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Pancreatic pseudocyst is a well-known complication of both acute and chronic pancreatitis. Although extension into other anatomical sites is common, extension into the retrofascial space causing an iliopsoas abscess is exceedingly rare. Although its low incidence creates a diagnostic challenge for clinicians, early diagnosis is essential to prevent significant complications and poor patient outcomes. We present a case of iliopsoas abscess with unusual culture fluid growth in the setting of acute on chronic pancreatitis secondary to extension of a pancreatic pseudocyst. We also offer a brief review of the literature and pathophysiology of the condition.

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.

Pseudocysts are localised fluid collections, usually developing as a complication of acute or chronic pancreatitis. Pancreatic ductal or parenchymal calcifications are commonly seen in routine radiological imaging, but calcification of pseudocyst is extremely rare. Calcified pseudocysts have been reported in literature as case reports, but a calcified pseudocyst in the lesser sac, without underlying pancreatic calcification, has not been reported. We report a case of a pancreatic pseudocyst with a calcified wall, requiring surgical excision and histological examination confirming the diagnosis.

The impact of fatty pancreas on pancreatic parenchymal changes is unclear. The aim of this study is to assess parenchymal alterations over time in patients with fatty pancreas (FP).This is a retrospective study (2014-2021) of patients with FP identified on endoscopic ultrasound (EUS). Subjects with follow up imaging studies including Computed Tomography (CT) scan, Magnetic Resonance Imaging (MRI), and EUS at least two years after the initial EUS were included.A total of 39 patients with a mean age of 51.21 ± 12.34 years were included. Mean initial weight was 80.17 ± 17.75 kg. Diabetes, hepatic steatosis, and EPI were present in 15%, 46% and 33% of the patients at baseline, respectively. In 25 patients with available follow up EUS over 2.4 ± 0.76 years, 16% progressed to chronic pancreatitis (CP) and 24% had progressive parenchymal changes without meeting the criteria for CP. One patient progressed from focal to diffuse FP, while one patient had resolution of FP. In multivariate analysis, progressive parenchymal changes on EUS were associated with an increase in weight over time (p-value 0.04), independent of the effects of gender, alcohol, or tobacco.Progressive parenchymal changes were noted in 44%. Our result suggests that FP is a dynamic process with the possibility of progression or regression over time.

Alterations in genes specifically expressed in the pancreas have been associated with chronic pancreatitis (CP). A significant percentage of patients with non-alcoholic CP, however, do not have mutations in known risk genes, suggesting the existence of further susceptibility genes. Four aquaporins are expressed in the exocrine pancreas: AQP1, AQP5, AQP8 and AQP12, the latter being found exclusively in this organ. Therefore, we investigated the two AQP12 genes, AQP12A and AQP12B, in CP patients.We analyzed all exons and adjacent intronic regions of AQP12A and AQP12B in 292 German patients with non-alcoholic CP and 143 control subjects by direct DNA sequencing.In total, we discovered 41 non-synonymous changes, three of which were nonsense variants. Genotype and allele frequencies of these variants did not differ significantly between patients and controls (all p-values0.05). Remarkably, we found a common nonsense variant in AQP12B, p.S152Tfs∗24, with an allele frequency of 15.7% in controls, including 2.8% homozygous subjects. This finding suggests that AQP12B is physiologically dispensable for normal pancreatic function.Our results suggest that genetic alterations in AQP12A and AQP12B do not predispose to the development of non-alcoholic CP.

/Objectives: Sequence variants in several genes have been identified as being associated with an increased inherited risk to develop chronic pancreatitis (CP). In a genetic survey of a CP patient we identified in the PRSS1gene a new c.380C G sequence variation, giving rise to a non-synonymous p.S127C mutation. Functional studies were performed to analyze the associated pathophysiology of the variant.Following generation of an expression vector for the new PRSS1 variant we compared its expression, secretion and catalytic activity with already known PRSS1 risk variants in HEK 293T cells. The intracellular protein accumulation and induction of endoplasmic reticulum (ER)-stress was analyzed.Prediction tool analysis indicated a probably deleterious effect of the p.S127C variant on protein function which was confirmed by detection of a secretion defect in HEK293T cells leading to intracellular protein accumulation. While protein misfolding was associated with reduced trypsin activity, the increased expression of BIP and presence of spliced XBP1 indicated that the p.S127C variant induces ER stress and activates the UPR signaling pathway.The disease mechanism of the PRSS1 p.S127C variant involves defective protein secretion and the induction of ER-stress due to accumulation of presumably misfolded trypsinogen within the ER. The new variant should be considered disease-causing with an incomplete penetrance. Our results confirm that in addition to dysregulated trypsin-activity or reduced fluid secretion, ER-stress induction is an important trigger for acinar cell damage and the development of recurrent or chronic pancreatic inflammation.

It is believed that acute pancreatitis (AP), recurrent AP (RAP) and chronic pancreatitis (CP) represent stages of the same disease spectrum. We aimed to identify risk factors, clinical presentation and outcomes in patients with prior RAP who develop CP.We retrospectively reviewed patients with CP who were seen at our Pancreas Center during 2016-2021. We divided them into two groups: with and without RAP (≥2 episodes of AP). We compared demographics, clinical presentation and resource utilization between the two groups.We identified 440 patients with CP, of which 283 (64%) patients had preceding RAP. These patients were younger (55.6 vs 63.1 years), active smokers (36% vs 20%) and had alcohol-related CP (49% vs 25%) compared to those without RAP and CP (p 0.05). More patients with RAP had chronic abdominal pain (89% vs 67.9%), nausea (43.3% vs 27.1%) and exocrine pancreatic insufficiency (65.8% vs 46.5%) (p 0.05). More patients with RAP used opioids (58.4% vs 32.3%) and gabapentinoids (56.6% vs 34.8%) (p 0.05). They also had more ED visits resulting in an opioid prescription (9.68% vs 2%) and more CP flares requiring hospitalization (3.09 vs 0.87) (p 0.05).Young age, smoking and alcohol use are seen in patients with RAP who progress to CP. These patients are highly symptomatic and use more healthcare resources, suggestive of an overall a more course compared to those patients who develop CP without preceding RAP. Early identification and counselling of these patients may slow down progression to CP.

