Pancreatic Fatty Infiltration Research Articles

CT Quantitation and Prediction of the Risk of Type 2 Diabetes Mellitus in Non-Obese Patients with Pancreatic Fatty Infiltration.

To examine the risk of type 2 diabetes mellitus in non-obese patients with pancreatic fatty infiltration through abdominal computed tomography (CT) quantitation. We carried out a retrospective analysis of abdominal CT and inpatient medical records of 238 inpatients from July 2019 to April 2021. The patients were divided into a normal non-obese group (BMI < 25, n = 135) and diabetic non-obese group (BMI < 25, n = 103). Abdominal CT-related parameters included body width; mean CT values of the pancreas, liver, and spleen; difference between pancreas and spleen CT values (P-S); pancreas-to-spleen attenuation ratio (P/S); and liver-to-spleen attenuation ratio (L/S). Logistic regression was used to estimate the risk factors for comorbid diabetes in a non-obese population. The P-values of the pancreas CT value, P-S, P/S, body width, and L/S were all <0.05 and correlated to comorbid diabetes in non-obese patients. Worsening pancreatic fatty infiltration increased the risk of developing diabetes. Using a P/S of 1.0 as reference, every successive decrease in this ratio by 0.1 increases patient risk by 3.981, 4.452, 6.037, and 12.937 times. The risk of developing type 2 diabetes mellitus in non-obese patients increases with the degree of pancreatic fatty infiltration as assessed by CT.

Quantitative imaging predicts pancreatic fatty infiltration on routine CT examination

PurposeThe purpose of this study was to assess the performance of quantitative computed tomography (CT) imaging for detecting pancreatic fatty infiltration, using the results of histopathological analysis as reference. Materials and methodsSixty patients who underwent pancreatic surgery for a pancreatic tumor between 2016 and 2019 were retrospectively included. There were 33 women and 27 men with a mean age of 56 ± 12 (SD) years (age range: 18–79 years). Patients with dilatation of the main pancreatic duct, chronic pancreatitis, or preoperative treatment were excluded to prevent any bias in the radiological-pathological correlation. Pancreatic fatty infiltration was recorded at pathology. Pancreatic surface lobularity, pancreatic attenuation, visceral fat area, and subcutaneous fat area were derived from preoperative CT images. The performance for the prediction of fatty infiltration was assessed using area under receiver operating characteristic curve (AUC) and backward binary logistic regression analysis. Results were validated in a separate cohort of 34 patients (17 women; mean age, 50 ± 14 [SD] years; age range: 18–73). ResultsA total of 28/60 (47%) and 17/34 (50%) patients had pancreatic fatty infiltration in the derivation and validation cohorts, respectively. In the derivation cohort, patients with pancreatic fatty infiltration had a significantly higher PSL (P < 0.001) and a lower pancreatic attenuation on both precontrast and portal venous phase images (P = 0.011 and 0.003, respectively), and higher subcutaneous fat area and visceral fat area (P = 0.010 and 0.007, respectively). Multivariable analysis identified pancreatic surface lobularity > 7.6 and pancreatic attenuation on portal venous phase images < 83.5 Hounsfield units as independently associated with fatty infiltration. The combination of these variables resulted in an AUC of 0.85 (95% CI: 0.74–0.95) and 0.83 (95% CI: 0.67–0.99) in the derivation and validation cohorts, respectively. ConclusionCT-based quantitative imaging accurately predicts pancreatic fatty infiltration.

Pancreatic CT density is an optimal imaging biomarker for earlier detection of malignancy in the pancreas with intraductal papillary mucinous neoplasm

