Obesity potentiates the growth and dissemination of pancreatic cancer

Zyromski, Nicholas J.; Mathur, Abhishek; Pitt, Henry A.; Wade, Terence E.; Wang, Sue; Nakshatri, Poornima; Swartz-Basile, Deborah A.; Nakshatri, Harikrishna

doi:10.1016/j.surg.2009.02.024

Cited by 111 publications

(84 citation statements)

References 23 publications

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“…The intratumoral adipocyte mass in tumors from obese mice was significantly greater than that in lean mice. These data could suggest that both insulin resistance and altered adipokine milieu could lead directly to changes of the microenvironment (12). In our study, the main risk factor of PanIN lesions in univariate and multivariate model was the fatty infiltration, especially in intralobular location (OR, 17.86; 95% CI, 4.935-88.12).…”

Section: Discussionmentioning

confidence: 52%

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

Rebours

Gaujoux

d’Assignies

et al. 2015

Clinical Cancer Research

178

107

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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 intraand 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 ¼ 0.02), and subcutaneous (P ¼ 0.02) and intravisceral fat (P ¼ 0.02). The number of PanIN lesions was correlated with intravisceral fat (r ¼ 0.22, P ¼ 0.04), but not with subcutaneous fat (r ¼ 0.14, P ¼ 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,.Conclusions: Obesity (especially android obesity) and pancreatic fatty infiltration are risk factors for pancreatic precancerous lesions.

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Section: Discussionmentioning

confidence: 52%

“…The median percentage of total, visceral, and SFA (regarding the total surface of the slide) represented: 21% (2-47), 7.3% (0. [8][9][10][11][12][13][14][15][16][17][18][19][20], and 13% (1.2-31.7), respectively. Liver steatosis was observed in 27%.…”

Section: Radiologic Characteristicsmentioning

confidence: 99%

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

Rebours

Gaujoux

d’Assignies

et al. 2015

Clinical Cancer Research

178

107

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“…Obesity is an independent risk factor for the development and progression of pancreatic cancer (2). Obese mice developed larger pancreatic tumors, more metastases and showed greater mortality (3).…”

Section: Introductionmentioning

confidence: 99%

“…Resistin, an adipocyte-secreted factor, was discovered in 2001 and proposed as a potential link between obesity, insulin resistance and inflammation (5,6), the three most significant risk factors for pancreatic cancer (3,7). The administration of recombinant resistin to diet-induced and genetically obese mice impaired glucose tolerance (4).…”

Section: Introductionmentioning

confidence: 99%

Expression of the adipocytokine resistin and its association with the clinicopathological features and prognosis of pancreatic ductal adenocarcinoma

et al. 2012

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Abstract. Fat tissue is viewed as an active endocrine organ that secretes a variety of bioactive substances. Resistin, an adipocyte-secreted factor, is thought to be closely related to obesity, insulin resistance and inflammation, the three most significant risk factors for the progression of pancreatic cancer. However, the association between resistin and pancreatic cancer is still unknown. In this study, pancreatic tumor samples from 45 patients with pancreatic ductal adenocarcinoma were analyzed with immunohistochemistry for the expression of resistin. The correlation between resistin expression and clinicopathological features and prognosis were evaluated. Resistin staining was observed in 48.9% (22 of 45) of the cases. Resistin expression was more frequent in poorly differentiated tumors (9 of 9, 100%) compared to moderately differentiated tumors (11 of 28, 39.3%) and welldifferentiated tumors (2 of 8, 25%) (p<0.01). The incidence of resistin expression in patients with Japan Pancreas Society stages III-IV (18 of 27, 66.7%) was significantly higher than in subjects with stages I-II (4 of 18, 22.2%) (p<0.01). Patients with resistin-stained tumors had significantly shorter relapsefree survival times (median, 9 months) than patients with negative tumors (median, 18 months) (p<0.05). In addition, multivariate analysis showed that resistin expression was an independent prognostic factor for relapse-free survival of patients with pancreatic ductal adenocarcinoma (p<0.05). These results demonstrate that resistin may influence the progression of pancreatic tumors and may be a useful predictor of relapse-free survival in patients with pancreatic ductal adenocarcinoma.

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“…In the NIH-AARP Diet and Health Study, it was observed that an excess of body weight across a lifetime remains significantly associated with increased risk of PC, in particular when comparing the category with BMI>25 to BMI=8.5-22.5 [2]. Results from several preclinical models suggest that obesity can initiate pancreatic carcinogenesis and promote metastasis [3]. A high fat diet activates oncogenic K-Ras and Cox2, causing inflammation and fibrosis in the pancreas, with subsequent pancreatic intraepithelial neoplasia (PanINs) and PC onset [4].…”

Section: Introductionmentioning

confidence: 99%