Diabetes-related pancreatic changes on MRI remain unclear. Thus, we evaluated the pancreatic changes on MRI in patients with both type 1 diabetes (T1D) and type 2 diabetes (T2D) using multiparametric MRI.

This prospective study involved patients with T1D or T2D who underwent upper abdominal 3-T MRI. Additionally, patients without impaired glucose metabolism were retrospectively included as a control. The imaging data included pancreatic anteroposterior (AP) diameter, pancreas-to-muscle signal intensity ratio (SIR) on fat-suppressed T1-weighted image (FS-T1WI), apparent diffusion coefficient (ADC) value, T1 value on T1 map, proton density fat fraction (PDFF), and mean secretion grade of pancreatic juice flow on cine-dynamic magnetic resonance cholangiopancreatography (MRCP). The MR measurements were compared using one-way analysis of variance and the Kruskal-Wallis test.

Sixty-one patients with T1D (n = 7) or T2D (n = 54) and 21 control patients were evaluated. The pancreatic AP diameters were significantly smaller in patients with T1D than in patients with T2D (p < 0.05). The average SIR on FS-T1WI was significantly lower in patients with T1D than in controls (p < 0.001). The average ADC and T1 values of the pancreas were significantly higher in patients with T1D than in patients with T2D (p < 0.01) and controls (p < 0.05). The mean secretion grade of pancreatic juice flow was significantly lower in patients with T1D than in controls (p = 0.019). The average PDFF of the pancreas was significantly higher in patients with T2D than in controls (p = 0.029).

Patients with T1D had reduced pancreas size, increased pancreatic T1 and ADC values, and decreased pancreatic juice flow on cine-dynamic MRCP, whereas patients with T2D had increased pancreatic fat content.

Fibrotic focus is a pivotal morphofunctional unit in developing fibrosis in various tissues. For most fibrotic diseases, including progressive forms, the foci are considered unable to remodel and contribute to the worsening of prognosis. Unfortunately, the dynamics of the fibrotic focus formation and resolution remains understudied. A number of data suggest that the key cell type for focus formation are activated stromal cells marked by fibroblast activated protein alpha (FAPα) due to their high capacity for extracellular matrix (ECM) remodeling. We evaluated the dynamics of fibrotic focus formation and the contribution of the main cell types, including FAPα+ cells, in this process using a murine model of bleomycin-induced lung fibrosis. We revealed the very early appearance of FAPα+ cells in lungs after injury and assumed their important involvement to the myofibroblast pool formation. During the first month after bleomycin administration, FAPα+ cells colocalize with CD206+ M2 macrophages. Interestingly, during the reversion stage, we unexpectedly observed the specific structured foci formed by CD90+FAPα+ cells, which we suggested calling "remodeling foci". Our findings highlight the crucial role of activated stromal cells in fibrosis initiation, progression, and reversion and provide emerging issues regarding the novel targets for antifibrotic therapy.

Acute on chronic pancreatitis(ACP) is a common cause of treatment in patients with chronic pancreatitis(CP). However, as far as we know, research on ACP has been few, and the quality may vary. This study intended to explore the risk factors related to acute exacerbation in patients with chronic pancreatitis.

313 patients with CP were analyzed based on clinical data from 2014 to 2023 and categorized into ACP and non-ACP groups. Their data, assessed across eleven parameters, were used to study risk variables associated with acute exacerbation in patients with chronic pancreatitis.

Of the 313 eligible patients, 163(52.1%) were ACP. Age > 50 years old (P = 0.049, OR = 0.614, 95%CI: 0.378-0.998), recurrent acute pancreatitis(RAP) history (P = 0.000, OR = 3.284, 95%CI: 1.972-5.467) and steatorrhea (P = 0.013, OR = 0.189, 95%CI: 0.051-0.704) were related factors for ACP.

The history of RAP was an independent risk factor for ACP. Age and steatosis were protective of the prevalence of ACP.

Infiltrating ductal adenocarcinoma of the pancreas, referred to here as "pancreatic cancer," is one of the deadliest of all of the solid malignancies. The five-year survival rate in the United States for individuals diagnosed today with pancreatic cancer is a dismal 12%. Many invasive cancers, including pancreatic cancer, however, arise from histologically and genetically well-characterized precursor lesions, and these precancers are curable. Precursor lesions therefore are an attractive target for early detection and treatment. This is particularly true for individuals with an increased risk of developing invasive cancer, such as individuals with a strong family history of pancreatic cancer, and individuals with a germline variant known to increase the risk of developing pancreatic cancer. There is therefore a need to understand the precursor lesions that can give rise to invasive pancreatic cancer in these individuals.

High-grade pancreatic intraepithelial neoplasia and invasive pancreatic ductal adenocarcinoma ≤10 mm are targets for early detection of pancreatic cancer. However, their imaging characteristics are unknown. We aimed to identify endoscopic ultrasound findings for the detection of these lesions.

Patients diagnosed with high-grade pancreatic intraepithelial neoplasia (n=29), pancreatic ductal adenocarcinoma ≤10 mm (n=11) (who underwent surgical resection), or benign main pancreatic duct stenosis (n=20) between January 2014 and January 2021 were retrospectively included. Six features differentiating these lesions were examined by endoscopic ultrasonography: main pancreatic duct stenosis, upstream main pancreatic duct dilation, hypoechoic areas surrounding the main pancreatic duct irregularities (mottled areas without demarcation or round areas with demarcation), branch duct dilation, prominent lobular segmentation, and atrophy. Interobserver agreement was assessed by two independent observers.