BackgroundIntraductal papillary mucinous neoplasms (IPMNs) are typically detected as incidental findings by computed tomography (CT); however, the conventional surveillance is not valid for the early detection of concomitant pancreatic cancer. The pancreas of IPMN is often accompanied by fatty infiltration in the parenchyma, and pancreatic fatty infiltration could be evaluated by pancreatic CT density (pancreatic index, PI). We aimed to investigate whether PI could be an imaging biomarker for the early prediction of malignancies in the pancreas with IPMN. MethodsTwo different cohorts were investigated. (Investigation cohort): A total of 1137 patients with initially low-risk IPMN were compensated by initial IPMN findings, and 2 groups (malignancy/possible benign, 50 cases each) were investigated for yearly changes in PI and for the cutoff value of PI indicating the development of malignancies. (Validation cohort): To validate the cutoff value, 256 patients radiologically suspected of having IPMNs were investigated. Results(Investigation-cohort): The malignancy group showed a gradual decrease in PI every year, and PI significantly differed among the 2 groups 1 year prior to the last investigation. The cutoff value of PI was set at 0.65. (Validation-cohort): A total of 55% of the patients with a PI below the cutoff value had malignancy in the pancreas, including concomitant pancreatic cancer, and the cutoff value was the most significant risk factors for the development of malignancies in the pancreas compared to the conventional risk factors for IPMN. ConclusionsDecreasing PI would be an optimal imaging biomarker for earlier detection of malignancies in the pancreas with IPMN.

Association of Pancreatic Fatty Infiltration With Age and Metabolic Syndrome Is Sex-Dependent

<h3>Background and Aims</h3> Fatty infiltration of the pancreas has been shown to be associated with both precancerous pancreatic lesions and pancreatic ductal adenocarcinoma. We aim to determine predictors of fatty infiltration of the pancreas in United States adults. <h3>Methods</h3> In this retrospective cohort study conducted at a large academic hospital in Chicago, Illinois, we calculated the relative fatty infiltration of the pancreas (corrected to spleen) of 265 cancer-free individuals based on their cross-sectional imaging. Demographic data and relevant laboratory results were obtained from medical records. <h3>Results</h3> We found that age was the strongest predictor of fatty infiltration of the pancreas in our series (<i>P</i> < .01). Fatty infiltration of the pancreas was also significantly associated with body mass index (<i>P</i> < .01) and hyperlipidemia (<i>P</i> < .05). In women, in addition to age (<i>P</i> < .05), elevated body mass index (<i>P</i> = .023), hyperlipidemia (<i>P</i> = .013), and fatty liver (<i>P</i> = .017) were predictors of fat in pancreas. We found a sex-dependent association between pancreatic fat and metabolic syndrome including fatty liver (<i>P</i> = .002). <h3>Conclusion</h3> Fatty infiltration of the pancreas increases by age and components of metabolic syndrome. These assertions could be sex-dependent.

Pancreatic steatosis: a giant step forward or recognition of ignorance

This review analyzes the terminology of pancreatic steatosis, the data about the prevalence of non-alcoholic fatty pancreas disease (NAFPD) were given.&#x0D; The etiological factors of NAFPD are usually subdivided into hereditary, metabolic, and toxic ones. The main etiopathogenetic factor of pancreatic fatty infiltration is obesity: it causes pancreatic infiltration by adipocytes, leading to the development of NAFPD. The pathogenesis of the disease is associated with adipocytic tissue dysfunction, which induces local and systemic inflammatory response with corresponding clinical consequences. Insulin resistance and oxidative stress play major role in the pathogenesis of NAFPD. From a histological point of view, NAFPD is a heterogeneous process, characterized by excessive intracellular accumulation of lipids and fatty infiltration followed by fatty replacement of the pancreas.&#x0D; NAFPD clinical picture is asymptomatic and nonspecific. Diagnosis of NAFPD is based primarily on the results of imaging methods (ultrasound, CT, MRI). A consequence of NAFPD is exocrine pancreatic insufficiency requiring enzyme replacement therapy. One of the NAFPD complications is the development of pancreatic adenocarcinoma.&#x0D; Currently, standards for the diagnosis, treatment and management of patients with NAFPD have not been developed yet, but on used the guidelines for the treatment of non-alcoholic fatty liver disease (rational diet, exercises, weight loss). The “gold standard” of enzyme replacement therapy, such as Creon®, is used for correction of exocrine pancreatic insufficiency. The detailed analysis of the clinical case of total pancreatic steatosis with severe exocrine pancreatic insufficiency was done in this article.

