Pancreatic Pathology Research Articles

Cystic fibrosis-related diabetes is associated with reduced islet protein expression of GLP-1 receptor and perturbation of cell-specific transcriptional programs

Insulin secretion is impaired in individuals with cystic fibrosis (CF), contributing to high rates of CF-related diabetes (CFRD) and substantially increasing disease burden. To develop improved therapies for CFRD, better knowledge of pancreatic pathology in CF is needed. Glucagon like peptide-1 (GLP-1) from islet α cells potentiates insulin secretion by binding GLP-1 receptors (GLP-1Rs) on β cells. We determined whether expression of GLP-1 and/or its signaling components are reduced in CFRD, thereby contributing to impaired insulin secretion. Immunohistochemistry of pancreas from humans with CFRD versus no-CF/no-diabetes revealed no difference in GLP-1 immunoreactivity per islet area, whereas GLP-1R immunoreactivity per islet area or per insulin-positive islet area was reduced in CFRD. Using spatial transcriptomics, we observed several differentially expressed α- and/or β-cell genes between CFRD and control pancreas. In CFRD, we found upregulation of α-cell PCSK1 which encodes the enzyme (PC1/3) that generates GLP-1, and downregulation of α-cell PCSK1N which inhibits PC1/3. Gene set enrichment analysis also revealed α and β cell-specific pathway dysregulation in CFRD. Together, our data suggest intra-islet GLP-1 is not limiting in CFRD, but its action may be restricted due to reduced GLP-1R protein levels. Thus, restoring β-cell GLP-1R protein expression may improve β-cell function in CFRD.

S2615 Unveiling the Unusual: Dedifferentiated Liposarcoma Mimicking Pancreatic Pathology in a Gastroenterology Setting

S2615 Unveiling the Unusual: Dedifferentiated Liposarcoma Mimicking Pancreatic Pathology in a Gastroenterology Setting

Clinical Utility of Serial Monitoring of C-Peptide in Diagnostic Dilemmas of Young-Onset Diabetes: A Case-Based Discussion

Abstract Diabetes in the young has been traditionally defined as onset of diabetes below 35 years of age. In this age bracket, a variety of distinct types of diabetes might occur which poses a unique challenge in the diagnosis and management. Phenotypic features such as age of onset, presence of obesity and family history have traditionally been used in differentiating the various types of diabetes. With the increasing prevalence of obesity and T2DM in youth, these features have become less reliable in classifying diabetes in this age group. Along with detailed patient history and physical examination, biochemical parameters such as C-peptide and presence or absence of pancreatic autoantibodies (along with imaging studies for pancreatic pathology and genetic testing for monogenic forms of diabetes) are assuming greater importance in appropriate diagnosis and understanding the types of diabetes. C-peptide test which is a proxy for pancreatic beta cell function plays an important role in classifying type / subtypes of diabetes. When used appropriately it also helps in personalized approach to treatment and practice of Precision Diabetes.

Domestic researchers who have made important contributions to the study of digestive system diseases: images in art. Nina Fedorivna Deyneko

Nina Fedorivna Deyneko is a Doctor of Medical Sciences, Professor, an honored worker of science and technology of Ukraine, an outstanding health care worker, a labor veteran, and an academician of the International Academy of Sciences in apiphytotherapy and beekeeping. Under Prof. N. F. Deyneko’s supervision, 86 clinical residents, including 34 foreign ones, and postgraduate students were taught during her tenure at the Kharkiv departments of therapy and gastroenterology. Additionally, 25 candidate dissertations and one doctorate thesis were defended. She served as the head of the Kharkiv Medical Institute’s state examination commission for 15 years, founded and presided over the Kharkiv Medical Society of Gastroenterologists for 20 years, was a member of the All‑Union Society of Gastroenterologists’ Presidium of the Board for more than 20 years, and worked as the deputy chairman of the board of the Ukrainian Republican Society of Gastroenterologists. More than 200 research publications, four monographs, textbooks, and copyright certificates have been produced by Nina Fedorivna. Kharkiv Railway Clinical Hospital №1 became the clinical base of the Department of Gastroenterology of the Ukrainian Institute for Advanced Medical Studies, which was headed by Professor Nina Fedorivna Deyneko. Contemporary diagnostic equipment made it possible to perform diagnosis and treatment of patients with pathologies of the gastrointestinal, liver, biliary and pancreatic pathologies. The goal of methodological and pedagogical work was to optimize the educational process by using modern techniques for tracking students’ practical skills and initial, intermediate, and final levels of learning. Four‑ and three‑ month specialty cycles, as well as pre‑certification and theme improvement in the field of gastroenterology, were implemented during the first five years of the department’s existence. In addition to receiving 20 copyright certificates and publishing over 300 research papers, department staff members have also developed 62 rationalization recommendations that have been put into practice in the healthcare industry. The staff of the department participated in many scientific forums, including those conducted abroad.

