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.

Single- and multiparameter magnetic resonance imaging for diagnosing and severity grading of chronic pancreatitis.

PURPOSE: The study aimed to determine the performance of advanced magnetic resonance imaging (MRI), including a multiparametric MRI-index, for diagnosing and severity grading of chronic pancreatitis (CP) at various functional stages with focus on detection of CP with preserved pancreatic function. METHODS: Fifty-four CP patients and 35 healthy controls underwent MRI including assessment of pancreatic volume, main pancreatic duct (MPD) diameter, T1 relaxation time, magnetic resonance elastography (MRE) derived stiffness, and intravoxel incoherent motion (IVIM) diffusion-weighted imaging. Patients were categorized into three subgroups: Preserved pancreatic function (n = 14), partial pancreatic insufficiency (exocrine insufficiency or diabetes, n = 25), and complete pancreatic insufficiency (exocrine insufficiency and diabetes, n = 15). A multiparametric MRI-index was based on ordinal logistic regression analysis. Diagnostic performances of MRI parameters for diagnosing CP at different functional stages were determined using receiver operating characteristic (ROC) analysis. RESULTS: All MRI parameters differed across CP subgroups and healthy controls (all P < 0.001), except for IVIM. T1 relaxation time (ROC area under the curve (ROC-AUC) 0.82), MRE (ROC-AUC 0.88), and MRI-index (ROC-AUC 0.86) showed the highest performance for detecting patients with preserved pancreatic function (early CP) vs. healthy controls. For detecting preserved pancreatic function vs. partial insufficiency, pancreatic volume, MRI-index, and T1 relaxation time performed best (all ROC-AUC > 0.75), with the MRI-index tending to outperform MRE (ROC-AUC 0.77 vs. 0.63; P = 0.10). CONCLUSION: Quantitative assessments of T1 relaxation time and MRE-derived stiffness seem promising for diagnosing CP at different functional stages and may together with multiparametric MRI-index be used for early identification, staging and monitoring of CP.

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.

Inter- and intra-observer variability of computed tomography-based parenchymal- and ductal diameters in chronic pancreatitis: a multi-observer international study.

PURPOSE: The need for incorporation of quantitative imaging biomarkers of pancreatic parenchymal and ductal structures has been highlighted in recent proposals for new scoring systems in chronic pancreatitis (CP). To quantify inter- and intra-observer variability in CT-based measurements of ductal- and gland diameters in CP patients. MATERIALS AND METHODS: Prospectively acquired pancreatic CT examinations from 50 CP patients were reviewed by 12 radiologists and four pancreatologists from 10 institutions. Assessment entailed measuring maximum diameter in the axial plane of four structures: (1) pancreatic head (PDhead), (2) pancreatic body (PDbody), (3) main pancreatic duct in the pancreatic head (MPDhead), and (4) body (MPDbody). Agreement was assessed by the 95% limits of agreement with the mean (LOAM), representing how much a single measurement for a specific subject may plausibly deviate from the mean of all measurements on the specific subject. Bland-Altman limits of agreement (LoA) were generated for intra-observer pairs. RESULTS: The 16 observers completed 6400 caliper placements comprising a first and second measurement session. The widest inter-observer LOAM was seen with PDhead (± 9.1 mm), followed by PDbody (± 5.1 mm), MPDhead (± 3.2 mm), and MPDbody (± 2.6 mm), whereas the mean intra-observer LoA width was ± 7.3, ± 5.1, ± 3.7, and ± 2.4 mm, respectively. CONCLUSION: Substantial intra- and inter-observer variability was observed in pancreatic two-point measurements. This was especially pronounced for parenchymal and duct diameters of the pancreatic head. These findings challenge the implementation of two-point measurements as the foundation for quantitative imaging scoring systems in CP.

Clinical Course of Medically Managed Patients With Large and Small Duct Chronic Pancreatitis.

INTRODUCTION: Pancreatic duct obstruction is the primary indication for endoscopic and/or surgical therapy in patients with chronic pancreatitis (CP). However, the clinical course of medically managed patients in relation to pancreatic duct obstruction is largely unknown. METHODS: This was a retrospective cohort study of medically managed patients with CP. We classified patients based on pancreatic duct obstruction from a stricture or stone using cross-sectional imaging (i.e., large vs small duct CP). We compared prevalence of diabetes and exocrine insufficiency (EPI) between subgroups at inclusion and investigated risk of new-onset diabetes, EPI, and all-cause mortality over a follow-up period of 5 years. Changes in pancreatic morphology were studied in patients who underwent follow-up imaging. RESULTS: A total of 198 patients (mean age 58 ± 12 years, 70% male, 60% alcoholic etiology, 38% large duct CP) were evaluated. At inclusion, patients with large vs small duct CP had a higher prevalence of both diabetes (43% vs 24%, P = 0.004) and EPI (47% vs 28%, P = 0.007). There was an increased risk of new-onset EPI in patients with large duct CP (hazard ratio 1.72; 95% confidence interval [1.05-2.80], P = 0.031) and higher rates of pancreatic atrophy ( P < 0.001). No differences between groups were observed for new-onset diabetes and all-cause mortality. Conversion from small to large duct CP or vice versa during follow-up was observed in 14% of patients. DISCUSSION: In a medically managed cohort of patients, large duct CP was associated with increased risk of EPI and pancreatic atrophy compared with small duct CP.