The Impact of Subchronic Soybean Milk and Genistein Supplementation on Pancreatic Fatty Infiltrations of Sprague Dawley Male Mice

Isoflavones (genistein, daidzein) on soybean milk have phytoestrogenic properties. In Asia, the blood phytoestrogen levels can reach 160 ng/ml (80 times higher than Western). This may potentially disrupt endocrine functions regarding its binding with estrogen receptors.. Since the function and distribution of adipose tissues are regulated by estrogen receptors, the reduction of estrogen receptor-α(ERα) results in ectopic fats distribution around visceral tissues, such as the pancreas. Aim: To investigate the impact of subchronic soybean milk and genistein supplementation on pancreatic fatty infiltrations in mice. Methods: The experiment used 35 Sprague dawley male mice under 7 treatment groups within 60 days: negative control with standard rationed food, 3 groups with a variable dose of soybean milk: 100 mg, 200 mg, and 400 mg, and 3 groups with a variable dose of genistein: 0.4 mg, 0.8 mg, and 1.6 mg. Histological measurements on the level of pancreatic fatty infiltrations were conducted after. Analyses used Kruskal-Wallis and post-hoc Mann-Whitney. Results: Medium to a high level of pancreatic fatty infiltrations were found at the control group while there is a decreasing trend on the level of pancreatic fatty infiltrations on groups with soybean milk and subchronic genistein compared with the control group, proportional to higher dosage supplementation. The reduction of pancreatic fatty infiltration levels on groups with soybean milk and subchronic genistein supplementation is not statistically significant compared to control. Conclusion:  Supplementation of soybean milk and subchronic genistein do not significantly reduce the levels of pancreatic fatty infiltrations in Sprague dawley male mice.

Islet inflammation is associated with pancreatic fatty infiltration and hyperglycemia in type 2 diabetes

IntroductionChronic inflammation is observed in type 2 diabetes islets, and fat deposition in the pancreas affects insulin secretion and glucose tolerance. However, the relationship between this inflammation and pancreatic fat...

Pancreatic Fat and Body Composition Measurements by Computed Tomography are Associated with Pancreatic Fistula After Pancreatectomy.

Postoperative pancreatic fistula (POPF) is the most threatening complication after pancreatectomy. This study aimed to directly assess pancreatic fatty infiltration with preoperative computed tomography (CT) imaging and to investigate whether a preoperative analysis of patient variables, including CT characteristics and clinical factors, can predict POPF. We enrolled 150 consecutive patients who underwent curative pancreatectomy. Radiographic factors, including pancreatic fat volume, were measured using preoperative CT imaging and the predictive factors were explored using univariate and multivariate analyses. POPF developed in 30 patients (20.0%). The ratio of pancreatic fat (RPF) ≥ 4.83% was associated with a risk of POPF, high body mass index (BMI), and obese body habitus. Patients with POPF were significantly more likely to have high BMI (≥ 25kg/m2), obese body habitus, and an RPF ≥ 4.83% than patients without POPF. In the multivariate analysis, visceral fat area/skeletal muscle index (VFA/SMI) ≥ 1.94 (odds ratio [OR] 4.28, 95% confidence interval [CI] 1.43-12.9, p = 0.0095) was the sole independent predictive factor for POPF. For patients with a soft pancreas, VFA/SMI ≥ 1.94 (OR 5.67, 95% CI 2.05-15.7, p = 0.0008) was again the sole independent predictive factor for POPF. Preoperative CT images can examine pancreatic fatty infiltration, and patients who had POPF were significantly associated with a high RPF. Among several parameters, VFA/SMI was the only independent predictive factor for clinically relevant POPF. Preoperative evaluation of these body composition variables and the pancreatic configuration could be useful for predicting POPF.

Beneficial Effects of n-3 Polyunsaturated Fatty Acids on Offspring's Pancreas of Gestational Diabetes Rats.