Abstract A081: Single-cell transcriptomic analysis of organoids derived from normal pancreata reveals epithelial cell heterogeneity and expression of PanIN-associated genes

Abstract Pancreatic intraepithelial neoplasia (PanIN) lesions are the microscopic pre-malignant precursor to pancreatic ductal adenocarcinoma (PDAC). Animal models have demonstrated that PanINs arise from acinar cells which have undergone acinar-to-ductal metaplasia (ADM), but the exact molecular mechanisms which govern this transformation remain poorly understood. Novel in vitro models of PanIN genesis are necessary to better characterize pancreatic carcinogenesis and identify clinically actionable biomarkers of early disease. Organoids cultured from normal human pancreata have generated promise in this regard, but the cellular identity and malignant potential of their component cells have not been comprehensively characterized. We performed single-cell RNA sequencing (10X Genomics) on 6 normal pancreatic organoid lines maintained in culture for 3 weeks as well as their parent pancreata obtained from donors with no history of PDAC or other exocrine pancreatic pathology. Integration of whole pancreatic and organoid data using the R package Seurat generated a UMAP with clearly defined “ductal” and “acinar” clusters based on marker gene expression. The majority of organoid cells (47.3-81.5%) colocalized to the “ductal” cluster, and expressed SOX9, KRT19, and PDX1. However, a subset of cells (1.0-33.3%) present in each organoid sample aligned with the “acinar” cluster and expressed PRSS1, PRSS3, REG3A, MUC1, and SPINK1. In accordance with prior reports, organoid cells did not meaningfully express the acinar/endocrine markers PTF1A, CPA1, CHGA, or INS. Further examination of the “acinar” organoid cells revealed heightened expression of CLDN18, TFF1, TFF2, CTSE, CA2, and LYZ, genes associated with PanIN in prior spatial RNA sequencing studies. Other genes significantly enriched in this “acinar” organoid cluster include MUC5AC, a known PanIN marker, OLFM4, a tumor suppressor implicated in intestinal carcinogenesis, and the chemokine CXCL17, which is expressed in cells undergoing ADM. Overall, this data suggests that organoids derived from normal pancreata represent a heterogeneous population of epithelial cells with both acinar and ductal features. Furthermore, these organoids may represent an in vitro model of ADM and/or early PanIN formation, though additional functional mechanistic studies are required for confirmation. Citation Format: Alexander W Bray, Eileen S Carpenter, Timothy L Frankel, Marina Pasca di Magliano. Single-cell transcriptomic analysis of organoids derived from normal pancreata reveals epithelial cell heterogeneity and expression of PanIN-associated genes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A081.

Bufalin alleviates inflammatory response and oxidative stress in experimental severe acute pancreatitis through activating Keap1-Nrf2/HO-1 and inhibiting NF-κB pathways

Severe acute pancreatitis (SAP) is a prevalent acute inflammatory disease that is clinically manifested by systemic inflammation dysregulation, resulting in a significantly elevated mortality rate. Bufalin has been verified to have potent pharmacological properties, including analgesic, anti-tumor and anti-inflammatory effects. However, it remains unclear whether bufalin inhibits SAP. Thus, we aim to explore the impact of bufalin in SAP rats and to evaluate the potential mechanisms of action. In addition to analyzing serum biochemistry and pancreatic tissue pathology, we elucidated its mechanisms of action through enzyme-linked immunosorbent assay (ELISA), immunohistochemical analysis, Western blot, and quantitative real-time PCR. The results demonstrated that bufalin dose-dependently reversed the elevation of serum Amylase (Amy) and Lipase (LPS) levels in SAP rats, alleviating pancreatic tissue pathological damage. Bufalin exhibited potent antioxidant effects by reducing malondialdehyde (MDA) levels, decreasing Superoxide dismutase (SOD) and glutathione(GSH) consumption, inhibiting the interaction of Keap1-Nrf2, and increasing HO-1 expression. Furthermore, bufalin inhibited TNF-α, IL-6, IL-1β, p-NF-κB-p65, p-IκBα, and NF-κB-p65 expression, while enhancing IκBα expression, ultimately confirming its anti-inflammatory effects on SAP. In summary, our findings suggest that bufalin exerts anti-inflammatory and antioxidant actions in NaT-SAP rats by inhibiting NF-κB and activating the Keap1-Nrf2/HO-1 pathway. This study represents the inaugural application of bufalin in NaT-induced SAP rats, indicating its potential as an effective therapeutic agent for SAP patients.

