Pancreatic Fatty Infiltration Research Articles

Obesity and Fatty Pancreatic Infiltration Are Risk Factors for Pancreatic Precancerous Lesions (PanIN).

The roles of intravisceral and subcutaneous fat are unknown, and the prevalence of precancerous lesions in obese patients was never evaluated. This study aims to assess the frequency and severity of pancreatic intraepithelial neoplasia (PanIN) and to correlate pathologic findings with metabolic abnormalities, type of fat, and fatty pancreatic infiltration. Normal pancreatic tissue from surgical specimens was analyzed. Fatty infiltration and fibrosis in intra- and extralobular locations and PanIN lesions were assessed. General characteristics were collected: body mass index (BMI), diabetes, and tobacco intake. Liver steatosis and subcutaneous and intravisceral fat were assessed by CT scan (ImageJ software). Of note, 110 patients were included [median age, 53.8 (17-85) years]. Arterial hypertension, diabetes, and tobacco intake were found in 19%, 9%, and 23%, respectively. Median BMI was 24 (16-37; BMI < 25: 45%, 25 ≤ 30: 24%, ≥30: 11%). Overall, PanIN lesions were found in 65% (type I, II, and III PanIN in 62%, 38%, and 1%, respectively). Fibrosis and fatty pancreas (intra- and extralobular locations) were found in 1% and 24% and in 30% and 51%, respectively. A correlation was observed between PanIN lesions and fatty pancreas [extralobular (0.01) and intralobular (<0.0001)], intralobular fibrosis (0.003), high BMI (P = 0.02), and subcutaneous (P = 0.02) and intravisceral fat (P = 0.02). The number of PanIN lesions was correlated with intravisceral fat (r = 0.22, P = 0.04), but not with subcutaneous fat (r = 0.14, P = 0.22). In multivariate analysis, PanIN lesions were associated with intralobular fibrosis [OR, 5.61; 95% confidence interval (CI), 1.18-42.99] and intralobular fat (OR, 17.86; 95% CI, 4.935-88.12). Obesity (especially android obesity) and pancreatic fatty infiltration are risk factors for pancreatic precancerous lesions.

Association of Pancreatic Fatty Infiltration With Pancreatic Ductal Adenocarcinoma

OBJECTIVES:Fatty infiltration (FI) in the pancreas is positively correlated with high body mass index (BMI) or obesity, and the prevalence of diabetes mellitus (DM), which are well-known risk factors of pancreatic cancer. However, the association of FI in the pancreas with pancreatic cancer is unclear. Recently, we have shown that Syrian golden hamsters feature FI of the pancreas, the severity of which increases along with the progression of carcinogenesis induced by a chemical carcinogen. To translate the results to a clinical setting, we investigated whether FI in the pancreas is associated with pancreatic cancer in a series of patients who had undergone pancreatoduodenectomy.METHODS:In the series, we identified 102 cases with pancreatic ductal adenocarcinoma (PDAC) and 85 controls with cancers except for PDAC. The degree of FI was evaluated histopathologically from the area occupied by adipocytes in pancreas sections, and was compared between the cases and controls.RESULTS:The degree of FI in the pancreas was significantly higher in cases than in controls (median 26 vs. 15%, P<0.001) and positively associated with PDAC, even after adjustment for BMI, prevalence of DM and other confounding factors (odds ratio (OR), 6.1; P<0.001). BMI was identified as the most significantly associated factor with FI in the pancreas.CONCLUSIONS:There is a positive correlation between FI in the pancreas and pancreatic cancer.

15. How frequently is breast conservation possible after neoadjuvant chemotherapy in women with breast cancer – Overview of our surgical practice

15. How frequently is breast conservation possible after neoadjuvant chemotherapy in women with breast cancer – Overview of our surgical practice

Preoperative CT Scan Helps to Predict the Occurrence of Severe Pancreatic Fistula After Pancreaticoduodenectomy

To assess the influence of body fat distribution, estimated by a preoperative computed tomographic (CT) scan, on pancreatic fistula (PF) risk after pancreaticoduodenectomy (PD). Pancreatic fatty infiltration is a predictive factor of PF, but accurate preoperative assessment is challenging. We hypothesized that it could be associated with an increased visceral obesity and could be assessed preoperatively. Over 18 months, 103 consecutive patients with PD and pancreaticogastrostomy were studied. Demographic, radiologic, and pathologic data were correlated to PF occurrence. Radiologic data included on a nonenhanced CT acquisition: pancreas, spleen, and liver density measures (Dpancreas, Dspleen, and Dliver [densities of the pancreas, spleen, and liver in hounsfield units], respectively), retro-renal fat thickness, and at the level of the umbilicus, total, visceral, and subcutaneous fat area (TFA [total fat area], VFA [visceral fat area], and SFA [subcutaneous fat area], respectively). Pancreatic fatty infiltration was graded histologically. Logistic regression analysis was used to identify independent predictors of PF-graded B and C according to the International Study Group on the Pancreatic Fistula. Among the 103 patients, 37% (n = 38) developed a PF (47.4% grade A, 39.5% grade B, and 13.1% grade C). PF risk was correlated with pancreatic fatty infiltration (P = 0.017). In univariate analysis, male gender (P = 0.023), body mass index (BMI) over 25 kg/m (P = 0.02), retro-renal fat thickness over 15 mm (P = 0.006), TFA over the median (>233 cm; P = 0.023), and VFA over the median (>84 cm; P < 0.0001) were significantly associated with an increased risk of symptomatic PF (grade B and C). In multivariate analysis, VFA greater than 84 cm (OR = 8.16, P = 0.002) was the only independent predictive factor of grade B or C PF. Using the same model, a VFA greater than 84 cm was the only independent factor associated with the presence of fatty pancreas on pathologic examination. Preoperative assessment of body fat distribution by a CT scan, as a surrogate for fatty pancreas infiltration, can help to predict the occurrence of clinically significant PF after PD.

