Is long-term follow-up solely by imaging tests safe in non-operated pancreatic neuroendocrine tumors?

Introduction: the diagnosis of asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has increased significantly due to the widespread use of high-resolution imaging tests, which is why the most appropriate management at the time of diagnosis is the subject of debate, as is how to follow-up patients. Aims: the objective of this study was to analyze the frequency of imaging and endoscopic studies performed during long-term follow-up. Methods: a retrospective review was performed of a database collected between January 2008 and December 2020 of patients with an incidental diagnosis of small NF-PNETs; follow-up was closed in March 2023. The imaging tests performed at the time of diagnosis and long-term follow-up were recorded. Growing less than 1 mm per year has not been considered as a worrisome feature. Follow-up was performed through imaging tests, considering endoscopic cytology for lesions with a faster grow rate. Results: fifty-eight patients were included; the median age was 69 years. The initial mean size of the lesions studied was 12.79 mm (5-27). Follow-up was carried out only with computed tomography (CT) or magnetic resonance imaging (MRI). The initial size did not influence the behavior of the lesion in a statistically significant manner. Twenty-eight tumors (45 %) increased in size, with a growth equal to or less than 4 mm in 24 cases. The mean follow-up time was 82.41 months (12-164). No patient developed metastasis or died from PNET progression. Conclusions: the follow-up of neuroendocrine tumors of small size can be performed safely with only imaging tests. (AU)

Pancreatic Ubap2 deletion regulates glucose tolerance, inflammation, and protection from cerulein-induced pancreatitis.

Ubiquitin-binding associated protein 2 (UBAP2) is reported to promote macropinocytosis and pancreatic adenocarcinoma (PDAC) growth, however, its role in normal pancreatic function remains unknown. We addressed this knowledge gap by generating UBAP2 knockout (U2KO) mice under a pancreas-specific Cre recombinase (Pdx1-Cre). Pancreatic architecture remained intact in U2KO animals, but they demonstrated slight glucose intolerance compared to controls. Upon cerulein challenge to induce pancreatitis, U2KO animals had reduced levels of several pancreatitis-relevant cytokines, amylase and lipase in the serum, reduced tissue damage, and lessened neutrophil infiltration into the pancreatic tissue. Mechanistically, cerulein-challenged U2KO animals revealed reduced NF-κB activation compared to controls. In vitro promoter binding studies confirmed the reduction of NF-κB binding to its target molecules supporting UBAP2 as a new regulator of inflammation in pancreatitis and may be exploited as a therapeutic target in future to inhibit pancreatitis.

Low dosage combination treatment with metformin and simvastatin inhibits obesity-promoted pancreatic cancer development in male KrasG12D mice.

Pancreatic ductal adenocarcinoma (PDAC), a highly lethal disease with limited therapeutic options, may benefit from repurposing of FDA-approved drugs in preventive or interceptive strategies in high-risk populations. Previous animal studies demonstrated that the use of metformin and statins as single agents at relatively high doses restrained PDAC development. Here, four-week-old mice expressing KrasG12D in all pancreatic lineages (KC mice) and fed an obesogenic high fat, high calorie diet that promotes early PDAC development were randomized onto low dosage metformin, simvastatin, or both drugs in combination administered orally. Dual treatment attenuated weight gain, fibro-inflammation, and development of advanced PDAC precursor lesions (pancreatic intraepithelial neoplasia [PanIN]-3) in male KC mice, without significant effect in females or when administered individually. Dual-treated KC mice had reduced proliferation of PanIN cells and decreased transcriptional activity of the Hippo effectors, YAP and TAZ, which are important regulators of PDAC development. Metformin and simvastatin also synergistically inhibited colony formation of pancreatic cancer cells in vitro. Together, our data demonstrated that a combination of low doses of metformin and simvastatin inhibits PDAC development and imply that both drugs are promising agents for being tested in clinical trials for preventing pancreatic cancer progression.

Association between sodium-glucose cotransporter 2 inhibitors and pancreatic cancer in the Japanese working-age population.