OBJECTIVE Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. RESEARCH DESIGN AND METHODS This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. RESULTS Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease–related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease–related factors were predominant for diabetes occurring after pancreatitis. CONCLUSIONS Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.

The recently proposed "new mechanistic definition of chronic pancreatitis (CP)" categorized early CP as a reversible condition. However, there is no clear explanation regarding the pathological condition of early CP, the reason for the development of the disease in only a small portion of the patients with risk factors, and the mechanism for transition from a reversible pathological condition to an irreversible one.Based on the available information, a mechanism that could provide answers to the queries associated with CP was proposed.Acinar-ductal coordination is very important for the physiological secretion of pancreatic juice. Inflammation originating from acinar cells undermines the function of proximal ducts and leads to a vicious cycle of sustained inflammation by increasing the viscosity and decreasing the alkalinity of pancreatic juice. Persistent elevation of ductal pressure due to stagnation of pancreatic juice caused by protein plugs, stones, or fibrous scar of ducts converts the reversible pathological condition of early CP to an irreversible one. Diagnostic criteria for early CP proposed by Japanese researchers have enabled to the recognition of patients showing a progression from early to established CP. However, most patients diagnosed with early CP do not experience progression of the disease, suggesting the inadequate specificity of the criteria.The "acinar-ductal hybrid mechanism" may explain the pathological condition and progression of early CP. To diagnose early CP more accurately, it is essential to discover specific biomarkers that can discriminate "early CP" from "acute pancreatitis (AP)/recurrent acute pancreatitis (RAP)" and "established CP." Therapeutic intervention in clinical practices through various new approaches is expected to improve the prognosis of patients with CP.

Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature.We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance.The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-92 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-937 U/mL, 39.7%, 94.1%, and 76.3%, respectively.The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.

Pancreatic intraductal pressure is related to the development of pancreatitis, including post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis. In this study, we investigate pancreatic intraductal pressure in various mouse models of acute and chronic pancreatitis.Post-ERCP pancreatitis was induced by retrograde infusion of normal saline or radiocontrast at the constant rate of 10 or 20 μL/min. Obstructive pancreatitis was induced by ligation of the pancreatic duct followed by a single injection of caerulein and the changes of intraductal pressure were recorded in day 3 for obstructive acute pancreatitis and day 14 for obstructive chronic pancreatitis. Non-obstructive pancreatitis was induced by repetitive intraperitoneal injections of caerulein. The changes of intraductal pressure were recorded right after the last caerulein injection for non-obstructive acute pancreatitis and after the completion of 4-week caerulein injections for non-obstructive chronic pancreatitis.Elevated pancreatic intraductal pressure was observed in both normal saline and radiocontrast infusion groups and was furtherly indicated that was positively correlated with the viscosity of solution but not genders. In the models of obstructive pancreatitis, a rise in intraductal pressure was observed in both acute and chronic pancreatitis; whereas in the models of non-obstructive pancreatitis, a rise in intraductal pressure was only observed in chronic, but not acute pancreatitis.During ERCP, the elevations in pancreatic intraductal pressure are induced by increasing rate or viscous solution of infusion. During different forms of experimental acute and chronic pancreatitis, obstructive or non-obstructive etiologies of pancreatitis also induces the elevations in pancreatic intraductal pressure.

This review aims to discuss recent developments in the nutritional management in chronic pancreatitis.Nutritional assessment should be comprehensive and include dietary history, anthropometry, and biochemical nutritional parameters. Micronutrients should be evaluated at least yearly and dual-energy X-ray absorptiometry (DEXA) at every 2-yearly intervals. Studies on pancreatic enzyme replacement therapy (PERT) have primarily evaluated coefficient of fat excretion (CFA), coefficient of nitrogen excretion (CNA), and stool weight. Two RCTs, in which patients were treated with PERT for 7 days in a blinded manner and subsequently extended for 6-12 months in an open-label manner, showed improvement in nutritional parameters. However, two subsequent RCTs failed to show any benefit, and the most recent observational study demonstrated persistence of malnutrition even after PERT. The reason for the latter findings were nonadherence to PERT and poor oral intake of calories. Therefore, it is essential to educate the patients on adherence, counsel on taking high-protein, high-calorie diet, and supplement nutrients in those with inadequate oral intake. Other associated manifestations, such as diabetes and related complications, and anxiety/depression could also contribute to malnutrition directly or indirectly, and should, therefore, be adequately managed.Nutritional assessment should be performed meticulously. Nutritional therapy should not be restricted to only PERT and nutritional supplementation, but should also include dietary counselling and disease related education.

