High circulating fibroblast growth factor-21 levels as a screening marker in fatty pancreas patients.

Background: The study aimed to detect the serum levels of fibroblast growth factor-21 (FGF-21) in fatty pancreas (FP) patients and to investigate their potential clinical value. Methods: We screened patients with FP using transabdominal ultrasound. The anthropometric, biochemical and serum levels of FGF-21 were compared between the FP group and the normal control (NC) group. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum FGF-21 for FP patients. Results: Compared with the NC group, body mass index, fasting blood glucose levels, uric acid levels and cholesterol levels of the FP group were significantly higher, while the high-density lipoprotein level was lower. In addition, levels of serum FGF-21, resistin, leptin and tumor necrosis factor-α were significantly higher than those in the NC group, while the serum adiponectin level was lower. Pearson analysis showed serum FGF-21 levels in FP patients were negatively correlated with leptin. The ROC curve showed the best critical value of the serum FGF-21 level in FP patients was 171 pg/mL (AUC 0.744, P = 0.002, 95% confidence intervals 0.636-0.852). Conclusion: Serum FGF-21 was closely related to fatty pancreas. Detecting serum FGF-21 levels may help identify the population susceptible to FP.

Pathophysiologic Mechanisms of Hypothermia-Induced Pancreatic Injury in a Rat Model of Body Surface Cooling.

OBJECTIVE: The mechanisms underlying hypothermia-induced pancreatic injury are unclear. Thus, we investigated the pathophysiology of hypothermia-induced pancreatic injury. METHODS: We created a normal circulatory model with body surface cooling in rats. We divided the rats into control (36°C-38°C), mild hypothermia (33°C-35°C), moderate hypothermia (30°C-32°C), and severe hypothermia (27°C-29°C) (n = 5 per group) groups. Then, we induced circulatory failure with a cooling model using high-dose inhalation anesthesia and divided the rats into control (36°C-38°C) and severe hypothermia (27°C-29°C) (n = 5 per group) groups. Serum samples were collected before the introduction of hypothermia. Serum and pancreatic tissue were collected after maintaining the target body temperature for 1 hour. RESULTS: Hematoxylin and eosin staining of the pancreas revealed vacuoles and edema in the hypothermia group. Serum amylase (P = 0.056), lactic acid (P < 0.05), interleukin 1ß (P < 0.05), interleukin 6 (P < 0.05), and tumor necrosis factor α (P = 0.13) levels were suppressed by hypothermia. The circulatory failure model exhibited pancreatic injury. CONCLUSIONS: Hypothermia induced bilateral effects on the pancreas. Morphologically, hypothermia induced pancreatic injury based on characteristic pathology typified by vacuoles. Serologically, hypothermia induced protective effects on the pancreas by suppressing amylase and inflammatory cytokine levels.

Combination of CA19-9 and Blood Free-Circulating Methylated RUNX3 May Be Useful to Diagnose Stage I Pancreatic Cancer.

BACKGROUND: Although serum carbohydrate antigen 19-9 (CA19-9) is widely used as a useful biomarker of pancreatic cancer for monitoring the response to therapy, it is not recommended for screening of early pancreatic cancer because of its limited sensitivity for small tumors. Thus, it is critical to discover novel serum biomarkers to complement CA19-9 in order to improve sensitivity. Although methylated runt-related transcription factor 3 (RUNX3) is a biomarker of pancreatic cancer, its detection by conventional bisulfite-based methylation assays from a small serum sample amount is very difficult. Therefore, we developed a new methylation assay, the combined restriction digital PCR (CORD) assay, that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. OBJECTIVES: We evaluated the sensitivity and specificity of serum DNA testing of methylated RUNX3 by the CORD assay in combination with and without CA19-9 for the detection of pancreatic cancer in 55 patients with pancreatic cancer, 12 patients with benign pancreatic disease, and 80 healthy individuals. RESULTS: The CORD assay of methylated RUNX3 had a sensitivity of 50.9% (28/55) and specificity of 93.5% (86/92). Combination of the CORD assay of methylated RUNX3 and CA19-9 resulted in a sensitivity of 85.5% (47/55) and specificity of 93.5% (86/92) for all stages of pancreatic cancer and a sensitivity of 77.8% (7/9) for stage I pancreatic cancer. CONCLUSIONS: ombination of the CORD assay and CA19-9 may provide an alternative screening strategy for detecting early-stage pancreatic cancer.