We studied the long-term influence of gestational diabetes mellitus (GDM) on the pancreas of offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on offspring's pancreas. GDM offspring were divided into three groups: GDM offspring, n-3 PUFA-adequate-GDM offspring, and n-3 PUFA-deficient GDM offspring. All healthy and GDM offspring were fed up to 11 months old. The pancreas of GDM offspring exhibited fatty infiltration at 11 months old, whereas n-3 PUFA improved the pancreatic fatty infiltration. n-3 PUFA lowered the pancreatic oxidative stress and inflammation. Surprisingly, n-3 PUFA postponed pancreatic telomere shortening of GDM offspring at old age. Nontargeted metabolomics showed that many metabolites were altered in the pancreas of GDM offspring at old age, including l-valine, ceramide, acylcarnitines, tocotrienol, cholesteryl acetate, and biotin. n-3 PUFA modulated some altered metabolites and metabolic pathways. Therefore, GDM caused the long-term effects on offspring's pancreas, whereas n-3 PUFA played a beneficial role.

Pancreatic fat is related to the longitudinal decrease in the increment of C-peptide in glucagon stimulation test in type2 diabetes patients.

Aims/IntroductionThe relationship between pancreatic fatty infiltration and diabetes is widely known, whereas the causal relationship is not clear. Furthermore, it is uncertain whether pathogenesis of pancreatic fat is similar to that of liver fat. We aimed to clarify the contribution of this type of fat to glucose metabolism in type 2 diabetes patients by cross‐sectional and longitudinal analyses.Material and MethodsA total of 56 patients with type 2 diabetes who had been hospitalized twice were analyzed. We evaluated the mean computed tomography values of the pancreas (P), liver (L) and spleen (S). Lower computed tomography values indicate a greater fat content. We defined indices of pancreatic or liver fat content as the differences between P or L and S. We assessed the associations among fat content for the two organs (P‐S, L‐S) and clinical parameters at the first hospitalization, and then analyzed the associations between these fat contents and changes in glycometabolic markers (the second data values minus the first).ResultsIn the cross‐sectional study, P‐S negatively correlated with the increment of C‐peptide in the glucagon stimulation test (r = −0.71, P < 0.0001) and body mass index (r = −0.28, P = 0.034). L‐S negatively correlated with homeostasis model assessment of insulin resistance (r = −0.73, P < 0.0001), body mass index (r = −0.62, P < 0.0001) and some other obesity‐related indicators, but not with the increment of C‐peptide in the glucagon stimulation test. In the longitudinal study, P‐S positively correlated with the change of the increment of C‐peptide in the glucagon stimulation test (r = 0.49, P = 0.021).ConclusionsIn type 2 diabetes patients, pancreatic fat was less associated with obesity‐related indicators than liver fat, but was more strongly associated with the longitudinal decrease in endogenous insulin‐secreting capacity.

Magnetic resonance imaging: Proton density fat fraction for assessment of pancreatic fatty infiltration during progression of T2DM bama minipigs.

Recent studies have highlighted the correlation between diabetes and pancreatic fat infiltration. However, pancreatic fat content (PFC) is rarely confirmed by pathological results, and a change of PFC during progression of type 2 diabetes (T2DM) is currently controversial. To evaluate the relationship of MRI-pancreatic proton density fat fraction to serologic changes and histology in an experimental model of diabetes. Prospective animal study. Thirteen Bama pigs were randomly assigned to diabetes (n = 7) or control (n = 6) groups. Pigs in the diabetic group received high-fat/high-sugar feed, combined with three doses of streptozotocin injections. 3.0T, IDEAL-IQ sequence. Starting in the fifth month, biochemical changes were evaluated; all pigs underwent axial MRI with the IDEAL-IQ sequence to measured pancreatic fat fraction (PFF). PFC was measured by the Soxhlet extraction method. Pancreatic fat distribution and pancreas islet morphology were observed by histopathology. A Mann-Whitney U-test, independent-samples t-test, Pearson correlation, Spearman correlation, single-measure intraclass correlation coefficient (ICC) were performed. During the development of T2DM, the PFF, weight, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein (LDL), and HOMA-IR (insulin resistance) of the experimental group showed an upward trend; fasting insulin (INS), high-density lipoprotein (HDL), and HOMA-β showed decreasing trends. At the end of the fifteenth month, FBG (mmol/L) was 18.06 ± 6.03 and 5.06 ± 1.41 (P < 0.001), PFF (%) was 36.52 ± 4.07 and 27.75 ± 3.73 (P = 0.002), INS (mU/L) was 21.59 ± 2.93 and 29.32 ± 3.27 (P = 0.001), HOMA-IR was 16.83 ± 4.22 and 6.70 ± 2.45 (P < 0.001), HOMA-β was 1.50 ± 0.24 and 2.77 ± 0.45 (P < 0.001), between the experimental and control groups. There were strong and moderate positive correlations between PFF and PFC (r = 0.968, P < 0.001), and FBG (r = 0.657, P = 0.015), and HOMA-IR (r = 0.608, P = 0.028). MRI-proton density fat fraction can measure the fat content of the pancreas with great accuracy and repeatability; PFF is a potential biomarker that can reflect the different stages of diabetes development. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1905-1913.

