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Purpose of reviewThe burdens of pancreatic ductal adenocarcinoma (PDAC) and acute pancreatitis are increasing globally. We reviewed current literature on whether acute pancreatitis is a causal factor for PDAC and examined clinical manifestations of PDAC-associated acute pancreatitis.Recent findingsRecent findings detail the timing of acute pancreatitis before and after PDAC occurrence, further solidifying the evidence for PDAC-associated acute pancreatitis and for acute pancreatitis as a causal risk factor for PDAC. The risk of PDAC remains elevated above the general population in patients with distant history of acute pancreatitis. PDAC risk also increases with recurrent acute pancreatitis episodes, independent of smoking and alcohol. Mechanisms linking acute pancreatitis to PDAC include inflammation and neutrophil infiltration, which can be attenuated by suppressing inflammation and/or epigenetic modulation, thus slowing the progression of acinar-to-ductal metaplasia. Clinical presentation and management of acute pancreatitis in the context of PDAC are discussed, including challenges acute pancreatitis poses in the diagnosis and treatment of PDAC, and novel interventions for PDAC-associated acute pancreatitis.SummaryPDAC risk may be reduced with improved acute pancreatitis prevention and treatment, such as antiinflammatories or epigenetic modulators. Increased acute pancreatitis and PDAC burden warrant more research on better diagnosis and management of PDAC-associated acute pancreatitis.

Background: Chronic pancreatitis is a long-standing inflammation of the pancreas that leads to permanent damage and impairment of its functions. Accurate diagnosis is crucial for effective management. This study aims to evaluate and compare the effectiveness of ultrasonography (US) and computed tomography (CT) in diagnosing chronic pancreatitis, highlighting their respective advantages and limitations. Materials and Methods: This observational study was conducted over 18 months in the Department of Radiodiagnosis at a tertiary care hospital. The study included 10 patients presenting with clinical symptoms suggestive of chronic pancreatitis. Initial evaluations were performed using a Samsung HS 40 ultrasonography machine, followed by CT scans using a Philips MX 16-slice CT scanner. The pancreas was assessed for size, echogenicity, duct dilatation, calcifications, and parenchymal changes. Data were analyzed using SPSS 22.0 software to determine the sensitivity, specificity, and diagnostic accuracy of both imaging modalities. Results: The study population consisted of 10 patients with a mean age of 29 years, predominantly male (70%). The most common etiologies were idiopathic (50%) and alcoholism (30%). Ultrasonography visualized the pancreas in all cases, identifying duct dilatation (90%) and calcifications (80%) as common findings. CT confirmed these findings and provided additional details, detecting calcifications in 90% of patients and pancreatic atrophy in 60%. Both modalities effectively visualized the pancreas, but CT demonstrated higher sensitivity in detecting calcifications and structural changes. Conclusion: Ultrasonography is valuable for the initial evaluation of chronic pancreatitis due to its non-invasive nature and accessibility. However, CT provides a more detailed and comprehensive assessment, essential for confirming the diagnosis and identifying complications. The complementary use of both imaging modalities enhances diagnostic accuracy and aids in effective management of chronic pancreatitis. [ABSTRACT FROM AUTHOR]

Background : Acute pancreatitis is a sudden inflammation of the pancreas that can range from mild discomfort to life-threatening illness. Accurate and timely diagnosis is crucial for effective management. While clinical and biochemical parameters play a role, imaging modalities such as ultrasonography (US) and computed tomography (CT) are essential for diagnosis and assessment. This study aims to evaluate and compare the effectiveness of US and CT in diagnosing acute pancreatitis and understanding their respective advantages and limitations. Materials and Methods: This observational study was conducted over 18 months in the Department of Radiodiagnosis at a tertiary care hospital. The study included 45 patients diagnosed with acute pancreatitis. Initial evaluation was performed using a Samsung HS 40 ultrasonography machine, followed by CT scans using a Philips MX 16-slice CT scanner. The pancreas was assessed for size, echogenicity, ductal changes, calcifications, focal lesions, and extra pancreatic findings. Data were analyzed using SPSS 22.0 software to determine the sensitivity, specificity, and diagnostic accuracy of both imaging modalities. Results: The study comprised 45 patients with acute pancreatitis, predominantly young adults (mean age 41 years) with a male predominance (84.4%). Alcoholism was the leading cause (51.1%), followed by idiopathic (28.9%) and gallstones (17.8%). Ultrasonography visualized the pancreas in 64.4% of cases, with common findings including a bulky pancreas (55.2%), hypoechoic echogenicity (44.8%), and ascites (37.7%). In contrast, CT visualized the pancreas in all cases, identifying a bulky pancreas (51.1%), fluid collections (26.7%), and exudates (73.3%). The CT severity index (CTSI) classified 31.1% as mild, 42.2% as moderate, and 26.7% as severe, with a mortality rate of 16.7% in the severe category. Ultrasonography had a sensitivity of 64%, dropping to 37.8% overall, while CT had a sensitivity of 96%. Conclusion: Ultrasonography is a valuable initial imaging modality for acute pancreatitis due to its non-invasive nature, costeffectiveness, and availability. However, CT provides a more detailed and accurate assessment, essential for diagnosing and managing acute pancreatitis. The complementary use of both imaging modalities enhances diagnostic accuracy, guides appropriate treatment strategies, and improves patient outcomes. [ABSTRACT FROM AUTHOR]

We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis. Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis. In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59–0.70]; p < 0.001). In multivariable analysis, necrosis 30–50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01–4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04–7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity. The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation. [ABSTRACT FROM AUTHOR]