Benign Pancreatic Hyperenzymemia, Also Known as Gullo's Syndrome.

Benign pancreatic hyperenzymemia, also known as Gullo's syndrome, is a little-known syndrome first described in 1996 in patients studied for an elevation of pancreatic enzymes while otherwise being asymptomatic. We describe the case of a 2-year-old patient who was found to have significant elevation of amylase and lipase levels while he was asymptomatic. Blood tests and imaging tests were performed to determine the etiology, but they gave normal results. The enzyme elevation can even be 10 times the normal value of the enzyme, and only 1 enzyme may elevate, although most often all pancreatic enzymes are elevated. The etiology is not known, although several hypotheses have been suggested. This enzyme elevation is described both in adults and children and also sporadically or with a familial pattern. Knowledge of it can limit the performance of the multiple complementary test, some of which are very invasive in patients who have elevated pancreatic enzymes while they are asymptomatic. It knowledge allows us to confirm a benign prognosis about it and reassure the family about this disease and that in the end it will not require aggressive treatments such as surgery or chemotherapy.

Effects of Pristine C60 Fullerenes on Liver and Pancreas in α-Naphthylisothiocyanate-Induced Cholangitis.

BACKGROUND: A significant role in pathogenesis of cholangitis is attributed to excessive reactive oxygen species production and oxidative stress. Therefore, antioxidants could be promising therapeutics. AIMS: The effects of powerful free radical scavenger C60 fullerene on hepatic and pancreatic manifestations of acute and chronic cholangitis in rats were aimed to be discovered. METHODS: Acute (AC, 3 days) and chronic (CC, 28 days) cholangitis models were simulated by single (AC) and 4 weekly (CC) α-naphthylisothiocyanate per os administrations. Pristine C60 fullerene aqueous colloid solution (C60FAS, 0.15 mg/ml, size of aggregates 1.2-100 nm) was administered either per os or intraperitoneally at a dose of 0.5 mg/kg C60 fullerene daily (AC) and every other day (CC). Prednisolone was used as a reference. Liver and pancreas autopsies were analyzed, and blood serum biochemical markers were measured. Pan-cytokeratin expression in HepG2 cells was assessed after 48-h incubation with C60FAS. RESULTS: On AC, C60FAS normalized elevated bilirubin, alkaline phosphatase, and triglycerides, diminished fibrotic alterations in liver, and improved pancreas state when applied by both ways. Additionally, C60FAS per os significantly reduced the signs of inflammation in liver and pancreas. On CC, C60FAS also mitigated liver fibrosis and inflammation, improved pancreas state, and normalized alkaline phosphatase and triglycerides. The remedy effect of C60FAS was more expressed compared to that of prednisolone on both models. Furthermore, C60FAS inhibited pan-cytokeratin expression in HepG2 cells in a dose-dependent manner. CONCLUSION: Pristine C60 fullerene inhibits liver inflammation and fibrogenesis and partially improved liver and pancreas state under acute and chronic cholangitis.

The Combined Use of Drainage Amylase Concentration and Serum C-reactive Protein as Predictors of Pancreas-Related Complications after Elective Gastrectomy.

INTRODUCTION: Postoperative pancreas-related complications (PPRC) can cause critical conditions, including sepsis and intra-abdominal bleeding. Thus, it is important to identify patients who are at risk of clinically significant PPRC as early as possible in the postoperative period. Some authors have reported the use of amylase concentration of the drainage fluid (dAmy) to predict PPRC. However, the positive predictive value of dAmy alone is not sufficient. OBJECTIVE: The aim of this study is to evaluate the predictive value of combined use of dAmy and serum C-reactive protein (sCRP) for PPRC. METHODS: The clinicopathological data of 327 patients who underwent elective gastrectomy for gastric cancer were reviewed. There were 18 patients who developed PPRC. Univariate and multivariate analyses were conducted to identify the risk factors of PPRC. Receiver operating characteristic curves were used to identify the cut-off values of dAmy and sCRP on postoperative day 3 (dAmy3 and sCRP3) to predict the risk of PPRC. RESULTS: In the multivariate analysis, splenectomy alone correlated with PPRC. The cut-off values of dAmy3 and sCRP3 were 761 IU/L and 15.15 mg/dL, respectively. Among the 17 patients with both dAmy3 and sCRP3 above the thresholds, 10 (58.8%) had PPRC with Clavien-Dindo classification (CD) ≥II and 7 (41.2%) had PPRC with CD ≥III. In contrast, among the 236 patients with both parameters below the thresholds, 233 (98.7%) did not develop PPRC, and only 1 (0.4%) had PPRC with CD ≥III. CONCLUSIONS: Splenectomy correlates with PPRC, which is consistent with results from large clinical trials. A combined use of dAmy3 and sCRP3 can be useful in predicting the risks of PPRC.

