Diagnosis Of Chronic Pancreatitis Research Articles

Quantitative MRI of chronic pancreatitis: results from a multi-institutional prospective study, magnetic resonance imaging as a non-invasive method for assessment of pancreatic fibrosis (MINIMAP).

PurposeTo determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study.MethodsThis study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n = 50) and CP (n = 51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI).ResultsThere was significantly higher T1 relaxation time; mean 669 ms (± 171) vs. 593 ms (± 82) (p = 0.006), ECV fraction; 40.2% (± 14.7) vs. 30.3% (± 11.9) (p < 0.001), and pancreatic fat signal fraction; 12.2% (± 5.5) vs. 8.2% (± 4.4) (p < 0.001) in the CP group compared to controls. The ADC was similar between groups (p = 0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76).ConclusionQuantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00261-022-03654-7.

Efficacy of shear wave elastography for the diagnosis of chronic pancreatitis.

Shear wave elastography (SWE) is a clinical method used to evaluate liver hardness. In this study, we assessed its applicability in assessing the pancreas and its potential for diagnosing chronic pancreatitis. We performed SWE on 59 patients who underwent abdominal ultrasound, and measured the computed tomography (CT) values of the pancreas. Patients were classified as having a normal pancreas (NP), early chronic pancreatitis (ECP), or chronic pancreatitis (CP). SW elasticity (SWe), SW dispersion (SWd), and CT values between groups were analyzed. SWe significantly differed between the CP and NP/ECP groups (NP vs CP; P=0.001, ECP vs CP; P=0.026,), while SWd showed a significant difference only between the NP and CP group (NP vs CP; P=0.001). The CT values were significantly different between the CP and NP/ECP groups (NP vs CP; P=0.0006, ECP vs CP; P=0.0027). Pancreatic SWE and CT values were helpful in the diagnosis of chronic pancreatitis. SWd may reveal status changes in ECP.

Clinical characteristics of smoking-related chronic pancreatitis.

ObjectiveThe pathogenesis of chronic pancreatitis (CP) is not completely clear. With further studies, smoking is toxic to the pancreas. This study classified smoking-related CP as a new etiology of CP and defined the cutoff of smoking.DesignPatients with CP admitted from January 2000 to December 2013 were included in the study. The characteristics were compared between smoking patients, drinking patients, and a group of patients who never smoke or drink (control group). The cumulative rates of steatorrhea, diabetes mellitus (DM), pancreatic pseudocyst (PPC), pancreatic stone, and biliary stricture after the onset of CP were calculated, respectively.ResultsA total of 1,324 patients were included. Among them, 55 were smoking patients, 80 were drinking patients, and 1,189 were controls. The characteristics of smokers are different from the other two groups, especially in age at the onset and diagnosis of CP, initial manifestation, and type of pain. The development of DM (P = 0.011) and PPC (P = 0.033) was significantly more common and earlier in the smokers than in the other two groups. Steatorrhea also developed significantly more in the smokers than in the controls (P = 0.029). Smokers tend to delay the formation of pancreatic stones and steatorrhea.ConclusionThe clinical characteristics of smoking-related CP is different from CP of other etiologies. A new type of CP, smoking-related CP, was put forward. Smoking-related CP should be separated from idiopathic CP and defined as a new independent subtype of CP different from alcoholic CP or idiopathic CP.

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis.

The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.

Salivary Biomarker Evaluation of Chronic Pancreatitis Patients Reveals Alterations in Human Proteins, Cytokines, Prostaglandin E2 Levels, and Bacterial Diversity.

Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified. Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls. Our results indicate the presence of various differentially expressed proteins, cytokines/chemokines, and a loss of oral bacterial diversity in the saliva of CP patients. The PGE2 levels trend toward elevation in CP patients. Area under the receiver operating characteristic curve models for proteomic, cytokine, and PGE2 assays ranged from 0.59 to 0.90. Collectively, our studies identify a range of putative CP biomarkers and alterations in human saliva requiring further validation. The biomarker discovery approaches we used might lead to identification of biomarkers useful for CP diagnosis and monitoring.

Clinical and translational markers of severity and prognosis in chronic pancreatitis.