Genetic alterations in digestive enzymes have been associated with chronic pancreatitis (CP). Recently, chymotrypsin like elastase 3B (CELA3B) emerged as a novel risk gene. Thus, we evaluated CELA3B in two European cohorts with CP.We analyzed all 8 CELA3B exons in 550 German non-alcoholic CP (NACP) patients and in 241 German controls by targeted DNA sequencing. In addition, we analyzed exons 6 and 7 by Sanger sequencing and the c.129+1GA variant by melting curve analysis in 1078 further German controls. As replication cohort, we investigated up to 243 non-German European NACP patients and up to 1665 controls originating from Poland, Hungary, and Sweden. We assessed the cellular secretion and the elastase activity of recombinant CELA3B variants.In the German discovery cohort, we detected a splice-site variant in intron 2, c.129+1GA, in 9/550 (1.64%) CP patients and in 5/1319 (0.38%) controls (P=0.007, OR=4.4, 95% CI=1.5-13.0). In the European replication cohort, this variant was also enriched in patients (9/178 [5.06%]) versus controls (13/1247 [1.04%]) (P=0.001, OR=5.1, 95% CI=2.1-12.0). We did not find the two previously reported codon 90 variants, p.R90C and p.R90L.Our data indicate that CELA3B is a susceptibility gene for CP. In contrast to previous reports suggesting that increased CELA3B activity is associated with CP risk, the splice-site variant identified here is predicted to cause diminished CELA3B expression. How reduced CELA3B function predisposes to pancreatitis remains to be elucidated.

Background & Aims Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP. Methods We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy. Results The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs 26.4%; P = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [CI], 1.15–1.45), female sex (OR, 3.08; 95% CI, 1.75–5.43), white race (OR, 2.68; 95% CI, 1.20–6.01), and underweight body mass index category (OR, 7.40; 95% CI, 1.56–34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and other patient and disease-related features of CP. Conclusion In the largest study of patients with CP who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP. ClinicalTrials.gov number, NCT03099850.

Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials.

Endoscopic stone removal and stenting of pancreatic strictures are the initial treatment for treating chronic pancreatitis-related pain. Surgery is considered when endoscopic interventions fail to improve symptoms. In this meta-analysis, we have compared early surgery versus endoscopic interventions.The study was performed as per the PRISMA statement. The literature search was conducted on online databases to identify studies that compared endoscopy and surgery for the management of chronic pancreatitis symptoms. Primary outcomes of interest were pain relief, complications, and exocrine/endocrine insufficiency. Secondary outcomes were mean length of stay and mean number of procedures. Pooled odds ratio (OR) was calculated using random-effects model with 95% confidence interval (CI).Of a total of 9880 articles that were screened, three randomized controlled trials and two retrospective studies with 602 patients (71.4% males) were found to be eligible. Endoscopic interventions were performed in 317 patients and 285 patients underwent early surgery. Early surgery provided significantly better pain relief compared to endoscopy (OR 0.46; 95%CI 0.27-0.80; p = 0.01; ICompared to endoscopy, early surgery appears to be better in controlling chronic pancreatitis-related pain, with no significant difference in procedure-related complications. However, larger randomized controlled trials are needed to ascertain their efficacy.

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

Pancreatic ductal adenocarcinoma (PDAC) is one of the highest-grade malignancies in the world. More effective biomarkers and treatment plans are necessary to improve the diagnosis rate and clinical outcome. The oncogenesis of PDAC is influenced by several factors, including chronic pancreatitis (CP). Keratin 8 (KRT8) is an important member of the keratin protein family and plays a role in regulating the cellular response to stress stimuli and mediating inflammatory reactions. However, the role of KRT8 in pancreatitis and PDAC is still poorly understood. Here we assessed the differentially expressed genes (DEGs) by bioinformatic methods with expression profiles available online for a caerulein-induced mouse model and human PDAC tissue. The prognostic value was evaluated by Kaplan–Meier analysis and Cox regression analysis. The diagnostic value was evaluated by Receiver Operating Characteristic analysis (ROC). The function of the genes was predicted by protein-protein interaction analysis, correlation analysis, and GO analysis. The conclusion was further validated in rat pancreatitis model, human tissue, and PDAC cell lines, including immunohistochemical staining (IHC), CCK-8 assay, wound healing assay, and flow cytometry. KRT8 was found to be upregulated in murine pancreatitis tissue, human CP tissue, and human PDAC tissue. High expression of KRT8 had a negative impact on the prognosis of PDAC patients. KRT8 was predicted to be involved in the regulation of the migration and viability of PDAC cells, which was validated in PDAC cell lines. Knockdown of KRT8 impaired the migration and proliferation and induced apoptosis in PDAC cell lines. In conclusion, keratin 8 is an inflammation-induced molecule and could serve as a diagnostic and prognostic marker for PDAC patients. More studies are needed for further validation from the perspective of precision and individualized medicine.

Endoscopic ultrasound (EUS) is an invaluable tool for assessing various GI diseases. However, using just the conventional B-mode EUS imaging may not be sufficient to accurately delineate the lesion's character. Using the principle of stress-induced tissue strain, EUS elastography (EUS-E) can help in the real-time sonographic assessment of the level of tissue stiffness or hardness of any organ of interest during a routine EUS procedure. Thus, EUS-E can better characterize the lesion's nature and highlight the more suspicious areas within an individual lesion. The most commonly studied lesions with EUS-E are the pancreatic lesions, namely, chronic pancreatitis, pancreatic cancer, and lymph nodes. However, EUS-E is gradually expanding its use for lesion characterization of the liver, bile duct, adrenals, gastrointestinal tract, and even therapy response. Moreover, the use of EUS-E along with other image enhancement techniques such as harmonic EUS and contrast-enhanced EUS can improve the accuracy of the diagnosis. However, several technical aspects need to be standardized before EUS-E can be truly used as a tool for "virtual biopsy". This review focuses on the various technical aspects of the use of EUS-E, it is established and expanding indications and an extensive outline of the various studies on EUS-E. We also discuss the current pitfalls and future trends in EUS-E.

