Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed at an advanced, incurable, stage and has an extremely poor prognosis. Systemic chemotherapy represents the standard treatment either in the pre-operative, adjuvant and palliative setting, which is associated with only modest improvement in survival. More recently, advances in cancer genomic sequencing have unravelled the molecular heterogeneity of PDAC and identified small patient subgroups harbouring unique actionable aberrations in BRCA, NTRK, NRG1 and mismatch repair genes paving the way to a more personalised approach for this tumour. However, the evolution of PDAC treatment towards a successful precision approach presents many challenges. In this review, we discuss the current standard treatments of PDAC, from early stage to advanced disease, and we illustrate the opportunities and challenges of precision medicine for this deadly cancer.

Circulating branched-chain amino acids (BCAA), a subgroup of the nine essential amino acids, has been associated with pancreatic cancer risk. The aim of this study is to estimate the relation between BCAA intake from diet and pancreatic cancer risk. We analysed data from a multicentric Italian case–control study, including 326 pancreatic cancer cases and 652 controls, matched to cases by study centre, sex and age. A validated FFQ was used to collect the participants’ usual diet before cancer diagnosis (or hospital admission for controls) and to compute dietary intakes of various nutrients, including BCAA. OR and the corresponding CI were computed through logistic regression models conditioned on the matching variables and adjusted for major confounding factors, including total energy intake. We found a positive association between BCAA intake and pancreatic cancer risk (OR for the third quartile = 1·88, 95 % CI = 1·08, 3·26; OR for the fourth quartile = 2·17, 95 % CI = 1·17, 4·06), with a significant trend in risk. The association persisted after excluding subjects with diabetes and family history of pancreatic cancer and across strata of selected covariates. These data support and quantify the association between dietary BCAA and pancreatic cancer, previously suggested by studies on circulating BCAA.

Pancreatic cancer is one of the most malignant tumours with a poor prognosis. In recent years, the incidence of pancreatic cancer is on the rise. Traditional chemotherapy and radiotherapy for pancreatic cancer have been improved, first-line and second-line palliative treatments have been developed, and adjuvant treatments have also been used in clinical. However, the 5-year survival rate is still less than 10% and new treatment methods such as targeted therapy and immunotherapy need to be investigated. In the past decades, many clinical trials of targeted therapies and immunotherapies for pancreatic cancer were launched and some of them showed an ideal prospect in a subgroup of pancreatic cancer patients. The experience of both success and failure of these clinical trials will be helpful to improve these therapies in the future. Therefore, the current research progress and challenges of selected targeted therapies and immunotherapies for pancreatic cancer are reviewed.

Dairy product intake was suggested to reduce the risk of gastrointestinal cancers. This study investigated the association between dairy product intake and the risk of pancreatic cancer (PAC) using a prospective cohort study and meta-analysis of prospective cohort studies. First, we included 59 774 people aged 40–79 years from the Japan Collaborative Cohort Study (JACC Study). The Cox regression was used to compute the hazard ratios (HR) and 95 % CI of incident PAC for individuals who reported the highest intakes of milk, cheese and yogurt compared with not consuming the corresponding dairy products. Then, we combined our results with those from other four prospective cohort studies that were eligible after searching several databases, in a meta-analysis, using the fixed-effects model before evaluating publication bias and heterogeneity across studies. In the JACC Study, the highest v. no intakes of milk, cheese and yogurt were not associated with the reduced risk of PAC after a median follow-up of 13·4 years: HR (95 % CI) = 0·93 (0·64, 1·33), 0·91 (0·51, 1·62) and 0·68 (0·38, 1·21), respectively. The results did not significantly change in the meta-analysis: 0·95 (0·82, 1·11) for milk, 1·16 (0·87, 1·55) for cheese and 0·91 (0·79, 1·05) for yogurt. The meta-analysis showed no signs of publication bias or heterogeneity across studies. To conclude, consumption of milk, cheese and yogurt was not associated with the risk of PAC either in the JACC Study or the meta-analysis.

