the whole-brain FA skeleton was reduced by 1.7% for both CP individuals and controls (P = 0.878). CONCLUSION: Individuals with CP had widespread cerebral white matter alterations at baseline that can likely be explained by the CP disease and exposure to toxic substances. Otherwise, further progression resembles that in healthy controls.

Tapentadol and oxycodone reduce cingulate glutamate in healthy volunteers.

Tapentadol and oxycodone are commonly used analgesics. Preclinical studies have shown that oxycodone modulates brain metabolites related to opioid pathways, whereas tapentadol also affects noradrenergic activity. However, knowledge about the function of the medications in the human brain is limited. The aim was to investigate effects of tapentadol and oxycodone on brain glutamate, the most important neurotransmitter in pain processing. Magnetic resonance spectroscopy was obtained in 21 healthy subjects from the anterior cingulate cortex, prefrontal cortex, and insula at baseline and after 14 days of treatment with either 50 mg tapentadol, 10 mg oxycodone (equipotent dose, both extended release) or placebo twice daily in a randomized double-blind cross-over study. Compared to baseline, decreased glutamate/creatine levels were identified in anterior cingulate cortex after tapentadol (1.26 ± 0.14 vs. 1.35 ± 0.18, P = .04) and oxycodone (1.26 ± 0.10 vs. 1.35 ± 0.12, P = .05) treatments, both with 7% reduction. This indicates that both analgesics modulate the glutamatergic system at the supraspinal level in humans.