Abstract Background Previous studies have documented vitamin D imbalance in dogs with acute pancreatitis (AP), but no studies have investigated serum vitamin D receptor (VDR) and vitamin D‐binding protein (VDBP) concentrations. Objectives Compare serum 25‐hydroxyvitamin D (25[OH]D), VDR, and VDBP concentrations in healthy dogs and dogs with AP and identify correlations between these concentrations with ionized calcium, C‐reactive protein (CRP), and canine‐specific pancreatic lipase (Spec cPL) concentrations. Animals Twenty‐two dogs with AP and 20 healthy control dogs. Methods Prospective cross‐sectional study. Serum 25(OH)D concentrations were measured using a chemiluminescence immunoassay, and VDR and VDBP concentrations were measured using a ELISA kit designed for dogs. Results Serum concentrations of 25(OH)D were lower in dogs with AP (mean ± SD, 66.1 ± 39.2 ng/mL) than in controls (96.8 ± 30.4 ng/mL; P = .01), and VDR concentrations were lower in dogs with AP (5.3 ± 3.5 ng/mL) than in controls (7.4 ± 2.5 ng/mL; P = .03). No difference was observed in serum VDBP concentrations between the groups. Serum VDR concentrations differed between survivors (median [interquartile range] = 6.6 [4.3‐8.2] ng/mL) and nonsurvivors (2.7 [0.5‐3.5] ng/mL; P = .01). Negative correlations were observed among serum VDR, CRP (rs = −0.55), and Spec cPL (rs = −0.47) concentrations in dogs with AP. Conclusions and Clinical Importance Dogs with AP had lower serum 25(OH)D and VDR concentrations than controls. Additionally, our study suggests a potential role of VDR expression in the inflammatory process of AP in dogs.

Background: Previous studies have documented vitamin D imbalance in dogs with acute pancreatitis (AP), but no studies have investigated serum vitamin D receptor (VDR) and vitamin D‐binding protein (VDBP) concentrations. Objectives: Compare serum 25‐hydroxyvitamin D (25[OH]D), VDR, and VDBP concentrations in healthy dogs and dogs with AP and identify correlations between these concentrations with ionized calcium, C‐reactive protein (CRP), and canine‐specific pancreatic lipase (Spec cPL) concentrations. Animals: Twenty‐two dogs with AP and 20 healthy control dogs. Methods: Prospective cross‐sectional study. Serum 25(OH)D concentrations were measured using a chemiluminescence immunoassay, and VDR and VDBP concentrations were measured using a ELISA kit designed for dogs. Results: Serum concentrations of 25(OH)D were lower in dogs with AP (mean ± SD, 66.1 ± 39.2 ng/mL) than in controls (96.8 ± 30.4 ng/mL; P =.01), and VDR concentrations were lower in dogs with AP (5.3 ± 3.5 ng/mL) than in controls (7.4 ± 2.5 ng/mL; P =.03). No difference was observed in serum VDBP concentrations between the groups. Serum VDR concentrations differed between survivors (median [interquartile range] = 6.6 [4.3‐8.2] ng/mL) and nonsurvivors (2.7 [0.5‐3.5] ng/mL; P =.01). Negative correlations were observed among serum VDR, CRP (rs = −0.55), and Spec cPL (rs = −0.47) concentrations in dogs with AP. Conclusions and Clinical Importance: Dogs with AP had lower serum 25(OH)D and VDR concentrations than controls. Additionally, our study suggests a potential role of VDR expression in the inflammatory process of AP in dogs. [ABSTRACT FROM AUTHOR]

Abstract Background Serum microRNAs have emerged as biomarkers of various diseases. Overexpression of serum miR‐216a and miR‐375 occurs in dogs with experimentally induced acute pancreatitis (AP). Objectives To identify the possibility of using serum miR‐216a and miR‐375 as biomarkers for the diagnosis and evaluation of treatment response in dogs with naturally occurring AP. Animals Twenty‐one dogs with AP and 20 healthy dogs. Methods Cross‐sectional study. The relative expression of serum hsa‐miR‐216a‐5p, cfa‐miR‐216a, and cfa‐miR‐375 were analyzed using reverse transcription and real‐time PCR. Results A significant difference in the serum expression of cfa‐miR‐375 was found between dogs with AP (median [interquartile range] 3.59 [1.55‐24.52]‐fold) and healthy dogs (0.81 [0.54‐2.21]‐fold, P .05). The area under the receiver operating characteristic curve of serum cfa‐miR‐375 for differentiating between AP dogs and healthy dogs was 0.84 (95% confidence interval [CI]: 0.71‐0.96). The expressions of hsa‐miR‐216a‐5p and cfa‐miR‐375 were positively correlated with the concentrations of serum C‐reactive protein (rs = .46, rs = .48, respectively), but not with the serum specific canine pancreatic lipase. The expression of cfa‐miR‐375 was significantly less after treatment in dogs with AP (P = .02). Conclusions and Clinical Importance Serum cfa‐miR‐375 could be a potential biomarker for the diagnosis and evaluation of treatment response of AP in dogs. In addition, miR‐216a and miR‐375 could be associated with inflammatory processes in dogs with AP.

