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

OBJECTIVES: Opioids used to manage severe pain in acute pancreatitis 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 acute pancreatitis and systemic inflammatory response syndrome at four Danish centers. Participants were randomized to receive five days of continuous intravenous methylnaltrexone (0.15mg/kg/day) or placebo added to the standard of care. The primary endpoint 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% males) 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% CI, -40.1 to 47.6]; P=0.87). At 48 hours, we found no differences between 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. CONCLUSIONS: Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of acute pancreatitis.

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.

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.

Optimizing examination time and diagnostic performance of the histamine-induced axon-reflex flare response in diabetes.

INTRODUCTION/AIMS: The axon-reflex flare response is a reliable method for functional assessment of small fibers in diabetic peripheral neuropathy (DPN), but broad adoption is limited by the time requirement. The aims of this study were to (1) assess diagnostic performance and optimize time required for assessing the histamine-induced flare response and (2) associate with established parameters. METHODS: A total of 60 participants with type 1 diabetes with (n = 33) or without (n = 27) DPN participated. The participants underwent quantitative sensory testing (QST), corneal confocal microscopy (CCM), and flare intensity and area size assessments by laser-Doppler imaging (FLPI) following an epidermal skin-prick application of histamine. The flare parameters were evaluated each minute for 15 min, and the diagnostic performance compared to QST and CCM were assessed using area under the curve (AUC). Minimum time-requirements until differentiation and to achieve results comparable with a full examination were assessed. RESULTS: Flare area size had better diagnostic performance compared with CCM (AUC 0.88 vs. 0.77, p < 0.01) and QST (AUC 0.91 vs. 0.81, p = 0.02) than mean flare intensity, and could distinguish people with and without DPN after 4 min compared to after 6 min (both p < 0.01). Flare area size achieved a diagnostic performance comparable to a full examination after 6 and 7 min (CCM and QST respectively, p > 0.05), while mean flare intensity achieved it after 5 and 8 min (CCM and QST respectively, p > 0.05). DISCUSSION: The flare area size can be evaluated 6-7 min after histamine-application, which increases diagnostic performance compared to mean flare intensity.

Feasibility and early clinical impact of precision medicine for late-stage cancer patients in a regional public academic hospital.

AIM: Our goal was to describe a precision medicine program in a regional academic hospital, characterize features of included patients and present early data on clinical impact. MATERIALS AND METHODS: We prospectively included 163 eligible patients with late-stage cancer of any diagnosis from June 2020 to May 2022 in the Proseq Cancer trial. Molecular profiling of new or fresh frozen tumor biopsies was done by WES and RNAseq with parallel sequencing of non-tumoral DNA as individual reference. Cases were presented at a National Molecular Tumor Board (NMTB) for discussion of targeted treatment. Subsequently, patients were followed for at least 7 months. RESULTS: 80% (N = 131) of patients had a successful analysis done, disclosing at least one pathogenic or likely pathogenic variant in 96%. A strongly or potentially druggable variant was found in 19% and 73% of patients, respectively. A germline variant was identified in 2.5%. Median time from trial inclusion to NMTB decision was one month. One third (N = 44) of patients who underwent molecularly profiling were matched with a targeted treatment, however, only 16% were either treated (N = 16) or are waiting for treatment (N = 5), deteriorating performance status being the primary cause of failure. A history of cancer among 1st degree relatives, and a diagnosis of lung or prostate cancer correlated with greater chance of targeted treatment being available. The response rate of targeted treatments was 40%, the clinical benefit rate 53%, and the median time on treatment was 3.8 months. 23% of patients presented at NMTB were recommended clinical trial participation, not dependent on biomarkers. CONCLUSIONS: Precision medicine in end-stage cancer patients is feasible in a regional academic hospital but should continue within the frame of clinical protocols as few patients benefit. Close collaboration with comprehensive cancer centers ensures expert evaluations and equality in access to early clinical trials and modern treatment.

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.

Sex differences in microvascular function across lower leg muscles in humans.

