Application of the pancreatic body suspension technique in laparoscopic splenectomy combined with selective pericardial varicosity dissection: An observational study.

To investigate the safety of pancreatic body suspension (PBS) technique in laparoscopic splenectomy combined with pericardial devascularization for patients. A retrospective study inclusive of 16 patients who underwent laparoscopic splenectomy combined with pericardial devascularization from 2017 to 2022 was performed. A total of 5 patients underwent PBS technique and 11 underwent the traditional technique. There was no significant difference in age, sex, body mass index (BMI), preoperative serum white cell count (WBC), platelets (PLT), hemoglobin (HB), albumin (ALB), prothrombin time (PT), total bilirubin (TBIL), or spleen size between the 2 groups (P > .05). In the PBS group, the operation time was 280 minutes. The estimated intraoperative blood loss (EBL) was 250 mL. The mean postoperative hospitalization length was 11.2 days. There was no conversion to an open procedure or postoperative bleeding. In the traditional method group, the mean operation time was 240.91 minutes. The EBL was 290.91 mL. There were 2 cases of conversion to open, 3 cases of postoperative bleeding, and 1 reoperation. The incidence of postoperative short-term complications (postoperative bleeding, reoperation) was significantly higher in the traditional method group than in the PBS group (36.36% vs 0%, P = .034). PBS technique improved the safety of laparoscopic splenectomy combined with pericardial dissection and is worthy of clinical promotion.

Minimally Invasive Pancreas Surgery: Is There a Benefit?

Minimally invasive procedures minimize trauma to the human body while maintaining satisfactory therapeutic results. Minimally invasive pancreas surgery (MIPS) was introduced in 1994, but questions regarding its efficacy compared to an open approach were widespread. MIPS is associated with several perioperative advantages while maintaining oncological standards when performed by surgeons with a robust training regimen and frequent practice. Future research should focus on addressing learning curve discrepancies while identifying factors associated with shortening the time needed to attain technical proficiency.

Epigenetic Regulation of Pancreas Development and Function.

The field of epigenetics broadly seeks to define heritable phenotypic modifications that occur within cells without changes to the underlying DNA sequence. These modifications allow for precise control and specificity of function between cell types-ultimately creating complex organ systems that all contain the same DNA but only have access to the genes and sequences necessary for their cell-type-specific functions. The pancreas is an organ that contains varied cellular compartments with functions ranging from highly regulated glucose-stimulated insulin secretion in the ß-cell to the pancreatic ductal cells that form a tight epithelial lining for the delivery of digestive enzymes. With diabetes cases on the rise worldwide, understanding the epigenetic mechanisms driving ß-cell identity, function, and even disease is particularly valuable. In this chapter, we will discuss the known epigenetic modifications in pancreatic islet cells, how they are deposited, and the environmental and metabolic contributions to epigenetic mechanisms. We will also explore how a deeper understanding of epigenetic effectors can be used as a tool for diabetes therapeutic strategies.

Development of the Pancreatic Ducts and Their Contribution to Organogenesis.

The pancreas is a dual-function organ, with exocrine cells that aid in digestion and endocrine cells that regulate glucose homeostasis. These cell types share common progenitors and arise from the embryonic ducts. Early signaling events in the embryonic ducts shape the neonatal, adolescent, and adult exocrine and endocrine pancreas. This chapter discusses recent advances in the tools used to study the ducts and our current understanding of how ductal development contributes to pancreatic organogenesis.

ß-Cell Regeneration Is Driven by Pancreatic Plasticity.

The pancreas has been considered a non-regenerative organ. ß cells lost in diabetes are not replaced due to the inability of the pancreas to regenerate. However, ample evidence generated in the last few decades using murine models has demonstrated that the pancreas has a remarkable plasticity wherein differentiated cells can change cell fate toward a ß-like cell phenotype. Although this process is observed after using rather artificial stimuli and the conversion efficiency is very limited, these findings have shed some light on novel pathways for ß-cell regeneration. In this chapter, we will summarize the different cellular interconversion processes described to date, the experimental details and molecular regulation of such interconversions, and the genomic technologies that have allowed the identification of potential new ways to generate ß cells.

Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism.

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.

Generation of a pancreas derived hydrogel for the culture of hiPSC derived pancreatic endocrine cells.