The incidence of chronic pancreatitis as a progressive inflammation and fibrosis syndrome is on the rise due to increasing awareness and improved imaging modalities. Numerous classification systems have been suggested in recent years to describe the disease, but only few of them have been used to classify the severity and prognostic significance of the disease. Biomarkers for severity and (early) chronic pancreatitis diagnosis are not yet ready for clinical application. In using the M-ANNHEIM and Chronic Pancreatitis Prognosis Score (COPPS) classification system, the severity assessment and short- and medium-term disease progression is available. A prospectively validated biomarker for early chronic pancreatitis diagnosis is not yet available, metabolome-based approaches seem to have the greatest potential for clinical translation. Currently, due to the lack of universal definition for the early disease stage of chronic pancreatitis, it is difficult to accurately classify these patient cohorts in existing scoring systems. In principle, setting up a suitable scoring system would allow surveillance and establish a therapy approaches flanked by corresponding biomarker panel development. Therapy management of chronic pancreatitis and monitoring by means of scoring systems (such as the COPPS) would make a decisive contribution to improving patient treatment.

Endoscopic ultrasound diagnostic gain over computed tomography and magnetic resonance cholangiopancreatography in defining etiology of idiopathic acute pancreatitis.

BACKGROUNDAbout 10%-30% of acute pancreatitis remain idiopathic (IAP) even after clinical and imaging tests, including abdominal ultrasound (US), contrast-enhanced computed tomography (CECT) and magnetic resonance cholangiopancreatography (MRCP). This is a relevant issue, as up to 20% of patients with IAP have recurrent episodes and 26% of them develop chronic pancreatitis. Few data are available on the role of EUS in clarifying the etiology of IAP after failure of one or more cross-sectional techniques.AIMTo evaluate the diagnostic gain after failure of one or more previous cross-sectional exams.METHODSWe retrospectively collected data about consecutive patients with AP and at least one negative test between US, CECT and MRCP, who underwent linear EUS between January 2017 and December 2020. We investigated the EUS diagnostic yield and the EUS diagnostic gain over different combinations of these cross-sectional imaging techniques for the etiologic diagnosis of AP. Types and frequency of EUS diagnosis were also analyzed, and EUS diagnosis was compared with the clinical parameters. After EUS, patients were followed-up for a median of 31.5 mo to detect cases of pancreatitis recurrence.RESULTSWe enrolled 81 patients (63% males, mean age 61 ± 18, 23% with previous cholecystectomy, 17% with recurrent pancreatitis). Overall EUS diagnostic yield for AP etiological diagnosis was 79% (20% lithiasis, 31% acute on chronic pancreatitis, 14% pancreatic solid or cystic lesions, 5% pancreas divisum, 5% autoimmune pancreatitis, 5% ductal abnormalities), while 21% remained idiopathic. US, CECT and MRCP, taken alone or in combination, led to AP etiological diagnosis in 16 (20%) patients; among the remaining 65 patients, 49 (75%) obtained a diagnosis at EUS, with an overall EUS diagnostic gain of 61%. Sixty-eight patients had negative US; among them, EUS allowed etiological diagnosis in 59 (87%). Sixty-three patients had a negative CECT; among them, 47 (74%) obtained diagnosis with EUS. Twenty-four had a negative MRCP; among them, 20 (83%) had EUS diagnosis. Twenty-one had negative CT + MRCP, of which 17 (81%) had EUS diagnosis, with a EUS diagnostic gain of 63%. Patients with biliary etiology and without previous cholecystectomy had higher median values of alanine aminotransferase (154 vs 25, P = 0.010), aspartate aminotransferase (95 vs 29, P = 0.018), direct bilirubin (1.2 vs 0.6, P = 0.015), gamma-glutamyl transpeptidase (180 vs 48, P = 0.006) and alkaline phosphatase (150 vs 72, P = 0.015) Chronic pancreatitis diagnosis was more frequent in patients with recurrent pancreatitis at baseline (82% vs 21%, P < 0.001). During the follow-up, AP recurred in 3 patients, one of which remained idiopathic.CONCLUSIONEUS is a good test to define AP etiology. It showed a 63% diagnostic gain over CECT + MRCP. In suitable patients, EUS should always be performed in cases of IAP. Further prospective studies are needed.