Endoscopic Management of Biliary and Pancreatic Pathologies in Roux-en-Y Gastric Bypass Patients: Development of a Treatment Algorithm Based on 9-Year Experience.

Management of biliopancreatic pathology in Roux-en-Y gastric bypass (RYGB) patients is challenging despite the availability of multiple approaches like single-balloon enteroscopy-assisted ERCP (SBE-ERCP), laparoscopy-assisted ERCP (LA-ERCP), and EUS-directed transgastric intervention (EDGI). We evaluated the outcomes of the interchangeable combination of endoscopic procedures to treat biliopancreatic pathology in RYGB patients. This is a monocentric retrospective study of consecutive RYGB patients with biliopancreatic pathology between June 2014 and September 2023. Primary endpoints were technical success, adverse events (AE), and parameters of endoscopic procedures according to etiology. A clinically useful management algorithm was developed. A total of 102 patients with RYGB (73 women; mean age 55 ± 10years) were included. A total of 113 SBE-ERCP (in 90 patients), 26 EDGI (in 23 patients), and 2 LA-ERCP (in 2 patients) were performed. Technical success of SBE-ERCP was lower compared to EDGI (74.4% vs 95.1%, p = 0.002). The AE rate was lower using SBE-ERCP compared to EDGI (12.4% vs 38.5%, p = 0.003). Two sub-groups based on etiology were identified as "common bile duct stone" (CBDS) and "Other." In the CBDS group, the mean number and time of procedures were lower in SBE-ERCP as the first-line technique compared to first-line EDGI (1.1 vs 2.7, p < 0.00 and 91 ± 20.7min vs 161 ± 61.3min, p < 0.00). A combination of endoscopic procedures can achieve high technical success in managing biliopancreatic pathology in RYGB patients with an acceptable AE rate. In the case of CBDS, SBE-ERCP appeared to be a good first-line single-step option. For other indications, EDGI should be proposed as the first line.

Not just a BLiP: early experience with a novel multidisciplinary case conference for benign hepatopancreatobiliary disease at a tertiary Canadian healthcare center.

Benign Liver and Pancreas (BLiPs) rounds, implemented in 2022 at our Canadian tertiary care center, are a novel concept of a multidisciplinary case conference (MCC) for discussion of benign hepatopancreatobiliary (HPB) disease. BLiPs Rounds are a monthly virtual meeting of surgeons, gastroenterologists, and interventional radiologists experienced in biliary and pancreatic disease. This case series was completed to review the patient cases discussed over the first year of BLiPs rounds, and to evaluate the effect of the multidisciplinary discussion on patient management plans. Meeting minutes were reviewed for BLiPs rounds between May 2022 and July 2023. Data were collected retrospectively on all discussed patients by review of the electronic medical record, and analyzed using frequencies and means with standard deviations. Between May 2022 and July 2023, 56 cases were discussed at 12 case conferences. 68% of cases concerned pancreatic pathology, 25% concerned biliary pathology, the remainder liver or duodenal pathology. 49 cases (88%) were presented to discuss therapeutic options, and 7 presented as diagnostic challenges. Cases were usually presented once, but 7 patients were discussed at multiple conferences due to complex issues or ongoing symptomatology. 40 patients (71%) had undergone previous endoscopic, percutaneous, or surgical interventions prior to discussion. Endoscopic intervention was recommended in 32% of cases, percutaneous interventional approach in 13%, a combined endoscopic and percutaneous approach in 9%, and surgery in 18%. Repeat imaging or observation was recommended in 29% of cases. Discussion at rounds led to a change or adjustment in the proposed management in 46 cases (82%). The plan recommended by the MCC was carried out in 71% of cases. BLiPs case conference provides a valuable venue to discuss cases, encourage interdisciplinary collaboration, and refine treatment approaches, leading to a change in proposed management plan in over three-quarters of cases presented.

