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In May 2015, my mother was diagnosed with stage IV pancreatic cancer and passed away three months later at the age of 78. Two years later, my older brother, only 53 at the time, was also diagnosed with pancreatic cancer. He passed away 15 months later. With this news, we engaged in the genetic retelling of family histories and connections, drawing genealogical maps on pieces of paper that reminded me of teaching Anthro 101 and starkly reimagined which relatives 'mattered' in our lives. As an anthropologist interested in subject formation and spatiality informed by a Foucauldian analytic, I have been propelled into exploring what it means to become 'high risk' (as a biologically related daughter and sister), subject to new regimes of surveillance and self‐management espoused by the field of precision medicine. This paper addresses this experience and thus contributes to questions of subject formation within the already‐existing truth‐making practices of genetic probability and personalized risk management. [ABSTRACT FROM AUTHOR]

Background: The impact of KRAS mutation testing on pancreatic ductal adenocarcinoma (PDAC) samples by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for reducing the need to repeat EUS-FNA has been demonstrated. Such testing however is not part of standard practice for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Objectives: We aim to analyse the proportion of non-contributive samples by EUS-FNB and to evaluate the impact of KRAS mutation testing on the diagnosis, theranostics and survival. Design: In this retrospective study, the impact on diagnosis and survival of KRAS testing for contributive and non-contributive samples by EUS-FNB was analysed. Methods: The EUS-FNB samples, combined with KRAS testing using the Idylla® technique on liquid-based cytology from patients with PDAC between February 2019 and May 2023, were retrospectively reviewed. The cytology results were classified according to the guidelines of the World Health Organization System for Reporting Pancreaticobiliary Cytopathology (WHOSRPC). Results: A total of 85 EUS-FNB specimens were reviewed. In all, 25 EUS-FNB samples did not lead to a formal diagnosis of PDAC according to the WHOSRPC (30.2%). Out of these 25, 11 (44%) could have been considered positive for a PDAC diagnosis thanks to the KRAS mutation test without carrying out further diagnosis procedures. The sensitivity of KRAS mutation testing using the Idylla technique was 98.6%. According to the available data, survival rates were not statistically different depending on the type of mutation. Conclusion: KRAS mutation testing on liquid-based cytology using the Idylla or equivalent technique, combined with the PDAC EUS-FNB sample, should become a standard for diagnosis to avoid delaying treatment by doing another biopsy. Furthermore, knowledge of the KRAS status from treatment initiation could be used to isolate mutations requiring targeted treatments or inclusion in clinical research trials, especially for wild-type KRAS PDAC. Plain language summary: Diagnostic and theranostic interest of searching for a KRAS mutation in echoendoscopic ultrasound biopsies of pancreatic adenocarcinomas The echoendoscopic ultrasound diagnostic of pancreatic adenocarcinomas sometimes remains difficult due to the nature of these tumors with a particular microenvironment. For more than 30 years, several authors have underlined the importance of searching for a KRAS mutation on samples taken by echoendoscopic ultrasound to improve diagnostic performance. However, this research is not common practice. Our retrospective study made it possible to review the files of 85 patients with pancreatic adenocarcinoma in whom an echoendoscopic ultrasound biopsy was performed with a search for the KRAS mutation (with second-generation fine needle biopsy). Forty-four percent could have been considered positive for the diagnosis of PDAC thanks to the search for the KRAS mutation without repeating new samples. Furthermore, knowledge of the KRAS mutation type from diagnosis would make it possible to isolate mutations justifying possible targeted treatments. [ABSTRACT FROM AUTHOR]