Pancreatic Elastography Predicts Endoscopic Secretin-Pancreatic Function Test Result in Patients With Early Changes of Chronic Pancreatitis: A Prospective, Cross-Sectional, Observational Study.

The endoscopic pancreatic function test (ePFT) has been proposed for the evaluation of patients with suspected early chronic pancreatitis (CP) in the appropriate clinical context, but the cost and duration of the test limit its clinical applicability. Pancreatic secretion decreases as pancreatic fibrosis develops in CP. Pancreatic fibrosis can be quantified by endoscopic ultrasound-elastography (EUS-E). We aim at evaluating whether EUS-E correlates with and could replace ePFT for the evaluation of patients with suspected CP. A prospective, cross-sectional, and observational study of patients with clinical suspicion of CP and inconclusive EUS findings was conducted. EUS-E and ePFT were performed. Diagnosis of CP was supported if the ePFT result (bicarbonate peak) was abnormally low (&lt;80 mEq/L). Correlation between EUS-E (strain ratio [SR]) and ePFT results was analyzed by linear regression. Diagnostic accuracy of EUS-E for CP was calculated using ePFT as a reference method. Sixty-one patients were included and analyzed. The mean peak bicarbonate concentration at the ePFT was 63.8 ± 23.6 mEq/L, and it was abnormally low in 50 patients (82.0%). The mean SR was 3.85 ± 1.24. Correlation between SR and bicarbonate secretion was highly significant ( r = 0.715, P &lt; 0.0001). Diagnostic accuracy of EUS-E for CP was 93.4%. The degree of pancreatic fibrosis as evaluated by EUS-E correlates significantly with the secretin-stimulated pancreatic secretion of bicarbonate in patients with clinical suspicion of CP and inconclusive EUS findings of the disease. EUS-E could replace ePFT for the evaluation of these patients in clinical practice.

St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis

BackgroundEarly diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP.MethodsData from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13−/− mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model.ResultsThe arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling.ConclusionSt13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

Clinical Profile and Management of Chronic Pancreatitis in Tertiary Care Centre

Background Constant inflammation and irreversible pancreatic tissue destruction are hallmarks of the disease of chronic pancreatitis (CP), which results in the decrease of both exocrine and endocrine function over time. It is a multifactorial disease, with a wide range of symptoms and geographic variation. Aim Aim of this study is to study clinical profile and management of CP with respect to demography, clinical findings, lab parameters, imaging investigations and management modalities. Methods A cross-sectional observational study was conducted which included the patients admitted to the tertiary care center presenting with the clinical diagnosis of CP. The study was conducted over a period of 2-years from November 2019 to October 2021. A total sample size of 71 patients was included. Results In the study, it was observed that the majority of patients were in the age group of 51-60-years (47.89%) followed by 41-50-years (21.12%) mean age ranges from 56.54±12.63-years. The majority of patients were male (76.06%) and females were 23.94%. The distribution of patients according to aetiology showed that the majority of patients had aetiology of alcoholism (43.66%) followed by idiopathic (29.57%) Gall/Biliary stones (21.12%) and post-operative (5.63%). Majority of patients presented with pain in the abdomen (85.92%). The distribution of patients according to ultrasound sonography test (USG) findings showed that majority of patients shows pancreatic calcification (54.93%) followed by pancreatic pseudocyst (32.39%) and gall stones (19.72%). The distribution of patients according to computed tomography (CT) findings showed that majority of patients shows pancreatic calcification (70.42%). In the present study, it was observed that majority of patients were managed conservatively (43.66%) followed by cystogastrostomy (18.31%) and cystojejunostomy (8.45%). Endoscopic retrograde cholangiopancreatography (ERCP) was done among 14 (19.72%) patients. Lateral pancreaticojejunostomy was done in 6 (8.45%) patients and pancreaticoduodenectomy (Classical Whipple’s) was done in 4 patients (5.63%). The distribution of patients according to pain relief by various management showed that majority of getting relief from pain by surgery (69.23%) followed by ERCP (35.71%) and the least by conservative/analgesics (6.45%). Conclusion Chronic pancreatitis is progressive inflammatory disease. Alcoholic pancreatitis being most common etiology. Pain is most common presenting symptom. CT scan abdomen most useful in confirming diagnosis in our set up. Pseudocyst being common complication seen. Surgery gives relief of pain in most of the cases. The key to a better outcome is making the right decisions in terms of diagnosis, patient selection for surgery, and surgical type.