ICD-10 Diagnosis Codes are Over-Utilized in the Diagnosis of Chronic Pancreatitis

ABSTRACT BACKGROUND Large databases, such as the OneFlorida Clinical Research Consortium1, rely on ICD-10 diagnosis codes to identify patients with specificity. Patients enrolled in retrospective research studies are often collected via the use of ICD-10 diagnosis codes. These codes can be subject to error due to over- or under-diagnosing, which is especially true in diseases that are difficult to diagnose, such as chronic pancreatitis (CP). Symptoms of chronic pancreatitis can be vague and non-specific, particularly in the early stages of the disease. This study aimed to determine if ICD-10 diagnosis codes for CP are overutilized and to recognize alternative pathologies that likely lead to the ICD-10 diagnosis code for CP being placed. METHODS A retrospective analysis was conducted of all patients with ICD-10 codes K86.0 (alcohol-induced chronic pancreatitis) and K86.1 (other chronic pancreatitis) who were seen in either an outpatient or inpatient setting at a tertiary care center from February 2018 to February 2020. Data was extracted from the institution’s integrated electronic data repository. This study was approved by the Institutional Review Board (IRB). A total of 1,360 unique patient charts were reviewed, of which 176 carried ICD-10 code K86.0 and 1,184 carried ICD-10 code K86.1. The diagnosis of CP was defined as either being made by a gastroenterologist, proven by biopsy, or having classic findings of CP on cross-sectional imaging with appropriate symptoms. RESULTS A total of 504 (37%) out of the 1,360 patient charts did not have any evidence of chronic pancreatitis despite being labeled with an ICD-10 code for CP. When broken down by diagnosis code, 41 of 176 charts (23.3%) with K86.0 and 461 of 1,184 charts (38.6%) with K86.1 did not have any evidence of CP. Of these patients, 163 had a single episode of acute pancreatitis of any etiology, 107 had recurrent acute pancreatitis, 29 had an episode of acute necrotizing pancreatitis, 22 had cancer (pancreatic or cholangiocarcinoma), 19 had pancreatic resection without underlying CP, 48 had chronic abdominal pain of non-pancreaticobiliary etiology (IBS, IBD, gastritis, PUD, gastroparesis), and 81 had no identifiable abdominal pathology. CONCLUSIONS We found that even at a tertiary care center and a pancreatic center of excellence, many patients with no evidence of chronic pancreatitis were labeled at some point in their care with an ICD-10 diagnosis code for CP. The majority of these had an alternative pancreatic pathology however a significant number had no evidence of a pancreaticobiliary pathology. Although the OneFlorida database makes multicenter research more accessible, it does not replace labor-intensive chart review for CP given the propensity for over-diagnosis.

Deep Machine Learning for Automatic Segmentation of the Pancreatic Parenchyma and its hypo- and hypervascular lesions on CT Images

Objective of the study. To develop and evaluate the effectiveness of a technology for segmenting the pancreatic parenchyma and its hyper- and hypovascular lesions on abdominal computed tomography (CT) scans using deep machine learning.Materials and methods. CT scans from the database of the A.V. Vishnevsky National Medical Research Center of Surgery were used for training and testing the algorithms – a total number of approximately 150 studies (arterial and venous phases). A test dataset of 46 anonymized CT scans (arterial and venous phases) was prepared for validation of the obtained algorithms, independently assessed by expert physicians. The primary segmentation neural network used is nn-UNet (M. Antonelli et al., 2022).Results. The average accuracy of the test dataset for the model determining segmentation masks of the pancreas on CT images had an AUC of 0.8 for the venous phase and 0.85 for the arterial phase. The segmentation masks of pancreatic formations had an AUC of 0.6.Conclusion. Automated segmentation of the pancreatic parenchyma structure using deep machine learning technologies demonstrated high accuracy. However, the segmentation of hypo- and hypervascular pancreatic lesions requires improvement. The overlap of the masks showed a rather low result, but in all cases, the location of the pathological formation was correctly identified by the algorithm. Enhancing the training dataset and the algorithm used could increase the accuracy of the algorithm.No false negative results were obtained when detecting pancreatic formations; in all cases, the INS detected “suspicious” areas of the pancreatic parenchyma. This can help reduce the omission of pancreatic pathologies in CT scans, and their further assessment can be carried out by the radiologist himself.

MTORC2 knockdown mediates lipid metabolism to alleviate hyperlipidemic pancreatitis through PPARα.