Hypoechoic areas surrounding the main pancreatic duct irregularities were observed more frequently in high-grade pancreatic intraepithelial neoplasia (82.8%) and pancreatic ductal adenocarcinoma ≤10 mm (90.9%) than in benign stenosis (15.0%) (p<0.001). High-grade pancreatic intraepithelial neoplasia exhibited mottled hypoechoic areas more frequently (79.3% vs 18.9%, p<0.001), and round hypoechoic areas less frequently (3.4% vs 72.7%, p<0.001), than pancreatic ductal adenocarcinoma ≤10 mm. The sensitivity and specificity of hypoechoic areas for differentiating high-grade pancreatic intraepithelial neoplasia, pancreatic ductal adenocarcinoma ≤10 mm, and benign stenosis were both 85.0%, with moderate interobserver agreement.

The hypoechoic areas surrounding main pancreatic duct irregularities on endoscopic ultrasound may differentiate between high-grade pancreatic intraepithelial neoplasia, pancreatic ductal adenocarcinoma ≤10 mm, and benign stenosis (Trial Registration: UMIN Clinical Trials Registry (UMIN000044789).

The development of tissue fibrosis is a complex process involving the interaction of multiple cell types, which makes the search for antifibrotic agents rather challenging. So far, myofibroblasts have been considered the key cell type that mediated the development of fibrosis and thus was the main target for therapy. However, current strategies aimed at inhibiting myofibroblast function or eliminating them fail to demonstrate sufficient effectiveness in clinical practice. Therefore, today, there is an unmet need to search for more reliable cellular targets to contribute to fibrosis resolution or the inhibition of its progression. Activated stromal cells, capable of active proliferation and invasive growth into healthy tissue, appear to be such a target population due to their more accessible localization in the tissue and their high susceptibility to various regulatory signals. This subpopulation is marked by fibroblast activation protein alpha (FAPα). For a long time, FAPα was considered exclusively a marker of cancer-associated fibroblasts. However, accumulating data are emerging on the diverse functions of FAPα, which suggests that this protein is not only a marker but also plays an important role in fibrosis development and progression. This review aims to summarize the current data on the expression, regulation, and function of FAPα regarding fibrosis development and identify promising advances in the area.

Endoscopic ultrasound (EUS) is a main tool in gastroenterology for both diagnosis and exclusion of pancreatic pathology. It allows minimally invasive assessment of various diseases or anatomic variations affecting the pancreas also with the help of new Doppler technologies, elastography, contrast-enhanced imaging including post hoc image processing with quantification analyses, three-dimensional reconstruction, and artificial intelligence. EUS also allows interventional direct access to the pancreatic parenchyma and the retroperitoneal space, to the pancreatic duct, pancreatic masses, cysts, and vascular structures.

This review aimed to summarize new developments of EUS in the field of pancreatology. We highlight the role of EUS in evaluating pancreatic pathology by describing normal anatomic variants like pancreas divisum, pancreatic lipomatosis, pancreatic fibrosis in the elderly and characterizing pancreatic masses, both in the context of chronic pancreatitis and within healthy pancreatic parenchyma. EUS is considered the optimal imaging modality for pancreatic masses of uncertain dignity and allows both cytological diagnosis and histology, which is essential not only for neoplastic conditions but also for tailoring therapy for benign inflammatory conditions.

EUS plays an indispensable role in pancreatology and the development of new diagnostic and interventional approaches to the retroperitoneal space and the pancreas exponentially increased over the last years. The development of computer-aided diagnosis and artificial intelligence algorithms hold the potential to overcome the obstacles associated with interobserver variability and will most likely support decision-making in the management of pancreatic disease.

Optical clearing with high-refractive-index (high-n) reagents is essential for 3D tissue imaging. However, the current liquid-based clearing condition and dye environment suffer from solvent evaporation and photobleaching, causing difficulties in maintaining the tissue optical and fluorescent features. Here, using the Gladstone-Dale equation [(n-1)/density=constant] as a design concept, we develop a solid (solvent-free) high-n acrylamide-based copolymer to embed mouse and human tissues for clearing and imaging. In the solid state, the fluorescent dye-labeled tissue matrices are filled and packed with the high-n copolymer, minimizing scattering in in-depth imaging and dye fading. This transparent, liquid-free condition provides a friendly tissue and cellular environment to facilitate high/super-resolution 3D imaging, preservation, transfer, and sharing among laboratories to investigate the morphologies of interest in experimental and clinical conditions.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer, partly because its early detection is difficult. This study aimed to identify computed tomography (CT) findings associated with PDAC prior to diagnosis.

Past CT images were retrospectively collected from the PDAC group (n = 54) and the control group (n = 90). The following imaging findings were compared: pancreatic mass, main pancreatic duct (MPD) dilatation with or without cutoff, cyst, chronic pancreatitis with calcification, partial parenchymal atrophy (PPA), and diffuse parenchymal atrophy (DPA). In the PDAC group, CT findings were examined during the pre-diagnostic period and 6-36 months and 36-60 months before diagnosis. Multivariate analyses were performed using logistic regression.