Clinical profile and management of chronic pancreatitis in tertiary care centre

Background: Chronic pancreatitis is a multifactorial disease, with a wide range of symptoms and geographic variation. Aim of this study is to study clinical profile and management of chronic pancreatitis with respect to demography, clinical findings, lab parameters, imaging investigations and management modalities.Methods: A cross sectional observational study was conducted which included the patients admitted in tertiary care centre presenting with clinical diagnosis of chronic pancreatitis. The study was conducted over period of 2 years from November 2019 to October 2021. A total sample size of 71 patients were included.Results: In the study, it was observed that majority of patients in age group of 51-60 years which were male (76.06%). Alcoholism (43.66%) was most common etiology and presented with pain in abdomen (85.92%). In the present study, majority of patients were managed conservatively (43.66%).The distribution of patients according to pain relief by various management showed that majority of get relief of pain by surgery (69.23%).Conclusions: Chronic pancreatitis is progressive inflammatory disease. Alcoholic pancreatitis being most common etiology. Pain is most common presenting symptom. CT-SCAN abdomen most useful in confirming diagnosis in our set up. Pseudocyst being common complication seen. Surgery gives relief of pain in most of the cases.

The Gemelli Ultrasound Chronic Pancreatitis Score: A Non-invasive Tool for the Diagnosis of Chronic Pancreatitis.

A dedicated ultrasound (US) score, the Gemelli Ultrasound Chronic Pancreatitis (USCP) score, could be useful in the follow-up of patients with chronic pancreatitis (CP). However, its role in the diagnosis of CP has not been investigated. We aimed to evaluate the role of the Gemelli USCP score in the diagnosis of CP and the agreement with standard imaging techniques. Ninety-three patients clinically suspected of having CP and referred to the pancreatic outpatient clinic of A. Gemelli Hospital for endoscopic ultrasound (EUS) were prospectively enrolled. All patients underwent pancreatic US to calculate the Gemelli USCP score. A receiver operating characteristic curve analysis was also performed to assess the performance of the US score in CP diagnosis. The Gemelli USCP score was inversely related to the Rosemont score for both total value (p < 0.0001) and each parameter evaluated (p < 0.0001). This score was significantly higher in patients with CP with an excellent area under the receiver operating characteristic curve (0.946) and the optimal cutoff of 5. Moreover, we found a significant correlation between the Gemelli USCP score and laboratory parameters related to pancreatic exocrine insufficiency (p < 0.0001). The development of a dedicated ultrasound score could be useful as a non-invasive tool in the diagnosis of CP.

Deep learning radiomics based on\xa0contrast-enhanced ultrasound images for assisted diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis

BackgroundAccurate and non-invasive diagnosis of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) can avoid unnecessary puncture and surgery. This study aimed to develop a deep learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) images to assist radiologists in identifying PDAC and CP.MethodsPatients with PDAC or CP were retrospectively enrolled from three hospitals. Detailed clinicopathological data were collected for each patient. Diagnoses were confirmed pathologically using biopsy or surgery in all patients. We developed an end-to-end DLR model for diagnosing PDAC and CP using CEUS images. To verify the clinical application value of the DLR model, two rounds of reader studies were performed.ResultsA total of 558 patients with pancreatic lesions were enrolled and were split into the training cohort (n=351), internal validation cohort (n=109), and external validation cohorts 1 (n=50) and 2 (n=48). The DLR model achieved an area under curve (AUC) of 0.986 (95% CI 0.975–0.994), 0.978 (95% CI 0.950–0.996), 0.967 (95% CI 0.917–1.000), and 0.953 (95% CI 0.877–1.000) in the training, internal validation, and external validation cohorts 1 and 2, respectively. The sensitivity and specificity of the DLR model were higher than or comparable to the diagnoses of the five radiologists in the three validation cohorts. With the aid of the DLR model, the diagnostic sensitivity of all radiologists was further improved at the expense of a small or no decrease in specificity in the three validation cohorts.ConclusionsThe findings of this study suggest that our DLR model can be used as an effective tool to assist radiologists in the diagnosis of PDAC and CP.