Hyperlipidemic pancreatitis (HP) is an inflammatory injury of the pancreas triggered by elevated serum triglyceride (TG) levels. The mechanistic target of rapamycin (mTOR) signaling pathway plays a crucial role in regulating lipid homeostasis and inflammation. This study aimed to investigate whether the activity of mTOR complex 2 (mTORC2) affects the progression of HP and its underlying mechanisms. In vivo, a high-fat diet and retrograde administration of sodium taurocholate were employed to establish theHP models in rats, with pancreatic tissue pathology evaluated. The expression of Rictor and peroxisome proliferator-activator receptor (PPAR) was examined. The serum levels of TG, fatty acid metabolites, inflammatory and lipid metabolism-related factors were determined. In vitro, pancreatic acinar cells (PACs) were exposed to palmitic acid and cholecystokinin-8. PAC apoptosis, pyroptosis, and ferroptosis were assessed. In the HP models, rats and PACs exhibited upregulated Rictor and downregulated PPARα, and Rictor knockdown promoted PPARα expression. In vivo, Rictor knockdown decreased the serum levels of TG, α-amylase, total cholesterol, low-density lipoprotein cholesterol, lactate dehydrogenase, and inflammatory factors, while increasing high-density lipoprotein cholesterol levels. Rictor knockdown increased ACOX1 and CPT1α and decreased SREBP-1, CD36, SCD1, ACLY, and ACACA. Rictor knockdown reduced damage to pancreatic tissue structure. In vitro, Rictor knockdown inhibited PAC apoptosis, pyroptosis, and ferroptosis. Treatment with the PPARα antagonist GW6471 abolished the beneficial effects of Rictor knockdown. Rictor/mTORC2 deficiency reduces serum TG levels, maintains lipid homeostasis, and suppresses inflammation by inhibiting PPARα expression. Weakening mTORC2 activity holds promise as a novel therapeutic strategy for HP.

Postoperative Pancreatic Fistula Following Duct To Mucosa Pancreaticojejunostomy After 100 Consecutive Whipple’s Surgery

Background: Postoperative pancreatic fistula (POPF) remains a concerning complication following pancreaticojejunostomy (PJ). Its incidence can be as high as 20%, with identified risk factors including soft gland texture, small main pancreatic duct (MPD) diameter, pancreatic pathology, and significant intraoperative blood loss. Our primary objective is to determine the incidence of POPF and assess its associated risk factors by consistently applying a uniform surgical technique and utilizing uniform suturing materials. Methods: Our study included patients who underwent PJ following pancreaticoduodenectomy at our center using a consistent duct-to-mucosa technique and the same suturing material, PDS 5-0. Data from 100 consecutive patients were collected and entered into the Statistical Package for the Social Sciences (SPSS 26) for analysis of postoperative pancreatic fistula (POPF). Results: Among the 100 patients, the incidence of clinically relevant POPF was 5%. Factors such as gland texture and main pancreatic duct (MPD) diameter did not demonstrate any statistically significant correlation with POPF, however the frequency of POPF was notably high in cases with an MPD diameter of less than 3 mm. Mortality following clinically relevant POPF was substantial, reaching 4%, and this association was statistically significant (p &lt; 0.001). Conclusion: POPF represents a severe complication associated with statistically significant mortality. Employing a uniform standard duct-to-mucosa anastomotic technique along with consistent use of suturing material is imperative to mitigate bias and minimize the risk of POPF.

Deep Learning Reconstruction of Prospectively Accelerated MRI of the Pancreas: Clinical Evaluation of Shortened Breath-Hold Examinations With Dixon Fat Suppression.

