Purpose: 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. Experimental Design: 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). Results: 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). Conclusions: Obesity (especially android obesity) and pancreatic fatty infiltration are risk factors for pancreatic precancerous lesions. Clin Cancer Res; 21(15); 3522–8. ©2015 AACR. See related commentary by Wang et al., p. 3369

Context: Asymptomatic sporadic nonfunctioning, well-differentiated pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed, and their management is controversial because of their overall good but heterogeneous prognosis. Objective: The objective of the study was to assess the natural history of asymptomatic sporadic NF-PNETs smaller than 2 cm in size and the risk-benefit balance of nonoperative management. Experimental Design: From January 2000 to June 2011, 46 patients with proven asymptomatic sporadic NF-PNETs smaller than 2 cm in size were followed up for at least 18 months with serial imaging in tertiary referral centers. Results: Patients were mainly female (65%), with a median age of 60 years. Tumors were mainly located in the pancreatic head (52%), with a median lesion size of 13 mm (range 9–15). After a median follow-up of 34 months (range 24–52) and an average of four (range 3–6) serial imaging sessions, distant or nodal metastases appeared on the imaging in none of the patients. In six patients (13%), a 20% or greater increase in size was observed. Overall median tumor growth was 0.12 mm per year, and neither patients nor tumor characteristics were found to be significant predictors of tumor growth. Overall, eight patients (17%) underwent surgery after a median time from initial evaluation of 41 months (range 27–58); all resected lesions were European Neuroendocrine Tumor Society T stage 1 (n = 7) or 2 (n = 1), grade 1, node negative, with neither vascular nor peripancreatic fat invasion. Conclusions: In selected patients, nonoperative management of asymptomatic sporadic NF-PNETs smaller than 2 cm in size is safe. Larger and prospective multicentric studies with long-term follow-up are now needed to validate this wait-and-see policy.

Cystic lesions of the pancreas are being identified more frequently, and a selective approach to resection is now recommended. The aim of this study was to assess the change in presentation and management of pancreatic cystic lesions evaluated at a single institution over 15 years. A prospectively maintained registry of patients evaluated between 1995 and 2010 for the ICD-9 diagnosis of pancreatic cyst was reviewed. The 539 patients managed from 1995 to 2005 were compared with the 885 patients managed from 2005 to 2010. A total of 1,424 patients were evaluated, including 1,141 with follow-up >6 months. Initial management (within 6 months of first assessment) was operative in 422 patients (37%) and nonoperative in 719 patients (63%). Operative mortality in patients initially submitted to resection was 0.7% (n = 3). Median radiographic follow-up in patients initially managed nonoperatively was 28 months (range 6 to 175 months). Patients followed radiographically were more likely to have cysts that were asymptomatic (72% versus 49%, p < 0.001), smaller (1.5 versus 3 cm, p < 0.001), without solid component (94% versus 68%, p < 0.001), and without main pancreatic duct dilation (88% versus 61%, p < 0.001). Changes prompting subsequent operative treatment occurred in 47 patients (6.5%), with adenocarcinoma identified in 8 (17%) and pancreatic endocrine neoplasm in 4 (8.5%). Thus, of the 719 patients initially managed nonoperatively, invasive malignancy was identified in 12 (1.7%), with adenocarcinoma seen in 1.1%. Cystic lesions of the pancreas are being identified more frequently, yet are less likely to present with concerning features of malignancy. Carefully selected patients managed nonoperatively had a risk of malignancy that was equivalent to the risk of operative mortality in those patients who initially underwent resection.