Benign pancreatic hyperenzymemia-Gullo's syndrome: focus on this clinical challenge. A monocentric retrospective study.

BACKGROUND: An abnormal and chronic rise of pancreatic enzymes in the blood is most often due to pancreatic diseases, primarily inflammatory or neoplastic, or to numerous extra-pancreatic pathologies. Benign chronic pancreatic hyperenzymemia was described for the first time - as a separate nosological entity - in 1996 by Lucio Gullo et al. They demonstrated the existence of a benign chronic pancreatic hyperenzymemia in asymptomatic subjects and without clinical implications; however, a follow-up of at least 1-2 years is necessary during which no specific symptomatology or morpho-functional impairment of the pancreas should occur, also evaluated through the aid of instrumental diagnostic investigations such as ultrasonography (US), computed tomography (CT) or magnetic resonance cholangio pancreatography (MRCP). METHODS: This study was performed with the analysis of a group of 43 subjects arrived at the observation of the Gastroenterology Team of Policlinico Hospital G. Rodolico in Catania-Italy which presented a chronic pancreatic hyperenzymemia, in order to establish the actual benignity of this condition over time. RESULTS: During the follow-up, pancreatic alterations and hyperenzymemia were found in 10 patients, while hyperenzymemia was not associated with pancreatic modification in 33 patients. CONCLUSIONS: Because of this enzymatic elevation - often conspicuous and lasting - the patient is often particularly anxious. For the same reason, the patient frequently undergoes very expensive laboratory and instrumental diagnostic methods. Good knowledge of the syndrome makes it possible to manage the event more rationally, also to reduce management costs to a minimum.

[Analysis of prognostic factors for hyperamylasemia following pancreaticoduodenectomy].

Objective: To investigate the prognostic factors of hyperamylasemia following pancreaticoduodenectomy (PD) . Methods: Clinical data of 359 patients were collected prospectively who underwent PD by the same group at Changhai Hospital of Navy Medical University from January 2017 to June 2018.There were 212 males and 147 females.The median age was 63 years old (range: 23 to 82 years old) .According to whether the patient's serum amylase was greater than 120 U/L at 0 or 1 day after surgery,the patients were divided into hyperamylasemia group and non-hyperamylasemia group. Univariate analysis and multivariate analysis were used to find out the prognostic factors of hyperamylasemia after PD. Results: Of the 359 patients, 238 cases (66.3%) developed hyperamylasemia.The incidence rate of clinically related pancreatic fistula (15.1% vs.2.5%, P<0.01) , grade B/C post pancreatectomy hemorrhage (8.8% vs. 2.5%, P<0.01) , and surgical site infection (9.2% vs. 3.3%, P=0.04) was significantly higher in the hyperamylasemia group.The severity of complications (CD grade≥Ⅲ: 11.3% vs.4.1%, P=0.023) and postoperative hospital stay (11 days vs. 9 days, P=0.001) were higher in the hyperamylasemia group.In the multivariate analysis, the main pancreatic duct diameter (MPD) ≤3 mm (OR=4.469, 95% CI: 2.563-7.793, P<0.01) , pathological type of disease (pancreatic cancer or pancreatitis) (OR=0.230, 95% CI: 0.122-0.436, P<0.01) and soft texture of pancreas (OR=3.297, 95%CI: 1.930-5.635, P<0.01) were independent prognostic factors for hyperamylasemia. Conclusions: Post-PD hyperamylasemia increased the incidence and severity of postoperative complications after PD.MPD≤3 mm, soft texture of pancreas and pathological type of disease were independent prognostic factors of hyperamylasemia.