Studies have reported sex-based differences in conduit artery function, however little is known about possible sex-based differences in microvascular function, and possible influence of muscle group. Blood-oxygen-level-dependent (BOLD) MR images acquired during ischemia-reperfusion assess the reactive hyperemic response in the microvasculature of skeletal muscle. We tested the hypothesis that women have greater microvascular reactivity, reflected by faster time-to-peak (TTP) and time-to-half-peak (TTHP) of the BOLD response, across all lower leg muscles. In healthy, young men (n = 18) and women (n = 12), BOLD images of both lower legs were acquired continuously during 30 s of rest, 5 min of cuff occlusion and 2 min of reperfusion, in a 3 T MR scanner. Segmentation of tibialis anterior (TA), soleus (SO), gastrocnemius medial (GM), and the peroneal group (PG) were performed using image registration, and TTP and TTHP of the BOLD response were determined for each muscle. Overall, women had faster TTP (p = 0.001) and TTHP (p = 0.01) than men. Specifically, women had shorter TTP and TTHP in TA (27.5-28.4%), PG (33.9-41.6%), SO (14.7-19.7%) and GM (15.4-18.8%). Overall, TTP and TTHP were shorter in TA compared with PG (25.1-31.1%; p ≤ 0.007), SO (14.3-16%; p ≤ 0.03) and GM (15.6-26%; p ≤ 0.01). Intra class correlations analyses showed large variation in absolute agreement (range: 0.10-0.81) of BOLD parameters between legs (within distinct muscles). Faster TTP and TTHP across all lower leg muscles, in women, provide novel evidence of sex-based differences in microvascular function of young adults matched for age, body mass index, and physical activity level.

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.

Two-Week Cervical Vagus Nerve Stimulation in Chronic Pancreatitis Patients Induces Functional Connectivity Changes of Limbic Structures.

OBJECTIVES: Noninvasive vagus nerve stimulation (nVNS) has not only shown antinociceptive effects, but also demonstrated anti-inflammatory and antidepressant effects. These effects could be beneficial in chronic pancreatitis (CP) patients suffering from chronic abdominal pain, even though the underlying central mechanisms remain unclear. The aim was to investigate the effect of cervical nVNS in patients with painful CP on brain functional connectivity and cerebral metabolites. MATERIALS AND METHODS: In a randomized double-blind, sham-controlled crossover trial, we used resting-state functional magnetic resonance imaging to investigate functional connectivity changes of limbic structures (seed-based analysis) after two weeks cervical nVNS treatment (GammaCore) as compared with two weeks sham treatment. Similarly, magnetic resonance spectroscopy was performed in the anterior cingulate cortex (ACC) with assessment of glutamate/creatine (Glu/cre) and N-acetylaspartate/creatine (NAA/cre). RESULTS: Sixteen CP patients (mean age 56.6 ± 9.4 years) completed the trial. nVNS induced reduced functional connectivity compared to sham treatment between 1) bilateral thalamus and bilateral superior frontal gyrus, 2) ACC and putamen, and 3) posterior cingulate cortex and right thalamus (all p < 0.05). No changes were observed in Glu/cre (p = 0.96) and NAA/cre (p = 0.43) levels between the nVNS and sham treatments. CONCLUSION: In our population of CP patients, cervical nVNS compared with sham treatment induced reduced functional connectivity of limbic structures, as also observed in other patient groups. The findings are relevant, since we have previously demonstrated an effect on pain scores in CP patients for both nVNS and sham treatment. Our results elucidate the effects in the central nervous system following nVNS treatment of CP patients, pointing at potential beneficial effects in this patient group.

Hepatic steatosis in patients with schizophrenia: a clinical cross-sectional study.

OBJECTIVE: With hepatic steatosis (HS) being an established risk factor for CVD in the general population, it may also be a predictor of CVD in patients with schizophrenia. The aim of the present study was to investigate if time since schizophrenia diagnosis, body mass index (BMI), sex, metabolic syndrome, alcohol use, smoking, alanine transaminase (ALT), and body fat percentage (as measured by bioelectrical impedance) were associated with HS, determined by computed tomography (CT), in a population of patients diagnosed with schizophrenia. METHODS: Moderate to severe HS (40 CT Hounsfield units as threshold) was determined utilizing non-contrast enhanced CT. The association between the explanatory variables and outcome of HS was assessed using multivariable logistic regression. RESULTS: In the present study, 145 patients diagnosed with schizophrenia (mean age 42.2 years (SD ± 13.8)) were included, with 88 (60.7%) being male. On average, patients had been diagnosed for 14.8 (SD ± 10.7) years. A total of 31 (21.4%) patients had HS as determined by CT. The presence of HS was associated with ALT (OR 1.06, 95% CI (1.02-1.10) per 1 U/L increase), and the presence of metabolic syndrome (OR 62.89, 95% CI (2.03-1949.55)). The presence of HS was not associated with BMI, body fat percentage or time since diagnosis in the multivariable analysis. CONCLUSION: Higher ALT and the presence of metabolic syndrome were associated with HS in patients with schizophrenia utilizing multivariable analysis. The findings suggest that risk factors for HS are similar in both the general population and in patients with schizophrenia.