Deep learning (DL)-enabled magnetic resonance imaging (MRI) reconstructions can enable shortening of breath-hold examinations and improve image quality by reducing motion artifacts. Prospective studies with DL reconstructions of accelerated MRI of the upper abdomen in the context of pancreatic pathologies are lacking. In a clinical setting, the purpose of this study is to investigate the performance of a novel DL-based reconstruction algorithm in T1-weighted volumetric interpolated breath-hold examinations with partial Fourier sampling and Dixon fat suppression (hereafter, VIBE-DixonDL). The objective is to analyze its impact on acquisition time, image sharpness and quality, diagnostic confidence, pancreatic lesion conspicuity, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). This prospective single-center study included participants with various pancreatic pathologies who gave written consent from January 2023 to September 2023. During the same session, each participant underwent 2 MRI acquisitions using a 1.5 T scanner: conventional precontrast and postcontrast T1-weighted VIBE acquisitions with Dixon fat suppression (VIBE-Dixon, reference standard) using 4-fold parallel imaging acceleration and 6-fold accelerated VIBE-Dixon acquisitions with partial Fourier sampling utilizing a novel DL reconstruction tailored to the acquisition. A qualitative image analysis was performed by 4 readers. Acquisition time, image sharpness, overall image quality, image noise and artifacts, diagnostic confidence, as well as pancreatic lesion conspicuity and size were compared. Furthermore, a quantitative analysis of SNR and CNR was performed. Thirty-two participants were evaluated (mean age ± SD, 62 ± 19 years; 20 men). The VIBE-DixonDL method enabled up to 52% reduction in average breath-hold time (7 seconds for VIBE-DixonDL vs 15 seconds for VIBE-Dixon, P < 0.001). A significant improvement of image sharpness, overall image quality, diagnostic confidence, and pancreatic lesion conspicuity was observed in the images recorded using VIBE-DixonDL (P < 0.001). Furthermore, a significant reduction of image noise and motion artifacts was noted in the images recorded using the VIBE-DixonDL technique (P < 0.001). In addition, for all readers, there was no evidence of a difference in lesion size measurement between VIBE-Dixon and VIBE-DixonDL. Interreader agreement between VIBE-Dixon and VIBE-DixonDL regarding lesion size was excellent (intraclass correlation coefficient, >90). Finally, a statistically significant increase of pancreatic SNR in VIBE-DIXONDL was observed in both the precontrast (P = 0.025) and postcontrast images (P < 0.001). Also, an increase of splenic SNR in VIBE-DIXONDL was observed in both the precontrast and postcontrast images, but only reaching statistical significance in the postcontrast images (P = 0.34 and P = 0.003, respectively). Similarly, an increase of pancreas CNR in VIBE-DIXONDL was observed in both the precontrast and postcontrast images, but only reaching statistical significance in the postcontrast images (P = 0.557 and P = 0.026, respectively). The prospectively accelerated, DL-enhanced VIBE with Dixon fat suppression was clinically feasible. It enabled a 52% reduction in breath-hold time and provided superior image quality, diagnostic confidence, and pancreatic lesion conspicuity. This technique might be especially useful for patients with limited breath-hold capacity.

Isolation Procedure for Rat Pancreatic Ductal Cells.

Isolating pancreatic ductal cells from rats is a critical procedure in pancreatic research, offering valuable insights into pancreatic function, pathology, and potential treatments. The process involves several key steps, beginning with the proper removal of the rat's pancreas, followed by the initiation of the ductal cell isolation procedure. This aims to obtain pure and viable ductal cell populations for further experimentation and analysis.

Epidermoid Cyst arising within an Intrapancreatic Accessory Spleen [ECIPAS] mimicking a pancreatic mucinous cystic neoplasm-a case report with literature review

Background: Accessory spleens are congenital embryological aberrations usually found within the splenic hilum with no clinical significance. An Intra Pancreatic Accessory Spleen (IPAS) is an uncommon benign pancreatic lesion encountered clinically. The occurrence of an Epidermoid Cyst arising within an IPAS (ECIPAS) is exceedingly rare and is often misdiagnosed as a pancreatic pathology such as mucinous cystic neoplasm, cystic degeneration within a solid tumor such as a neuroendocrine tumor, or a lymph node. Case report: A 68-year-old male presented with intermittent post-prandial abdominal pain for over 2 years. Abdominal computer tomography identified a 5.2 cm calcified cyst within the pancreatic tail and a mucinous pancreatic neoplasm/pancreatic pseudocyst was considered in the differential diagnosis. The results of endoscopic ultrasound and fine needle aspiration were indeterminate. Due to persistent abdominal pain, the patient underwent a laparoscopic distal pancreatectomy with splenectomy. A gross examination of the distal pancreatic/splenectomy specimen confirmed a well-demarcated cystic lesion with brownish fluid within the pancreatic tail. Microscopic examination revealed a nonpathological pancreas separated by a fibrous capsule with a large cyst arising within an intrapancreatic accessory spleen. The cyst was lined with multilayered non-keratinized stratified squamous epithelium positive for pancytokeratin, CA 19-9, CK5/6, and p63 with no lymphocytic infiltrates and absent hair/ dermal appendages confirming an epidermoid cyst. CD8 outlined the dendritic network of the littoral cells of the splenic tissue in the cyst wall. Post-operative follow-up at 6 weeks was uneventful. Conclusion: The preoperative diagnosis of ECIPAS is extremely difficult as this entity shares overlapping radiological features with other cystic lesions such as mucinous pancreatic cysts. It is important for anatomic pathologists to recognize and consider the intrapancreatic compartment as a possible site for accessory spleen. As histopathology is the final determinant of this diagnosis, increased clinical awareness with an accurate diagnosis of this entity may prevent patients from unnecessary surveillance and/or extensive oncological-based surgical resection.