MPD dilatation with cutoff (P < 0.0001) and PPA (P = 0.023) were identified as significant imaging findings 6-36 months before diagnosis. DPA was identified as a novel imaging finding at 6-36 months (P = 0.003) and 36-60 months (P = 0.009) before diagnosis.

DPA, MPD dilatation with cutoff, and PPA were identified as imaging findings associated with pre-diagnostic PDAC.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant.

As part of the aging process, fibrotic changes, fatty infiltration, and parenchymal atrophy develop in the pancreas. The pancreatic duct also becomes wider with age. This article provides an overview of the diameter of the pancreatic duct in different age groups and different examination methods. Knowledge of these data is useful to avoid misinterpretations regarding the differential diagnosis of chronic pancreatitis, obstructive tumors, and intraductal papillary mucinous neoplasia (IPMN).

During the aging process, typical morphological changes occur in the pancreas, which leads to a specific "patchy lobular fibrosis in the elderly." The aging process in the pancreas is associated with changes in volume, dimensions, contour, and increasing intrapancreatic fat deposition. Typical changes are seen in ultrasonography, computed tomography, endosonography, and magnetic resonance imaging. Typical age-related changes must be distinguished from lifestyle-related changes. Obesity, high body mass index, and metabolic syndrome also lead to fatty infiltration of the pancreas. In the present article, age-related changes in morphology and imaging are discussed. Particular attention is given to the sonographic verification of fatty infiltration of the pancreas. Ultrasonography is a widely used screening examination method. It is important to acknowledge the features of the normal aging processes and not to interpret them as pathological findings. Reference is made to the uneven fatty infiltration of the pancreas. The differential diagnostic and the differentiation from other processes and diseases leading to fatty infiltration of the pancreas are discussed.

In recent years, there has been a significant increase in age-related diseases due to the improvement in life expectancy worldwide. The pancreas undergoes various morphological and pathological changes with aging, such as pancreatic atrophy, fatty degeneration, fibrosis, inflammatory cell infiltration, and exocrine pancreatic metaplasia. Meanwhile, these may predispose the individuals to aging-related diseases, such as diabetes, dyspepsia, pancreatic ductal adenocarcinoma, and pancreatitis, as the endocrine and exocrine functions of the pancreas are significantly affected by aging. Pancreatic senescence is associated with various underlying factors including genetic damage, DNA methylation, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and inflammation. This paper reviews the alternations of morphologies and functions in the aging pancreas, especially β-cells, closely related to insulin secretion. Finally, we summarize the mechanisms of pancreatic senescence to provide potential targets for treating pancreatic aging-related diseases.

Pancreatic intraepithelial neoplasia (PanIN) and islet cell microadenoma are exocrine and endocrine neoplasms of human pancreas that have been linked to pancreatic ductal adenocarcinoma (PDAC) and neuroendocrine tumor, respectively. However, in health and at the surgical margin of pancreatic cancer, it remains unresolved how to simultaneously characterize duct and islet remodeling to investigate the exocrine-endocrine association in the lesion microenvironment. Here, we develop a new vibratome-based approach to detect, confirm, and analyze the two types of pancreas remodeling via stereo/three-dimensional (3-D) and classic/two-dimensional (2-D) histology. Surgical margins of PDAC (n = 10, distal) and cadaveric donor pancreases (n = 10, consecutive cases) were fixed, sectioned by vibratome (350 µm), and surveyed for PanIN and microadenoma via stereomicroscopy. After lesion detection, PanIN and microadenoma were analyzed with 3-D fluorescence imaging and clinical microtome-based histology for confirmation and assessment of microenvironment. Multimodal imaging of PDAC surgical margins and cadaveric donor pancreases detected the peri-PanIN islet aggregation with duct-islet cell clusters. Organ-wide survey of cadaveric donor pancreases shows a marked 2.3-fold increase in the lesion size with the PanIN-islet association vs. without the association. In the survey, we unexpectedly detected the islet cell microadenoma adjacent to (<2 mm) PanIN. Overall, among the 53 early lesions in the cadaveric donor pancreases (PanINs and microadenomas), 81% are featured with the associated exocrine-endocrine tissue remodeling. Multimodal 3-D/2-D tissue imaging reveals local and simultaneous duct and islet remodeling in the cancer surgical margin and cadaveric donor pancreas. In the cadaveric donor pancreas, the peri-PanIN islet aggregation and PanIN-microadenoma association are two major features of pancreas remodeling in the early lesion microenvironment.NEW & NOTEWORTHY We develop a new multimodal 3-D/2-D imaging approach (matched stereomicroscopic, fluorescence, and H&E signals) to examine human duct-islet association in the PDAC surgical margin and cadaveric donor pancreas. In both conditions, peri-PanIN islet aggregation with duct-islet cell clusters was identified. The PanIN-islet cell microadenoma association was unexpectedly detected in the donor pancreas. Our work provides the technical and morphological foundations to simultaneously characterize human islets and ducts to study their association in health and disease.

To investigate the morphological changes with age in the pancreases of healthy individuals undergoing magnetic resonance imaging (MRI).