OBJECTIVE: Pancreatic cancer-related mortality is increasing worldwide, and prevention methods and effective novel therapies are required. In pancreatic cancer, sodium-glucose cotransporters (SGLT) are involved in glucose uptake. This study aimed to clarify the association between SGLT2 inhibitors and pancreatic cancer development. MATERIALS AND METHODS: A nested case-control study was conducted using the JMDC administrative claims database (January 2005 to June 2020). Patients newly diagnosed with type 2 diabetes mellitus (T2DM) were included, and cases were defined as patients who developed pancreatic cancer. Patients with outcomes were randomly matched to a maximum of 20 controls according to age (± 5 years), sex, and calendar date (month and year) of the first T2DM diagnosis through risk set sampling. RESULTS: Of the 181,107 T2DM patients, 363 cases and 7,043 controls were selected with 14 and 457 patients prescribed SGLT2 inhibitors, respectively. Cumulative administration of SGLT2 inhibitors for > 180 days was significantly inversely associated with the development of pancreatic cancer (adjusted odds ratio: 0.58, 95% confidence interval: 0.31 - 0.99). CONCLUSION: SGLT2 inhibitors may reduce the risk of developing pancreatic cancer in T2DM patients. The number of patients over 65 years of age was small in this study due to the nature of the data source. Further studies with larger sample sizes including older patients are needed.

Can Echinococcus Granulosus Infestation Prevent Pancreatic Cancer? An invivo Experimental Study.

Hydatid cyst is a zoonotic infestation caused by Echinococcus granulosus, and it is known that some parasites found in humans cause cancer in humans or some may have a protective effect against cancer. Cancer is one of the most serious health problems of today and it has been shown in some studies that parasites such as Echinococcus granulosus can have an inhibitory effect. The aim of this study was determined as whether Echinococcus granulosus has an inhibitory effect on exocrine pancreatic cancer with the help of the azaserine-rat model used in different cancer studies.  Material and Methods: During experimental process a total of 45 male Wistar rats used, 14-day-old male Wistar rats were divided into groups according to the experimental protocol, administered azaserine injection protocol or kept as a control group without azaserine injection. Animals are grouped as Group 1, Control Group (group not treated with Azaserine and not injected with protoscolex.) (E-A-) (n=7); Group 2, Group injected with (IP) Azaserine only (30mg/kg) (E-A+)  (n=8);Group 3, Group injected (IP) with protoscolex suspension of 1 cc only (E+A-) (n=15);Group 4, Group injected both Azaserine (IP) and protoscolex suspension (IP) (E+A+) (n=15). Atypical Acinar Cell Foci (AACF) load in the exocrine pancreas of each rat was measured quantitatively with the help of a video image analyzer and the AACF load was calculated with the help of a mathematical model. Results: Findings showed that the Atypical Acinar Cell Foci (AACF) burden was statistically significantly lower in the Azaserine+ protoscolex (Azaserine-injected-protoscolex-implanted) rat group compared to the other groups, suggesting that Echinococcosis in the azaserine-rat model could inhibit the development of precursor foci of neoplastic changes in the exocrine pancreas. Conclusion: The most significant aspect of our study is that it contributes new insights into the controversy that Echinococcosis suppresses pancreatic cancer.

Plant-based diets and the risk of pancreatic cancer: a large prospective multicenter study.

BACKGROUND: Plant-based diets have been recommended for improving health outcomes, including cancer. However, previous studies on plant-based diets and the risk of pancreatic cancer are scarce and fail to consider plant food quality. OBJECTIVES: We sought to examine the potential associations of 3 plant-based diet indices (PDIs) with the risk of pancreatic cancer in a US population. METHODS: A population-based cohort of 101,748 US adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The overall PDI, healthful PDI (hPDI), and unhealthful PDI (uPDI) were constructed to qualify adherence to overall, healthy, and less healthy plant-based diets, respectively, with higher scores indicating better adherence. Multivariable Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was conducted to identify the potential effect modifiers. RESULTS: Over a mean follow-up of 8.86 years, 421 pancreatic cancer cases occurred. Participants in the highest compared with the lowest quartiles of overall PDI had a lower risk of pancreatic cancer [HRquartile 4 versus 1: 0.74; 95% confidence interval (CI): 0.57, 0.96; Ptrend = 0.023]. A stronger inverse association was observed for hPDI (HRquartile 4 versus 1: 0.56; 95% CI: 0.42, 0.75; Ptrend < 0.001). Conversely, uPDI was positively associated with the risk of pancreatic cancer (HRquartile 4 versus 1: 1.38; 95% CI: 1.02, 1.85; Ptrend = 0.012). Subgroup analyses revealed a stronger positive association for uPDI in participants with BMI <25 (HRquartile 4 versus 1: 3.22; 95% CI: 1.56, 6.65) than in those with BMI ≥25 (HRquartile 4 versus 1: 1.08; 95% CI: 0.78, 1.51) (Pinteraction = 0.001). CONCLUSIONS: In this US population, adherence to a healthy plant-based diet confers a lower risk of pancreatic cancer, whereas adherence to a less healthy plant-based diet confers a higher risk. These findings highlight the importance of considering plant food quality in preventing pancreatic cancer.

Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention.

Pancreatic cancer usually results in poor survival with limited options for treatment, as most affected individuals present with advanced disease. Early detection of preinvasive pancreatic neoplasia and identifying molecular therapeutic targets provide opportunities for extending survival. Although screening for pancreatic cancer is currently not recommended for the general population, emerging evidence indicates that pancreatic surveillance can improve outcomes for individuals in certain high-risk groups. Changes in the epidemiology of pancreatic cancer, experience from pancreatic surveillance, and discovery of novel biomarkers provide a roadmap for new strategies for pancreatic cancer risk assessment, early detection, and prevention.

Carrot Intake and Risk of Developing Cancer: A Prospective Cohort Study.

A prospectively followed Danish cohort of 55,756 citizens with an observation time upwards of 25 years was investigated for association between eating raw carrots on a regular basis and developing various adenocarcinoma-dominant cancers and leukemia. Mean age at inclusion was 56.2 years (SD 4.4 years), and 52% were females. A dose-dependent reduction in incidence was seen for cancer of the lung (HR 0.76, CI95% 0.66; 0.87) and pancreas (HR 0.79, CI95% 0.61; 1.03), as well as leukemia (HR 0.91, CI95% 0.68; 1.21). Only for lung cancer was the association significant. In the case of pancreatic cancer, a possible type 1 error was present due to a low number of cancers. In cases of breast and prostate cancer, no association and no dose response were demonstrated. The association seen for lung and pancreatic cancer parallels that earlier demonstrated for large bowel cancer and indicates a cancer-protective effect from daily intake of raw carrots not limited to gastrointestinal adenocarcinomas. Processed carrots exhibited no effect. The preventive effect could be due to the polyacetylenic compounds falcarinol and falcarindiol in carrots, whereas carotene may not have an effect. The polyacetylenes are inactivated by heating, supporting our findings that only raw carrot intake has an effect. Indirect evidence for the cancer preventive effect of carrots in humans has reached a level where a prospective human trial is now timely.

Adherence to Mediterranean Diet and Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis.

Pancreatic cancer (PC) represents the 6th cause of cancer death. Although the aetiology of PC is not completely understood, numerous risk factors have been identified in association with this cancer, among them diet. However, little is known about the association between the Mediterranean Diet (MedDiet) and the risk of PC. For this reason, we conducted a systematic review with meta-analysis according to the PRISMA guidelines, searching on three databases (PubMed/MEDLINE, Scopus, and EMBASE). The protocol was registered in PROSPERO. Both fixed and random effect models were performed. The Effect size was reported as a hazard ratio (HR) with a 95% Confidence Interval (CI). A total of eight articles were included. The methodological quality of the included meta-analyses was high. Our results show that a higher adherence to the MedDiet is associated with a lower risk of PC [HR:0.82 (0.76-0.88) p < 0.001, based on 1,301,320 subjects]. The results were also confirmed in sensitivity and subgroups analyses (avoidance of potential overlapping effects, type of tools used to assess dietary intake and the diagnosis of PC, prevalence and incidence of PC risk, country where the studies took place, sex, and cancer site). Promoting a higher adherence to the MedDiet could be an effective approach to reduce the risk of PC.

[Prevention of pancreatic cancer]. / Prävention des Pankreaskarzinoms.

The incidence of pancreatic cancer is rising in Germany. At present pancreatic cancer is the third commonest cause of cancer death but is expected to become the second in 2030 and finally the leading cause of cancer death in 2050. Pancreatic ductal adenocarcinoma (PC) is generally diagnosed at far advanced stages and 5-year-survival has remained poor. Modifiable risk factors of PC are tobacco smoking, excess body weight, alcohol use, type 2-diabetes and the metabolic syndrome. Smoking cessation and -in case of obesity- intentional weight loss can reduce PC risk by as much as 50 %. Early detection of asymptomatic sporadic PC at stage IA - stage IA-PC now has a 5-year-survival rate of about 80 %- has become a realistic chance for people older than 50 years with new-onset diabetes.