Background: Serum microRNAs have emerged as biomarkers of various diseases. Overexpression of serum miR‐216a and miR‐375 occurs in dogs with experimentally induced acute pancreatitis (AP). Objectives: To identify the possibility of using serum miR‐216a and miR‐375 as biomarkers for the diagnosis and evaluation of treatment response in dogs with naturally occurring AP. Animals: Twenty‐one dogs with AP and 20 healthy dogs. Methods: Cross‐sectional study. The relative expression of serum hsa‐miR‐216a‐5p, cfa‐miR‐216a, and cfa‐miR‐375 were analyzed using reverse transcription and real‐time PCR. Results: A significant difference in the serum expression of cfa‐miR‐375 was found between dogs with AP (median [interquartile range] 3.59 [1.55‐24.52]‐fold) and healthy dogs (0.81 [0.54‐2.21]‐fold, P <.001), and no significant differences were observed in hsa‐miR‐216a‐5p and cfa‐miR‐216a (P >.05). The area under the receiver operating characteristic curve of serum cfa‐miR‐375 for differentiating between AP dogs and healthy dogs was 0.84 (95% confidence interval [CI]: 0.71‐0.96). The expressions of hsa‐miR‐216a‐5p and cfa‐miR‐375 were positively correlated with the concentrations of serum C‐reactive protein (rs =.46, rs =.48, respectively), but not with the serum specific canine pancreatic lipase. The expression of cfa‐miR‐375 was significantly less after treatment in dogs with AP (P =.02). Conclusions and Clinical Importance: Serum cfa‐miR‐375 could be a potential biomarker for the diagnosis and evaluation of treatment response of AP in dogs. In addition, miR‐216a and miR‐375 could be associated with inflammatory processes in dogs with AP. [ABSTRACT FROM AUTHOR]

BackgroundHormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by progressive loss of adipose tissue. Consequently, pharmacological inhibitors of HSL have been proposed for the treatment of cancer-associated cachexia. In the present study we used the conditional KrasG12D (KC) mouse model of pancreatic ductal adenocarcinoma (PDAC) with a deficiency in HSL to determine the impact of HSL suppression on the development of PDAC.MethodsKC;Hsl+/+ and KC;Hsl-/- mice were fed standard rodent chow for 20 weeks. At sacrifice, the incidence of PDAC was determined and inflammation in the mesenteric adipose tissue and pancreas was assessed histologically and by immunofluorescence. To determine statistical significance, ANOVA and two-tailed Student's t-tests were performed. To compare PDAC incidence, a two-sided Fisher's exact test was used.ResultsCompared to KC;Hsl+/+ mice, KC;Hsl-/- mice gained similar weight and displayed adipose tissue and pancreatic inflammation. In addition, KC;Hsl-/- mice had reduced levels of plasma insulin and leptin. Importantly, the increased adipose tissue and pancreatic inflammation was associated with a significant increase in PDAC incidence in KC;Hsl-/- mice.ConclusionsHSL deficiency is associated with adipose tissue and pancreatic inflammation and accelerates PDAC development in the KC mouse model.

Interleukin-35 (IL-35) is a novel protein comprising IL-12α and IL-27β chains. The IL12A and EBI3 genes are responsible for its production. The study of IL-35 has experienced a substantial increase in interest in recent years, as demonstrated by many research papers. Recent clinical studies have shown that individuals who do not have a C-peptide have notably reduced amounts of IL-35 in their blood serum. This is accompanied by a drop in the percentage of IL-35 + Treg cells, regulatory B cells, and CD8 + FOXP3 + cells that produce IL-35. This article em-phasizes the potential significance of IL-35 expression in governing the immune response and its involvement in chronic inflammatory autoimmune diabetes in pancreatic inflammation. It demonstrates IL-35's ability to regulate cytokine proportions, modulate B cells, and protect against autoimmune diabetes. However, further investigation is necessary to ascertain the precise mechanism of IL-35, and meticulous planning is essential for clinical studies., Competing Interests: Conflict-of-interest statement: All of the authors have no relevant financial or non-financial interests to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cannabis-induced pancreatitis (CIP) is an emerging clinical entity that presents unique challenges in diagnosis and management. This narrative review explores the current understanding of CIP, synthesizing evidence from epidemiological, pathophysiological, and clinical studies. The rising prevalence of cannabis use worldwide has been paralleled by an increase in reported cases of CIP, particularly among younger populations. Pathophysiological mechanisms involve the interaction of exogenous cannabinoids with pancreatic cannabinoid receptors, potentially disrupting normal pancreatic function and triggering inflammation. Clinical presentation of CIP often mimics other forms of acute pancreatitis (AP), necessitating a high index of suspicion and thorough history-taking for accurate diagnosis. Management strategies align with established protocols for AP, with an emphasis on supportive care and cannabis cessation to prevent recurrence. While short-term outcomes are generally favorable, the risk of progression to chronic pancreatitis in cases of continued cannabis use underscores the importance of long-term follow-up and abstinence counseling. This review also highlights significant knowledge gaps, including the need for standardized diagnostic criteria, a better understanding of dose-response relationships, and potential interactions with other risk factors. Future research directions should focus on elucidating precise pathophysiological mechanisms, developing targeted therapies, and investigating the impact of different cannabis formulations and consumption methods on pancreatic health. As cannabis use continues to increase globally, a comprehensive understanding of its effects on pancreatic function is crucial for improving patient outcomes and informing public health policies., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tanvir et al.)