Stem cell-derived ß-cells (SC-BCs) represent a potential source for curing diabetes. To date, in vitro generated SC-BCs display an immature phenotype and lack important features in comparison to their bona-fide counterparts. Transplantation into a living animal promotes SC-BCs maturation, indicating that components of the in vivo microenvironment trigger final SC-BCs development. Here, we investigated whether cues of the pancreas specific extracellular matrix (ECM) can improve the differentiation of human induced pluripotent stem cells (hiPSCs) towards ß-cells in vitro. To this aim, a pancreas specific ECM (PanMa) hydrogel was generated from decellularized porcine pancreas and its effect on the differentiation of hiPSC-derived pancreatic hormone expressing cells (HECs) was tested. The hydrogel solidified upon neutralization at 37 °C with gelation kinetics similar to Matrigel. Cytocompatibility of the PanMa hydrogel was demonstrated for a culture duration of 21 days. Encapsulation and culture of HECs in the PanMa hydrogel over 7 days resulted in a stable gene and protein expression of most ß-cell markers, but did not improve ß-cell identity. In conclusion, the study describes the production of a PanMa hydrogel, which provides the basis for the development of ECM hydrogels that are more adapted to the demands of SC-BCs.

Indocyanine green fluorescence in the evaluation of post-resection pancreatic remnant perfusion after a pancreaticoduodenectomy: a clinical study protocol.

BACKGROUND: Pancreaticoduodenectomy is associated with an incidence of postoperative complications of approximately 41%. One of the most severe complications is a postoperative pancreatic fistula. The exact cause of postoperative fistula development is still unknown, but it appears to be multifactorial. Proper perfusion of pancreatic remnant is essential for the healing of pancreaticojejunostomy. To date, there is no method to reliably evaluate the vascular supply of the remnant. One of the methods for the assessment of organ perfusion is the indocyanine green fluorescence. This study aims to determine if indocyanine green fluorescence is a reliable method to measure the perfusion of the post-resection pancreatic remnant. The secondary outcome is to determine if intraoperative evaluation of the vascular supply of the post-resection remnant may predict the increased risk of postoperative pancreatic fistula development. METHODS: This study is designed as a prospective, observational study. All consecutive patients undergoing open or robotic pancreaticoduodenectomies at our department during the 1st May 2024-31st December 2026 period will be enrolled. The exclusion criteria are an allergy to indocyanine green and refusal by the patient. The adequacy of the vascular supply of the post-resection pancreatic remnant will be intraoperatively evaluated using a fluorescence detector. Patients will be divided into two groups: Those with high risk of pancreatic fistula development and those with low risk. The incidence of pancreatic fistulas in both groups is to be compared. Postoperative data including morbidity, mortality, hospital stay, intensive care unit stay and postoperative fistula development will be collected. DISCUSSION: If an intraoperative assessment of the perfusion of post-resection pancreatic remnant using indocyanine green is proven to be a suitable method to estimate the increased risk of the pancreatic fistula, the list of the existing known risk factors could be expanded. In the most high-risk patients the modification of the surgical procedure could be considered. TRIAL REGISTRATION: Number: NCT06198400 ClinicalTrials.Gov. Date 08.01.2024.

Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches.

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

Enhanced Insulin Secretion Through Upregulation of Transcription Factors by Hydroalcoholic Extract of Securigera securidaca Seeds in Diabetic Animal Model.

AIM: In previous studies, the researchers observed an increase in insulin secretion in STZ-treated diabetic rats following treatment with the hydroalcoholic extract of Securigera securidaca (HESS) seeds. This study focuses on the relationship between the antioxidant properties of HESS with changes in diabetic pancreatic tissue and the gene expression of factors that impact insulin secretion. METHODS: In this controlled experimental study, three varying doses of HESS were administered to three groups of diabetic rats induced by STZ. Oxidative stress indicators like total antioxidant capacity (TAC), total oxidant status (TOS) and malondialdehyde were assessed in both pancreatic and liver tissues. Pancreatic histology was studied post-haematoxylin staining. Insulin and FGF21 levels in the blood were measured using the ELISA method. The expression of Nrf2 and FGF21 genes in the pancreas and liver, along with MafA and PDX-1 genes in the pancreas, was quantified using real-time PCR. RESULTS: The administration of HESS in varying doses led to a dose-dependent rise in blood insulin levels and a decrease in blood glucose levels and oxidative stress. By reducing oxidative stress, HESS treatment lowered the heightened levels of NRF2 and FGF21 in the liver and pancreas of diabetic rats, improving pancreatic tissue health. As oxidative stress decreased, the expression of MafA and PDX1 genes in the pancreas approached levels seen in healthy rats. CONCLUSION: HESS elicits an increase in insulin secretion through the mitigation of oxidative stress and tissue damage, as well as the modulation of gene expression related to the insulin transcription factors PDX-1 and MafA.

In vivo and computational investigation of butin against alloxan-induced diabetes via biochemical, histopathological, and molecular interactions.