Thrombotic complications after total pancreatectomy with islet autotransplantation (TPIAT) are common. However, the systemic changes to coagulation in the perioperative period have not been well studied. Our objective was to evaluate the derangements in coagulation in the perioperative period for this procedure.This was a prospective observational study of patients undergoing elective TPIAT for chronic pancreatitis. Multiple methods of evaluating coagulation, including 2 viscoelastic assays and standard laboratory assays were obtained at defined intraoperative and postoperative intervals.Fifteen patients were enrolled. Laboratory values demonstrated initial intraoperative hypercoagulability before significant systemic anticoagulation after islet infusion with heparin. Hypercoagulability is again seen at postoperative days 3 and 7. Subgroup analysis did not identify any major coagulation parameters associated with portal vein thrombosis formation.Apart from the immediate period after islet cell and heparin infusion, patients undergoing TPIAT are generally hypercoagulable leading to a high rate of thrombotic complications. Portal vein thrombosis development had minimal association with systemic derangements in coagulation as it is likely driven by localized inflammation at the time of islet cell infusion. This study may provide the groundwork for future studies to identify improvements in thrombotic complications.

BACKGROUND & AIMS: Mitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production. METHODS: Two models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histological and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in two distinct human pancreatitis cohorts. RESULTS: Blocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss-of-ERRγ in primary acini abrogates mRNA expression and protein levels of mitochondrial oxidative phosphorylation (OXPHOS) complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, ER stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared to normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants (SNVs) for ERRγ that associated with chronic pancreatitis. CONCLUSIONS: Collectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.

Chronic pancreatitis (CP) is characterized by abdominal pain, recurrent hospitalizations, frequent exposure to antibiotics, nutritional deficiencies, and chronic opioid use. Data describing the gut microbial community structure of patients with CP is limited. We aimed to compare gut microbiota of a group of patients with severe CP being considered for total pancreatectomy with islet autotransplantation (TPIAT) with those of healthy controls and to associate these differences with severity of clinical symptoms.We collected stool from healthy donors (n = 14) and patients with CP (n = 20) undergoing workup for TPIAT, in addition to clinical metadata and a validated abdominal symptoms severity survey.Patients with CP had significantly lower alpha diversity than healthy controls ( Plt; 0.001). There was a significantly increased mean relative abundance of Faecalibacterium in healthy controls compared with patients with CP ( P = 0.02). Among participants with CP, those with lower alpha diversity reported worse functional abdominal symptoms ( P = 0.006).These findings indicate that changes in gut microbial community structure may contribute to gastrointestinal symptoms and provide basis for future studies on whether enrichment of healthy commensal bacteria such as Faecalibacterium could provide clinically meaningful improvements in outcomes for CP patients undergoing TPIAT.

To determine if islet autotransplantation (IAT) independently improves the quality of life (QoL) in patients after total pancreatectomy and islet autotransplantation (TP-IAT).TP-IAT is increasingly being used for intractable chronic pancreatitis. However, the impact of IAT on long-term islet function and QoL is unclear.TP-IAT patients at our center1 year after TP-IAT with ≥1 Short Form-36 QoL measure were included. Patients were classified as insulin-independent or insulin-dependent, and as having islet graft function or failure by C-peptide. The associations of insulin use and islet graft function with QoL measures were analyzed by using a linear mixed model, accounting for time since transplant and within-person correlation.Among 817 islet autograft recipients, 564 patients [median (interquartile range) age: 34 (20, 45) years, 71% female] and 2161 total QoL surveys were included. QoL data were available for5 years after TP-IAT for 42.7% and for10 years for 17.3%. Insulin-independent patients exhibited higher QoL in 7 of 8 subscale domains and for Physical Component Summary and Mental Component Summary scores ( P0.05 for all). Physical Component Summary was 2.91 (SE=0.57) higher in insulin-independent patients ( P0.001). No differences in QoL were observed between those with and without graft function, but islet graft failure was rare (15% of patients). However, glycosylated hemoglobin was much higher with islet graft failure.QoL is significantly improved when insulin independence is present, and glycosylated hemoglobin is lower with a functioning islet graft. These data support offering IAT, rather than just performing total pancreatectomy and treating with exogenous insulin.

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, Plt; 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.

Both environmental factors, such as alcohol consumption and smoking, and genetic factors are strongly associated with the risk of developing chronic pancreatitis (CP). However, comprehensive understanding of their impacts on the progression of CP remains elusive.A prospective cohort study was performed on a large cohort of CP patients with known genetic backgrounds. The cumulative incidence of pancreatic insufficiency after the onset of CP was analyzed using Kaplan-Meier survival curves. Multivariate Cox proportional hazards regression analysis also was performed.A total of 798 patients were enrolled in the study and followed up for 10.5 years. Rare pathogenic genotypes in the SPINK1, PRSS1, CTRC, or CFTR genes were identified in 410 (51.4%) patients. The development of pancreatic insufficiency was significantly earlier in patients with a history of smoking and/or alcohol consumption in both the positive (P.001) and negative (P = .001) gene mutation groups. However, the development of pancreatic insufficiency did not differ significantly between patients with and without gene mutations despite alcohol and/or smoking status, with P values of .064 and .115, respectively. Multivariate Cox regression analysis showed that age at onset of CP (hazard ratio, [HR], 1.02; P.001) and alcohol consumption (HR, 1.86; P.001) were independent risk factors for the development of diabetes, while male sex (HR, 1.84; P = .022) and smoking (HR, 1.56; P = .028) were predictors of steatorrhea.Although rare pathogenic mutations in the 4 major susceptibility genes for CP were not correlated significantly with the development of pancreatic insufficiency, environmental factors (either alcohol consumption or smoking) significantly accelerated disease progression (ClinicalTrials.gov: NCT04574297).