Objectives: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis., Methods: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis., Results: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity., Conclusions: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation., Competing Interests: Declaration of competing interest All authors have no conflicts of interests relevant to this article to disclose., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Pancreatic inflammation and fibrosis are typical pathological features in chronic pancreatitis (CP). Activated pancreatic stellate cells (PSCs) have been regarded as the core event in the development of pancreatic fibrosis and are considered to be the key target for treatment of CP. Baicalin (C21H18O11), the main chemical composition of Baikal skullcap in the traditional Chinese medicines Dachaihu decoction (DCHD) and Xiaochaihu decoction (XCHD), has shown significant effects in the treatment of pancreatic fibrosis in CP mice; however, whether baicalin can inhibit the activation of PSCs and its underlying mechanism remain unclear. In this study, the influence of baicalin on activated PSCs in vitro and in vivo was investigated, and the results showed that Baicalin could significantly ameliorate the degree of pancreatic inflammation and fibrosis, while decreasing the levels of alpha-smooth muscle actin (α-SMA), F4/80 (surface markers of mouse macrophages), nuclear factor kappa-B (NF-κB), monocyte chemotactic protein 1 (MCP-1), and collagen type I alpha 1 (COL1A1)in the pancreas. Moreover, NF-κB and α-SMA were co-expressed in the pancreas of CP mice. Baicalin treatment markedly reduced the expression of co-location of α-SMA and NF-κB. In vitro, the protein expression levels of transforming growth factor-β receptor 1 (TGF-βR1), phosphorylated TGF-β activated kinase 1 p-TAK 1, and NF-κBp65 in PSCs were all remarkably reduced after treatment with baicalin. In addition, baicalin could inhibit MCP-1 mRNA expression in supernatant of activated PSCs, as well as the excessive migration of macrophages. Taken together, our findings indicated that baicalin could inhibit the TGF-β1/TGF-βR1/TAK1/NF-κB signaling pathway of activated PSCs, reduce the secretion of MCP-1, and further decrease the infiltration of macrophages and inflammation cells of the local microenvironment of the pancreas. Thus, this study provides a reliable experimental basis for baicalin in the prevention and treatment of CP.

Nuclear receptor subfamily 5 group A member 2 (Nr5a2) is widely involved in the physiological and pathological processes of the pancreas. However, the cytological and molecular evidence regarding how Nr5a2 implicated in acute pancreatitis (AP) remains insufficient. Here, we explored this problem by using cellular AP model in both normal and Nr5a2 silenced AR42J pancreatic acinar cells. An in vitro cellular model of AP was established by stimulating AR42J cells with caerulein (CAE) for 24 h. Reduced Nr5a2 expression was observed in the CAE-treated cells. Nr5a2 silencing led to AP-like inflammation, with increased interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α mRNA levels. In the cellular AP model, Nr5a2 silencing further increased IL-1β, IL-6, and TNF-α mRNA levels, as well as amylase activity. In addition, we found that Nr5a2 silencing did not affect IL-10 level under physiological conditions but inhibited the anti-inflammatory response of IL-10 in AP model. Moreover, in CAE-induced pancreatic inflammation, Nr5a2 silencing increased the apoptosis and necrosis of acinar cells and inhibited the proliferation of acinar cells, which has not been shown previously. Further experiments showed, for the first time, that Nr5a2 silencing downregulated the expression of β-catenin and its downstream target gene T-cell factor (TCF)-4 in the cellular AP model but increased the expression of nuclear factor (NF)-κB. In conclusion, in CAE-induced pancreatic inflammation, lower Nr5a2 level leads to downregulation of β-catenin and its downstream target gene TCF-4 and upregulation of NF-κB, which exacerbates the inflammatory response and cell damage and inhibits the proliferation and regeneration of acinar cells.

Abstract Background Hormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by progressive loss of adipose tissue. Consequently, pharmacological inhibitors of HSL have been proposed for the treatment of cancer-associated cachexia. In the present study we used the conditional KrasG12D (KC) mouse model of pancreatic ductal adenocarcinoma (PDAC) with a deficiency in HSL to determine the impact of HSL suppression on the development of PDAC. Methods KC;Hsl +/+ and KC;Hsl −/− mice were fed standard rodent chow for 20 weeks. At sacrifice, the incidence of PDAC was determined and inflammation in the mesenteric adipose tissue and pancreas was assessed histologically and by immunofluorescence. To determine statistical significance, ANOVA and two-tailed Student’s t-tests were performed. To compare PDAC incidence, a two-sided Fisher’s exact test was used. Results Compared to KC;Hsl +/+ mice, KC;Hsl −/− mice gained similar weight and displayed adipose tissue and pancreatic inflammation. In addition, KC;Hsl −/− mice had reduced levels of plasma insulin and leptin. Importantly, the increased adipose tissue and pancreatic inflammation was associated with a significant increase in PDAC incidence in KC;Hsl −/− mice. Conclusions HSL deficiency is associated with adipose tissue and pancreatic inflammation and accelerates PDAC development in the KC mouse model.

Nuclear receptor subfamily 5 group A member 2 (Nr5a2) is widely involved in the physiological and pathological processes of the pancreas. However, the cytological and molecular evidence regarding how Nr5a2 implicated in acute pancreatitis (AP) remains insufficient. Here, we explored this problem by using cellular AP model in both normal and Nr5a2 silenced AR42J pancreatic acinar cells. An in vitro cellular model of AP was established by stimulating AR42J cells with caerulein (CAE) for 24 h. Reduced Nr5a2 expression was observed in the CAE-treated cells. Nr5a2 silencing led to AP-like inflammation, with increased interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α mRNA levels. In the cellular AP model, Nr5a2 silencing further increased IL-1β, IL-6, and TNF-α mRNA levels, as well as amylase activity. In addition, we found that Nr5a2 silencing did not affect IL-10 level under physiological conditions but inhibited the anti-inflammatory response of IL-10 in AP model. Moreover, in CAE-induced pancreatic inflammation, Nr5a2 silencing increased the apoptosis and necrosis of acinar cells and inhibited the proliferation of acinar cells, which has not been shown previously. Further experiments showed, for the first time, that Nr5a2 silencing downregulated the expression of β-catenin and its downstream target gene T-cell factor (TCF)-4 in the cellular AP model but increased the expression of nuclear factor (NF)-κB. In conclusion, in CAE-induced pancreatic inflammation, lower Nr5a2 level leads to downregulation of β-catenin and its downstream target gene TCF-4 and upregulation of NF-κB, which exacerbates the inflammatory response and cell damage and inhibits the proliferation and regeneration of acinar cells. [ABSTRACT FROM AUTHOR]

Background: Possibly any tumor that can cause mechanical obstruction of the distal bile duct can induce acute pancreatitis. However, acute pancreatitis as the first clinical manifestation of duodenal lymphoma is extremely rare. Objective: To report the case of a patient with acute pancreatitis as an extremely rare first manifestation of duodenal MALT lymphoma and possible association with erythema nodosum. Methods: Case report of a 66-year-old woman who was diagnosed with acute pancreatitis caused by infiltration with duodenal lymphoma. Results: Acute pancreatitis was confirmed by CT imaging. Detailed investigation revealed a duodenal mass causing pancreatic injury. Histological analysis established the diagnosis of MALT lymphoma. The patient's medical history also included erythema nodosum. Complete remission of the malignancy was achieved with chemotherapy. Conclusion: This is the first published case report of acute pancreatitis caused by the growth of duodenal MALT lymphoma. An association with erythema nodosum is possible.