Endoscopic ultrasound findings and pathological features of pancreatic carcinoma in situ.

Abstract Background and study aims Few studies have evaluated detection of pancreatic carcinoma in situ (PCIS). We evaluated findings of endoscopic ultrasound (EUS) and pathological features of PCIS. Patients and methods We histopathologically studied 16 patients with PCIS following EUS. Diagnostic features evaluated retrospectively included stricture of the main pancreatic duct (MPD) on EUS, presence or absence of hypoechoic areas surrounding the MPD stricture on EUS, the noncancerous part (pancreas of background) on EUS and histopathology, and histological findings adjacent to the area of PCIS. Results On EUS, stricture of the MPD was found in 15 patients (93.8 %). Hypoechoic areas surrounding the MPD stricture were observed in 9 patients (56.3 %), including three (18.8 %) with a 10- to 11-mm hypoechoic mass. EUS findings of the noncancerous part indicated chronic pancreatitis in six patients (37.5 %), pancreatic fatty infiltration in seven (43.8 %), early chronic pancreatitis in two (12.5 %), and normal pancreas in one (6.3 %). Histological findings of the noncancerous part (proximal to the MPD stricture) indicated chronic pancreatitis in 13 patients (81.3 %) and pancreatic fatty infiltration in five patients (31.3 %). Histopathologically, subepithelial inflammatory cell infiltration and fibrosis were present in all 16 patients with PCIS. Conclusions PCIS frequently causes localized changes in inflammation and fibrosis around the pancreatic duct. PCIS often accompanies chronic pancreatitis and pancreatic fatty infiltration in the background of the pancreas. EUS offers sufficient resolution to demonstrate pancreatic changes of PCIS.

Fatty pancreas: A possible risk factor for pancreatic cancer in animals and humans.

Obesity, type 2 diabetes mellitus (T2DM) and aging are associated with pancreatic cancer risk, but the mechanisms of pancreatic cancer development caused by these factors are not clearly understood. Syrian golden hamsters are susceptible to N‐nitrosobis(2‐oxopropyl)amine (BOP)‐induced pancreatic carcinogenesis. Aging, BOP treatment and/or a high‐fat diet cause severe and scattered fatty infiltration (FI) of the pancreas with abnormal adipokine production and promote pancreatic ductal adenocarcinoma (PDAC) development. The KK‐A y mouse, a T2DM model, also develops severe and scattered FI of the pancreas. Treatment with BOP induced significantly higher cell proliferation in the pancreatic ducts of KK‐A y mice, but not in those of ICR and C57BL/6J mice, both of which are characterized by an absence of scattered FI. Thus, we hypothesized that severely scattered FI may be involved in the susceptibility to PDAC development. Indeed, severe pancreatic FI, or fatty pancreas, is observed in humans and is associated with age, body mass index (BMI) and DM, which are risk factors for pancreatic cancer. We analyzed the degree of FI in the non‐cancerous parts of PDAC and non‐PDAC patients who had undergone pancreatoduodenectomy by histopathology and demonstrated that the degree of pancreatic FI in PDAC cases is significantly higher than that in non‐PDAC controls. Moreover, the association with PDAC is positive, even after adjusting for BMI and the prevalence of DM. Accumulating evidence suggests that pancreatic FI is involved in PDAC development in animals and humans, and further investigations to clarify the genetic and environmental factors that cause pancreatic FI are warranted.

Sonographic pancreas echogenicity in cystic fibrosis compared to exocrine pancreatic function and pancreas fat content at Dixon-MRI.