Chronic pancreatitis for the clinician: complications and special forms of the disease. Interdisciplinary position paper of the Catalan Society of Digestology (SCD) and the Catalan Pancreatic Society (SCPanc).

Chronic pancreatitis tends to develop a number of complications that may constitute the form of presentation of the disease. Some societies have issued guidelines for diagnosis and treatment of chronic pancreatitis complications, but the level of evidence for any topic is usually low and recommendations tend to be weak. We aimed to provide defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The goal was to propose defined terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 14 sections related to complications and special forms of chronic pancreatitis (early chronic, groove and autoimmune pancreatitis) were reviewed by 21 specialists from 6 different fields to generate 32 statements. Featured statements assert common bile duct stenosis does not require invasive treatment (endoscopic or surgical) unless cholestasis, cholangitis, lithiasis or other symptoms develop. Pancreatic duct strictures and calculi should be approached (after ruling out malignancy) if causing pain, pancreatitis, pseudocysts or other complications. Treatment of symptomatic pseudocysts must be individualized, considering associated main duct stenosis, vascular and pericystic complications. Higher risk conditions for pancreatic cancer are advance age, smoking, genetic background, recent diagnosis of chronic pancreatitis or diabetes, and appearance of new symptoms. Groove pancreatitis can initially be treated with conservative measures. Both prednisolone or rituximab can induce remission and maintenance of autoimmune pancreatitis. Internal fistula, vascular complications, bacterial overgrowth, osteoporosis and renal lithiasis require specific therapeutic approaches.

EP261: The spectrum of CFTR and PRSS1 pathogenic variants in chronic pancreatitis

Chronic pancreatitis is defined as persistent inflammation of the pancreas that is ongoing for 6 months or longer. Chronic pancreatitis often develops by early adulthood in affected individuals and can lead to permanent tissue damage and loss of pancreatic function, including both exocrine and endocrine pancreatic insufficiency. Chronic pancreatitis increases the risk for diabetes and pancreatic cancer, more so with smoking and use of alcohol. Variants in several genes have been identified to be causative for, or induce susceptibility to, chronic pancreatitis. Genetic testing for hereditary chronic pancreatitis can aid in differential diagnosis of chronic pancreatitis from other disorders which also present with pancreatitis and may inform treatment strategy. This study reports the spectrum of pathogenic variants in individuals referred for chronic pancreatitis panel testing. This study included 747 individuals who underwent chronic pancreatitis panel testing at a single clinical laboratory (PreventionGenetics) between June 15, 2018 and September 24, 2021. Clinical information was obtained from provider-completed test requisition forms. Next generation sequencing (NGS) with copy number variant (CNV) detection was performed on patient-derived DNA using the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA) and Sanger sequencing as necessary. Testing provided 100% coverage for the coding regions of the CASR, CFTR, CTRC, PRSS1, and SPINK1 genes plus ∼10 bases of non-coding DNA flanking each exon, as well as non-coding regions in which pathogenic variants had been identified by the clinical testing laboratory or reported elsewhere. The test also included sequencing of CFTR regions within intron 11 and intron 21, along with a complete analysis of the compound (TG)n(T)n sequence (5T/TG tract) in intron 8. Variations in the 5T/TG tract have been reported to cause congenital absence of the vas deferens, non-classic cystic fibrosis, and classic cystic fibrosis. At time of testing, the patients ranged in age from 1 week to 87 years, with a median age of 32 years. Of the patients tested, 68% were negative for variants in genes included on the panel that are likely to cause disease while 27% were found to be indeterminate, where variants were identified but the results were not diagnostic. Overall, 5% of patients were positive, with a clear molecular diagnosis identified. Pathogenic and likely pathogenic variants in CFTR and PRSS1 accounted for 90% of positive cases overall, with 42% of positive cases being attributed to CFTR-related pancreatitis (1 homozygous or 2 heterozygous causative variants identified) and 33% of positive cases attributed to PRSS1-related pancreatitis (1 heterozygous causative variant). An additional 15% of positive cases were found to have pathogenic or likely pathogenic variants in both CFTR and PRSS1 (1 heterozygous causative variant in both CFTR and PRSS1). The CFTR c.1210-34TG[12]T[5] variant (more commonly referred to as 5T/12TG) contributed to ∼21% of CFTR-related pancreatitis. Importantly, ∼72% of pathogenic and likely pathogenic variants identified in this patient cohort are approved as therapy responsive variants for FDA approved CFTR modulators. In approximately 40% of patients with PRSS1-related pancreatitis, we detected a ∼600kb copy number gain encompassing the whole PRSS1 gene, compared to an estimated 6% of patients in the literature. These data indicate that variants in CFTR are a common cause of chronic pancreatitis and highlights the clinic utility of including complete analysis of the compound (TG)n(T)n sequence (5T/TG tract) in intron 8 of CFTR in this patient cohort. Additionally, the high frequency of treatment responsive variants suggests that a molecular diagnosis in patients with chronic pancreatitis may alter treatment strategy, particularly in the context of CFTR-related pancreatitis. Furthermore, these data suggest that whole gene deletions/duplications may be more frequent that previously thought in this patient cohort and that complex copy number variants in the PRSS1 gene may escape detection by other NGS testing strategies.