Background Pancreatic abnormalities during canine parvovirus ( CPV) enteritis have not been studied prospectively. Objectives The objective of this study was to evaluate the diagnostic significance of canine serum pancreas-specific lipase (Spec cPL) concentration in dogs with CPV enteritis for the presence of acute pancreatitis ( AP). Puppies with naturally occurring CPV enteritis were recruited and prospectively allocated into 2 groups according to normal or increased serum Spec cPL concentration. Clinical signs, laboratory findings, and pancreas-associated variables were compared between groups, and the impact of possible AP on disease course, duration of hospitalization, and outcome was assessed. Results Serum Spec cPL concentration in 35 puppies was above the upper limit of the RI in 17/35 (48.6%) dogs (Group A) and within the RI in 18 dogs (Group B). An increased serum lipase activity was present in 29/35 (82.9%) dogs, and Group A dogs had a higher serum lipase activity than Group B ( P = .006). Serum Spec cPL in Group A dogs was positively correlated with serum lipase activity at the day of presentation ( r = .667; P = .003) and day of discharge ( r = .628; P = .007). No statistically significant difference was found between groups ( P = .233) for the presence of systemic inflammatory response syndrome ( SIRS) (6/17 or 35.3% dogs Group A, and 8/18 or 44.4% dogs Group B), the disease course, duration of hospitalization, or outcome between groups. Conclusions Increased serum Spec cPL is relatively common in dogs with CPV enteritis. However, such increases do not seem to correlate with the outcome of disease. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether pancreatic function is impaired in children with severe acute malnutrition, is different between edematous vs nonedematous malnutrition, and improves by nutritional rehabilitation.Study Design: We followed 89 children with severe acute malnutrition admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Stool and blood samples were taken on admission and 3 days after initial stabilization to determine exocrine pancreatic function via fecal elastase-1 (FE-1) and serum trypsinogen and amylase levels.Results: A total of 33 children (37.1%) had nonedematous severe acute malnutrition, whereas 56 (62.9%) had edematous severe acute malnutrition. On admission, 92% of patients showed evidence of pancreatic insufficiency as measured by FE-1 <200 μg/g of stool. Patients with edematous severe acute malnutrition were more likely to have low FE-1 (98% vs 82.8%, P = .026). FE-1 levels remained low in these individuals throughout the assessment period. Serum trypsinogen was elevated (>57 ng/mL) in 28% and amylase in 21% (>110 U/L) of children, suggesting pancreatic inflammation.Conclusion: Exocrine pancreatic insufficiency is prevalent in children with severe acute malnutrition and especially in children with edematous severe acute malnutrition. In addition, biochemical signs suggestive of pancreatitis are common in children with severe acute malnutrition. These results have implications for standard rehabilitation treatment of children with severe acute malnutrition who may benefit from pancreatic enzyme replacement therapy.Trial Registration: ISRCTN.com: 13916953. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the immunomodulatory effects of mouse cathelicidin-related-antimicrobial peptide (CRAMP) on experimental acute-pancreatitis (AP). AP is a common clinical condition characterized-by acute abdominal inflammation. Innate immune-cells and mediators are intrinsically linked to the pathogenesis-of AP. Cathelicidins are innate immunity-derived-antimicrobial peptides that exert immunomodulatory effects-on various host cells. However, how cathelicidins are involved-and modulate the severity and inflammatory responses of AP-remains unclear. In the present study, the mouse CRAMP-gene-deficient cnlp-/- mice and their wild-type C57BL/6J-littermates were induced with AP by multiple hourly injections-of supramaximal doses of caerulein. Serum amylase-levels, pancreatic myeloperoxidase activity and histological-examination were performed in order to determine the disease-severity and the levels of inflammatory cytokines. Disease-severity and inflammatory markers were subsequently evaluated-in the control mice, cnlp-/- C57BL/6J mice with AP, and-wild-type C57BL/6J mice with AP. The results demonstrated-that cnlp-/- mice exhibited a more severe phenotype and-inflammatory response following AP induction compared-with the wild-type mice, as evidenced by increased serum-amylase levels, pancreatic myeloperoxidase release, and early-inflammatory mediator tumor necrosis factor-α production. Histological examination confirmed that CRAMP deficiency worsened the pancreatic inflammatory condition. These results indicate that CRAMP may be considered a novel modulatory mediator in mouse experimental AP. [ABSTRACT FROM AUTHOR]

Background. Possibly any tumor that can cause mechanical obstruction of the distal bile duct can induce acute pancreatitis. However, acute pancreatitis as the first clinical manifestation of duodenal lymphoma is extremely rare. Objective. To report the case of a patient with acute pancreatitis as an extremely rare first manifestation of duodenal MALT lymphoma and possible association with erythema nodosum. Methods. Case report of a 66-year-old woman who was diagnosed with acute pancreatitis caused by infiltration with duodenal lymphoma. Results. Acute pancreatitis was confirmed by CT imaging. Detailed investigation revealed a duodenal mass causing pancreatic injury. Histological analysis established the diagnosis of MALT lymphoma. The patient's medical history also included erythema nodosum. Complete remission of the malignancy was achieved with chemotherapy. Conclusion. This is the first published case report of acute pancreatitis caused by the growth of duodenal MALT lymphoma. An association with erythema nodosum is possible. [ABSTRACT FROM AUTHOR]

Letter to the Editor.