Target-Specific Nanoparticle Polyplex Down-Regulates Mutant Kras to Prevent Pancreatic Carcinogenesis and Halt Tumor Progression.

Survival from pancreatic cancer is poor because most cancers are diagnosed in the late stages and there are no therapies to prevent the progression of precancerous pancreatic intraepithelial neoplasms (PanINs). Inhibiting mutant KRASG12D, the primary driver mutation in most human pancreatic cancers, has been challenging. The cholecystokinin-B receptor (CCK-BR) is absent in the normal pancreas but becomes expressed in high grade PanIN lesions and is over-expressed in pancreatic cancer making it a prime target for therapy. We developed a biodegradable nanoparticle polyplex (NP) that binds selectively to the CCK-BR on PanINs and pancreatic cancer to deliver gene therapy. PanIN progression was halted and the pancreas extracellular matrix rendered less carcinogenic in P48-Cre/LSL-KrasG12D/+ mice treated with the CCK-BR targeted NP loaded with siRNA to mutant Kras. The targeted NP also slowed proliferation, decreased metastases and improved survival in mice bearing large orthotopic pancreatic tumors. Safety and toxicity studies were performed in immune competent mice after short or long-term exposure and showed no off-target toxicity by histological or biochemical evaluation. Precision therapy with target-specific NPs provides a novel approach to slow progression of advanced pancreatic cancer and also prevents the development of pancreatic cancer in high-risk subjects without toxicity to other tissues.

Dietary Inflammatory Index, Alternative Healthy Eating Index-2010, Mediterranean Diet Score and the risk of pancreatic cancer.

BACKGROUND: Previous studies of dietary patterns and pancreatic cancer risk have been inconclusive; we aimed to investigate the association of Mediterranean Diet Score (MDS), Alternative Healthy Eating Index-2010 (AHEI-2010), and Dietary Inflammatory Index (DII®) with risk of pancreatic cancer. METHODS: We used data from the Melbourne Collaborative Cohort Study including 33,690 men and women aged 40-69 years at recruitment in 1990-1994. A total of 258 incident cases of pancreatic cancer was identified over an average of 23.7 years of follow-up. Hazard ratios (HR) were estimated using Cox regression, with age as the underlying time metric, adjusting for potential confounders including sex, height, country of birth, education, socio-economic position, physical activity, energy intake, smoking status, pack-years smoking, years since quitting smoking, and alcohol intake. RESULTS: A healthier diet as assessed by the AHEI-2010 was associated with a lower risk of pancreatic cancer [HRQuartile4 vs Quartile1 = 0.58; 95%CI 0.40 - 0.85; p for trend 0.003]. Weaker but consistent evidence was observed for the other indexes [DII® HRQuartile4 vs Quartile1 = 1.30; 95%CI 0.82 - 2.06; p for trend 0.1], [MDS HRCategory3 vs Category1 = 0.79; 95%CI 0.49 - 1.26; p for trend 0.06]. CONCLUSION: Adherence to a healthier diet, as assessed by the AHEI-2010, may reduce the risk of pancreatic cancer.

Aspirin Use and Risk of Pancreatic Ductal Adenocarcinoma: A Large Case-Control Study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a five-year survival rate of approximately 5%. The incidence and mortality rates of PDAC are increasing, and the results of medical treatments remain unsatisfactory. Some conflicting evidence suggests that aspirin intake may reduce the risk of PDAC. This study aimed to evaluate the association between regular low-dose aspirin use (80-mg aspirin tablets, 5-7 tablets/week) and the risk of PDAC. METHODS: This prospective, hospital-based, case-control study was performed on 470 PDAC patients (case group) and 526 sex and age-matched controls, in Tehran, Iran from 2011 to 2018. The participants were interviewed regarding the patterns of aspirin use. Data are expressed as mean±SD or frequency and percentage as appropriate. Differences in frequency between the case and control groups were evaluated based on the analysis of the contingency table (χ2 test and Fisher's exact test). Propensity score models were designed to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) for PDAC with respect to aspirin use, adjusted for age, sex, smoking status, opium use, diabetes mellitus, place of residence, and family history of cancer in first-degree relatives. RESULTS: About 60% of PDAC patients were male in this study. Also, 25.2% of PDAC patients had a family history of cancer in one of their first-degree relatives, 21.99% were smokers, 13.9% were opium users, and 11.7% had a history of diabetes. Aspirin was used by 22.77% of PDAC patients and 18.25% of the controls. Ever aspirin use (OR: 1.01, 95% CI: 0.89 - 1.14) was not associated with PDAC. CONCLUSION: Overall, aspirin use was not associated with a reduced risk of PDAC.

