Objective: Our aim was to propose a preoperative computer-aided diagnosis scheme to differentiate pancreatic serous cystic neoplasms from other pancreatic cystic neoplasms, providing supportive opinions for clinicians and avoiding overtreatment. Materials and Methods: In this retrospective study, 260 patients with pancreatic cystic neoplasm were included. Each patient underwent a multidetector row computed tomography scan and pancreatic resection. In all, 200 patients constituted a cross-validation cohort, and 60 patients formed an independent validation cohort. Demographic information, clinical information, and multidetector row computed tomography images were obtained from Picture Archiving and Communication Systems. The peripheral margin of each neoplasm was manually outlined by experienced radiologists. A radiomics system containing 24 guideline-based features and 385 radiomics high-throughput features was designed. After the feature extraction, least absolute shrinkage selection operator regression was used to select the most important features. A support vector machine classifier with 5-fold cross-validation was applied to build the diagnostic model. The independent validation cohort was used to validate the performance. Results: Only 31 of 102 serous cystic neoplasm cases in this study were recognized correctly by clinicians before the surgery. Twenty-two features were selected from the radiomics system after 100 bootstrapping repetitions of the least absolute shrinkage selection operator regression. The diagnostic scheme performed accurately and robustly, showing the area under the receiver operating characteristic curve = 0.767, sensitivity = 0.686, and specificity = 0.709. In the independent validation cohort, we acquired similar results with receiver operating characteristic curve = 0.837, sensitivity = 0.667, and specificity = 0.818. Conclusion: The proposed radiomics-based computer-aided diagnosis scheme could increase preoperative diagnostic accuracy and assist clinicians in making accurate management decisions.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide, and the mortality of patients with PDAC has not significantly decreased over the last few decades. Novel strategies exhibiting promising effects in preclinical or phase I/II clinical trials are often situated in an embarrassing condition owing to the disappointing results in phase III trials. The efficacy of the current therapeutic regimens is consistently compromised by the mechanisms of drug resistance at different levels, distinctly more intractable than several other solid tumours. In this review, the main mechanisms of drug resistance clinicians and investigators are dealing with during the exploitation and exploration of the anti-tumour effects of drugs in PDAC treatment are summarized. Corresponding measures to overcome these limitations are also discussed.

Pancreatic cancer is one of the leading causes of cancer-related mortality in both developed and developing countries. The incidence of pancreatic cancer in China accounts for about a quater of the global incidence, and the epidemiological characteristics and therapeutic strategies differ due to social, economic, cultural, environmental, and public health factors. Non-domestic guidelines do not reflect the clinicopathologic characteristics and treatment patterns of Chinese patients. Thus, in 2018, the Chinese Society of Clinical Oncology (CSCO) organized a panel of senior experts from all sub-specialties within the field of pancreatic oncology to compile the Chinese guidelines for the diagnosis and treatment of pancreatic cancer. The guidelines were made based on both the Western and Eastern clinical evidence and updated every one or two years. The experts made consensus judgments and classified evidence-based recommendations into various grades according to the regional differences, the accessibility of diagnostic and treatment resources, and health economic indexes in China. Here we present the latest version of the guidelines, which covers the diagnosis, treatment, and follow-up of pancreatic cancer. The guidelines might standardize the diagnosis and treatment of pancreatic cancer in China and will encourage oncologists to design and conduct more clinical trials about pancreatic cancer.

Antitumor effect of gemcitabine-loaded albumin nanoparticle on gemcitabine-resistant pancreatic cancer induced by low hENT1 expression Zhongyi Guo,1 Feng Wang,2 Yang Di,1 Lie Yao,1 Xinzhe Yu,1 Deliang Fu,3 Ji Li,3 Chen Jin1 1Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China; 2School of Pharmacy & Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai, China; 3Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai, China Purpose: Gemcitabine is currently the standard first-line chemotherapeutic drug for treating pancreatic cancer. However, many factors can contribute to gemcitabine resistance. One of the most important reasons is the low hENT1 expression. In this study, we tested the antitumor effect of gemcitabine-loaded human serum albumin nanoparticle (GEM-HSA-NP) on gemcitabine-resistant pancreatic cancer induced by low hENT1 expression. Materials and methods: S-(4-nitrobenzyl)-6-thioinosine was utilized to inhibit the activity of hENT1 and simulate low hENT1 expression. Growth inhibition assays and cell cycle and apoptosis analyses were performed on human pancreatic cancer cell lines such as BxPC-3 and SW1990. The in vivo antitumor effect was studied by using patient-derived xenograft (PDX) models. The in vivo toxicity assessment was performed on healthy Kunming mice. Results: In in vitro studies, GEM-HSA-NP showed its ability to inhibit cell proliferation, arrest cell cycle and induce apoptosis when tumor cells were resistant to gemcitabine. In in vivo studies, GEM-HSA-NP was more effective than gemcitabine on inhibiting tumor growth whether the expression levels of hENT1 were high or low in PDX models. The in vivo toxicity assessment showed that the biotoxicity of GEM-HSA-NP did not increase compared with gemcitabine. Conclusion: GEM-HSA-NP can overcome gemcitabine resistance induced by low hENT1 expression, which suggests its potential role for the clinical application. Keywords: pancreatic cancer, gemcitabine resistance, albumin nanoparticles, low hENT1 expression, PDX model

Increased insulin level (or “hyperinsulinemia”) is a common phenomenon in pancreatic ductal adenocarcinoma (PDA) patients and signals poor clinical outcomes. Insulin is safe in low PDA risk population, while insulin significantly promotes PDA risk in high PDA risk population. The correlation between insulin and PDA is a reciprocal self-reinforcing relationship. On the one hand, pancreatic cancer cells synthesize multiple molecules to cause elevated peripheral insulin resistance, thus enhancing hyperinsulinemia. On the other hand, insulin promotes pancreatic cancer initiation and sustains PDA development by eliciting tumorigenic inflammation, regulating lipid and glucose metabolic reprogram, overcoming apoptosis through the crosstalk with IGF-1, stimulating cancer metastasis, and activating tumor microenvironment formation (inflammation, fibrosis, and angiogenesis). Currently, taking glucose sensitizing agents, including metformin, SGLT-2 inhibitor, and GLP-1 agonist, is an effective way of lowering insulin levels and controlling PDA development at the same time. In the future, new drugs targeting insulin-related signal pathways may pave a novel way for suppressing PDA initiation and progression.