Robotic‑assisted minimally invasive pancreas surgery. Review

The use robotics in surgery is gaining momentum. This approach holds substantial promise in pancreas surgery. Minimally invasive techniques have been increasingly used in oncologic surgery and pancreatic surgery in particular. Minimally invasive pancreatectomy (MIP) has been performed with increasing frequency in all pancreatic pathologies, including pancreatic neuroendocrine tumors (PNETs), including pancreaticoduodenectomy (PD), distal pancreatectomy (DP), and pancreatic enucleation. Robotic‑assisted surgery using the DaVinci platform has accelerated the adoption of MIP. The proportion of robotic DP between 2015 and 2016 was nearly 4 times greater than between 2010 and 2012 (16% vs 4%), with a similar increase in proportion of robotic PD (7% vs 2%) over the same time frame. Advantages of robotic surgery over laparoscopy include three‑dimensional visualization, increased degrees of motion with endo‑articulation, stable camera platform, surgeon ergonomics, and single surgeon’s ability to control four instruments. Systematic adoption of MIP has been facilitated by the creation of multiple multicenter training programs in robotic DP and PD, aiming to standardize the oncologic safety and technical performance of these operations. Robotic surgery for pancreatic lesions and malignancies has become well accepted and is expanding to more and more center annually. The number of centers using robotics in pancreatic surgery is rapidly increasing. The most studied robotic pancreas surgeries are PD and DP. Most studies are in their early phases, but they report that robotic pancreas surgery is safe feasible. Robotic pancreas surgery offers several advantages over open and laparoscopic techniques. Data regarding costs of robotics versus conventional techniques is still lacking. Robotic pancreas surgery is still in its early stages. It holds promise to become the new surgical standard for pancreatic resections in the future, however, more research is still needed to establish its safety, cost effectiveness and efficacy in providing the best outcomes.

Label-free differentiation of pancreatic pathologies from normal pancreas utilizing end-to-end three-dimensional multimodal networks on CT

To investigate the utilization of an end-to-end multimodal convolutional model in the rapid and accurate diagnosis of pancreatic diseases using abdominal CT images. In this study, a novel lightweight label-free end-to-end multimodal network (eeMulNet) model was proposed for the rapid and precise diagnosis of abnormal pancreas. The eeMulNet consists of two steps: pancreatic region localization and multimodal CT diagnosis integrating textual and image data. A research dataset comprising 715 CT scans with various types of pancreas diseases and 228 CT scans from a control group was collected. The training set and independent test set for the multimodal classification network were randomly divided in an 8:2 ratio (755 for training and 188 for testing). The eeMulNet model demonstrated outstanding performance on an independent test set of 188 CT scans (Normal: 45, Abnormal: 143), with an area under the curve (AUC) of 1.0, accuracy of 100%, and sensitivity of 100%. The average testing duration per patient was 41.04 seconds, while the classification network took only 0.04 seconds. The proposed eeMulNet model offers a promising approach for the diagnosis of pancreatic diseases. It can support the identification of suspicious cases during daily radiology work and enhance the accuracy of pancreatic disease diagnosis. The codes and models of eeMulNet are publicly available at Rudeguy1/eeMulNet (github.com).

Association of human interpretable features derived from pancreatic ductal adenocarcinoma pathology slides with disease-free survival.

e16368 Background: Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second cause of cancer death in the US by 2040. For the minority of patients who are candidates for curative-intent surgical resection, a neoadjuvant approach with chemotherapy or chemotherapy followed by chemoradiotherapy (chemoRT) has become the standard of care. The tumor microenvironment (TME) has been recognized as a key factor in therapeutic resistance and disease progression. This study aims to explore the prognostic value of human-interpretable machine learning image features (HIFs) derived from whole-slide H&amp;E images. Methods: Consecutive PDAC patients who underwent neoadjuvant therapy followed by surgical resection were studied in this single-institution retrospective study. Clinical variables collected include tumor site (head/body/tail), surgery extent, histology, sex, age at diagnosis, grade, treatment response (4-point scale), LVI, PNI, resection margin status, pathological TNM staging, number of lymph nodes removed/positive, neoadjuvant strategy (chemotherapy vs chemoRT), and number of neoadjuvant chemo cycles. These factors were analyzed with a multivariable Cox proportional hazards model for disease-free survival (DFS) after surgery. Additionally, 420 human-interpretable image features (HIFs) derived from a commercial machine learning software were analyzed with a univariable Cox model on a binary outcome of 1-yr DFS, applying a Bonferroni correction for multiple comparisons to identify significant predictors. Results: Increased neoadjuvant chemotherapy cycles (HR = 0.62, p = 0.001, [median: 8, IQR: 6-12]) and receipt of combination neoadjuvant therapy (HR = 0.15, p = 0.020, [29% chemo, 71% +chemoRT]) exhibited a protective effect in the multivariable DFS model. 3 HIFs quantifying immune cells and macrophages within the cancerous tissue and its stroma were associated with an improved probability of 1-year DFS. Conclusions: In addition to clinical factors, HIFs may offer valuable insights into the tumor microenvironment's influence on PDAC progression, paving the way for improved prognostic models and therapeutic strategies. Future work will integrate clinical predictors with HIFs in a combined model.