Aetiological risk factors are associated with distinct imaging findings in patients with chronic pancreatitis: A study of 959 cases from the Scandinavian Baltic Pancreatic Club (SBPC) imaging database.

OBJECTIVES: The relation between aetiology and structural changes of the pancreas in patients with chronic pancreatitis (CP) is not fully understood. Earlier studies are limited by focusing on selected factors in studies of limited sample size. We aimed to use a large dataset to explore associations between aetiology and pancreatic morphology in CP. METHODS: Subjects with definite or probable CP according to the M-ANNHEIM diagnostic criteria were included in this multicentre cross-sectional observational study and assessed using a standardized and validated CP imaging system. We performed multivariate logistic regression to analyse if aetiological factors adjusted for covariates were independently associated with morphological pancreatic features. RESULTS: We included 959 patients (66% males). Mean (SD) age was 55 (14) years. Pancreatic structural changes were found in 94% of the subjects: 67% had calcifications, 59% main pancreatic duct dilatation, 33% pseudo-cysts and 22% pancreatic atrophy. Alcohol abuse was independently associated with pancreatic calcifications (odds ratio (OR, [95% CI]); 1.61, [1.09, 2.37]) and focal acute pancreatitis (OR; 2.13, [1.27, 3.56]), whereas smoking was independently associated with more severe calcifications (OR; 2.09, [1.34, 3.27]) and involvement of the whole gland (OR; 2.29, [1.61, 3.28]). Disease duration was positively associated with calcifications (OR; (per year) 1.05 [1.02, 1.08]) and pancreatic atrophy (OR; 1.05 [1.02, 1.08]) and negatively associated with focal acute pancreatitis (OR 0.91, [0.87, 0.95] and pseudo cysts (OR; 0.96, [0.93, 0.98]). CONCLUSION: In this large-scale study, etiological risk factors and disease duration in CP were independently associated with specific structural pancreatic imaging changes.

Pancreatic atrophy and exocrine insufficiency associate with the presence of diabetes in chronic pancreatitis patients, but additional mediators are operative.

OBJECTIVES: Diabetes mellitus is a frequent complication of chronic pancreatitis (CP) and has traditionally been considered to develop as a consequence of pancreatic islet cell loss. However, additional mechanisms may be operative including accumulation of pancreatic fat and fibrosis. We used advanced magnetic resonance imaging (MRI) to study pancreatic morphology and exocrine function in a reference population and in CP patients with and without diabetes. METHODS: This was a cross-sectional mono centre study. All subjects underwent advanced MRI including assessment of pancreatic ductal parameters (Cambridge classification and main pancreatic duct diameter), parenchymal parameters (DIXON technique and diffusion weighted imaging as proxies for pancreatic fat content and fibrosis, as well as pancreatic volume segmentation). Pancreatic exocrine function was determined as duodenal secretion following secretin stimulation and by the faecal elastase test. RESULTS: The study included 76 patients with definite CP of whom 23 (30.1%) had diabetes and 23 sex- and age matched healthy volunteers. Compared to their non-diabetic counterparts, diabetic patients were characterised by a low pancreatic volume (20 vs. 36 ml; p = .02) and impaired pancreatic exocrine function (faecal elastase 19 vs. 48 µg/g; p = .008), while no difference between patients with and without diabetes were seen in relation to MRI derived proxies for fibrosis and pancreatic fat accumulation and pancreatic duct parameters. A large proportion of non-diabetic patients (49%) had similar morphological and functional characteristics as patients with diabetes. CONCLUSION: Pancreatic atrophy and exocrine insufficiency are present in most CP patients with diabetes, but additional mediators seem to be operative in post pancreatitis diabetes mellitus.

Coronary artery calcium in patients with schizophrenia.