OBJECTIVE: Non-alcoholic chronic pancreatitis (NACP) frequently develops in the setting of genetic susceptibility associated with alterations in genes that are highly expressed in the pancreas. However, the genetic basis of NACP remains unresolved in a significant number of patients warranting a search for further risk genes. DESIGN: We analyzed CUZD1, which encodes the CUB and zona pellucida-like domains 1 protein that is found in high levels in pancreatic acinar cells. We sequenced the coding region in 1,163 European patients and 2,018 European controls. In addition, we analyzed 297 patients and 1,070 controls from Japan. We analyzed secretion of wild-type and mutant CUZD1 from transfected cells using Western blotting. RESULTS: In the European cohort, we detected 30 non-synonymous variants. Using different prediction tools (SIFT, CADD, PROVEAN, PredictSNP) or the combination of these tools, we found accumulation of predicted deleterious variants in patients (p-value range 0.002–0.013; OR range 3.1–5.2). No association was found in the Japanese cohort, in which 13 non-synonymous variants were detected. Functional studies revealed >50% reduced secretion of 7 variants, however, these variants were not significantly enriched in European CP patients. CONCLUSION: Our data indicate that CUZD1 might be a novel susceptibility gene for chronic pancreatitis. How these variants predispose to pancreatitis remains to be elucidated.

Chronic pancreatitis (CP) is an irreversible fibro-inflammatory disease of the pancreas with no current targeted therapy. Pirfenidone, an anti-fibrotic and anti-inflammatory drug, is FDA approved for treatment of Idiopathic Pulmonary Fibrosis (IPF). Its efficacy in ameliorating CP has never been evaluated before. We recently reported that pirfenidone improves acute pancreatitis in mouse models. The aim of the current study was to evaluate the therapeutic efficacy of pirfenidone in mouse models of CP. We used caerulein and L-arginine models of CP and administered pirfenidone with ongoing injury, or in well-established disease. We evaluated for fibrosis by Sirius-red staining for collagen, immunohistochemistry, western blotting, and qPCR for fibrosis markers to show the salutary effects of pirfenidone in CP. Our results suggest that treatment with pirfenidone ameliorated CP related changes in the pancreas (i.e., atrophy, acinar cell loss, fibrosis, and inflammation) not only when administered with ongoing injury, but also in well-established models of caerulein as well as L-arginine induced CP. It reduces the pro-fibrotic phenotype of macrophages (in-vivo and in-vitro), reduces macrophage infiltration into the pancreas and alters the intra-pancreatic cytokine milieu preceding changes in histology. The therapeutic effect of pirfenidone is abrogated in absence of macrophages. Furthermore, it reduces collagen secretion, cytokine levels and fibrosis markers in pancreatic stellate cells in-vitro. As it is FDA approved, our findings in mouse models simulating clinical presentation of patients to the clinic, can be used as the basis of a clinical trial evaluating the efficacy of this drug as a therapeutic agent for CP.

Chronic pancreatitis results in permanent parenchymal destruction of the pancreas gland leading to anatomical and physiological consequences for patients. Surgical management varies, and some patients require total pancreatectomy with autologous islet cell transplantation (TPIAT). Patients undergoing TPIAT require complex and diligent management after surgery. This encompasses the management of glucose control (endocrine function of the pancreas) and supplementing loss of exocrine function of the pancreas with digestive enzymes. Other areas of management include optimizing pain relief while reducing narcotic usage, providing antimicrobial prophylaxis, and reducing loss of islet cells by improving its integrity through anticoagulation and use of anti-inflammatory agents. Each aspect of care is unique to this population. However, comprehensive reviews on its pharmacological management are scarce. This review will discuss the available literature to date surrounding all aspects of pharmacological management of patients undergoing TPIAT.

OBJECTIVES: Abdominal pain, emergency department visits and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). However, data on health-related quality of life (HRQOL) in this population remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL. METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment. RESULTS: The sample included 368 children (54.3% females, mean age = 12.7 years, SD = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B =−10.28, p < .001), episodic and constant abdominal pain (B =−4.66, p =.03; B =−13.25, p

The selection of surgery between parenchymal preserving (PPS) and total pancreatectomy (TP) with/without islet cell autotransplantation (IAT) for chronic pancreatitis (CP) patients varies based on multiple factors with a scarcity in literature addressing both at the same time. The aim of this manuscript is to present an algorithm for the surgery selection based on dominant area of disease, ductal dilatation, and glycemic control and compare outcomes.From 2017 to 2021, CP patients offered surgery at a single institution were retrospectively evaluated.51 patients underwent surgery (20 [39.2%] TPIAT, 4 [7.8%] TP, and 27 [52.9%] PPS - 9 Whipple procedures, 15 distal pancreatectomies, and 3 duct drainage procedures). No significant difference was observed in baseline characteristics or perioperative outcomes except median length of stay (8 days [IQR 6-10] vs. 13 days [IQR 9-15.5], p 0.001), attributed to insulin requirement and education for TPIAT group. No differences in postoperative complications, such as clinically significant leak and intrabdominal fluid collection (3 [11.1%] vs 2 [10%], p = 1.0), hemorrhage (0 vs. 2 [10.0%], p = 0.2), delayed feeding (1 [3.7%] vs. 5 [25.0%], p = 0.07), or wound infection (4 [14.8%] vs. 0, p = 0.1) between PPS and TPIAT groups, respectively, were observed nor requirement of long-acting insulin at discharge (2 [15.4%] vs. 7 [43.8%], p = 0.1) for pre-operatively non-diabetic patients. No significant difference in weaning off narcotics and no mortality observed.The most appropriate selection of surgery based on the algorithm yields good and comparable outcomes.