Circulating levels of lipocalin-2 are associated with fatty pancreas but not fatty liver.

Lipocalin-2 (LCN-2), a peptide with diverse expression pattern, has been identified as a biomarker of various diseases as well as a factor contributing to inflammatory responses associated with excess adiposity and ensuing metabolic disorders. Although the inter-relationship between LCN-2 and excess adiposity is increasingly recognized, little is known about the inter-relationship between LCN-2 and ectopic fat deposition. The present study aimed to investigate the associations between LCN-2 and fatty pancreas as well as fatty liver. In addition, the associations between LCN-2 and pro-inflammatory cytokines were studied. Magnetic resonance imaging was used to quantify intra-pancreatic fat deposition and visceral-to-subcutaneous fat volume ratio whereas magnetic resonance spectroscopy was used to quantify liver fat deposition. Fasting venous blood was analyzed for LCN-2, C-C motif chemokine ligand 2, interleukin-6, leptin, tumor necrosis factor-α, glycated hemoglobin, glucose, and insulin. Binary logistic regression and linear regression analyses were conducted. Three statistical models were built to adjust for demographics, comorbidities, levels of glycated hemoglobin, insulin resistance, and abdominal fat distribution. A total of 79 individuals were studied, of whom 20 had fatty pancreas, 14 had fatty liver, and 4 had both. Lipocalin-2 was significantly associated with fatty pancreas in all the adjusted models (p = 0.014 in the most adjusted model) but was not significantly associated with fatty liver in any of the studied models. Lipocalin-2 was significantly associated with interleukin-6 and tumor necrosis factor-α, in both the unadjusted and adjusted models. Leptin and C-C motif chemokine ligand 2 were not significantly associated with LCN-2 in any of the studied models. These findings suggest that LCN-2 is a potential biomarker of fatty pancreas, independent of abdominal fat distribution, insulin resistance, and other covariates. The role of LCN-2 in intra-pancreatic fat deposition and related low-grade inflammation warrants further investigations.

Pancreatic panniculitis in active systemic lupus erythematosus.

This report documents the case of a 64-year-old African-American female with new end-stage renal disease (ESRD), diagnosed with systemic lupus erythematosus (SLE) on renal biopsy and serologies including a positive ANA (>1:2560), positive anti-Sm antibodies, low titer anti-RNP antibodies, high titer anti-Ro antibodies, anti-dsDNA antibodies, lupus anticoagulant, and hypocomplementemia. She was also noted to have tender nodules on the bilateral shins. Excisional biopsy of one of the nodules showed marked fat necrosis with "ghost cells" and patchy basophilic granular debris consistent with pancreatic panniculitis. Further examination for pancreatic pathology showed an elevated lipase of 585 U/L (reference range 8-78 U/L) and amylase of 214 U/L (reference range 25-125 U/L). However, computed tomography imaging showed no evidence of pancreatitis or pancreatic tumors. This is very similar to another case recently reported in the literature. Similarities of these two cases (African-American females with lupus nephritis on dialysis) may represent a particular subset of SLE patients at increased risk for pancreatic panniculitis.

Chronic Asymptomatic Pancreatic Hyperenzymemia: A Long-term Follow-up.

OBJECTIVES: Chronic asymptomatic pancreatic hyperenzymemia (CAPH) was described as a benign disease. However, we already described clinically relevant findings requiring surgery or follow-up in half of the subjects. The aim of this study was to evaluate the long-term outcome of CAPH in terms of symptoms and evolution toward chronic pancreatitis. METHODS: Subjects previously enrolled in the first phase of the study (from 2005 to 2010) were reinvestigated from December 2013 to January 2017 with a phone call ± magnetic resonance cholangiopancreatography with secretin stimulation. RESULTS: A total of 133 subjects were eligible for the follow-up study (75 males, 58 females; age, 48.4 [standard deviation {SD}, 14] years); 24 (18%) of them dropped out. During a mean follow-up of 9.3 (SD, 5.2) years after the first diagnosis of CAPH, no episode of acute pancreatitis or abdominal pain was reported. Sixty-three subjects (58%) of 109 underwent magnetic resonance cholangiopancreatography with secretin stimulation with a mean follow-up of 5.7 [SD, 3.1] years (range, 1-11 years). Secretin stimulation-MRCP resulted unchanged in 54 (90%) of 60 subjects, worsened in 3 (5%) and improved in 3 (5%). Two subjects died from causes unrelated to pancreatic disease. CONCLUSIONS: Excluding subjects with a pancreatic disease at index magnetic resonance imaging, CAPH is a benign condition.