The participants were selected from adults who were undergoing physical examinations from January 2017 to September 2020 at Huadong Hospital. They were divided according to age, as broken down by decades into seven groups ranging from 20 to 29 years to ≥80 years of age. There were 30 to 35 cases for each decade. They were then divided into a young and middle-aged group (<60 years of age) and an elderly group (≥60 years of age). The morphological characteristics of the pancreases of each participant in the group were measured on magnetic resonance images. The characteristics included the pancreatic anteroposterior diameters and volumes. The relationships between the anteroposterior diameters of the pancreatic head, body, and tail and pancreatic volume and age were analyzed.

A total of 226 magnetic resonance images from 112 (49.56%) men and 114 (50.44%) women, aged 22-93 (54.68 ± 19.52) years. The age ranges of the seven groups consisted of the following: 20-29 years (n = 33), 30-39 years (n = 32), 40-49 years (n = 32), 50-59 years (n = 31), 60-69 years (n = 35), 70-79 years (n = 33) and ≥80 years (n = 30). The age range and numbers of patients in the young and middle-aged group was 22-59 (40.09 ± 10.88) years (n = 128) and in the elderly group was 60-93 (73.74 ± 8.99) years (n = 98). The MRI findings characteristic of aging included pancreatic atrophy (especially of the pancreatic tail), pancreatic lobulation, uneven signal intensity, fatty degeneration, and widening of the main pancreatic duct. The respective anteroposterior diameters of the pancreatic head, body, and tail and the pancreatic volumes peaked at 30 to 39 years as follows: 28.03 ± 4.45 mm, 24.10 ± 4.27 mm, 24.57 ± 4.94 mm, 98.54 ± 26.56 cm3; and then gradually decreased to 19.05 ± 3.59 mm, 16.00 ± 3.81 mm, 13.83 ± 3.39 mm, 45.02 ± 9.15 cm3 at ≥80 years, for respective decreases of 32.03%, 33.60%, 43.71%, and 54.31%. The respective anteroposterior diameters of the pancreatic head, body, tail, and pancreatic volume in the elderly patients were 21.45 ± 4.15 mm, 18.14 ± 4.09 mm, 16.81 ± 4.37 mm, and 59.02 ± 21.44 cm3, which were significantly smaller than the respective corresponding measurements in the young and middle-aged patients (26.09 ± 4.40 mm, 22.30 ± 4.42 mm, 22.08 ± 4.53 mm, and 88.32 ± 23.92 cm3). The differences were statistically significant (t = 8.06, 7.24, 8.79, 9.54, respectively, p < 0.001). The anteroposterior diameters of the pancreatic head, body, tail, and pancreatic volume were negatively correlated with age (r = -0.53, -0.47, -0.56, -0.57, respectively, p < 0.001).

The anteroposterior diameters of the pancreatic head, body, tail, and the pancreatic volume all peaked at the age range of 30-39 years and then gradually decreased with increasing age. After the age of 60 years, pancreatic atrophy became increasingly obvious, with changes in shape and widening with age of the main pancreatic duct.

Islets are thought to be stably present in the adult human pancreas to maintain glucose homeostasis. However, identification of the pancreatic intraepithelial neoplasia (PanIN)-islet complex in mice and the presence of PanIN lesions in adult humans suggest that similar remodelling of islet structure and environment may occur in the human pancreas. To identify islet remodelling in a clinically related setting, we examine human donor pancreases with 3D histology to detect and characterise the human PanIN-islet complex.

Cadaveric donor pancreases (26-65 years old, n = 10) were fixed and sectioned (350 μm) for tissue labelling, clearing and microscopy to detect local islet remodelling for 3D analysis of the microenvironment. The remodelled microenvironment was subsequently examined via microtome-based histology for clinical assessment.

In nine pancreases, we identified the unique peri-lobular islet aggregation associated with the PanIN lesion (16 lesion-islet complexes detected; size: 3.18 ± 1.34 mm). Important features of the lesion-islet microenvironment include: (1) formation of intra-islet ducts, (2) acinar atrophy, (3) adipocyte association, (4) inflammation (CD45⁺), (5) stromal accumulation (α-SMA⁺), (6) increase in Ki-67 proliferation index but absence of Ki-67⁺ alpha/beta cells and (7) in-depth and continuous duct-islet cell contacts, forming a cluster. The duct-islet cell cluster and intra-islet ducts suggest likely islet cell neogenesis but not replication.

We identify local islet remodelling associated with PanIN-islet complex in the adult human pancreas. The tissue remodelling and the evidence of inflammation and stromal accumulation suggest that the PanIN-islet complex is derived from tissue repair after a local injury.

Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, shows a dismal and grim overall prognosis and survival rate, which have remained virtually unchanged for over half a century. PDAC is the most lethal of all cancers, with the highest mortality-to-incidence ratio. PDAC responds poorly to current therapies and remains an incurable malignancy. Therefore, novel therapeutic targets and drugs are urgently needed for pancreatic cancer treatment. Selective induction of apoptosis in cancer cells is an appealing approach in cancer therapy. Apoptotic cell death is highly regulated by different signaling routes that involve a variety of subcellular organelles. Endoplasmic reticulum (ER) stress acts as a double-edged sword at the interface of cell survival and death. Pancreatic cells exhibit high hormone and enzyme secretory functions, and thereby show a highly developed ER. Thus, pancreatic cancer cells display a prominent ER. Solid tumors have to cope with adverse situations in which hypoxia, lack of certain nutrients, and the action of certain antitumor agents lead to a complex interplay and crosstalk between ER stress and autophagy-the latter acting as an adaptive survival response. ER stress also mediates cell death induced by a number of anticancer drugs and experimental conditions, highlighting the pivotal role of ER stress in modulating cell fate. The alkylphospholipid analog prototype edelfosine is selectively taken up by tumor cells, accumulates in the ER of a number of human solid tumor cells-including pancreatic cancer cells-and promotes apoptosis through a persistent ER-stress-mediated mechanism both in vitro and in vivo. Here, we discuss and propose that direct ER targeting may be a promising approach in the therapy of pancreatic cancer, opening up a new avenue for the treatment of this currently incurable and deadly cancer. Furthermore, because autophagy acts as a cytoprotective response to ER stress, potentiation of the triggering of a persistent ER response by combination therapy, together with the use of autophagy blockers, could improve the current gloomy expectations for finding a cure for this type of cancer.