Background & Aims: Predicting level of fluid sequestration could help identify patients with acute pancreatitis (AP) who need more or less aggressive fluid resuscitation. We investigated factors associated with level of fluid sequestration in the first 48 hours after hospital admission in patients with AP and effects on outcome. Methods: We analyzed data from consecutive adult patients with AP admitted to the Brigham and Women’s Hospital in Boston, Massachusetts, from June 2005 to December 2007 (n = 266) or the Alicante University General Hospital in Spain from September 2010 to December 2012 (n = 137). Level of fluid sequestration in the first 48 hours after hospital admission was calculated by subtracting the total amount of fluid administered and lost in the first 48 hours of hospitalization. Demographic and clinical variables obtained in the emergency department were analyzed to identify factors associated with level of fluid sequestration in the first 48 hours after hospital admission. Outcome assessed included length of hospital stay, acute fluid collection(s), pancreatic necrosis, persistent organ failure, and mortality. Results: The median level of fluid sequestration in the first 48 hours after hospital admission was 3.2 L (1.4–5 L). The simple and multiple linear regression models showed that younger age, alcohol etiology, hematocrit, glucose, and systemic inflammatory response syndrome were significantly associated with increased levels of fluid sequestration in the first 48 hours after hospital admission. Increased level of fluid sequestration in the first 48 hours was significantly associated with longer hospital stays and higher rates of acute fluid collection, pancreatic necrosis, and persistent organ failure. There was a nonsignificant trend toward a higher level of fluid sequestration in the first 48 hours among patients who died. Conclusion: Age, alcoholic etiology of AP, hematocrit, glucose, and presence of systemic inflammatory response syndrome in the emergency department were independent predictors of increased levels of fluid sequestration in the first 48 hours after hospital admission. These patients have higher risks of local and systemic complications and longer hospital stays. [Copyright &y& Elsevier]

Objective To review current and emerging nutritional approaches in the management of acute pancreatitis (AP) in people, dogs, and cats, and to provide a framework for further investigation in this field. Data sources Veterinary retrospective studies and reviews, human prospective clinical trials and reviews, and experimental animal studies focusing on nutritional management during AP. Summary Nutritional management is an important part of the treatment plan for patients with AP. In human medicine, the general approach for providing nutrition in patients with AP has changed in recent years and favors enteral over parenteral nutrition with an emphasis on early enteral nutrition (EN). Although there are limited data available, there is increasing evidence in the veterinary literature that supports the beneficial role of EN in AP and contradicts previous assumptions about poor tolerance to enteral feeding in this patient population. Parenteral nutrition may be appropriate alone or in combination with EN as a temporary measure in malnourished patients that do not tolerate adequate EN; however, enteral feeding should be attempted first in most cases. Immunonutrition is being investigated for its positive role in modulating pancreatic inflammation and improving gut barrier function in cases of human AP. Conclusions The nutritional management of veterinary patients with AP remains challenging. Based on clinical evidence in people, experimental animal studies, and preliminary studies in dogs and cats, the choice of EN over parenteral nutritional support during AP in dogs and cats appears to be beneficial and well tolerated. Optimization of nutritional therapies in dogs and cats including the use of immunonutrition during AP warrants further investigation. [ABSTRACT FROM AUTHOR]

Background & Aims: Placement of pancreatic duct (PD) stents prevents pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). There is evidence that rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) also prevents post-ERCP pancreatitis, but the 2 approaches alone have not been compared directly. We conducted a network meta-analysis to indirectly compare the efficacies of these procedures. Methods: PubMed and Embase were searched by 2 independent reviewers to identify full-length clinical studies, published in English, investigating use of PD stent placement and rectal NSAIDs to prevent post-ERCP pancreatitis. We identified 29 studies (22 of PD stents and 7 of NSAIDs). We used network meta-analysis to compare rates of post-ERCP pancreatitis among patients who received only rectal NSAIDs, only PD stents, or both. Results: Placement of PD stents and rectal administration of NSAIDs were each superior to placebo in preventing post-ERCP pancreatitis. The combination of rectal NSAIDs and stents was not superior to either approach alone. Pooled results showed that rectal NSAIDs alone were superior to PD stents alone in preventing post-ERCP pancreatitis (odds ratio, 0.48; 95% confidence interval, 0.26–0.87). Conclusions: Based on a network meta-analysis, rectal NSAIDs alone are superior to PD stents alone in preventing post-ERCP pancreatitis, and should be considered first-line therapy for selected patients. However, these findings were limited by the small number of studies assessed (only 29 studies), potential publication bias, and the indirect nature of the comparison. High-quality, randomized, controlled trials are needed to compare these 2 interventions and confirm these findings. [Copyright &y& Elsevier]