Verification of the effectiveness of fucosylated haptoglobin as a pancreatic cancer marker in clinical diagnosis.

BACKGROUND: Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose α1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA. METHODS: PhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA. RESULTS: The sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA. CONCLUSION: PhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9.

Nodular subcutaneous lesion - an alarming sign for an upcoming pancreatic disorder.

Pancreatic panniculitis represents a rare dermatological manifestation mainly due to a pancreatic disorder, but other etiologies are possible. Even rarer, it can occur prior to the clinical signs of the underlying disease, and its presence must orientate the investigations especially towards pancreas, liver and neuroendocrine system. We report a rare case of a 47-year-old male patient who presented to the Emergency Unit complaining about a two weeks-long-persistent pain in the upper abdomen and biliary vomiting. The medical history included alcohol abuse. Several days prior to the onset of these symptoms, the patient has noticed the occurrence of a nodular inflammatory lesion of 5∕3 cm on the right calf (this makes the case even rarer). Based on clinical aspect and high levels of pancreatic enzymes, acute pancreatitis was diagnosed. Contrast-enhanced abdominal computed tomography (CT) revealed a cystic pancreatic mass and dilated intrahepatic biliary ducts. Abdominal magnetic resonance imaging (MRI) revealed a cystic tumor of the pancreatic head and thrombosis of the portal vein, which increased the suspicion of pancreatic adenocarcinoma. Biopsy was performed from the calf nodular lesion, with the diagnosis of panniculitis. This case, besides its rarity, supports the clinical important value of a pancreatic workup in case of histologically proved panniculitis, even without pancreatic related symptoms.

Pancreatic function and histoarchitecture in Wistar rats following chronic exposure to Bushfire®: the mitigating role of zinc.

Objectives To assess the toxicopathologic effects of chronic exposure to the glyphosate-based herbicide Bushfire® on the pancreas of Wistar rats and the protective role of zinc. Methods We exposed the rats to daily doses of 14.4 to 750 mg/kg body weight of the glyphosate-based herbicide Bushfire® and to 50 or 100 mg/kg zinc, and measured blood glucose levels and serum insulin levels. Tissue samples were evaluated for histopathological alterations. Results Levels of both blood glucose and serum insulin increased in glyphosate-exposed rats, and moderate to severe degenerative changes were observed in both glandular pancreatic acinar cells and islets of Langerhans in all rats exposed to glyphosate. These effects were prevented by pretreatment with zinc. Conclusion Chronic exposure to glyphosate can alter pancreatic function and histoarchitecture, but zinc supplementation can mitigate these toxicopathologic effects.

Increase in breath hydrogen concentration was correlated with the main pancreatic duct stenosis.

BACKGROUND: Hydrogen is produced from unabsorbed carbohydrates in the intestine through degradation and metabolism by hydrogenase of intestinal bacteria. The hydrogen is then partially diffused into blood flow and released and detected in exhaled breath. Pancreatic juice production is decreased in patients with reduced pancreatic exocrine function, including those with pancreatic cancer, thus decreasing digestion and absorption of nutrients including carbohydrates, which may increase undigested carbohydrates in the intestine and increase breath hydrogen concentration (BHC). The aim of this study was to investigate the association between BHC and pancreatic diseases. METHODS: A retrospective study was designed and 68 patients underwent morning fasting breath hydrogen test. Since there is no clear standard, normal BHC, the median of the measured values from the subjects (9 ppm) was adopted as the standard. The subjects were classified into those with a value exceeding the median (BHC high group: 32 patients) and a value equal to or below the median (BHC low group: 36 patients). Patients characteristics, blood test results and imaging findings characteristic of pancreatic diseases were compared between the groups. RESULTS: The age was significantly higher (P = 0.010) and the incidences of pancreatic ductal adenocarcinoma and autoimmune pancreatitis were significantly higher (P = 0.018 and P = 0.004, respectively) in the BHC high group. With respect to the blood test items, the Alb level was significantly lower in the BHC high group (P = 0.005). With respect to the characteristic imaging findings of pancreatic diseases, the proportions of patients with pancreatic enlargement, the main pancreatic duct (MPD) stenosis, and the MPD dilatation were significantly higher in the BHC high group (P = 0.022, P < 0.001, and P = 0.002, respectively). On univariate analysis, only the MPD stenosis was extracted as an independent factor (P = 0.014). CONCLUSION: It was suggested that the fasting BHC is associated with pancreatic diseases causing stenosis of the MPD, including pancreatic cancer (UMIN000020777).