This study analyzes the clinicopathologic findings and their impact on outcome of patients so as to identify which patients benefit most from surgical treatment in chronic pancreatitis, especially in regard to pain relief.

The predominant symptom of chronic pancreatitis is chronic pain resulting in reduced quality of life. It is well known that the main reason for development of the disease is abuse of alcohol and nicotine, but only little data on factors influencing outcome are available.

One thousand one hundred forty-six consecutive patients who underwent surgery for chronic pancreatitis were included. Clinicopathologic data, including morphology of the pancreas in preoperative diagnostics and the histopathologic results, were evaluated. A long-term follow-up including Quality of Life and pain scores was performed. Additionally, we describe the novel Chronic Pancreatitis Pain Relief Score (CPPR-Score) as a tool for prediction of pain relief.

Overall the rate of pain relief was 79.8% after surgery. The presence of an inflammatory mass in the pancreatic head larger than 4 cm (P < 0.001), presence of a dilated main pancreatic duct of over 4 mm (P < 0.001), histopathologically detected severe calcifications (P = 0.001) and severe fibrosis (P < 0.001) as well as ethanol induced disease (P < 0.001) found to be strong independent prognostic factors for pain relief. The CPPR-Score (0-5 points) proved to be a very good predictive score for pain-relief (P < 0.001).

The rate of pain relief after surgical treatment in chronic pancreatitis is high and the commonly used procedures can be performed with acceptable morbidity and mortality. The Chronic Pancreatitis Pain Relief Score allows identifying patients who will benefit most from surgery.

To develop a radiomics model and a combined model for preoperative prediction of clinically relevant postoperative pancreatic fistula (CR-POPF) in patients undergoing pancreaticoduodenectomy and to compare the predictive performance of the two models with the traditional Fistula Risk Score system.

A total of 250 patients who underwent pancreaticoduodenectomy (PD) with preoperative computed tomography (CT) were divided into a training set (n = 175) and validation set (n = 75). The pancreatic area was automatically segmented on the portal venous phase CT images using a 3D U-Net segmentation model. A radiomics model was developed using radiomics features extracted from the volume of interest (VOI) and a combined model was developed using radiomics features, demographic information and radiological features. The FRS was also used to predict POPF. The predictive performance of the prediction models was assessed using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA).

Eleven and 18 features were extracted for the radiomics model and combined model, respectively. The combined model showed excellent predictive value, with an AUC of 0.871 (95 %CI 0.816,0.926) and 0.869 (95 %CI 0.779,0.958) in the training cohort and validation cohort, respectively. Calibration curves and DCA showed that the combined model outperformed the traditional FRS system and radiomics model.

The combined model exhibited excellent predictive performance and outperformed the traditional FRS system and radiomics model in the preoperative prediction of CR-POPF.

Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions, such as pancreatic intra-epithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). The prognosis of high-grade precancerous lesions, including high-grade PanIN and high-grade IPMN, without invasive carcinoma is good, despite the overall poor prognosis of PDAC. High-grade PanIN, as a lesion preceding invasive PDAC, is therefore a primary target for intervention. However, detection of localized high-grade PanIN is difficult when using standard radiological approaches. Therefore, most studies of high-grade PanIN have been conducted using specimens that harbor invasive PDAC. Recently, imaging characteristics of high-grade PanIN have been revealed. Obstruction of the pancreatic duct due to high-grade PanIN may induce a loss of acinar cells replaced by fibrosis and lobular parenchymal atrophy. These changes and additional inflammation around the branch pancreatic ducts (BPDs) result in main pancreatic duct (MPD) stenosis, dilation, retention cysts (BPD dilation), focal pancreatic parenchymal atrophy, and/or hypoechoic changes around the MPD. These indirect imaging findings have become important clues for localized, high-grade PanIN detection. To obtain pre-operative histopathological confirmation of suspected cases, serial pancreatic-juice aspiration cytologic examination is effective. In this review, we outline current knowledge on imaging characteristics of high-grade PanIN.

Despite advances in diagnostics and therapeutics, the prognosis of pancreatic cancer remains dismal. Because of a lack of early diagnostic methods, aggressive local progression, and high incidence of distant metastasis, most pancreatic cancers are inoperable; therefore, the characteristics of early pancreatic cancer have not been well understood. Autopsy studies revealed the characteristics of prediagnostic pancreatic malignancies, including precancerous lesions, early stage pancreatic cancer, and pancreatic cancer without clinical symptoms (occult cancers). Animal models using hamsters and genetically engineered mice have focused on mechanisms of carcinogenesis, thereby providing insights into risk factors and prevention and serving as a preclinical test for the development of novel diagnostic and treatment modalities. In this review, we have summarized pathological changes in the pancreas of humans and experimental animals during carcinogenesis.