BACKGROUND: Coronary heart disease (CHD) is a major cause of increased mortality rates in patients with schizophrenia. Moreover, coronary artery calcium (CAC) score is associated with CHD. We hypothesized that patients with schizophrenia have more CAC than the general population and aimed to investigate the CAC score in patients with schizophrenia compared to norms based on the general population. Additionally, this study investigated if age, sex, diabetes, dyslipidemia and smoking were associated with the CAC score. METHODS: In a cross-sectional study, 163 patients with schizophrenia underwent cardiac computed tomography, and the CAC score was measured and compared to norms by classifying the CAC scores in relation to the age- and gender matched norm 50th, 75th and 90th percentiles. Logistic and linear regression were carried out to investigate explanatory variables for the presence and extent of CAC, respectively. RESULTS: A total of 127 (77.9%) patients had a CAC score below or equal to the matched 50th, 20 (12.3%) above the 75th and nine (5.5%) above the 90th percentile. Male sex (P < 0.05), age (P < 0.001) and smoking (P < 0.05) were associated with the presence of CAC while age (P < 0.001) and diabetes (P < 0.01) were associated with the extent of CAC. CONCLUSIONS: The amount of CAC in patients with schizophrenia follows norm percentiles, and variables associated with the CAC score are similar in patients with schizophrenia and the general population. These findings indicate that the CAC score may not be sufficient to detect the risk of CHD in patients with schizophrenia. Future studies should explore other measures of subclinical CHD, including measures of peripheral atherosclerosis or cardiac autonomic neuropathy to improve early detection and intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02885792 , September 1, 2016.

Colorectal dimensions in the general population: impact of age and gender.

PURPOSE: Constipation is among the most common gastrointestinal disorders, although, there is no generally accepted objective diagnostic criteria thereof. It has been proposed that colorectal dimensions assessed with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) may support the diagnosis, but normative data are lacking. The aim of this study was to describe colorectal dimensions in a sample of the general population and to investigate whether the dimensions were under influence by age and gender. METHODS: The maximum diameters and cross-sectional areas of the ascending colon, descending colon and rectum were determined from 119 CT scans of trauma patients (age groups from 15 to 70 years, 84 men and 35 women). A regression model was applied to explore the impact of age and gender on colorectal dimensions. RESULTS: Overall, great variations were found for all colorectal diameters and cross-sectional areas (median diameter (5% percentiles; 95% percentiles): ascending 46 (26; 63) mm; descending 29 (16; 48) mm; rectum 39 (22; 67) mm. Women had larger rectal cross-sectional areas, reflecting more rectal content, compared to men (p = 0.003). Age did not affect colorectal diameters or cross-sectional areas (all p > 0.10). CONCLUSION: Great variations of colorectal dimensions were found. Larger rectal cross-sectional areas in women could likely reflect the fact that women have increased prevalence of constipation. Future studies should take gender into consideration when evaluating colorectal dimensions.

Progression of pancreatic morphology in chronic pancreatitis is not associated with changes in quality of life and pain.

OBJECTIVES: In patients with chronic pancreatitis (CP), the aim was to explore the association between pancreatic morphological progression over four years and corresponding changes in disease characteristics, including quality of life (QOL), pain, and exocrine pancreatic function. METHODS: Twenty-five patients with CP were followed by magnetic resonance imaging (MRI). Data were obtained at baseline and after 4-year follow-up, including clinical information, QOL, and pain as assessed by validated questionnaires. Morphological assessments were derived from the same MRI scanner and included pancreatic gland volume, apparent diffusion coefficient values, fat signal fraction, and main pancreatic duct diameter. RESULTS: After four years, CP patients showed significant progression in morphological parameters of the pancreas, except for the ductal-related changes (p < .13). Hence, patients developed reduced pancreatic volume by 13.5% (p < .001), an increase of fibrosis by 10.8% (p < .001), and an increase of fat infiltration by 7.6% (p < .001). In contrast, the patient-reported outcomes of QOL and pain did not change significantly over four years (all p > .05). Moreover, the progression of morphological imaging findings was not related to changes in QOL, pain severity, and pain interference (all p > .05). There was, however, an association between the 4-year progression of pancreatic atrophy and the decrease in fecal elastase concentration (r = 0.61; p < .001). CONCLUSIONS: Progression of gland morphology in CP did not correlate with changes in the quality of life or pain symptoms. Advanced pancreatic imaging techniques may be a highly sensitive tool for monitoring morphological disease progression, but do not directly reflect patients' disease burden.

Guidelines for the Diagnostic Cross Sectional Imaging and Severity Scoring of Chronic Pancreatitis.