Quantification of gastric emptying with magnetic resonance imaging in healthy volunteers: A systematic review.

BACKGROUND: Several magnetic resonance imaging (MRI) protocols have been used to assess gastric emptying (GE) with MRI. This systematic review summarizes the current literature on the topic. The aim was to provide an overview of the available imaging protocols and underline the items that appear most agreed upon and those that deserve further investigation. METHODS: According to PRISMA guidelines, two independent reviewers conducted a systematic literature search with a pre-specified strategy in different databases. Peer-reviewed articles that utilized MRI techniques to assess GE in healthy volunteers (HVs) were included. The quality and the outcomes of the studies were reported and analyzed. KEY RESULTS: The literature search yielded 30 studies (531 HVs, weighted mean age 27.4, weighted mean body mass index 23.0 kg/m2 ), T2-weighted sequences, balanced turbo field echo, and balanced gradient echo were evenly utilized, with volunteers in the supine position (74% of the studies). After overnight fasting, both liquid (56%) and mixed (44%) meals were equally utilized. Segmentation of the volumes was predominantly performed manually (63%) with a reported mean T50 ranging from 7 to 330 min. CONCLUSIONS & INFERENCES: As observed in this systematic review, MRI is a flexible tool for assessing GE. Different protocols were analyzed, showing an equal capacity to assess the GE. However, many items in these protocols still require further investigation to obtain a common standard and increase this assessment quality.

Overlap and cumulative effects of pancreatic duct obstruction, abnormal pain processing and psychological distress on patient-reported outcomes in chronic pancreatitis.

OBJECTIVE: Several factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs). DESIGN: We performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses. RESULTS: Clinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (p<0.001) and pain interference scores (p<0.001), and a reduction in quality of life (p<0.001). All factors had independent and direct effects on PROs, with the strongest effect size observed for psychological distress. CONCLUSION: Pain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management. TRIAL REGISTRATION NUMBER: The study was registered with ClinicalTrials.gov (NCT03434392).

T1 relaxation times and MR elastography-derived stiffness: new potential imaging biomarkers for the assessment of chronic pancreatitis.

PURPOSE: Non-invasive imaging methods to detect morphological changes of the pancreas in patients with mild chronic pancreatitis (CP) are needed. This study aimed to compare magnetic resonance imaging-based parameters, pancreatic volume, T1 mapping, magnetic resonance elastography (MRE), and proton density fat fraction between CP patients and controls, and determine the diagnostic performance for diagnosing different stages of CP. METHODS: Nineteen patients with mild CP (Cambridge grade 2 or less or recurring acute pancreatitis; n = 19), 30 with moderate/severe CP (Cambridge grade 3 and 4), and 35 healthy controls underwent pancreatic magnetic resonance imaging to assess the above mentioned magnetic resonance imaging-based parameters. The diagnostic performance of each parameter for detecting any mild and moderate/severe CP was determined using receiver operating characteristic analysis. RESULTS: Pancreatic volume, T1 relaxation times, MRE-derived stiffness, and proton density fat fraction differed significantly between patients with mild CP, moderate/severe CP, and healthy controls (all p < 0.05). T1 mapping and MRE showed a very high diagnostic performance for distinguishing the mild CP group from the control group (T1 mapping: receiver operating characteristic area under the curve (ROC-AUC): 0.94; sensitivity: 84%; specificity: 91%, MRE: ROC-AUC: 0.93; sensitivity: 89%; specificity: 94%). T1 mapping and MRE also had the highest performance for diagnosing the presence of any CP from the control group (ROC-AUCs of 0.98 and 0.97, respectively). CONCLUSION: Quantitative assessments of T1 relaxation time and MRE-derived stiffness had high performance in detecting mild CP and could probably reflect the early fibrotic changes in CP.

Practical and clinical applications of pancreatic magnetic resonance elastography: a systematic review.

Magnetic resonance elastography (MRE) is a non-invasive technique suitable for assessing mechanical properties of tissues, i.e., stiffness. MRE of the pancreas is relatively new, but recently an increasing number of studies have successfully assessed pancreas diseases with MRE aiming to differentiate healthy from pathological pancreatic tissue with or without fibrosis. This review will systematically describe the practical and clinical applications of pancreatic MRE. We conducted a systematic literature search with a pre-specified search strategy using PubMed and Embase according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. English peer-reviewed articles applying MRE of the pancreas were included. Two independent reviewers assessed the studies. The literature search yielded 14 studies. The pancreatic stiffness for healthy volunteers ranged from 1.11. to 1.21 kPa at a driver frequency of 40 Hz. In benign tumors, the stiffness values were slightly higher or sometimes even lower (range 0.78 to 2.00 kPa), compared to the healthy pancreas parenchyma whereas, in malignant tumors, the stiffness values tended to be higher (1.42 to 6.06 kPa). The pancreatic stiffness was increased in both acute (median: 1.99 kPa) and chronic pancreatitis (> 1.50 kPa). MRE is a promising technique for detecting and quantifying pancreatic stiffness. It is related to fibrosis and seems to be useful in assessing treatment response and clinical follow-up of pancreatic diseases. However, most of the described practical settings were characterized by a lack of uniformity and inconsistency in reporting standards across studies. Harmonization between centers is necessary to achieve more consensus and optimization of pancreatic MRE protocols.

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.