Thoracopancreatic fistulae are a rare complication of chronic pancreatitis. The aim of the present study is to evaluate potential risk factors for endoscopic treatment failure and explore the safety of surgery when utilized either upfront or as a "bail-out" procedure after failed endoscopic treatment.A comprehensive literature search was conducted on the MedLine, Scopus, Embase, and Web of Knowledge databases for cases of thoracopancreatic fistulae. Data regarding patient demographics, fistula anatomy, and treatment interventions performed were extracted for further analysis.The study pool consisted of 75 case reports and 19 case series published between the years 1972 and 2020. Duct disruption in the pancreatic body was most commonly encountered (41.1%), and a left pleural effusion was the most common manifestation (46%). Endoscopic treatment was attempted for 104 patients with an overall success rate of 42.3% (n = 44). Predictive factors for eventual success of endoscopic treatment were the ability of endoscopic retrograde cholangiopancreatography to diagnose the thoracopancreatic leak (odds ratio 9.76, 95% confidence interval 2.71-35.09, P.001), the use of pancreatic duct stents (odds ratio 22.1, 95% confidence interval 7.92-61.61, P.001), and the use of sphincterotomy (odds ratio 7.96, 95% confidence interval 2.1-30.1, P.001). Conversely, the presence of pancreatic duct calculi was associated with endoscopic treatment failure (odds ratio 0.34, 95% confidence interval 0.12-0.94, P = .03). Pooled results suggest that surgical outcomes were comparable between the primary and salvage surgery groups.A step-up approach from endoscopic management to salvage surgery may be effectively employed in cases of thoracopancreatic fistulae refractory to endoscopic treatment.

Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP).ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed.There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes.We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI.

Malnutrition in chronic pancreatitis (CP) has prognostic value and there is limited data on the prevalence, predictors of malnutrition in CP and its effect on Quality of life (QoL).A retrospective study was conducted in patients with CP to assess the prevalence of malnutrition as per the Global Leadership Initiative on Malnutrition (GLIM) criteria. Multivariable-adjusted regression was used to identify independent predictors of both malnutrition and global QoL.A total of 297 patients were included and the most common etiology of CP was idiopathic (75%) and alcohol (25%). The prevalence of malnutrition was 46.4% as per GLIM criteria. On univariate analysis, the risk of malnutrition was significantly higher in alcoholic etiology (p = 0.001), current alcohol consumption (p = 0.001), smokers (p 0.001), those having higher cumulative days of pain in last 6 months (p 0.001) and lower daily calorie intake (p = 0.019). On multivariate analysis, malnutrition was independently associated with current alcohol consumption (Odds ratio: 3.22, p = 0.017), current smokers (OR: 2.23, p = 0.042) and those having higher cumulative days of abdominal pain (OR: 1.01, p 0.001), while higher daily calorie intake (per 100 kcal) (OR:0.94, p = 0.023) has reduced risk of malnutrition. Malnutrition (p = 0.015) and higher cumulative days of abdominal pain (p 0.001) were independently associated with lower global QoL in patients with CP.Malnutrition is frequent in patients with CP; and current alcohol consumption, smoking and higher cumulative days of abdominal pain independently predicts risk of developing malnutrition. Patients with malnutrition and higher cumulative days of pain has poorer quality of life.

Background/objectives: There is scarce information about risk factors for exocrine pancreas insufficiency (EPI) in chronic pancreatitis (CP), and how it associates with other complications. The aim of the present study was to examine risk factors for EPI and associations to procedures and other CP related complications in a large, Northern European cohort.Patients and methods: We retrieved cross-sectional data on demographics, status on EPI, aetiological risk factors for CP, CP related complications as well as surgical and endoscopic treatment from the Scandinavian Baltic Pancreatic Club Database. Associations were assessed by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals.Results: We included 1869 patients with probable or definitive CP in the study. Exocrine pancreas insufficiency was present in 849 (45.4%) of patients. In multivariate analyses, EPI associated with smoking aetiology (OR 1.47 (1.20-1.79), p < 0.001), and nutritional/metabolic aetiology (OR 0.52 (0.31-0.87), p = 0.01) to CP. Pancreatic or common bile duct stenting procedure and pancreatic resection were both associated with EPI (ORs 1.44 (1.15-1.80), p = 0.002 and 1.54 (1.02-2.33), p = 0.04, respectively). The presence of diabetes mellitus (OR 2.45 (1.92-3.15), p < 0.001), bile duct stenosis (OR 1.48 (1.09-2.00), p = 0.02) and underweight (2.05 (OR 1.40-3.02), p < 0.001) were all associated with presence of EPI.Conclusions: Smoking, bile duct stenosis, previous stenting and resection procedures are all associated with EPI in patients with CP. Presence of EPI were also associated with malnutrition and diabetes mellitus. Hence, intensive nutritional surveillance is needed in these patients. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC.

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 (p0.0001) and each parameter evaluated (p0.0001). 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 (p0.0001). The development of a dedicated ultrasound score could be useful as a non-invasive tool in the diagnosis of CP.

Malnutrition in chronic pancreatitis is complex and multifactorial, with malabsorption, pain, toxic dependencies and co-morbidities, such as diabetes, each playing a role. The aims of this systematic review were to assess the impact of nutritional intervention on markers of nutritional status in this complex patient group.A systematic review of EMBASE and PubMed was carried out in February 2020, identifying 2620 articles. After screening to exclude those reporting short term changes (less than 3 months), with only one data point, or in the wrong population, eight papers were selected for analysis.Seven studies documented the impact of a nutritional intervention, one was an observational study only. Overall, studies were limited by predominantly retrospective designs, heterogenous populations and poor control of potentially confounding variables. Data could not be combined due to variability in reporting methods. All studies exploring nutritional intervention, whether that consisted of advice by a specialist dietitian, dose escalation of pancreatic enzymes, oral nutritional supplements or enteral feeding, demonstrated improved body weight and pain control, whereas patients who did not receive an intervention deteriorated nutritionally.Patients with chronic pancreatitis benefit from nutritional intervention. Further work is required to explore the impact of nutritional intervention on body composition and functional outcomes.