Cytologic characteristics of circulating epithelioid cells in pancreatic disease.

BACKGROUND: Circulating epithelioid cells (CECs), also known as circulating tumor, circulating cancer, circulating epithelial, or circulating nonhematologic cells, are a prognostic factor in various malignancies that can be isolated via various protocols. In the current study, the authors analyzed the cytomorphologic characteristics of CECs isolated by size in a cohort of patients with benign and malignant pancreatic diseases to determine whether cytomorphological features could predict CEC origin. METHODS: Blood samples were collected from 9 healthy controls and 171 patients with pancreatic disease who were presenting for surgical evaluation before treatment. Blood was processed with the ScreenCell size-based filtration device. Evaluable CECs were analyzed in a blinded fashion for cytomorphologic characteristics, including cellularity; nucleoli; nuclear size, irregularity, variability, and hyperchromasia; and nuclear-to-cytoplasmic ratio. Statistical differences between variables were analyzed via the Fisher exact test. RESULTS: No CECs were identified among the 9 normal healthy controls. Of the 115 patients with CECs (positive or suspicious for), 25 had nonmalignant disease and 90 had malignancy. There were no significant differences in any of the cytologic criteria noted between groups divided by benign versus malignant, neoplastic versus nonneoplastic, or pancreatic ductal adenocarcinoma versus neuroendocrine tumor. CONCLUSIONS: CECs were observed in patients with malignant and nonmalignant pancreatic disease, but not in healthy controls. There were no morphologic differences observed between cells from different pancreatic diseases, suggesting that numerous conditions may be associated with CECs in the circulation and that care must be taken not to overinterpret cells identified by cytomorphology as indicative of circulating tumor cells of pancreatic cancer. Additional studies are required to determine the origin and clinical significance of these cells. Cancer Cytopathol 2017;125:332-340. © 2017 American Cancer Society.

Betaine Attenuates Alcohol-Induced Pancreatic Steatosis.

OBJECTIVES: To explore the effect of betaine on alcoholic pancreatic steatosis and its mechanism. METHODS: Rats were randomly assigned to control, ethanol, or ethanol + betaine groups. Changes in pancreatic morphology; serum lipid levels; and pancreatic lipid, amylase and lipase levels were determined. The serum and adipose tissue adiponectin level was measured by an enzyme-linked immunoassay. Adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, and fatty acid synthetase expression levels were quantified. The SREBP-1c expression in SW1990 cells treated with various concentrations of ethanol or ethanol plus betaine and/or adiponectin was assessed. RESULTS: Alcohol-induced changes in pancreatic morphology were attenuated by betaine. Pancreatic triglyceride, free fatty acid and expression levels of SREBP-1c and fatty acid synthetase were elevated after ethanol feeding but remained at control levels after betaine supplementation. Alcohol-induced decreases in serum and adipose tissue adiponectin, pancreatic AdipoR1, amylase, and lipase were attenuated by betaine. Serum triglyceride and free fatty acid levels were elevated after alcohol consumption and remained higher after betaine supplementation compared with controls. Betaine and/or adiponectin suppressed alcohol-induced SREBP-1c upregulation in vitro. CONCLUSIONS: Betaine attenuated alcoholic-induced pancreatic steatosis most likely by suppressing pancreatic SREBP-1c both directly and through the restoration of adiponectin signaling.

α-Lipoic Acid Protects Against Ischemia-Reperfusion Injury in Simultaneous Kidney-Pancreas Transplantation.