Diagnosing high-grade intraepithelial neoplasia without invasion, traditionally referred to as carcinoma in situ (CIS), is essential for improving prognosis. We examined the imaging findings of patients with and without CIS to identify significant aspects for the diagnosis of CIS.

Forty-six patients strongly suspected of early pancreatic cancer without nodule on imaging (CIS group, n = 27; non-malignant group, n = 19) were retrospectively evaluated according to ten factors of computed tomography/magnetic resonance imaging (CT/MRI), endoscopic ultrasonography (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) using hierarchical cluster and univariate analyses.

Two clusters were formed by hierarchical cluster analysis. One cluster consisted of 83.3% CIS cases with similar image findings such as focal pancreatic parenchymal atrophy (FPPA) on CT/MRI, main pancreatic duct (MPD) stricture surrounded by hypoechoic areas on EUS, and MPD stricture with upstream MPD dilation on ERCP. On univariate analysis, the CIS and non-malignant groups had FPPA on CT/MRI in 15 (55.6%) and 3 (15.8%) cases (p = 0.013), and MPD stricture surrounded by hypoechoic areas on EUS in 20 (74.1%) and 4 (21.1%) cases (p = 0.001), respectively. MPD stricture surrounded by hypoechoic areas was observed in 80% (12/15) of CIS cases with FPPA on CT/MRI and correlated with FPPA. Moreover, FPPA and MPD stricture surrounded by hypoechoic areas had histopathologically observed fibrosis or fat replacement due to pancreatic parenchymal atrophy.

FPPA and MPD stricture surrounded by hypoechoic areas are significant findings for the diagnosis of CIS.

Reduced pancreatic volume, often referred to as atrophy, is a commonly reported imaging feature of chronic pancreatitis (CP). This study evaluated whether there is an association between pancreatic volume and fibrosis, the criterion standard of CP, in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for recurrent acute pancreatitis (RAP) and CP.

All adult patients who underwent TPIAT between 2010 and 2019 were categorized into 3 groups: RAP, definite CP and indeterminate CP. Pancreatic volume was calculated by summing up the areas from each thin section of the pancreas on 3D CT imaging. Excisional biopsies of the pancreatic head as well as body/tail region were obtained at the time of TPIAT. Two different fibrosis scores were used for histologic assessment.

A total of 16, 29 and 15 patients underwent TPIAT for RAP, definite CP and indeterminate CP, respectively. The mean pancreatic volumes for patients with RAP, definite CP and indeterminate CP were 65.7 ± 28.5 cc, 54.9 ± 22.9 cc and 61.8 ± 23.6 cc, respectively (p = 0.3). The mean fibrosis scores were significantly higher in patients with definite CP compared to RAP (p < 0.001) and indeterminate CP (p < 0.001). Pancreatic volume was not associated with either fibrosis score after adjusting for age, gender, duration of disease, BMI and diabetes in the multivariable analysis.

While the fibrosis scores were higher in definite CP compared to both RAP and indeterminate CP, there was no correlation between pancreatic volume and fibrosis. This suggests that atrophy alone cannot be used to diagnose CP.

To define normal pancreas elasticity and velocity values with shear wave elastography (SWE) in healthy children and assess associations with gender, age, and body mass index (BMI).

This prospective study included a total of 100 cases (male: 50; female: 50), aged 3-17 years. Preschool, school, and adolescent periods of 3-6 years (n = 27), 7-12 years (n = 30), and 13-17 years (n = 43), respectively, were created in addition to two groups representing prepubertal and postpubertal periods of 3-10 years (n = 50) and 11-18 years (n = 50), respectively. Demographic data regarding the gender, age, height, body weight, and BMI were recorded. Pancreatic head, corpus, and tail SWE measurements were performed with a convex transducer (3.5-5 MHz). Correlations and comparisons were made for stiffness values between groups. Statistical analyses used Mann-Whitney U, Kruskal-Wallis, and Spearman's correlation tests.

Medians (25-75th percentage) of age and BMI were 7 (4.25-10) years and 15 (13-17) years and 17.47 (14.94-19.23) kg/m² and 21.22 (17.41-24) kg/m² in the two age groups, respectively. The median (interquartile range) elasticity and velocity values for the head, corpus, and tail sections of the pancreas were measured as 9.35 (2.9) kPa and 1.76 (0.26) m/s; 9.3 (2.5) kPa and 1.74 (0.21) m/s; and 8.75 (2) kPa and 1.69 (0.15) m/s, respectively. No significant differences were identified for stiffness values between gender and pancreatic section. Pancreatic stiffness values were significantly different among two (p = 0.001) and three (p = 0.028) age groups, and presented mild positive correlations with age (r: 0.23, p: 0.002), height (r: 0.18, p: 0.01), body weight (r: 0.38, p: 0.003), and BMI (r: 0.37, p: 0.045).

Normal elasticity and velocity values were defined for the pancreas with SWE in children. Pancreatic stiffness does not significantly change among pancreas parts, but it increases with the transition from childhood to adolescence.

