Explore the vast range of titles available.

Objectives We aimed to assess the ability of CT-determined resectability, as defined by a recent version of NCCN criteria, and associated CT findings to predict margin-negative (R0) resection in patients with PDAC after neoadjuvant FOLFIRINOX chemotherapy. Methods Sixty-four patients (36 men and 28 women; mean age, 58.8 years) with borderline resectable or unresectable PDAC who received neoadjuvant FOLFIRINOX were evaluated retrospectively. CT findings were independently assessed by two abdominal radiologists according to NCCN criteria (version 3. 2019). Tumor resectability was classified as resectable, borderline resectable, or unresectable, and change in resectability was classified as regression, stability, or progression. The associations of R0 resection rate with CT-determined resectability and change in resectability categories were evaluated, as were the sensitivity and specificity of NCCN criteria for R0 resection. Factors associated with R0 resection were identified by logistic regression analysis. Results R0 resection rate did not differ significantly among the resectable, borderline resectable, or unresectable PDAC (67–73%, p  = 0.95) or among PDAC with regression, stability, or progression (56–77%, p  = 0.39). The sensitivity and specificity for R0 resection were 67% and 37%, respectively, for resectability (resectable/borderline vs. unresectable) and 80% and 21%, respectively, for changes in resectability (regression/stable vs. progression). Low-contrast enhancement of soft tissue contacting artery (≤ 46.4 HU) was independently associated with R0 resection ( p  = 0.01). Conclusion CT-determined resectability after neoadjuvant FOLFIRINOX chemotherapy was relatively insensitive and non-specific for predicting R0 resection. Low-contrast enhancement of soft tissue contacting artery may increase the ability of CT to predict R0 resection. Key Points • Margin-negative resection rate of pancreatic cancer following FOLFIRINOX therapy did not differ among each resectability (67–73%, p = 0.95) based on NCCN criteria or changes in resectability categories (56–77%, p = 0.39). • The sensitivity and specificity for margin-negative resection were 67% and 37% for resectability (resectable/borderline vs. unresectable) and 80% and 21% for changes in resectability (regression/stable vs. progression). • Low-contrast enhancement of soft tissue contacting artery (≤ 46.4 HU) was independently associated with margin-negative resection (p = 0.01).

Early recurrence in pancreatic ductal adenocarcinoma (PDAC) is a decisive factor in determining a patient's prognosis. We determined in our current study whether circulating tumour cells (CTCs) exist in the blood of PDAC patients and can be used as a predictor of recurrence patterns (i.e. time and site) after surgical resection. Between December 2017 and November 2018, the mononuclear cell layer was obtained from the peripheral blood of 36 patients diagnosed with PDAC. CTCs were then isolated using the CD-PRIME™ platform and detected via immunostaining. The patient records were analyzed to correlate these data with survival and recurrence patterns. Twelve patients were CTC-positive (33.3%) and showed a significantly frequent rate of systemic recurrence (distant metastases and peritoneal dissemination) (p = 0.025). On multi-variable logistic regression analysis, CTC positivity was an independent risk factor for early recurrence (p = 0.027) and for systemic recurrence (p = 0.033). In summary, the presence or absence of CTC in the blood of the patients with PDAC could help predict the recurrence pattern after surgery. PDAC patients with CTC positivity at tumour diagnosis should therefore undergo a comprehensive strategy for systemic therapy and active monitoring to detect possible early recurrence.

Background Obesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). Results Total mRNA-seq data were generated with 27 AC and 21 preAC samples purified from human visceral AT collected during resection surgery in cancer patients, where the samples were classified into lean and obese categories by BMI > 25 kg/m 2 . We defined four classes of differentially expressed genes (DEGs) by comparing gene expression between (1) lean and obese ACs, (2) lean and obese preACs, (3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL-6 , TNF-α and IL-1β , i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. The analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was significantly greater for lean than for obese conditions. We validated our observations using previously published microarray transcriptome data deposited in the GEO database (GSE80654). Conclusions Taken together, our analyses suggest that inflammatory genes are expressed at lower levels in obese ACs than in lean ACs because lean adipogenesis involves even greater enhancement of inflammatory responses than does obese adipogenesis.