Impact of Obesity and Body Fat Distribution on Survival After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Epidemiologic studies have reported a positive correlation between body mass index (BMI) and pancreatic cancer risk, but clinical relevance of obesity and/or body fat distribution on tumor characteristics and cancer-related outcome remain controversial. We sought to assess the influence of obesity and body fat distribution on pathologic characteristics and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Demographic and biometric data were collected on 328 patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In a subset of patients, pancreatic fatty infiltration and fibrosis were assessed pathologically, and visceral fat area (VFA) was evaluated. Influence of BMI and body fat distribution on tumor characteristics and survival were evaluated. A significant positive correlation between BMI and VFA was observed, with a wide range of VFA value within each BMI class. According to BMI or VFA distribution, there were no significant differences in patient characteristics, intraoperative or perioperative outcome, or pathologic characteristics, with the exception of significantly higher blood loss in patients with an increased body weight or VFA. Unadjusted overall and disease-free survival between BMI class and VFA quartile were not significantly different. In this study, obesity and body fat distribution were not correlated with specific tumor characteristics or cancer-related outcome.

Enhancement of Carcinogenesis and Fatty Infiltration in the Pancreas in N-Nitrosobis(2-Oxopropyl)Amine-Treated Hamsters by High-Fat Diet

Obesity is associated with increased pancreatic cancer risk, although the mechanisms have yet to be detailed. This study aimed to elucidate promotion of pancreatic cancer by obesity and hyperlipidemia. Six-week-old female Syrian golden hamsters were treated with N-nitrosobis(2-oxopropyl)amine (BOP) and after 1 week were fed a high-fat diet (HFD) or standard diet (STD) for 6 or 17 weeks. Body weight and serum levels of lipids and leptin were significantly higher in the HFD than the STD group at 14 weeks of age. Pancreatic ductal adenocarcinomas developed only in the BOP + HFD group, with an incidence of 67% (P < 0.01) at 14 weeks of age. In addition, the multiplicity was 2-fold greater in the BOP + HFD group than in the BOP + STD group (P < 0.05) at 25 weeks of age. Pancreatic fatty infiltration was increased by BOP treatment and further enhanced by the HFD, correlating with progression of BOP-induced pancreatic ductal adenocarcinoma and up-regulated expression of adipocytokines and cell proliferation-related genes in the pancreas. High-fat diet is shown to increase serum lipid levels and enhance fatty infiltration in the pancreas with abnormal adipocytokine production, which may accelerate and enhance pancreatic cancer.

Measurement of Pancreatic Fat by Magnetic Resonance Imaging

The purpose of this study was to determine whether patients who develop a pancreatic fistula after pancreatoduodenectomy are more likely to have higher pancreatic fat levels than matched controls and if so, to investigate whether preoperative dual gradient-echo magnetic resonance (MR) imaging can be used to measure pancreatic fat and predict the development of postoperative pancreatic fistula. Pancreatic fistula is a major complication and its most frequently reported risk factors tend to be anatomic features of the pancreatic remnant, such as a soft pancreatic texture. Between January 2007 and September 2007, a total of 96 cases of pancreatoduodenectomy were performed at Seoul National University Hospital. Of total, 20 patients (20.8%) who developed a pancreatic fistula were carefully matched for multiple parameters including age, gender, pancreatic pathology, surgeon, and type of operation with 20 control patients who did not develop a pancreatic fistula. In the pancreatic fistula group, 9 patients (45%) had a grade A fistula and 11 (55%) grade B fistula. Degrees of pancreatic fatty infiltration and fibrosis were assessed quantitatively. In-phase and opposed-phase images were obtained by dual-gradient-echo MR imaging. Percentage decreases in pancreatic signal intensity on opposed-phase images relative to those on in-phase images were calculated and defined as relative signal intensity decreases (RSID). More patients in the pancreatic fistula group had a soft pancreatic texture or a smaller pancreatic duct and total fat and RSID were significantly higher. In soft pancreatic texture group, intralobular, interlobular, and total fat were significantly elevated. Furthermore, pancreatic fat levels were found to be correlated positively with RSID (P=0.013). RSID was correlated with total pancreatic fat and when an RSID criterion more than 7.032 was used, pancreatic fistula could be predicted as 72.7% sensitivity and 75.9% specificity. Our findings suggest that increased pancreatic fat is a risk factor of postoperative pancreatic fistula. Preoperative measurements of pancreatic fat by MRI offer a noninvasive predicting the occurrence of pancreatic fistula.