Background & Aims: The transcription factor nuclear factor-κB (NF-κB) (a heterodimer of NF-κB1p50 and RelA) is activated rapidly in acute pancreatitis (AP). However, it is not clear whether NF-κB promotes or protects against AP. We used the NF-κB inhibitor protein, inhibitor of κB (IκB)α, to study the roles of NF-κB in the development of AP in mice. Methods: IκBα or the combination of IκBα and RelA selectively were deleted from pancreas of mice using the Cre/locus of cross-over P strategy; cerulein or L-arginine were used to induce AP. We performed microarray analyses of the IκBα- and RelA-deficient pancreata. DNA from healthy individuals and patients with acute or chronic pancreatitis were analyzed for variants in coding regions of alpha-1-antichymotrypsin. Results: Mice with pancreas-specific deletion of IκBα had constitutive activation of RelA and a gene expression profile consistent with NF-κB activation; development of AP in these mice was attenuated and trypsin activation was impaired. However, AP was fully induced in mice with pancreas-specific deletion of IκBα and RelA. By using genome-wide expression analysis, we identified a cluster of NF-κB–regulated genes that might protect against the development of AP. The serine protease inhibitor 2A (Spi2a) was highly up-regulated in IκBα-deficient mice. Lentiviral-mediated expression of Spi2A reduced the development of AP in C57BL/6 and RelA-deficient mice. However, we did not correlate any variants of alpha-1-antichymotrypsin, the human homologue of Spi2a, with acute or chronic pancreatitis. Conclusions: Pancreas-specific deletion of IκBα results in nuclear translocation of RelA and reduces AP induction and trypsin activation in mice after administration of cerulein or L-arginine. Constitutive activation of RelA up-regulates Spi2A, which protects mice against the development of AP. [Copyright &y& Elsevier]

Chronic pancreatitis is a severe inflammation of the pancreas associated with destruction of the parenchyma, fibrosis, and persistent abdominal pain. Cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandins, key mediators of the inflammatory response, are elevated in patients with chronic pancreatitis. Previous studies investigated COX-2 as a therapeutic target. These reports showed a reduced pathology in COX-2-deficient mice with a better outcome. Here we compared the role of COX-2 in acute and chronic pancreatic inflammation using the same COX-2-/- mouse model of cerulein-induced pancreatitis. In a setting of acute pancreatitis, juvenile COX-2-/- mice exhibited a reduced histopathological score compared with wild-type littermates; on the contrary, adult mice did not show any difference in the development of the disease. Similarly, in a setting of chronic pancreatitis induced over a period of 4 wk, adult mice of the two strains showed comparable histological score and collagen deposition. However, the abundance of mRNAs coding for profibrotic genes, such as collagen, α-smooth muscle actin, and transforming growth factor-β was consistently lower in COX-2-/- mice. In addition, comparable histological scores and collagen deposition were observed in wild-type mice treated with a COX-2 inhibitor. We conclude that, in contrast to what was observed in the rat pancreatitis models, COX-2 has a limited and age-dependent effect on inflammatory processes in the mouse pancreas. These results suggest that COX-2 modulates the inflammatory process during the development of pancreatitis in a species-specific manner. Thus the pathophysiological roles of COX-2 and its therapeutic implications in patients with pancreatitis should be reexamined. [ABSTRACT FROM AUTHOR]

Background & Aims: A goal of radiologists is to use computed tomography (CT) imaging less frequently in younger patients because of radiation exposure. We evaluated abdominal CT use among patients hospitalized for acute pancreatitis at a tertiary care hospital and compared estimated radiation doses with disease severity and patient age. Methods: We performed a retrospective analysis of numbers and types of CTs performed on patients with acute pancreatitis (1036 admissions, 869 patients; mean age, 50.8 y); 566 had 1081 abdominopelvic CTs performed from October 1, 2001, to September 30, 2006. Effective dose estimates for abdominopelvic CTs were used to estimate exposure. Disease severities were stratified using Balthazar CT grades and severity indexes. Results: The mean number of abdominopelvic CTs per patient, per hospitalization, was 1.9 (range, 1–12); the mean number was 3.0 over the 5-year period (range, 1–19). During hospitalization, each patient was exposed to a mean estimated radiation dose of 31.03 ± 26.4 mSv (range, 14.7–176.9 mSv). Patients with pancreatitis grades D or E (n = 233) compared with grades A through C (n = 333) had longer periods of hospitalization (mean, 23.3 vs 10.8 d; P < .001), more days as an inpatient (mean, 2.54 vs 1.45 d; P < .001), more total CT scans (mean, 4.02 vs 2.37; P < .001), and higher total effective radiation doses (mean, 53.5 vs 35 mSv; P < .0001). Linear regression revealed a relationship between dose and disease grade, but not patient age. Conclusions: Regardless of age, patients with severe acute pancreatitis undergo more abdominopelvic CTs as inpatients and outpatients and are exposed to higher doses of radiation compared with patients with less severe disease. Awareness of CT ordering patterns for patients with acute pancreatitis may aid in the development of alternate imaging strategies to reduce radiation exposure in this population, especially for younger patients. [Copyright &y& Elsevier]

Background: Pancreatic inflammation plays a key role in diabetes pathogenesis and progression. Urolithin A (UA), an intestinal flora metabolite of pomegranate, has anti-diabetic, anti-inflammatory and kidney protection effects among others. However, its effects on pancreatic inflammation and the potential mechanisms have not been clearly established.Purpose: This study aimed at investigating the molecular mechanisms of UA anti-pancreatic inflammation under a diabetic environment.Methods: Diabetes induction in male C57BL/6 mice was achieved by a high fat diet and intraperitoneal streptozotocin injections. Then, diabetic mice were orally administered with UA for 8 weeks. In vitro, endoplasmic reticulum stress and MIN6 pancreatic β cell inflammation were induced using 25 mM glucose and 0.5 mM palmitic acid. The effects of UA were evaluated by immunohistochemistry, Western blot, and enzyme linked immunosorbent assays. Finally, the underlying mechanisms were elucidated using an autophagy inhibitor (chloroquine, CQ) and an AMPK inhibitor (dorsomorphin dihydrochloride).Results: UA significantly inhibited IL-1β secretion and TXNIP/NLRP3 expression in the pancreas of diabetic mice and in MIN6 pancreatic cells. UA downregulated the ER stress protein, p-PERK, and promoted AMPK phosphorylation. UA activated autophagy to inhibit TXNIP/NLRP3 IL-1β inflammatory signal, an effect that was reversed by CQ. Dorsomorphin 2HCL, reversed the autophagy-activation and anti-inflammatory effects of UA. Verapamil, clinically applied as an antiarrhythmic drug, is a TXNIP inhibitor for prevention of beta cell loss and diabetes development, but limited by its cardiac toxicity. In this study, verapamil (as positive control) inhibited NLRP3 /IL-1β signaling in MIN6 cells. Inhibitory effects of UA on TXNIP and IL-1β were weaker than those of verapamil (both at 50 μM, p < 0.05, p < 0.01). Conversely, inhibitory effects of UA on p62 were stronger, relative to those of verapamil (p < 0.05), and there were no differences in AMPK activation and LC3 enhancement effects between UA and verapamil.Conclusion: UA is a potential anti-pancreatic inflammation agent that activates AMPK and autophagy to inhibit endoplasmic reticulum stress associated TXNIP/NLRP3/IL-1β signal pathway. [ABSTRACT FROM AUTHOR]