Objectives To identify multiparametric MRI biomarkers to predict the tumor response to neoadjuvant FOLFIRINOX therapy in patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Methods From May 2016 to March 2018, adult patients with BR or LA PDAC were prospectively enrolled in this study. They received eight cycles of FOLFIRINOX therapy and underwent multiparametric MRI twice (at baseline and after the second cycle). MRI evaluations included dynamic contrast-enhanced MRI, intravoxel incoherent motion diffusion-weighted imaging, and assessment of T2* relaxivity (R2*) and the change in T1 relaxivity (ΔR1, equilibrium phase R1 minus non-enhanced R1) of the tumors. Factors to predict the responders determined by the best overall response during FOLFIRINOX therapy and those to predict progression-free survival (PFS) and overall survival (OS) were evaluated using multivariable logistic regression and the Cox proportional hazard model. Results Forty-one patients (mean age, 60.3 years ± 9.3; 24 men) were included. Among the clinical and MRI factors, the baseline ΔR1 (adjusted odds ratio, 31.07; p = 0.008) was the only independent predictor for tumor response. The baseline ΔR1 was also an independent predictor for PFS (adjusted hazard ratio, 0.40; p = 0.033) along with R0 resection. The use of a cutoff ΔR1 value of ≥ 1.31 s -1 enabled prognostic stratification (median PFS, 16.0 months vs.10.0 months; p = 0.029; median OS, 34.9 months vs. 16.6 months; p = 0 .023, respectively). Conclusions The baseline tumor ΔR1 value may be useful to predict tumor response and survival in patients with BR or LA PDAC receiving FOLFIRINOX neoadjuvant therapy. Key Points • Baseline ΔR1 was an independent predictor for tumor response (adjusted odds ratio, 31.07; p = 0.008) and progression-free survival (adjusted hazard ratio, 0.40; p = 0.033) in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma receiving neoadjuvant FOLFIRINOX therapy. • The criterion of baseline ΔR1 value ≥ 1.31 s -1 allowed for the prediction of favorable tumor response and survival outcome after neoadjuvant FOLFIRINOX therapy.

Cell-free nucleic acids (cfNAs) in liquid biopsy samples are emerging as important biomarkers for cancer diagnosis and monitoring, and for predicting treatment outcomes. Many cfNA isolation methods have been developed recently. However, most of these techniques are time-consuming, complex, require large equipment, and yield low-purity cfNAs because the genetic background of normal cells is amplified during cell lysis, which limits their clinical application. Here, we report a rapid and simple cfNA sampling platform that can overcome the limitations of conventional methods. We synthesised a biocomposite by combining amine-modified diatomaceous earth (DE) and cucurbituril (CB). The biocomposite platform showed high capture efficiency (86.78–90.26%) with genomic DNA and amplified DNA products (777, 525 and 150 bp). The biocomposite platform allowed the isolation of high purity and quantity cfDNAs from the plasma of 13 cancer patients (three colorectal cancer and ten pancreatic cancer samples) without requiring a lysis step or special equipment. The biocomposite platform may be useful to isolate cfNAs for the diagnosis and treatment of cancers in clinical applications.

The prognosis for patients with pancreatic cancer is extremely poor, as they are resistant to first line chemotherapy. The long-term goal of this study was to identify effective combination chemotherapy for pancreatic cancer using pancreatic cancer surgical specimens in the histoculture drug response assay (HDRA) based on three-dimensional culture of tumour fragments, which maintains nature tumour histology in vitro. From 2015 to 2017, the HDRA was performed with tumour specimens from 52 pancreatic cancer patients from Asan Medical Hospital. First, combination drug regimens showed higher drug efficacy and less patient variation than single drugs. Initially, 5-Fluorouracil(5-FU)/Belotecan/Oxaliplatinum and Tegafur/Gimeracil (TS-1)/Oxaliplatinum/Irinotecan were found to be effective. Second, we were able to correlate the efficacy of some drugs with tumour stage. Third, when designing new combination regimens containing 5-FU or gemcitabine, we could identify more effective drug combinations. This is the first study to demonstrate usefulness of the HDRA for pancreatic cancer. Using this technique, we could identify novel candidate combination drug regimens that should be effective in treating pancreatic cancer.

Post-operative pancreatic fistula (POPF) following pancreatic resection is a life-threatening surgical complication. Cell sheets were prepared and harvested using temperature-responsive culture dishes and transplanted as patches to seal POPF. Two different mesenchymal stem cell (MSC) sheets were compared in terms of the preventative ability for pancreatic leakage in a rat model. Both rat adipose-derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus maintained their cell-cell junctions and adhesion proteins with intact fibronectin on the basal side, as well as characteristics of MSCs. The rats with post-pancreatectomy rADSC- or rBMSC-sheet patches had significantly decreased abdominal fluid leakage compared with the control group, demonstrated by MR image analysis and measurement of the volume of abdominal fluid. Amylase level was significantly lower in the rats with rADSC-sheet and rBMSC-sheet patches compared with the control groups. The rADSC sheet patches had increased adhesive and immune-cytokine profiles (ICAM-1, L-selectin, TIMP-1), and the rBMSC sheets had reduced immune reactions compared to the control. This is first project looking at the feasibility of tissue engineering therapy using MSC-sheets as tissue patches preventing leakage of abdominal fluid caused by POPF.