Herbs have been used as medicines since antiquity, and it has been discovered that the human body responds well to herbal remedies. Research on the effect of butin was conducted in the current study in the alloxan-induced diabetic rat paradigm. A total of 30 Wistar rats were randomly assigned into the following groups (n = 6): I-Normal; II-Alloxan-induced (50 mg/kg); III-Alloxan + butin 25 mg/kg; IV-Alloxan + butin 50 mg/kg; V-Butin per se 50 mg/kg. Various diabetic parameters (blood glucose, insulin, HbA1c), lipid profile, inflammatory (TNF-α, IL-1ß, IL-6 and NF-κB), antioxidant enzymes (CAT, SOD and GSH), oxidative stress indicators (MDA), apoptosis marker (caspase-3), hepatic markers (ALT and AST), and histopathological changes were assessed. Additionally, molecular docking and dynamics were performed to evaluate the interaction of butin with target proteins. Butin treatment, at both doses, significantly restored biochemical parameters and preserved pancreatic histopathology in diabetic rats. It effectively modulated blood parameters, lipid profiles, inflammatory markers, apoptosis, antioxidant enzyme activity, oxidative stress, and hepatic markers. Molecular docking revealed that butin binds to proteins such as caspase-3 (1NME), NF-κB (1SVC), and serum insulin (4IBM) with binding affinities of - 7.4, - 6.5, and - 8.2 kcal/mol, respectively. Molecular dynamics simulations further suggested that butin induces significant conformational changes in these proteins. Butin exhibits potential effects against alloxan-induced diabetic rats by restoring biochemical balance, reducing inflammation, and protecting pancreatic tissue. Its binding to key proteins involved in apoptosis and inflammation highlights its therapeutic potential in diabetes management.

Diagnostic Efficacy of Cell Block and Liquid-Based Cytology for Endoscopic Ultrasound-Guided Fine Needle Aspiration in Pancreatic Tumors.

This study aimed to evaluate the diagnostic efficacy of cell block (CB) and liquid-based cytology (LBC) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic tumors. The study included patients who underwent EUS-FNA for pancreatic tumors between January 2015 and February 2021 and whose cytology samples were both processed for LBC and CB. Data of 390 patients (220 men, mean age: 64.2 ± 11.4 years) were retrospectively analyzed. Of the detected lesions (size: 17-120 mm; mean: 39.9 ± 13.9 mm), 220 (56.4%) were located in the head and uncinate process of the pancreas. Lesions in 339 (86.9%) patients were diagnosed as malignant using CB and/or LBC and suspicious for malignancy in 44 (11.3%) patients. In 7 patients with non-diagnostic (6 cases) or negative for malignancy (1 case) EUS-FNA results using both methods, the diagnosis of malignancy was established via ultrasound-guided percutaneous biopsy. Malignancy was detected in 324 (92.4%), 313 (87.9%), and 298 (87.9%) patients using CB, LBC, and both CB and LBC, respectively. Final diagnosis was obtained in 339 (98%) patients by using CB and/or LBC. The combined use of the both methods exhibited significantly superior diagnostic accuracy compared with CB and LBC alone (P < .001). Liquid-based cytology and CB exhibit high diagnostic accuracy for the detection of pancreatic tumors in patients undergoing EUS-FNA. The combined use of both methods showed a significantly higher diagnostic accuracy than LBC and CB alone.

Residue profiles of peptides with cholesterol esterase and pancreatic lipase inhibitory activities through virtual screening and sequence analysis.

The detailed characterization of the structural features of peptides targeting cholesterol esterase (CEase) or pancreatic lipase (PPL) will benefit the management of hyperlipidemia and obesity. This study employed the Glide SP (standard precision)-peptide method to predict the binding modes of 202 dipeptides and 203 tripeptides to these targets, correlating residue composition and position with binding energy. Strong preferences for Trp, Phe, and Tyr were observed at all positions of potential inhibitory peptides, whereas negatively charged residues Glu and Asp were disfavored. Notably, Arg and aromatic rings significantly influenced the peptide conformation at the active site. Tripeptide IWR demonstrated the high efficacy, with IC50 values of 0.214 mg/mL for CEase and 0.230 mg/mL for PPL. Five novel IWR scaffold-tetrapeptides exhibited promising inhibitory activity. Non-covalent interactions and energy contributions dominated the formation of stable complexes. Our results provide insights for the development of new sequences or peptide-like molecules with enhanced inhibitory activity.

[Isolated pancreatic injury after blunt abdominal trauma: severe pathology in initially asymptomatic patient]. / Pancreasletsel na een stomp buiktrauma.