Experimental studies suggest that abnormal levels of Ca, Mg and phosphorus are implicated in pancreatic carcinogenesis. We investigated the associations between intakes of these minerals and the risk of pancreatic cancer in a case-control study conducted in 1994–1998. Cases of pancreatic cancer (n 150) were recruited from all hospitals in the metropolitan area of the Twin Cities and Mayo Clinic, Minnesota. Controls (n 459) were randomly selected from the general population and frequency matched to cases by age, sex and race. All dietary variables were adjusted for energy intake using the residual method prior to data analysis. Logistic regression was performed to evaluate the associations between intake of three nutrients examined and the risk of pancreatic cancer. Total intake of Ca (936 v. 1026 mg/d) and dietary intake of Mg (315 v. 331 mg/d) and phosphorus (1350 v. 1402 mg/d) were significantly lower in cases than in controls. After adjustment for confounders, there were not significant associations of total and dietary intakes of Ca, Mg and phosphorus with the risk of pancreatic cancer. In addition, no significant interactions exist between intakes of these minerals and total fat on pancreatic cancer risk. In conclusion, the present study does not suggest that intakes of Ca, Mg and phosphorus were significantly associated with the risk of pancreatic cancer.

Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6–51 and HR = 7.0, 95% CI 1.5–33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88–1.5) or diabetes (HR = 1.1, 95% CI 0.9–1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84–20) or general population (SIR: 1.9, 95% CI 1.0–3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.

Sarcopenia, defined as decrease in skeletal muscle mass (SMM) and strength, might be associated with reduced survival. We investigated the impact of sarcopenia and decrease in SMM in patients with advanced pancreatic cancer during FOLFIRINOX (FX) therapy. Consecutive sixty-nine patients who received FX were evaluated. Skeletal muscle index (SMI) (cm2/m2) was used to evaluate SMM. The cut-off value of sarcopenia was defined as SMI <42 for males and <38 for females, based on the Asian Working Group for sarcopenia criteria. Sarcopenia was diagnosed in thirty-three (48 %) subjects. Comparison of baseline characteristics of the two groups (sarcopenia group: non-sarcopenia group) showed a significant difference in sex, tumour size and BMI. There was no significant difference in the incidence of adverse events with grades 3–5 and progression-free survival (PFS) during FX between the two groups (PFS 8·1 and 8·8 months; P = 0·88). On the multivariate analysis, progressive disease at the first follow-up computed tomography (hazard ratio (HR) 3·87, 95 % CI 1·53, 9·67), decreased SMI ≥ 7·9 % in 2 months (HR 4·02, 95 % CI 1·87, 8·97) and carcinoembryonic antigen ≥ 4·6 (HR 2·52, 95 % CI 1·10, 6·11) were significant risk factors associated with poor overall survival (OS), but sarcopenia at diagnosis was not. OS in patients with decreased SMI of ≥7·9 % and <7·9 % were 10·9 and 21·0 months (P < 0·01), respectively. In conclusion, decrease in SMM within 2 months after the initiation of chemotherapy had significantly shorter OS, although sarcopenia at diagnosis did not affect OS. Therefore, it might be important to maintain SMM during chemotherapy for a better prognosis.

Pancreatic cancer is currently one of the most lethal tumors because of delayed diagnosis and treatment. Aminopeptidase N (CD13/APN), expressed in pancreatic cancer cells, is closely related to the malignant biological behavior, for instance, angiogenesis formation, tumor proliferation, and metastasis. In this study, asparagine–glycine–arginine (Asn–Gly–Arg, NGR), selectively binding to CD13 receptor, was modified to construct a novel contrast agent of QDs@Gd3+-NGR for targeted diagnosis and treatment of pancreatic cancer. It consists of QDs-unit for fluorescence imaging, Gd3+-unit for magnetic resonance imaging (MRI), and NGR for binding to CD13 receptor. PANC-1 cells labeled by QDs@Gd3+-NGR showed significant red fluorescence and high intensity on fluorescence and MR imaging, respectively. Besides, it was confirmed that QDs@Gd3+-NGR could inhibit theproliferation, metastasis, and invasion of PANC-1 cells, and increase reactive oxygen species production and death rate in vitro. Reasonably, we believe the targeted contrast agent of QDs@Gd3+-NGR can sensitively detect pancreatic cancer via MR-fluorescence dual-modality imaging, and plays an active role in inhibition of tumor progression. The promising results in this study provide integration of diagnostic and therapeutic strategy for the management of pancreatic cancer in future.