Cancer cachexia is a highly debilitating condition characterized by weight loss and muscle wasting that contributes significantly to the morbidity and mortality of pancreatic cancer. The factors that induce cachexia in pancreatic cancer are largely unknown. We previously showed that pancreatic adenocarcinoma upregulated factor (PAUF) secreted by pancreatic cancer cells is responsible for tumor growth and metastasis. Here, we analyzed the relation between pancreatic cancer-derived PAUF and cancer cachexia in mice and its clinical significance. Body weight loss and muscle weight loss were significantly higher in mice with Panc-1/PAUF tumors than in those with Panc-1/Mock tumors. Direct administration of rPAUF to muscle recapitulated tumor-induced atrophy, and a PAUF-neutralizing antibody abrogated tumor-induced muscle wasting in Panc-1/PAUF tumor-bearing mice. C2C12 myotubes treated with rPAUF exhibited rapid inactivation of Akt-Foxo3a signaling, resulting in Atrogin1/MAFbx upregulation, myosin heavy chain loss, and muscle atrophy. The neutrophil-to-lymphocyte ratio and body weight loss were significantly higher in pancreatic cancer patients with high PAUF expression than in those with low PAUF expression. Analysis of different pancreatic cancer datasets showed that PAUF expression was significantly higher in the pancreatic cancer group than in the nontumor group. Analysis of The Cancer Genome Atlas data found associations between high PAUF expression or a high DNA copy number and poor overall survival. Our data identified tumor-secreted circulating PAUF as a key factor of cachexia, causing muscle wasting in mice. Neutralizing PAUF may be a useful therapeutic strategy for the treatment of pancreatic cancer-induced cachexia. Pancreatic cancer: Protein promotes cancer-related weight loss A protein involved in tumor growth is also a likely cause of weight loss during pancreatic cancer, and may be a useful target for prognosis and treatment. Pancreatic adenocarcinoma upregulated factor (PAUF) is secreted by pancreatic cancer cells and is also found in other cancers where significant weight loss occurs. Wonbeak Yoo, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea, and co-workers examined the role of PAUF in cancer-related weight loss in mice. Mice inoculated with PAUF-expressing cancer cells experienced weight loss despite no change in food consumption. PAUF increased muscle atrophy and triggered muscle wasting pathways. PAUF is routinely measured in cancer patients, and could therefore provide a convenient biomarker to inform treatment decisions. The researchers suggest that neutralising PAUF could be a valuable therapeutic option.

Stent migration is a significant obstacle to successful stent placement. There has been no investigation of the effect and quantitative interpretation of flaps attached to a plastic stent (PS) on antimigration. The antimigration effects of the number of flaps on a PS in a 3D-printed pancreatic phantom (3DP) and extracted porcine pancreas (EPP) were investigated. Four PS types were used in this study: stent without flaps (type 1), stent with two flaps (type 2), stent with four horizontally made flaps (type 3), and stent with four vertically made flaps (type 4). The stents were measured and compared for antimigration force (AMF) in the 3DP and EPP using a customized measuring method and an integrated measuring device. The mean maximum AMFs (MAMFs) in types 2, 3, and 4 were significantly higher than that in type 1 (all p < 0.001). Moreover, the mean MAMFs in types 3 and 4 were significantly higher than that in type 2 (all p < 0.001). When the flaps were removed from the pancreatic duct, the AMF decreased rapidly. As the number of flaps increased, the antimigration effects significantly increased in the 3DP and EPP. However, the direction of the flaps did not affect the MAMF. The position of the flaps attached to the surface of the stent affected the AMF.

In this study, we evaluated the prognostic value of inflammation-based prognostic scores in patients undergoing curative surgery for pancreatic ductal adenocarcinoma (PDAC). A retrospective analysis was conducted for 914 patients undergoing curative surgical resection for PDAC between January 2011 and April 2016. Inflammation-based scores of modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio were assessed. mGPS was classified as high (1 or 2) or low (0). Median age was 63 (range, 33–88) years; 538 patients (58.9%) were male. A high mGPS was independently associated with poor overall survival (OS) and disease-free survival (DFS) (median OS: 25.4 months vs. 20.4 months, p = 0.001; median DFS: 11.6 months vs. 9.3 months, p = 0.002), poor OS in patients with TNM stage I PDAC (44 months vs. 24.8 months, p = 0.001), and poor OS and DFS in patients with tumors located at the pancreatic head or uncinate process (OS: 25.4 months vs. 20.4 months; p = 0.007, DFS: 11.4 months vs. 8.87 months; p = 0.005). Preoperative mGPS was a significant prognostic factor for PDAC after curative resection; thus, mGPS can be a useful prognostic predictive factor in patients with TNM stage I PDAC, especially for tumors located at the head and uncinate.