BACKGROUND: Isolated pancreatic injury after blunt abdominal trauma is rare but unreliably excludable based on clinical symptoms. A CT-abdomen is the golden standard in diagnosing. Undiagnosed pancreatic injury can result in severe complications as abscesses and fistulas. CASE DESCRIPTION: A sixteen-year old patient was brought to the Emergency Department (ED) with epigastric pain, two days after a low-energy scooter accident. No (abdominal) alarming symptoms were objectified during direct assessment by the general practitioner. However, a complete pancreatic transection was diagnosed after assessment at the ED, eventually resulting in a distal pancreatectomy with postoperative associated complications. CONCLUSION: In all traumas, the mechanism of injury should be judged critically for the possibility of abdominal injury (as pancreatic damage) and thus the need for imaging. An initially harmless clinical condition can mask extensive injury. This case illustrates the importance of thoughtful expectant policies with return instructions or demarcated follow-up when no CT-scan is performed.

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis.

BACKGROUND: Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation. METHODS: Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. RESULTS: Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR-/- pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR-/- animals at 80- and 120-days gestation, as are stellate cells at term. CONCLUSION: The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.

Prevalence of Pancreatic Steatosis and Its Associated Factors in Turkey: A Nation-Wide Multicenter Study.

BACKGROUND/AIMS:  Pancreatic steatosis (PS) is a pathology associated with metabolic syndrome (MS), endocrin and exocrine disfunctions of the pancreas, and fatty liver. The data on the frequency of PS are very limited. We aimed to evaluate the frequency of PS detected by transabdominal ultrasonography (TAU) in gastroenterology clinics located in different geographical regions of Turkey and the factors associated with it. MATERIALS AND METHODS:  Volunteers were evaluated by TAU for PS and hepatosteatosis (HS), and its degree. Pancreatic stiffness was evaluated by ultrasonographic shear wave elastography (SWE). All demographic, physical, and biochemical parametres were measured. RESULTS:  A total of 1700 volunteers from 14 centers throughout Turkey were included in the study. Mean age was 48.03 ± 20.86 years (56.9% female). Prevalance of PS was detected in 68.9%. In the PS group, age, body mass index (BMI), waist circumference, systolic blood pressure, fasting blood glucose (FBG), lipid levels, insulin resistance, diabetes mellitus, hypertension, MS frequency, and pancreatic SWE score were increasing, and fecal elastase level was decreasing in correlation with the degree of PS. The frequency of HS was 55.5%. Hepatosteatosis [odds ratio (OR): 9.472], increased age (OR: 1.02), and BMI (OR: 1.089) were independent risk factors for the occurrence of PS. Lean-PS rate was 11.8%. The lean-PS group was predominantly female and younger than non-lean PS. Also it has lower blood pressure, FBG, liver enzymes, lipid levels, and HS rates. CONCLUSION:  The frequency of PS was found 68.9% in Turkey. Its relationship was determined with age, BMI, HS, MS (and its components), pancreatic stiffness, and fecal elastase level.

Non-human primate model of long-COVID identifies immune associates of hyperglycemia.

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects.

Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology.

Ras-related Rap1A GTPase is implicated in pancreas ß-cell insulin secretion and is stimulated by the cAMP sensor Epac2, a guanine exchange factor and activator of Rap1 GTPase. In this study, we examined the differential proteomic profiles of pancreata from C57BL/6 Rap1A-deficient (Null) and control wild-type (WT) mice with nanoLC-ESI-MS/MS to assess targets of Rap1A potentially involved in insulin regulation. We identified 77 overlapping identifier proteins in both groups, with 8 distinct identifier proteins in Null versus 56 distinct identifier proteins in WT mice pancreata. Functional enrichment analysis showed four of the eight Null unique proteins, ERO1-like protein ß (Ero1lß), triosephosphate isomerase (TP1), 14-3-3 protein γ, and kallikrein-1, were exclusively involved in insulin biogenesis, with roles in insulin metabolism. Specifically, the mRNA expression of Ero1lß and TP1 was significantly (p < 0.05) increased in Null versus WT pancreata. Rap1A deficiency significantly affected glucose tolerance during the first 15-30 min of glucose challenge but showed no impact on insulin sensitivity. Ex vivo glucose-stimulated insulin secretion (GSIS) studies on isolated Null islets showed significantly impaired GSIS. Furthermore, in GSIS-impaired islets, the cAMP-Epac2-Rap1A pathway was significantly compromised compared to the WT. Altogether, these studies underscore an essential role of Rap1A GTPase in pancreas physiological function.