This study aimed to evaluate and identify the specific CT findings by focusing on abnormalities in the main pancreatic duct (MPD) and pancreatic parenchyma in patients with small pancreatic cancer (PC) including carcinoma in situ (CIS).

Nine CT findings indicating abnormalities of MPD and pancreatic parenchyma were selected as candidate findings for the presence of small PC ≤ 10 mm. The proportions of patients positive for each finding were compared between small PC and benign MPD stenosis groups. Interobserver agreement between two independent image reviewers was evaluated using kappa statistics.

The final analysis included 24 patients with small PC (including 11 CIS patients) and 28 patients with benign MPD stenosis. The proportion of patients exhibiting partial pancreatic parenchymal atrophy (PPA) corresponding to the distribution of MPD stenosis (45.8% vs. 7.1%, p < 0.01), upstream PPA arising from the site of MPD stenosis (33.3% vs. 3.6%, p = 0.01), and MPD abrupt stenosis (45.8% vs. 14.3%, p = 0.03) was significantly higher in the small PC group than in the benign MPD stenosis group.

The presence of partial PPA, upstream PPA, and MPD abrupt stenosis on a CT image was highly suggestive of the presence of small PCs including CIS.

Diagnosis of early chronic pancreatitis is a clinical challenge and hindered by the lack of a gold standard. Endoscopic ultrasound (EUS) and the endoscopic pancreatic function test (ePFT) are the most sensitive morphological and functional methods in this setting. EUS-elastography allows for the quantification (strain ratio) of pancreatic fibrosis, and the dynamic evaluation of the main pancreatic duct compliance provides additional information. We developed a multimodal EUS-based approach for the evaluation of the pancreas by integrating these four methods in a single procedure.

We aim to describe morphological and functional pancreatic abnormalities in patients with clinical suspicion of chronic pancreatitis and inconclusive EUS findings by using the multimodal EUS-based approach.

This was a prospective, cross-sectional, observational study of patients with clinically suspected chronic pancreatitis and indeterminate EUS criteria of the disease. EUS criteria of chronic pancreatitis, quantitative pancreatic elastography, ePFT and compliance of the main pancreatic duct were evaluated in a single procedure.

In total, 53 patients with 3-4 EUS criteria of chronic pancreatitis were included (mean age 39.7 years, 29 male). Strain ratio was abnormally high in all patients. Peak bicarbonate concentration was decreased in 43 patients (81.1%) and the main pancreatic duct compliance was reduced in 41 patients (77.3%). Some 34 patients (64.1%) had abnormal results at EUS, elastography, ePFT and compliance of the main pancreatic duct.

A multimodal EUS-based test for the morphological and functional evaluation of the pancreas is presented, which allows detecting mild pancreatic abnormalities in patients with suspected early chronic pancreatitis. The presence of abnormal morphological and functional evaluation of the pancreas could support the clinical suspicion of early chronic pancreatitis in the appropriate clinical setting.

Chronic pancreatitis is a complex multifactorial fibro-inflammatory disease. Consensus guidelines are needed for the histopathological evaluation of non-autoimmune chronic pancreatitis (CP).

An international working group with experts on the histopathology of CP evaluated 15 statements generated from evidence on seven key clinically relevant questions. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the statements for strength of agreement, using a nine-point Likert scale, and Cronbach's alpha reliability coefficients were calculated.

Strong consensus was obtained for 12 statements relating to all seven key questions including that: the cardinal features of CP are the triad of fibrosis, loss of acinar tissue and duct changes; there are no unique histopathological features that distinguish the different aetiologies of CP; clinical history and laboratory investigations, including genetic testing, are important in establishing the aetiology of CP; there is no reproducible and universally accepted histological grading system for assessing severity of CP, although classification as "mild", "moderate" and "severe" is usually applied; scoring systems for fibrosis are not validated for clinical use; asymptomatic fibrosis is a common finding associated with ageing, and not necessarily evidence of CP; there are no obvious diagnostic macroscopic features of early CP; histopathology is not the gold standard for the diagnosis of CP; and cytology alone is not a reliable method for the diagnosis of CP.

Cardinal histopathological features of CP are well-defined and internationally accepted and pathological assessment is relevant for the purpose of differential diagnosis with other pancreatic diseases, especially cancer. However, a reliable diagnosis of CP requires integration of clinical, laboratory and imaging features and cannot be made by histology alone.

The pancreas is a vital organ which has both endocrine and exocrine functions and plays an essential role in food digestion and glucose metabolism. Pancreatic structure and function undergo a series of changes with aging and senescence. Pancreatic exocrine and endocrine function gradually change, which may lead to conditions such as dyspepsia and diabetes mellitus. Hence, clinicians need to be familiar with the characteristics of pancreatic senescence. This article reviews the manifestations of pancreatic senescence and its significance for clinical practice.