A Comparison of CT-Based Pancreatic Segmentation Deep Learning Models

Rationale and ObjectivesPancreas segmentation accuracy at CT is critical for the identification of pancreatic pathologies and is essential for the development of imaging biomarkers. Our objective was to benchmark the performance of five high-performing pancreas segmentation models across multiple metrics stratified by scan and patient/pancreatic characteristics that may affect segmentation performance. Materials and MethodsIn this retrospective study, PubMed and ArXiv searches were conducted to identify pancreas segmentation models which were then evaluated on a set of annotated imaging datasets. Results (Dice score, Hausdorff distance [HD], average surface distance [ASD]) were stratified by contrast status and quartiles of peri-pancreatic attenuation (5mm region around pancreas). Multivariate regression was performed to identify imaging characteristics and biomarkers (n=9) that were significantly associated with Dice score. ResultsFive pancreas segmentation models were identified: Abdomen Atlas [AAUNet, AASwin, trained on 8448 scans], TotalSegmentator [TS, 1204 scans], nnUNetv1 [MSD-nnUNet, 282 scans], and a U-Net based model for predicting diabetes [DM-UNet, 427 scans]. These were evaluated on 352 CT scans (30 females, 25 males, age 58±7 years old [±1SD], 327 age unknown) from 2000-2023. Overall, TS, AAUNet, and AASwin were the best performers, Dice=80±11%, 79±16%, and 77±18% respectively (pairwise Sidak test not-significantly different). AASwin and MSD-nnUNet performed worse (for all metrics) on non-contrast scans (vs contrast, P<.001). The worst performer was DM-UNet (Dice=67±16%). All algorithms except TS showed lower Dice scores with increasing peri-pancreatic attenuation (P<.01). Multivariate regression showed non-contrast scans, (P<.001; MSD-nnUNet), smaller pancreatic length (P=.005, MSD-nnUNet), and height (P=.003, DM-UNet) were associated with lower Dice scores. ConclusionThe convolutional neural network-based models trained on a diverse set of scans performed best (TS, AAUnet, and AASwin). TS performed equivalently to AAUnet and AASwin with only 13% of the training set size (8488 vs 1204 scans). Though trained on the same dataset, a transformer network (AASwin) had poorer performance on non-contrast scans whereas its convolutional network counterpart (AAUNet) did not. This study highlights how aggregate assessment metrics of pancreatic segmentation algorithms seen in other literature are not enough to capture differential performance across common patient and scanning characteristics in clinical populations.

Redefining Immune Dynamics in Acute Pancreatitis: The Protective Role of Galectin-3 Deletion and Treg Cell Enhancement.

Acute pancreatitis (AP) is a complex inflammatory condition that can lead to systemic inflammatory responses and multiple organ dysfunction. This study investigates the role of Galectin-3 (Gal-3), a β-galactoside-binding lectin, in modulating acquired immune responses in AP. Acute pancreatitis was induced by ligation of the bile-pancreatic duct in wild-type and Galectin-3-deficient C57BL/6 mice. We determined the phenotypic and molecular features of inflammatory cells, serum concentrations of amylase, pancreatic trypsin activity, and pancreatic and lung pathology. Galectin-3 deficiency decreased the total number of CD3+CD49- T cells and CD4+ T helper cells, downregulated the production of inflammatory cytokine and IFN-γ, and increased the accumulation of IL-10-producing Foxp3+ T regulatory cells and regulatory CD4+ T cells in the pancreata of diseased animals. The deletion of Galectin-3 ameliorates acute pancreatitis characterized by lowering serum amylase concentration and pancreatic trypsin activity, and attenuating of the histopathology of the lung. These findings shed light on the role of Galectin-3 in acquired immune response in acute pancreatitis and identify Galectin-3 as an attractive target for investigation of the immunopathogenesis of disease and for consideration as a potential therapeutic target for patients with acute inflammatory disease of the pancreas.