The paper presents the international guidelines for imaging evaluation of chronic pancreatitis. The following consensus was obtained: Computed tomography (CT) is often the most appropriate initial imaging modality for evaluation of patients with suspected chronic pancreatitis (CP) depicting most changes in pancreatic morphology. CT is also indicated to exclude other potential intraabdominal pathologies presenting with symptoms similar to CP. However, CT cannot exclude a diagnosis of CP nor can it be used to exclusively diagnose early or mild disease. Here magnetic resonance imaging (MRI) and MR cholangiopancreatography (MRCP) is superior and is indicated especially in patients where no specific pathological changes are seen on CT. Secretin-stimulated MRCP is more accurate than standard MRCP in the depiction of subtle ductal changes. It should be performed after a negative MRCP, when there is still clinical suspicion of CP. Endoscopic ultrasound (EUS) can also be used to diagnose parenchymal and ductal changes mainly during the early stage of the disease. No validated radiological severity scoring systems for CP are available, although a modified Cambridge Classification has been used for MRCP. There is an unmet need for development of a new and validated radiological CP severity scoring system based on imaging criteria including glandular volume loss, ductal changes, parenchymal calcifications and parenchymal fibrosis based on CT and/or MRI. Secretin-stimulated MRCP in addition, can provide assessment of exocrine function and ductal compliance. An algorithm is presented, where these imaging parameters can be incorporated together with clinical findings in the classification and severity grading of CP.

Quantification of parenchymal calcifications in chronic pancreatitis: relation to atrophy, ductal changes, fibrosis and clinical parameters.

OBJECTIVES: Parenchymal calcifications are considered a hallmark finding of chronic pancreatitis (CP), but little is known about its relation to the clinical presentation and other morphological features such as atrophy, fibrosis and ductal changes. The aim was to quantify the number and maximal size of parenchymal calcifications assessed on computed tomography (CT) and to explore the association with other CT and magnetic resonance imaging (MRI)-based pancreatic features and clinical parameters. METHODS: A well-characterised cohort of 54 CP patients was included. CT measurements included number and size of parenchymal calcifications, gland diameter and ductal diameter. MRI measurements included gland volume, ductal diameter, fibrosis (diffusion) and fatty infiltration (Dixon). Clinical parameters included body mass index (BMI), CP duration and aetiology, M-ANNHEIM clinical stage, tobacco use, alcohol consumption, the presence of diabetes, faecal elastase, clinical pain score and quality of life. RESULTS: There were no correlations between the number and size of parenchymal calcifications and any of the other morphological CT and MRI parameters (all p > .05), except for larger size of calcifications in patients with high number of calcifications (p < .001). The number of parenchymal calcifications was negatively correlated with BMI (r = -0.35, p = .0088). The number and size of parenchymal calcifications did not correlate with any of the other clinical parameters (all p > .2). CONCLUSION: Our findings could indicate the existence of parenchymal calcifications as an independent pathophysiological process involved in the development of CP. Translational impact: Quantifications of calcifications could, in combination with other imaging biomarkers, be a useful imaging marker relevant for characterising CP.

Keep Ventilating the Lungs While the Heart is Still Ejecting on Femoro-femoral Cardiopulmonary Bypass.

Femoro-femoral cardiopulmonary bypass (CPB) followed by deep hypothermic circulatory arrest is one of the modalities used for ascending aortic pseudoaneurysm repair to achieve cardiac unloading and to avoid severe hemorrhage due to the risk of rupture during the sternal entry. However, due to the limited size of the cannulas, it can be challenging to achieve total cardiopulmonary support. Therefore, despite the achievement of total cardiopulmonary support, the heart may still be able to eject antegrade blood flow that meets the retrograde blood flow from the arterial side of the CPB. The point where the blood flow meets in the aorta is called the watershed area. If the antegrade blood flow is large due to a left ventricular ejection, the watershed area will be located in the descending aorta. Therefore, if ventilation is stopped, deoxygenated blood will be ejected to the cerebral circulation. Cerebral near-infrared spectroscopy (NIRS) may be used as a noninvasive and continuous measurement of regional brain oxygen saturation (rSO2). This case demonstrates that cerebral desaturation due to discontinued mechanical ventilation, when the heart was still ejecting during the initial phase of femoro-femoral CPB, immediately was detected by a pronounced drop bilaterally: In the left frontal lobe, rSO2 fell from 56% to 21%, and in the right frontal lobe it fell from 47% to 25%. The authors recommend monitoring cerebral saturation using NIRS in the case of femoro-femoral CPB.