BACKGROUND: Multiple factors have been implicated in the process of ischemia-reperfusion injury (IRI) in organ transplantation. Among these factors, oxidative damage seems to initiate the injury. α-lipoic acid (ALA) is a potent antioxidant that is used in patients with diabetic polyneuropathy. The aim of the present study was to determine the effect of ALA in patients undergoing simultaneous kidney-pancreas transplant by evaluating the functional recovery of the graft and biochemical markers of IRI. METHODS: Twenty-six patients were included in the following groups: (i) untreated control; (ii) donor and recipient (DR) ALA-treated, in which ALA was administered both to the deceased donor and to the recipients; and (iii) recipient ALA-treated group. The expression of inflammatory genes, as observed in biopsies taken at the end of surgery, as well as the serum cytokines, secretory leukocyte protease inhibitor, regenerating islet-derived protein 3ß/pancreatitis-associated protein, amylase, lipase, glucose, and creatinine levels were quantified as markers of organ function. RESULTS: The DR group showed high levels of TGFß and low levels of C3 and TNFα in the kidneys, whereas high levels of C3 and heme oxygenase were identified in pancreas biopsies. Decreases in serum IL-8, IL-6, secretory leukocyte protease inhibitor, and regenerating islet-derived protein 3 ß/pancreatitis-associated protein were observed after surgery in the DR group. Serum lipase and amylase were lower in the DR group than in the control and recipient groups. Early kidney dysfunction and clinical pancreatitis were higher in the control group than in either treatment group. CONCLUSIONS: These results show that ALA preconditioning is capable of reducing inflammatory markers while decreasing early kidney dysfunction and clinical posttransplant pancreatitis.

IgG4-unrelated type 1 autoimmune pancreatitis.

A 50-year-old male was referred to our hospital for the evaluation of hyperproteinemia. Fluorodeoxyglucose positron emission tomography revealed high fluorodeoxyglucose uptake in the pancreas, bilateral lacrimal glands, submandibular glands, parotid glands, bilateral pulmonary hilar lymph nodes, and kidneys. Laboratory data showed an elevation of hepatobiliary enzymes, renal dysfunction, and remarkably high immunoglobulin (Ig) G levels, without elevated serum IgG4. Abdominal computed tomography revealed swelling of the pancreatic head and bilateral kidneys. Endoscopic retrograde cholangiopancreatography showed an irregular narrowing of the main pancreatic duct in the pancreatic head and stricture of the lower common bile duct. Histological examination by endoscopic ultrasonography-guided fine-needle aspiration revealed findings of lymphoplasmacytic sclerosing pancreatitis without IgG4-positive plasma cells. Abnormal laboratory values and the swelling of several organs were improved by the treatment with steroids. The patient was diagnosed as having type 1 autoimmune pancreatitis (AIP) based on the International Consensus Diagnostic Criteria. Therefore, we encountered a case of compatible type 1 AIP without elevated levels of serum IgG4 or IgG4-positive plasma cells. This case suggests that AIP phenotypes are not always associated with IgG4.

Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more than ectopic fat.

OBJECTIVE: The aim of this study was to evaluate the metabolic effects of fatty pancreas (nonalcoholic fatty pancreas disease - NAFPD) in a group of obese paediatric patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We included 121 consecutive children with echographic evidence of hepatic steatosis. All patients underwent to abdominal ultrasound to evaluate pancreatic echogenic pattern. We divided the patients into two groups on the basis of the presence of fatty pancreas. In all patients liver function tests, lipid and gluco-insulinemic profile were evaluated. A selected subset of patients (67) underwent to liver biopsy. RESULTS: Of these 121 patients, 58 showed NAFPD and 63 patients exhibited a normal pancreatic echogenic pattern. No differences were found in age, transaminases serum levels, lipid profile and pancreatic enzymes between the two groups. The patients with NAFPD had a significantly higher z-BMI, fasting insulin, insulin resistance (HOMA-IR) and lower ISI respect to the group without fatty pancreas. The patients with fatty pancreas showed a more advanced form of liver disease, with higher values of fibrosis, ballooning and NAS score with respect to the group without NAFPD. CONCLUSIONS: Our study demonstrated that NAFPD is a frequent condition in obese paediatric patients affected by NAFLD. Our data suggest that pancreatic fat should not be considered an inert accumulation of fat, but as an additional factor able to affect glucose metabolism and severity of liver disease, increasing the risk of develop metabolic syndrome.