Background Data are limited regarding pancreatic cancer diagnosed following a pancreaticobiliary endoscopic ultrasound (EUS) that does not diagnose pancreatic cancer. We have studied the frequency of, and factors associated with, post-EUS pancreatic cancer (PEPC) and 1-year mortality. Methods Between 2010 and 2017, patients with pancreatic cancer and a preceding pancreaticobiliary EUS were identified in a national cohort using Hospital Episode Statistics. Patients with a pancreaticobiliary EUS 6–18 months before a later pancreatic cancer diagnosis were the PEPC cases; controls were those with pancreatic cancer diagnosed within 6 months of pancreaticobiliary EUS. Multivariable logistic regression models examined the factors associated with PEPC and a Cox regression model examined factors associated with 1-year cumulative mortality. Results 9363 pancreatic cancer patients were studied; 93.5 % identified as controls (men 53.2 %; median age 68 [interquartile range (IQR) 61–75]); 6.5 % as PEPC cases (men 58.2 %; median age 69 [IQR 61–77]). PEPC was associated with older age (≥ 75 years compared with 5, OR 1.90, 95 %CI 1.49–2.43), chronic pancreatitis (OR 3.13, 95 %CI 2.50–3.92), and diabetes mellitus (OR 1.58, 95 %CI 1.31–1.90). Metal biliary stents (OR 0.57, 95 %CI 0.38–0.86) and EUS-FNA (OR 0.49, 95 %CI 0.41–0.58) were inversely associated with PEPC. PEPC was associated with a higher cumulative mortality at 1 year (hazard ratio 1.12, 95 %CI 1.02–1.24), with only 14 % of PEPC patients (95 %CI 12 %–17 %) having a surgical resection, compared with 21 % (95 %CI 20 %–22 %) of controls. Conclusions PEPC occurred in 6.5 % of patients and was associated with chronic pancreatitis, older age, more co-morbidities, and specifically diabetes mellitus. PEPC was associated with a worse prognosis and lower surgical resection rates.

The objective of this study was to analyze the value of artificial intelligence algorithm-based computerized tomography (CT) image combined with serum tumor markers for diagnoses of pancreatic cancer. In the study, 68 hospitalized patients with pancreatic cancer were selected as the experimental group, and 68 hospitalized patients with chronic pancreatitis were selected as the control group, all underwent CT imaging. An image segmentation algorithm on account of two-dimensional (2D)-three-dimensional (3D) convolution neural network (CNN) was proposed. It also introduced full convolutional network (FCN) and UNet network algorithm. The diagnostic performance of CT, serum carbohydrate antigen-50 (CA-50), serum carbohydrate antigen-199 (CA-199), serum carbohydrate antigen-242 (CA-242), combined detection of tumor markers, and CT-combined tumor marker testing (CT-STUM) for pancreatic cancer were compared and analyzed. The results showed that the average Dice coefficient of 2D-3D training was 84.27%, which was higher than that of 2D and 3D CNNs. During the test, the maximum and average Dice coefficient of the 2D-3D CNN algorithm was 90.75% and 84.32%, respectively, which were higher than the other two algorithms, and the differences were statistically significant ( P < 0.05 ). The penetration ratio of pancreatic duct in the experimental group was lower than that in the control group, the rest were higher than that in the control group, and the differences were statistically significant ( P < 0.05 ). CA-50, CA-199, and CA-242 in the experimental group were 141.72 U/mL, 1548.24 U/mL, and 83.65 U/mL, respectively, which were higher than those in the control group, and the differences were statistically significant ( P < 0.05 ). The sensitivity, specificity, positive predictive value, and authenticity of combined detection of serum tumor markers were higher than those of CA-50, CA-199, and CA-242, and the differences were statistically significant ( P < 0.05 ). The results showed that the proposed algorithm 2D-3D CNN had good stability and image segmentation performance. CT-STUM had high sensitivity and specificity in diagnoses of pancreatic cancer.

The Hedgehog signaling pathway (Hh) probably plays a role in development and progression of pancreatic ductal adenocarcinoma (PDAC).In our study, 114 patients (83 with PDAC and 31 with chronic pancreatitis [CP]) after pancreatic surgery were enrolled. The immunoexpression of Sonic hedgehog (Shh), Smoothened (Smo), and Glioblastoma transcription factor 1 (Gli1) and Ki-67 were detected in tissue specimens.Mean (standard deviation) immunoexpression of all Hh pathway molecules was significantly higher in PDAC than in CP patients: Shh, 2.24 (0.57) versus 1.17 (0.25) (P0.01); Smo, 2.62 (0.34) versus 1.21 (0.23) (P0.01); and Gli1, 1.74 (0.74) versus 1.15 (0.72) (P0.01). Patients with a lower expression level (z score0) of Shh and Ki-67 have longer overall survival when compared with z score0 (15.97 vs 8.53 months [P = 0.0087] and 15.20 vs 5.53 months [P = 0.0004], respectively). In addition, Shh sensitivity in PDAC detection was 84.3%; specificity, 93.5%; positive predictive value, 97.2%; and negative predictive value, 69%.Our results suggest the prognostic role of the Hh pathway in PDAC and a role in the differential diagnosis with CP.