Chronic Pancreatitis Is a Risk Factor for Pancreatic Cancer, and Incidence Increases With Duration of Disease: A Systematic Review and Meta-analysis.

INTRODUCTION:Observational studies have suggested an increased risk of pancreatic ductal adenocarcinoma (PDAC) in patients with acute and chronic pancreatitis. We conducted a systematic review and meta-analysis to evaluate the magnitude of this association and summarize the published epidemiological evidence.METHODS:We searched electronic databases (MEDLINE, Embase, Web of Science, Cochrane, and Scopus) and reference lists until January 18, 2021. Studies reporting quantitative association between pancreatitis and PDAC were included and assessed for eligibility, data abstraction, and risk of bias. Standardized incidence ratios (SIRs) were pooled using the random-effects model.RESULTS:Twenty-five cohort and case-control studies met inclusion criteria. Meta-analysis of 12 chronic pancreatitis (CP) studies demonstrated an increased risk of PDAC in patients with CP (SIR: 22.61, 95% confidence interval [CI]: 14.42–35.44). This elevated risk persisted in subgroup analysis of studies that excluded patients diagnosed with PDAC within 2 years of CP diagnosis (SIR: 21.77, 95% CI: 14.43–32.720). The risk was higher in hereditary pancreatitis (SIR: 63.36, 95% CI: 45.39–88.46). The cumulative incidence rates of PDAC in CP increased with follow-up duration. Limited evidence in acute pancreatitis indicates higher PDAC risk in the subset of patients eventually diagnosed with CP. PDAC seems to be uncommon in patients with autoimmune pancreatitis, with 8 reported cases in 358 patients with autoimmune pancreatitis across 4 studies.DISCUSSION:There is an increased risk of PDAC in patients with CP, and incidence rates increase with CP disease duration. Our results indicate that PDAC surveillance may be considered in individuals with long-standing CP.

Paraduodenal pancreatitis – problem in the groove

Background Paraduodenal pancreatitis (PDP) is a particular form of chronic pancreatitis (CP) occurring in and around the duodenal wall. Despite its low prevalence, this rare condition presents a significant challenge in clinical practice. Methods We retrospectively analysed the electronic medical charts of all patients with a diagnosis of chronic pancreatitis and identified those with PDP, between January 1999 and December 2020. Results There were 35 patients diagnosed with PDP (86% males and 14% females); median age of 56 ± 11 (range 38–80). Alcohol overconsumption was reported in 81% and smoking in 90% of patients. Abdominal pain was the leading symptom (71%), followed by weight loss, nausea and vomiting, jaundice, and diarrhoea. In 23 patients (66%), recurrent acute pancreatitis attacks were noted. Focal duodenal wall thickening was present in 34 patients (97%), cystic lesions in 80%, pancreatic duct dilatation in 54% and common bile duct dilatation in 46%. Endoscopic treatment was performed on nine patients (26%) and five patients (14%) underwent surgery. Complete symptom relief was reported in 12 patients (34%), partial symptom relief in three (9%), there was no improvement in five (14%), data were not available in three (9%) and 12 (34%) patients died before data analysis. Conclusions PDP is a rare form of pancreatitis, most commonly occurring in the 5th or 6th decade of life, with a predominance in males and patients with a history of smoking and high alcohol consumption. Focal thickening and cystic lesions of the duodenal wall are the most common imaging findings, followed by pancreatic duct and common bile duct dilatation. A minority of patients requires surgery.