Oxygen-derived free radicals mediate tissue damage in acute and chronic pancreatitis. Low levels of natural antioxidants in pancreatitis indicate their increased utilization as scavengers of free radicals. Combination therapy with selenium, β-carotene, methionine, and vitamins C and E are known to improve symptoms of chronic and recurrent pancreatitis. This, however, requires many tablets to be taken daily, which is impractical and may reduce compliance. Three patients with chronic pancreatitis (two with a history of alcohol excess and one idiopathic) are reported. Treatment with narcotic analgesics and pancreatic enzyme supplements had failed to control their symptoms. The addition of a commercially available IH636 grape seed proanthocyanidin extract (commercially known as ActiVin) to their treatment regimen led to a reduction in the frequency and intensity of abdominal pain as well as resolution of vomiting in 1 patient.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Pancreatic inflammation and fibrosis are typical pathological features in chronic pancreatitis (CP). Activated pancreatic stellate cells (PSCs) have been regarded as the core event in the development of pancreatic fibrosis and are considered to be the key target for treatment of CP. Baicalin (C21H18O11), the main chemical composition of Baikal skullcap in the traditional Chinese medicines Dachaihu decoction (DCHD) and Xiaochaihu decoction (XCHD), has shown significant effects in the treatment of pancreatic fibrosis in CP mice; however, whether baicalin can inhibit the activation of PSCs and its underlying mechanism remain unclear. In this study, the influence of baicalin on activated PSCs in vitro and in vivo was investigated, and the results showed that Baicalin could significantly ameliorate the degree of pancreatic inflammation and fibrosis, while decreasing the levels of alpha-smooth muscle actin (α-SMA), F4/80 (surface markers of mouse macrophages), nuclear factor kappa-B (NF-κB), monocyte chemotactic protein 1 (MCP-1), and collagen type I alpha 1 (COL1A1)in the pancreas. Moreover, NF-κB and α-SMA were co-expressed in the pancreas of CP mice. Baicalin treatment markedly reduced the expression of co-location of α-SMA and NF-κB. In vitro , the protein expression levels of transforming growth factor-β receptor 1 (TGF-βR1), phosphorylated TGF-β activated kinase 1 p-TAK 1, and NF-κBp65 in PSCs were all remarkably reduced after treatment with baicalin. In addition, baicalin could inhibit MCP-1 mRNA expression in supernatant of activated PSCs, as well as the excessive migration of macrophages. Taken together, our findings indicated that baicalin could inhibit the TGF-β1/TGF-βR1/TAK1/NF-κB signaling pathway of activated PSCs, reduce the secretion of MCP-1, and further decrease the infiltration of macrophages and inflammation cells of the local microenvironment of the pancreas. Thus, this study provides a reliable experimental basis for baicalin in the prevention and treatment of CP. [ABSTRACT FROM AUTHOR]

Melissa officinalis L. (Labiatae; lemon balm) is a traditional medicinal plant with hypoglycemic and hypolipidemic effects; however, how it imparts its beneficial effects remains unclear. We thus hypothesized that the herbal extract ALS-L1023, isolated from Melissa officinalis, inhibits obesity and diabetes, and tested our hypothesis using Otsuka Long-Evans Tokushima fatty (OLETF) rats, which are an established animal model of type 2 diabetes. In this study, 28-week-old OLETF rats were fed a high-fat diet for 4 weeks to induce a marked impairment of the insulin response and were treated with or without ALS-L1023. Subsequently, the variables and determinants of glucose metabolism and pancreatic function were assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction. The administration of ALS-L1023 resulted in a weight reduction without changes in food intake. It also markedly inhibited hyperglycemia and hypoinsulinemia, and restored β-cell mass that was severely impaired in OLETF rats. There was a decrease in lipid accumulation in the liver and skeletal muscle of the obese rats after treatment with ALS-L1023. Concomitantly, there was an increase in the expression levels of fatty acid-oxidizing enzymes (AMPKα2, ACOX, MCAD, and VLCAD) in the liver and skeletal muscle after ALS-L1023 treatment. Furthermore, ALS-L1023 attenuated the pancreatic inflammation including the infiltration of CD68-positive macrophages and mast cells, in addition to attenuating the expression of inflammatory factors (IL-6 and CD68). These results suggest that treatment with ALS-L1023 may reduce weight gain, elevated glucose levels, and β-cell loss, by changing the expression of fatty acid-oxidizing enzymes in the liver and skeletal muscle, including inflammatory factors in the pancreas. These findings indicate that ALS-L1023 may be an effective therapeutic strategy to treat human obesity and type 2 diabetes. Image 1 [ABSTRACT FROM AUTHOR]