Adherence to Pro-Vegetarian Food Patterns and Risk of Oesophagus, Stomach, and Pancreas Cancers: A Multi Case-Control Study (The PANESOES Study).

We aimed to evaluate the association between three previously defined pro-vegetarian (PVG) food patterns and the cancers of the oesophagus, stomach, and pancreas in a multi case-control study. We analyzed data from a multi-case hospital-based study carried out in two Mediterranean provinces in Spain. A total of 1233 participants were included in the analyses: 778 incident cancer cases, histologically confirmed (199 oesophagus, 414 stomach, and 165 pancreas) and 455 controls. A dietary assessment was performed using a validated food frequency questionnaire (FFQ). Three PVG food patterns (general, healthful, and unhealthful) were estimated using 12 food groups for the general PVG (gPVG), scoring positive plant-based foods and negative animal-based foods, and 18 food groups, for the healthful (hPVG) and unhealthful (uPVG) food patterns. Multinomial logistic regression was used to estimate relative risk ratios (RRR) and confidence intervals (95% CI) for quintiles of adherence to PVG patterns and as a continuous variable. The RRR (95% CI) for the highest vs. the lowest quintile of gPVG were, RRR = 0.37 (0.32, 0.42) for the oesophagus, RRR = 0.34 (0.27, 0.43) for the stomach, and RRR = 0.43 (0.35, 0.52) for pancreas cancer. For the hPVG, the RRR were RRR = 0.72 (0.58, 0.90) for the oesophagus, RRR = 0.42 (0.34, 0.52) for the stomach, and RRR = 0.74 (0.59, 0.92) for pancreas cancer. The uPVG was associated with a higher risk of stomach cancer RRR = 1.76 (1.42, 2.18). Higher adherence to gPVG and hPVG food patterns is associated with a lower risk of oesophageal, stomach, and pancreas cancers, while a higher adherence to a uPVG food pattern is associated with a higher risk of stomach cancer.

Dietary patterns associated with the risk of pancreatic cancer: Case-control study findings.

Diet is an important modifiable lifestyle factor, but epidemiological studies evaluating the association between dietary patterns and pancreatic cancer (PC) have reported inconsistent findings. This study aimed to evaluate the impact of several dietary choices on the risk of PC among newly diagnosed Jordanian patients. A case-control study was conducted at major teaching and general hospitals, including a Jordanian oncology center. The study included 101 patients with incident pancreatic cancer and 314 controls. Data was collected using interview-based questionnaires. Dietary intake was estimated using a validated Arabic and reproducible food-frequency questionnaire. Dietary patterns were derived using Principal Component Analysis. Multinomial logistic regression was used to estimate the association between dietary patterns and PC. Four dietary patterns were identified. The "Traditional" dietary pattern, which presented a diet rich in fresh fruits, vegetables, milk, yogurt, and lentils, was associated with a significant decrease in the odds of PC (OR = 0.42, 95% CI = 0.21-0.84) for the third quartile compared to first one. The "High-fruit" dietary pattern, which was loaded with strawberry, melon, watermelon, and other fruits, significantly reduced the odds of PC (OR = 0.38, 95% CI = 0.19-0.75) for the second quartile compared to the first one. The "Soup" dietary pattern was mainly composed of vermicelli soup, vegetable soup, lentil soup, and mushroom soup, which decreased the odds of PC (OR = 0.18, 95% CI = 0.07-0.38). There was no relation between PC and the "Western" dietary pattern, loaded with beer, wine, roasted lamb, meat, chicken sandwich, beefsteak, and fried fish. The "Traditional," "High-fruit," and "Soup" dietary patterns were associated with reduced risk of PC among Jordanians.

[Pancreatic cancer risk: alcoholic and non-alcoholic beverages].