Approximately one in five adults in the United States experiences chronic pain. Over the last 50 years, spinal cord stimulation has become increasingly recognized as a minimally invasive, efficacious treatment modality for the management of chronic pain. The authors report a case study of a 46-year-old female in the first documented spinal cord stimulation simultaneously targeting intractable neuropathic and visceral pain caused by post-laminectomy syndrome and chronic pancreatitis, respectively. This case study demonstrates near-total relief of the patient's neuropathic low back/leg pain and visceral epigastric pain, showing evidence of potential clinical usefulness for spinal cord stimulation as a treatment option in patients who present with a combination of visceral and somatic pain symptoms.Lay abstract Approximately one in five adults in the United States experiences chronic pain. Over the last 50 years, a treatment for chronic pain referred to as spinal cord stimulation has become a promising alternative to back surgery and may minimize the need for strong opioid pain medications. The authors report a case study of a 46-year-old female patient who suffered from chronic pain following back surgery as well as persistent pain from chronic pancreatitis. This case study demonstrates the use of spinal cord stimulation to provide near-total relief of the patient's low back/leg pain and pain from visceral inflammatory symptoms.

Genetic mutations in various pancreatic enzymes or their counteracting proteins have been linked to chronic pancreatitis. In particular, variants in the genes encoding pancreatic lipase (PNLIP) and carboxyl ester lipase (CEL) have been associated with pancreatitis. Therefore, we investigated pancreatic phospholipase A2 (PLA2G1B) as a promising candidate gene in patients with chronic pancreatitis.We analyzed all coding exons and adjacent intronic regions of PLA2G1B in 416 German patients with non-alcoholic chronic pancreatitis (NACP) and 186 control subjects by direct DNA sequencing.We detected 2 frequent synonymous variants in exon 3: c.222TC (p.Y74 = ) and c.294GA (p.S98 = ). The genotype and allele frequencies of these variants were similar between patients and controls (c.222 TC: 9.6% in NACP vs. 9.7% in controls; c.222CC: 0.2% in NACP vs. 0% in controls; c.294 GA: 31.3% in NACP vs. 28.0% in controls; c.294AA: 2.4% in NACP vs. 1.1% in controls). All p-values were non-significant. In addition, we found one synonymous variant, c.138CT (p.N46 = ) and one non-synonymous variant, c.244AG (p.S82G), in a single case each.Our results suggest that genetic alterations in PLA2G1B do not predispose to the development of non-alcoholic chronic pancreatitis.

Management of complications in patients with chronic pancreatitis is often suboptimal. This review discusses detailed endoscopic approaches for managing complications in CP.CP is characterized by progressive and irreversible destruction of pancreatic parenchyma and ductal system resulting in fibrosis, scarring, and loss of glandular function. Abdominal pain remains is the most common symptom of the disease and the main aim of medical, endoscopic, and surgical therapy is to help relieve symptoms, prevent disease progression, and manage complications related to CP. In fact, advances in our understanding of CP have improved medical care and quality of life in these patients. With significant sequela, morbidity and a progressive nature, a thorough understanding of the pathophysiology, natural course, diagnostic approaches, and optimal management strategies for this disease is warranted. The existing modalities and new innovations in this field are safe, effective, and likely to have a positive impact on management of complication in CP whenever used in the right context.

To investigate the prevalence, pathogenesis, diagnosis, clinical sequelae, and management of sarcopenia to improve mortality and quality of life in those with Chronic Pancreatitis.Sarcopenia is prevalent in chronic pancreatitis and can significantly affect clinical outcomes. Sarcopenia is prevalent in chronic pancreatitis. While effects on some clinical outcomes is has been shown, there is a significant gap in knowledge regarding effects on outcomes, pathophysiology, and options for management.

OBJECTIVE Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement ( RESULTS At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 41 (20%) had high insulin requirement. Insulin-independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; P = 0.03). Patients with insulin independence had a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (P = 0.03). Higher peak C-peptide measured by stimulated mixed-meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at 1 year (P = 0.006 and 0.03, respectively). CONCLUSIONS We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.

IntroductionDespite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency.MethodsAn online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years.ResultsOverall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency.ConclusionThis survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence. Introduction: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. Methods: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. Results: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. Conclusion: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

Objective. Type 2 diabetes mellitus (T2DM) is one of diseases that develops in a setting of polymorbid processes or more often promotes their development, forming in this spectrum the phenomenon of comorbidity. The aim of this study was to evaluate changes in the lipid panel data in T2DM patients with comorbid obesity and chronic pancreatitis (CP) taking into account the C/A polymorphism of the insulin receptor substrate 1 (IRS1) gene (rs2943640). Methods. The study involved 34 T2DM patients and 10 healthy individuals. The rs2943640 IRS1 gene polymorphism was genotyped using the TaqMan real-time polymerase chain reaction (PCR) method. Blood serum lipid panel data were determined with commercially available kits on a Cobas 6000 analyzer. Results. In patients with only T2DM and T2DM + comorbid obesity, an association between IRS1 gene polymorphism (rs2943640) and lipid profile abnormalities with maximum changes of the lipid characteristics recorded in C/C genotype carriers was found. Within the C/C genotype of the IRS1 gene (rs2943640) in type 2 diabetic patients with comorbid obesity and CP, significantly lower high-density lipoprotein cholesterol (HDL-C) levels and significantly higher levels of triglycerides (TG), non-HDL-C and remnant cholesterol (RC) in relation to type 2 diabetic patients with comorbid obesity were found. At the same time, within the C/A genotype of the IRS1 gene (rs2943640), significant changes of lipid panel data were found in type 2 diabetic patients with comorbid obesity relative to the control group (p Conclusions. Our data indicate that the presence of the C allele of IRS1 gene (rs2943640) in both homozygous and heterozygous states may indicate increased risk of dyslipidemia in type 2 diabetic patients with comorbidities.