The incidence and mortality rates of pancreatic cancer, which has a poor prognosis, are rising rapidly. Endoscopic ultrasonography (EUS) provides superior spatial resolution compared with other imaging modalities such as transabdominal ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), and it is considered among the most reliable and efficient diagnostic modalities for pancreatic diseases. In this review, we show that EUS is useful for detection of pancreatic solid lesions and staging of pancreatic cancer. EUS also plays an important role in screening patients with high-risk factors for pancreatic cancer. Although EUS is useful for detection of small pancreatic lesions, pancreatic lesions are difficult to characterize using this modality, because most pancreatic solid lesions appear hypoechoic on EUS. From this point of view, contrast-enhanced harmonic EUS (CH-EUS) plays an important role in the differential diagnosis of pancreatic lesions. EUS and CH-EUS are also useful for staging pancreatic cancer. Moreover, EUS-guided fine-needle aspiration (EUS-FNA) is superior to other modalities in terms of cytopathological diagnosis. Although EUS-FNA has a high diagnostic ability for pancreatic cancer, the combination of EUS-FNA and CH-EUS improves the diagnostic ability by decreasing the number of false-negative cases. Thus, conventional EUS, EUS-FNA, and CH-EUS are essential in clinical practice for the diagnosis of pancreatic solid lesions.

Age-related pathological changes in the pancreas have been unclear because they are often minor and nonspecific. However, recent studies have shown that they are closely related to various pathological conditions such as pancreatic cancer and diabetes mellitus. Knowledge of age-related changes is important to determine appropriate prevention, detection, and treatment strategies for various diseases observed in elderly patients. We present a review of the pathological age-related non-neoplastic changes in the exocrine pancreas such as pancreatic fatty replacement, lobulocentric pancreatic atrophy, pancreatic duct ectasia, and metaplasia of exocrine pancreas, as well as changes in islet cells. We have discussed common pancreatic neoplasms in elderly patients, such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMNs), and pancreatic ductal adenocarcinoma (PDAC). Age-related pathological changes play a key role in pancreatic carcinogenesis via telomere dysfunction. Further studies are warranted to clarify molecular mechanisms of pancreatic carcinogenesis in elderly patients.

The desmoplastic reaction of pancreas cancer may begin as a wound healing response to the nascent neoplasm, but it soon creates an insidious shelter that can sustain the growing tumor and rebuff therapy. Among the many cell types subverted by transformed epithelial cells, fibroblasts are recruited and activated to lay a foundation of extracellular matrix proteins and glycosaminoglycans that alter tumor biophysics and signaling. Their near-universal presence in pancreas cancer and ostensible support of disease progression make fibroblasts attractive therapeutic targets. More recently, however, it has also become apparent that diverse subpopulations of fibroblasts with distinct phenotypes and secretomes inhabit the stroma, and that targeted depletion of particular fibroblast subsets could either provide substantial therapeutic benefit or accelerate disease progression. An improved characterization of these fibroblast subtypes, along with their potential relationships to tumor subtypes and mutational repertoires, is needed in order to make anti-fibroblast therapies clinically viable.

To evaluate whether pancreatic parenchymal abnormalities on magnetic resonance imaging (MRI) are associated with pancreatic intraepithelial neoplasia (PanIN) on histology.

Retrospective study approved by institutional review board. One hundred patients (48 men, 52 women; mean age, 53.2 ± 16.29 [SD]) underwent MRI before pancreatectomy for pancreatic tumors analyzed by two independent observers blinded to histopathological results for the presence of non-communicating microcysts and pancreatic atrophy (global or focal) beside tumors. MRI findings were compared to histopathological findings of resected specimens. Interobserver agreement was calculated. The association between parenchymal abnormalities and presence of PanIN was assessed by uni- and multivariate analyses.

PanIN was present in 65/100 patients (65%). The presence of microcysts on MRI had a sensitivity of 52.3% (34/65 [95%CI, 51.92-52.70%]), a specificity of 77.1% (27/35 [95%CI, 76.70-77.59]), and accuracy of 61% (61/100 95%CI [50.7-70.6]) for the diagnosis of PanIN while global atrophy had a sensitivity of 24.6% (16/6 [95%CI, 24.28-24.95]) and a specificity of 97.1% (34/35 [95%CI, 96.97-97.32%]). In multivariate analysis, the presence of microcysts (OR, 3.37 [95%CI, 1.3-8.76]) (p = 0.0127) and global atrophy (OR, 9.79 [95%CI, 1.21-79.129]) (p = 0.0324) were identified as independent predictors of the presence of PanIN. The combination of these two findings was observed in 10/65 PanIN patients and not in patients without PanIN (p = 0.013 with an OR of infinity [95%CI, 1.3-infinity]) and was not discriminant for PanIN-3 and lower grade (p = 0.22). Interobserver agreement for the presence of microcysts was excellent (kappa = 0.92), and for the presence of global atrophy, it was good (kappa = 0.73).

The presence of non-communicating microcysts on pre-operative MRI can be a significant predictor of PanIN in patients with pancreatic tumors.

• In patients with pancreatic tumors who had partial pancreatectomy, MR non-communicating pancreatic microcysts have a 52.3% sensitivity, a 77.1% specificity, and a 61% accuracy for the presence of PanIN with univariate and with an odds ratio of 3.37 with multivariate analyses. • The association of global atrophy and non-communicating microcysts increases the predictive risk of PanIN.

Pancreatic cancer is a lethal malignancy, whose precursor lesions are pancreatic intraepithelial neoplasm, intraductal papillary mucinous neoplasm, intraductal tubulopapillary neoplasm, and mucinous cystic neoplasm. To better understand the biology of pancreatic cancer, it is fundamental to know its precursors and to study the mechanisms of carcinogenesis. Each of these precursors displays peculiar histological features, as well as specific molecular alterations. Starting from such pre-invasive lesions, this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer, with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.