This article provides an overview of the metaanalyzes (PubMed, 19952019) of alcohol and non-alcoholic (coffee, tea, dairy products) beverage consumption in relation to risk of pancreatic cancer PC (PubMed, 19952019). Increased the PC risk was associated with high alcohol intake. The increased risk for heavy drinking did not explained by residual confounding by history of pancreatitis or tobacco smoking or diabetes. Light-moderate alcohol intake may reduced the PC risk, probably due to the fasting insulin levels decrement, which leads to the diminished the РС risk. The association between alcohol and the PC was stronger in men than in women. Some metaanalyzes demonstrated that a small amount of coffee may reduce PC risk, and a large amount to increase PC risk. Another meta-analyzes have not confirmed any association between the PC risk and coffee or tea consumption. One meta-analysis revealed a direct association of the PC risk with the dairy products consumption, but most research showed no such connection. Nutrition is considered to be associated with the PC risk, but the degree of risk due to structure of beverages consumption (dose, duration, alcohol, coffee, tea, dairy products pattern) is still not clear.

Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study.

Molecular mechanisms and observational studies have found that diet-derived antioxidants are associated with digestive system cancers, whereas there is a lack of causal evidence from randomized clinical trials. In this study, we aimed to assess the causality of these associations through a Mendelian randomization (MR) study. Single nucleotide polymorphisms of diet-derived circulating antioxidants (i.e., α- and γ-tocopherol, ascorbate, retinol, ß-carotene, lycopene, and urate), accessed by absolute levels and relative metabolite concentrations, were used as genetic instruments. Summary statistics for digestive system cancers were obtained from the UK Biobank and FinnGen studies. Two-sample MR analyses were performed in each of the two outcome databases, followed by a meta-analysis. The inverse-variance weighted MR was adopted as the primary analysis. Five additional MR methods (likelihood-based MR, MR-Egger, weighted median, penalized weighted median, and MR-PRESSO) and replicate MR analyses for outcomes from different sources were used as sensitivity analyses. Genetically determined antioxidants were not significantly associated with five digestive system cancers, after correcting for multiple tests. However, we found suggestive evidence that absolute ascorbate levels were negatively associated with colon cancer in UK Biobank-the odds ratio (OR) per unit increase in ascorbate was 0.774 (95% confidence interval [CI] 0.608-0.985, p = 0.037), which was consistent with the results in FinnGen, and the combined OR was 0.764 (95% CI 0.623-0.936, p = 0.010). Likewise, higher absolute retinol levels suggestively reduced the pancreatic cancer risk in FinnGen-the OR per 10% unit increase in ln-transformed retinol was 0.705 (95% CI 0.529-0.940, p = 0.017), which was consistent with the results in UK Biobank and the combined OR was 0.747 (95% CI, 0.584-0.955, p = 0.020). Sensitivity analyses verified the above suggestive evidence. Our findings suggest that higher levels of antioxidants are unlikely to be a causal protective factor for most digestive system cancers, except for the suggestive protective effects of ascorbate on colon cancer and of retinol on pancreatic cancer.

Brown-fat-mediated tumour suppression by cold-altered global metabolism.

Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1-6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1-the key mediator for BAT-thermogenesis-ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers.

Adherence to 5 Diet Quality Indices and Pancreatic Cancer Risk in a Large US Prospective Cohort.

Few prospective studies have examined associations between diet quality and pancreatic ductal adenocarcinoma (PDAC), or comprehensively compared diet quality indices. We conducted a prospective analysis of adherence to the Healthy Eating Index (HEI)-2015, alternative HEI-2010, alternate Mediterranean diet (aMed), and 2 versions of Dietary Approaches to Stop Hypertension (DASH; Fung and Mellen) and PDAC within the National Institutes of Health (NIH)-AARP Diet and Health Study (United States, 1995-2011). The dietary quality indices were calculated using responses from a 124-item food frequency questionnaire completed by 535,824 participants (315,780 men and 220,044 women). We used Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each diet quality index and PDAC. During follow-up through 2011 (15.5-year median), 3,137 incident PDAC cases were identified. Compared with those with the lowest adherence quintile, participants with the highest adherence to the HEI-2015 (HR = 0.84, 95% CI: 0.75, 0.94), aMed (HR = 0.82, 95% CI: 0.73, 0.93), DASH-Fung (HR = 0.85, 95% CI: 0.77, 0.95), and DASH-Mellen (HR = 0.86, 95% CI: 0.77, 0.96) had a statistically significant, lower PDAC risk; this was not found for the alternative HEI-2010 (HR = 0.93, 95% CI: 0.83, 1.04). This prospective observational study supports the hypothesis that greater adherence to the HEI-2015, aMed, and DASH dietary recommendations may reduce PDAC.