ObjectiveFatty infiltration of the pancreas is a dominating feature in cystic fibrosis (CF). We evaluate the association between pancreatic fat content assessed by Dixon magnetic resonance imaging (MRI), pancreatic echogenicity at ultrasonography (US) and exocrine function in CF patients and healthy controls (HC).Material and methodsTransabdominal US, pancreatic Dixon-MRI and diffusion-weighted imaging (DWI) were performed in 21 CF patients and 15 HCs. Exocrine function was assessed by endoscopic secretin test and fecal elastase.ResultsCF patients were grouped according to exocrine pancreatic function as subjects with normal (CFS: n = 11) or reduced (CFI: n = 10) function. Among CFI 90% (9/10) had visual hyperechogenicity. CFI also had increased echo-level values (p<0.05 vs others). All CFI (10/10) had markedly increased pancreatic fat content estimated by MRI compared to sufficient groups, p<0.001). Among CFS patients and HC, 27% (3/11) and 33% (5/15), respectively, had hyperechoic pancreas. However, all these had low pancreatic fat-content at MRI compared to CFI. In CFI, pancreatic fat content was correlated to ADC (r = -0.93, p<0.001).ConclusionPancreas insufficient CF patients exhibit severe pancreatic fatty-infiltration at MRI and hyperechoic pancreas at US. Pancreas hyperechogenicity in pancreatic sufficient subjects does not co-exist with fatty infiltration at MRI. MRI evaluates pancreatic fatty infiltration more accurately than US and fat infiltration estimated by MRI outperforms sonographic hyper-echogenicity as a marker for exocrine pancreatic failure in CF.

Glucose Intolerance After Pancreatectomy Was Associated With Preoperative Hemoglobin A1c, Insulin Resistance, and Histological Pancreatic Fatty Infiltration

Glucose Intolerance After Pancreatectomy Was Associated With Preoperative Hemoglobin A1c, Insulin Resistance, and Histological Pancreatic Fatty Infiltration

Research advances of pancreatic fatty infiltration

Pancreatic fatty infiltration is defined as the deposition of excess adipose tissue (mainly consisting of triacylglyceride) in the pancreas.Epidemiological studies have revealed that the prevalence of pancreatic fatty infiltration is high, but the research is still at a preliminary stage and there is no consensus on the relevant pathophysiological mechanisms so far. The diagnosis of pancreatic fatty infiltration relies on histopathologic examination and imaging techniques. This article reviews the recent research advances on the pancreatic fat infiltration in order to improve our understanding of the disease. Key words: Obesity; Metabolic syndrome; Type 2 diabetes mellitus; Pancreatic fatty infiltration; Fatty liver disease

Effect of intrapancreatic fat on diabetes outcomes after total pancreatectomy with islet autotransplantation

Pancreatic fat may adversely affect β-cell mass and function, possibly via local release of non-esterified fatty acids, and proinflammatory and vasoactive factors released by adipose tissue. However, the effects of intrapancreatic fat in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation (TPIAT) have not been studied. This study investigated whether pancreatic fatty infiltration has a negative effect on metabolic outcomes following TPIAT. The association between pancreatic fatty infiltration and diabetes outcomes was studied in 79 patients with low or high pancreatic fat content (LPF [n = 53] and HPF [n = 26], respectively) undergoing TPIAT. Pancreatic fatty infiltration was stratified using gross examinations during isolation and validated with histomorphometry of archived histology samples. Fat area percentage in histology samples differed significantly between the LPF and HPF groups (2.1% ± 4.3% vs 10.6% ± 8.9%, respectively; P = 0.0009). Insulin dependence was more common in the HPF group, whereas more patients in the LPF group were insulin independent or on partial insulin supplementation at 1 year (P = 0.022). Furthermore, 1- and 2-h glucose concentrations during mixed-meal tolerance tests were significantly higher in the HPF group (P = 0.032 and 0.027, respectively) and β-scores (a composite measure of islet function and metabolic control) were significantly greater in the LPF than HPF group (6.1 ± 1.7 vs 4.6 ± 2.0; P = 0.034). Patients with HPF were more likely to be insulin dependent, with higher postprandial glucose excursion, suggesting that intrapancreatic fat may lead to β-cell dysfunction with detrimental effects on diabetes outcomes after TPIAT.