Previous studies have shown that various dietary components may be implicated in the aetiology of pancreatic cancer. However, the possible relationship between diet-related inflammation and the risk of pancreatic cancer has not yet been investigated. We examined the ability of a newly developed literature-derived dietary inflammatory index (DII) to predict the risk of pancreatic cancer in a case–control study conducted in Italy between 1991 and 2008. This included 326 incident cases and 652 controls admitted to the major teaching and general hospitals for non-neoplastic diseases, frequency-matched to cases by study centre, sex and age. The DII was computed based on dietary intake assessed using a validated and reproducible seventy-eight-item FFQ. Logistic regression models were used to estimate multivariable OR adjusted for age, sex, study centre, education, BMI, smoking status, alcohol drinking and history of diabetes. Energy adjustment was performed using the residual method. Subjects with higher DII scores (i.e. representing a more pro-inflammatory diet) had a higher risk of pancreatic cancer, with the DII being used as both a continuous variable (ORcontinuous 1·24, 95 % CI 1·11, 1·38) and a categorical variable (i.e. compared with the subjects in the lowest quintile of the DII, those in the second, third, fourth and fifth quintiles had, respectively, ORquintile2 v. 1 1·70, 95 % CI 1·02, 2·80; ORquintile3 v. 1 1·91, 95 % CI 1·16, 3·16; ORquintile4 v. 1 1·98, 95 % CI 1·20, 3·27; ORquintile5 v. 1 2·48, 95 % CI 1·50, 4·10; Ptrend= 0·0015). These data suggest that a pro-inflammatory diet increases the risk of pancreatic cancer.

The palliative treatment of patients with advanced pancreatic cancer (APC) has undergone little advancement in the last 15 years. Novel therapies that have been investigated to extend survival have shown little benefit over existing chemotherapy regimens. Patients with APC often experience significant weight loss, which is one of the primary factors involved in declining quality of life. Recently, the ability of n-3 fatty acid rich oral preparations to attenuate or reverse tumour-related weight loss has been investigated in this patient group with encouraging results. Laboratory investigation has also yielded promising results suggesting a potential direct tumouricidal effect of n-3 fatty acids as well as the putative potentiation of existing chemotherapy regimes. The present review aims to examine the potential applications of fish oils rich in n-3 fatty acids in patients with APC, present a selection of the studies carried out to date and outline avenues of possible further clinical investigation.

The proximity of abdominal tumors to non-target organs has motivated exploration of intensity modulated radiation therapy (IMRT), with its demonstrated capability to create conformal dose gradients, in abdominal tumors. However, substantial extra-target dose may be observed to radiosensitive organs remote from the treatment field.

We present dosimetric data from two patients receiving abdominal IMRT using a sequential tomotherapy technique, demonstrating substantial dose to extra-target organs.

Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by BIA, has been found to be a prognostic indicator in several chronic conditions, such as HIV, liver cirrhosis, chronic obstructive pulmonary disease and lung cancer, and in patients undergoing dialysis. The present study investigated the prognostic role of phase angle in advanced pancreatic cancer. We evaluated a case series of fifty-eight stage IV pancreatic cancer patients treated at Cancer Treatment Centers of America® at Midwestern Regional Medical Center (Zion, IL, USA) between January 2000 and July 2003. BIA was conducted on all patients using a bioelectrical impedance analyser that operated at 50kHz. The phase angle was calculated as capacitance (Xc)/resistance (R) and expressed in degrees. The Kaplan–Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of other clinical and nutritional variables. The correlations between phase angle and traditional nutritional measures were evaluated using Pearson and Spearman coefficients. Patients with phase angle <5·0° had a median survival time of 6·3 (95% CI 3·5, 9·2) months (n 29), while those with phase angle >5·0° had a median survival time of 10·2 (95% CI 9·6, 10·8) months (n 29); this difference was statistically significant (P=0·02). The present study demonstrates that phase angle is a strong prognostic indicator in advanced pancreatic cancer. Similar studies in other cancer settings with larger sample sizes are needed to further validate the prognostic significance of the phase angle.