Спектр короткоцепочечных жирных кислот при хроническом панкреатите

The aim was to evaluate the metabolic activity of the colonic microbiota in patients with chronic pancreatitis (CP) as a marker of changes in the functional state of the pancreas. Material and methods. 40 patients (20 men and 20 women) aged 35 to 74 years (50.6 ± 9.4 years) were examined, 26 patients of which had external secretory pancreatic insufficiency (ESPI), which was confirmed by the data of the elastase test, and 14 patients had no ESPI. The diagnosis of CP was established on the basis of instrumental data. Patients with proven ESPI received enzyme replacement therapy (ERT) in accordance with international and Russian recommendations. The concentration and spectrum of short-chain fatty acids were evaluated by gas-liquid chromatography. The control group consisted of 22 healthy volunteers (13 women and nine men aged 43.4± 6.2 years). Results. As a result of the analysis of the profiles of short-chain fatty acids (SCFAs), a significant change in the content of propionic acid was revealed in patients with CP without GNP when compared with a group of healthy volunteers, no differences were found between the groups of patients with CP. These studies indicate a decrease in the activity of certain types of colon microbiota that produce C3 (propionic acid) in patients with CP without ESPI and, accordingly, who did not receive ERT. This, apparently, is due to the violation of the fermentation of individual substrates entering the lumen of the colon. Conclusion. Indicators of the concentration and spectrum of SCFAs can serve as additional tools for detecting changes in the metabolic activity of the colonic microbiota as a marker of the functional state of the pancreas in CP.

Imaging of Fibrosis in Chronic Pancreatitis.

Chronic pancreatitis (CP) describes long-standing inflammation of the pancreas, which leads to irreversible and progressive inflammation of the pancreas with fibrosis. CP also leads to abdominal pain, malnutrition, and permanent impairment of exocrine/endocrine functions. However, it is difficult to assess CP pathologically, and imaging modalities therefore play an important role in the diagnosis and assessment of CP. There are four modalities typically used to assess CP. Pancreatic duct features are assessed with magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). However, ERCP is a rather invasive diagnostic modality for CP, and can result in adverse events such as post-ERCP pancreatitis. Computed tomography (CT) is often the most appropriate initial imaging modality for patients with suspected CP, and has high diagnostic specificity. However, CT findings typically only appear in advanced stages of CP, and it is difficult to detect early CP. Endoscopic ultrasonography (EUS) provides superior spatial resolution compared with other imaging modalities such as CT and magnetic resonance imaging (MRI), and is considered the most reliable and efficient diagnostic modality for pancreatic diseases. The EUS-based Rosemont classification plays an important role in diagnosing CP in clinical practice. Evaluation of tissue stiffness can be another option to assess the diagnosis and progression of CP, and MRI and EUS can be used to assess CP not only with imaging, but also with elasticity measurement. MR and EUS elastography are expected to provide new alternative diagnostic tools for assessment of fibrosis in CP, which is difficult to evaluate pathologically.

Endoscopic ultrasonography in the diagnosis of pathology of the gastrointestinal tract

Endoscopic ultrasonography is a relatively new endoscopic method of examination to determine the invasion of tumors of the gastrointestinal tract, detection and sizing of pancreatic tumors, diagnosis of chronic pancreatitis, pathology of the biliary tract. The method combines the possibilities of two studies: endoscopic and ultrasound. The study is performed using a video endoscope, at the end of which is a scanning ultrasound sensor. The advantages of endoscopic ultrasound over traditional ultrasound examination through the anterior abdominal wall are that the ultrasound sensor under visual control through the lumen of the digestive tract can be carried out directly to the investigated object. The use of very high frequencies of ultrasound provides high image quality with a resolution of less than 1 mm, inaccessible to other research methods (ultrasound, computer tomography and magnetic resonance imaging, endoscopic cholangiopancreatography).