Human pancreatic neuro-insular network in health and fatty infiltration.

Identification of a pancreatic neuro-insular network in mice suggests that a similar integration of islets and nerves may be present in the human pancreas. To characterise the neuro-insular network and the intra-pancreatic ganglia in a clinically related setting, we examined human pancreases in health and with fatty infiltration via 3-dimensional (3D) histology and compared the human pancreatic microenvironment with its counterpart in mice. Human pancreatic specimens from individuals with normal BMI, high BMI (≥25) and type 2 diabetes were used to investigate the neuro-insular network. Transparent specimens were prepared by tissue clearing for transmitted light and deep-tissue fluorescence imaging to simultaneously visualise infiltrated adipocytes, islets and neurovascular networks. High-definition images of human islets reveal that both the sympathetic and parasympathetic nerves enter the islet core and reside in the immediate microenvironment of islet cells. Around the islets, the neuro-insular network is visualised with 3D histology to identify the intra-pancreatic ganglia (peri-lobular and intra-parenchymal ganglia) and the islet-ganglionic association. In humans, but not in mice, pancreatic fatty infiltration (BMI dependent) features adipocytes infiltrating into the parenchyma and accumulating in the peri-lobular space, in which the peri-lobular ganglia also reside. We identified the formation of adipose-ganglionic complexes in the peri-lobular space and enlargement of ganglia around adipocytes. In the specimen from the individual with type 2 diabetes, an increase in the number of nerve projections from the intra-parenchymal ganglia is associated with severe fatty infiltration. We present new perspectives of human pancreas and islet innervation via 3D histology. Our results strongly suggest that fatty infiltration in the human pancreas creates a neurotrophic microenvironment and promotes remodelling of pancreatic innervation.

Evaluation of the degree of pancreatic fatty infiltration by area-based assessment of CT images: comparison with histopathology-based and CT attenuation index-based assessments.

The purpose of this study was to evaluate the degree of fatty infiltration (FI) of the pancreas using area-based assessment on computed tomography (CT) (CT area-based assessment) in its correlation and agreement/concordance with histopathology-based assessment. Furthermore, we examined whether CT area-based assessment was better than CT attenuation index-based assessment. We retrospectively evaluated the degree of FI of the pancreas in 37 pancreatic cancer patients who had undergone preoperative CT and pancreaticoduodenectomy. The degree of FI of the pancreas was examined by histopathology-based assessment using surgical resection samples, and CT area-based and CT attenuation index-based assessments. Mean values of pancreatic FI measured by area-based assessment on unenhanced CT and by histopathology-based assessments were 14.4±23.2% (range 0-77.7%) and 16.2±17.4% (range 0.2-60.2%), respectively. Area-based assessment on unenhanced CT showed higher correlation and concordance with histopathology-based assessment, demonstrating a Spearman correlation coefficient of 0.78 (P<0.0001) and a Kendall's tau-b coefficient of 0.69 (P<0.0001). For CT attenuation index-based assessment, the corresponding values were -0.66 (P<0.0001) and -0.39 (P=0.008), respectively. To order/categorize subjects according to the degree of FI of the pancreas, CT area-based assessment is suggested to be better than CT attenuation index-based assessment.

A correlation analysis between pancreatic fatty infiltration and metabolic syndrome

The multiple levels of indicators in 1 190 residents going through physical examination were analyzed. The results showed that fatty pancreas was associated with higher levels for metabolism index than the control group(P<0.05); Body mass index was the strongest correlated risk factor of pancreatic fatty infiltration(OR=5.755), followed by fatty liver(OR=2.522); fatty pancreas was found to have higher frequency and greater parameter numbers of metabolic syndrome than the control group(2.5±1.1 vs 1.4±1.2, P<0.01). The presence of fatty pancreas represents a meaningful manifestation of metabolic syndrome. (Chin J Endocrinol Metab, 2015, 31: 971-973) Key words: Pancreas; Fatty infiltration; Epidemiological characteristics; Metabolic syndrome