Abstract 2478: Early and enhanced development of N-nitrosobis(2-oxopropyl)amine-induced hamster pancreatic adenocarcinomas by high-fat diet

Abstract Epidemiologically, obesity is associated with pancreatic cancer risk, but the mechanisms of obesity-associated carcinogenesis have not yet been clearly understood. Hypertrophic white adipose tissues secrete many adipokines and inflammatory factors, which are expected to enhance cancer development. Syrian golden hamsters, which are used in pancreatic carcinogenesis studies, are in a hyperlipidemic state even under normal diet conditions. We previously have shown that pioglitazone, a PPAR γ ligand, improves hyperlipidemia and suppresses N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic ductal carcinoma development. In the present study, effects of a high-fat diet (HFD) on hyperlipidemia and pancreatic carcinogenesis in BOP-treated hamsters were examined. Six-week-old female Syrian golden hamsters were subcutaneously injected with BOP (10 mg/kg body weight) four times in a week and from 8 weeks of age, the animals in the HFD groups were fed Quick Fat Diet (CLEA Japan, crude fat 14.3 %) for 6 or 17 weeks. At 14 weeks of age, serum levels of triglycerides, total cholesterol, free fatty acids and leptin were significantly elevated in hamsters fed the HFD, and pancreatic ductal adenocarcinomas were already observed in the BOP + HFD group. Pancreatic fatty infiltration was observed to increase in BOP-treated and HFD-fed hamsters. At 25 weeks of age, serum levels of total cholesterol and free fatty acids were further increased in each group and pancreatic ductal adenocarcinomas developed both in the BOP + standard diet group and BOP + HFD group. The numbers of dysplasia and adenocarcinomas in the pancreas were significantly higher in the BOP + HFD group than in the BOP + standard diet group. Apparent fatty infiltration was observed in relatively large adenocarcinomas in the BOP + HFD group. In conclusion, the HFD aggravated the hyperlipidemia, shortened the latency periods of cancer and increased numbers of BOP-induced pancreatic precancerous lesions and adenocarcinomas. Fatty infiltration was apparent in the pancreas of the HFD group and may be associated with pancreatic cancer development in hamsters. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2478.

The Role of “Fatty Pancreas” and of BMI in the Occurrence of Pancreatic Fistula After Pancreaticoduodenectomy

IntroductionPancreatic fistula (PF) after pancreaticoduodenectomy (PD) is still a serious complication. We hypothesized that the amount of fatty tissue in the pancreatic parenchyma could be associated with the occurrence of PF after PD with pancreatogastrostomy. Material and methodsFrom January 2004 to December 2006, 111 consecutive patients underwent PD with pancreatogastrostomy. The microscopic amount of fatty tissue in the pancreas was evaluated. ResultsThe morbidity and mortality rates were 35.1% and 1.8%, respectively. PF occurred in 10.8% (n = 12). PF was of grade A in nine, grade B in two, and grade C in one patient. Univariate analysis showed that a body mass index (BMI) > 25 (P = 0.035), a soft pancreatic parenchyma (P = <0.003), a pancreatic duct size <3 mm (P = 0.015), and a fatty infiltration of the pancreas of more than 10% (P = 0.0003) were associated with the occurrence of PF. The advanced age (P = 0.049) and the BMI (P < 0.0001) were significantly associated with the presence of >10% of pancreatic fat. ConclusionsA pancreatic fatty infiltration of the pancreas over 10% constitutes a risk factor for PF after PD. Age and BMI are useful preoperative predictors of the percentage of pancreatic fat.

Donor and Isolation Variables Predicting Human Islet Isolation Success

Recent advances in the fields of islet transplantation and in vitro islet cell expansion place a renewed emphasis on the optimization of islet isolation from cadaveric human donor organs. We retrospectively analyzed 171 islet isolations to identify variables that predict islet yield and isolation success. Cadaveric human donor pancreata were procured and processed according to established protocols. Donor-, procurement-, and isolation-related variables were analyzed for correlation with islet yield and isolation success (> or =250,000 islet equivalents). Univariate analysis suggested correlations between islet yield and donor age (P<0.005), body surface area (P<0.005), duration of enzymatic digestion (P<0.001), and pancreatic beta-cell volume (P<0.05). Donor sex (P<0.01), procurement team (P<0.05), and peridigestion serine protease inhibition (P<0.05) affected islet yield, whereas enzyme lot (P<0.01) and pancreatic fatty infiltration (P<0.05) influenced isolation success. By logistic regression, donor sex and age, and duration of enzymatic digestion could predict a successful isolation with 72% accuracy. The use of Liberase CI improved islet yield (P<0.05) in young donors (< or =25 years). While donor-related variables are useful in predicting islet yield, these are likely surrogates for pancreatic beta-cell volume. Enzyme lot, and the associated duration of enzymatic digestion (P<0.05), appears to be key determinants of isolation success.