Background. Pancreatic mucinous cystic neoplasm (PMCN) with associated invasive carcinoma is a rare entity. According to the World Health Organisation (WHO) 2010, PMCN with associated invasive carcinoma is referred to the malignant lesions of the pancreatic epithelial tumour. Case report. A 52-year-old female patient presented with pain in the umbilical and epigastric regions for 5 months and noticed a solid visible tumour on the left side of the abdomen 3 months ago when she lied down. The level of the CA125 was 47.64 U/ml (normal value <35 U/ml). Abdominal and pelvic magnetic resonance imaging (MRI) showed a cystic multiseptal mass in the left iliac region, defined as a left ovary tumour, while Computed tomography scan revealed a cystic tumour of the pancreatic tail. The patient underwent a resection of the pancreatic tail with a 20 cm cystic solid tumour, splenectomy and left hemicolectomy. Histopathology report confirmed mucinous cystic neoplasm of the pancreatic tail with associated invasive carcinoma (combined badly differentiated (G3) ductal (40%) and undifferentiated (G4) anaplastic (60%) carcinoma) pT1bN0. Postoperative course complicated with wound infection. The patient was discharged on postoperative day 10. The patient is still alive 2 years on follow-up. Conclusions. PMCN with associated invasive carcinomas are rare lesions of pancreas with relatively benign course. This malignant pancreatic tumour displays morphologies as pleomorphic epithelial cells and relatively mononuclear spindle cells, and not always tends to have underlying ovarian type stroma. The comprehensive histopathological examination of the tumour is necessary in order to cure most MCN patients with minimally invasive types. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the safety and preliminary efficacy of the combined treatment of focused ultrasound (FUS) and chemotherapy (nab-paclitaxel plus gemcitabine, nPac/Gem) for patients with unresectable pancreatic cancer. Methods: Patients pathologically diagnosed with unresectable pancreatic cancer were included. Low (Isppa = 1.5 kW/cm2), intermediate (2.0 kW/cm2), and high (2.5 kW/cm2) FUS intensity treatment groups were predefined. A 1% duty cycle and the 3+3 scheme were used. Six combined treatments were performed, and adverse events were assessed. Changes in tumor size and tumor response, CA 19-9 level, and patient-reported outcomes at the immediate follow-up (F/U) and/or at the 3-month F/U and survival were evaluated. Results: Three participants were enrolled in each intensity group. No adverse device effect or dose-limiting toxicity occurred in any of the participants. Seven of the nine participants experienced a >15% tumor size decrease at the immediate F/U CT and at the 3-month F/U CT. The CA 19-9 level decreased in all of the participants at the immediate F/U. All participants in the intermediate-intensity treatment group showed a > 30% tumor size decrease, partial response, and a significant decrease in the CA 19-9 level at 3-month F/U and longer survival (p < 0.05). Conclusion: FUS with an intensity of 1.5 to 2.5 kW/cm2 was safe in the combined treatment of FUS and nPac/Gem. Considering the results of the change in tumor size, the change in CA 19-9 level, tumor response, and survival, these FUS parameters can be used for subsequent clinical trials. Key Points: • No adverse device effect or dose-limiting toxicity occurred in any of the participants when focused ultrasound with an intensity of 1.5–2.5 kW/cm2and a low duty cycle of 1% was combined with chemotherapy. • The intermediate-intensity group showed a >30% tumor size decrease, partial response, and a significant decrease in CA 19-9 in all of the participants at the 3-month follow-up and the longest survival. • Any focused ultrasound setting used in this study could be safe and optimal for subsequent clinical trials. [ABSTRACT FROM AUTHOR]

Background: Tumors occurring within the pancreatic head commonly arise from the pancreas, duodenal ampulla, distal bile duct, or duodenum. However, they are difficult to distinguish on standard preoperative imaging. Purpose: To assess the ability of specialist reporting of preoperative computed tomography (CT) scans to determine the organ of origin of pancreatic cancer (PC). Material and Methods: Blinded re-reporting of preoperative imaging from five hospitals was undertaken of a consecutive cohort of 411 patients undergoing surgery for PC between January 2006 and May 2014. Radiological identification of tumor site was determined by the presence of the main tumor bulk within the pancreatic head parenchyma and estimation of the pathological organ of origin of the PC was based on all the reported features. Results: Each pathological tumor type was noted to have distinct radiological features. Localization of a visible tumor within the pancreatic parenchyma was seen most commonly in PC (92%) than other tumor types (P < 0.0001). Local invasion into the duodenum was a characteristic feature seen in 79% of patients with ampullary tumors and isolated dilation of the bile duct without dilation of the pancreatic duct was seen most commonly in patients with ampullary or bile duct cancer. In the assessment of tumor origin, good agreement (kappa = 0.6, 0.51–0.68) was noted between the consensus radiology opinion and the final histology result. Overall accuracy was greatest for ampullary cancer (88.1%) and lowest for PC (83.2%). Conclusion: Radiological assessment of preoperative imaging provides a high degree of accuracy in predicting the organ of origin of peri-ampullary cancer. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the MR findings of the solid components within pancreatic solid pseudopapillary neoplasms (SPNs) to characterize solid SPN without degeneration. Methods: After case matching, 23 patients with SPNs, 23 with pancreatic neuroendocrine neoplasms (PNENs), and 46 pancreatic ductal adenocarcinomas (PDACs) were included in this retrospective comparative study. The MR findings of the solid components within the pancreatic tumors were assessed qualitatively and semi-quantitatively. Results: In the qualitative assessment, significant differences were noted in T2-weighted imaging and MR cholangiopancreatography (MRCP). SPNs with a score of 4–5 (iso- to hyper-intense compared with the renal cortex) were observed in 18/19 (94.7%) by reader 1 and 15/19 (78.9%) by reader 2 (score 5, 52.6% and 47.4%) on fast spin-echo (FSE) T2-weighted imaging. On MRCP, the two readers identified 12 (63.2%) and 8 (42.1%) SPNs, respectively. The semi-quantitative signal-intensity ratio (SIR, signal intensity of tumor/signal intensity of the pancreatic parenchyma) of SPNs on FSE T2-weighted imaging was significantly higher (mean, 1.99–2.01) than that of PNENs (1.30–1.31) or PDACs (1.26–1.28). The sensitivity/specificity of 'hyper' on T2-weighted imaging (qualitative score of 4–5, or SIR of ≥ 1.5) were 78.9–100.0%/63.8–79.7%. The sensitivity/specificity of 'remarkably hyper' (score of 5, SIR of ≥ 2.0, or visible on MRCP) or salt-and-pepper pattern were 36.8–68.4%/85.5–98.6%. Conclusion: T2-weighted imaging may be the key sequence for solid SPN. Solid tumors with hyper-intensity on T2-weighted imaging (especially, more hyper-intense than the renal cortex, more than twice the signal of the pancreatic parenchyma, depicted on MRCP, or salt-and-pepper appearance) may be suspected to be SPNs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the value of multi-slice computed tomography (MSCT) in preoperatively diagnosing perineural invasion (PNI) of periampullary carcinoma (PAC). Methods: Of 81 patients pathologically diagnosed as PAC, 73 patients were included. Their clinical documents and preoperative upper abdominal enhanced MSCT images were retrospectively reviewed to analyse clinical characteristics and MSCT features. MSCT features included tumor size, classification of fat tissue around celiac trunk and superior mesenteric artery. Chi-square test, Mann–Whitney U test or Fisher's exact test were used to compare the differences between PNI group and Non-PNI group. ROC analysis was performed to evaluate diagnostic efficiency for PAC PNI. Results: There were significant differences in some clinical characteristics and MSCT features. PAC PNI patients had significantly higher CA19-9 levels, higher CEA levels, larger tumor size and higher classification of fat tissue around celiac trunk than Non-PNI patients (All P values < 0.05). In univariate analysis, tumor size had the highest AUC as 0.806, fat tissue around celiac trunk and CEA had the highest specificity as 100% (P < 0.001). In multivariate analysis, classification of fat tissue around celiac trunk incorporated with tumor size, CA19-9, CEA, age and sex, showed the highest AUC as 0.939, with specificity of 95.0% and sensitivity of 90.4% (P < 0.001). Conclusion: PAC PNI could be diagnosed preoperatively by evaluating abdominal enhanced MSCT images with high accuracy, combined with serum tumor marker could be more helpful. [ABSTRACT FROM AUTHOR]

Introduction: Systemic treatment of pancreatic adenocarcinoma in the population of people over 65 years old is a challenge resulting from both the extremely unfavourable prognosis of this cancer and the particularly high sensitivity to the toxicity of chemotherapy in the elderly. This article presents the effectiveness and side effects of first-line chemotherapy according to the FOLFIRINOX regimen in patients over 65 years of age diagnosed with advanced pancreatic adenocarcinoma. Material and methods: The analysis was conducted in a group of 43 patients diagnosed with locally advanced inoperable pancreatic cancer or metastatic pancreatic cancer. Patients were treated between 2017 and 2021 in the Clinical Oncology Department, University Clinical Centre, Katowice, Poland. Results: In the study group, the median overall survival was 9.8 months; the median progression-free survival was 8.8 months. Treatment toxicity occurred in all patients. Adverse events of G3 and G4 severity (common terminology criteria for adverse events 5.0) occurred in 8% of patients. In 2 patients (5%), chemotherapy toxicity was the reason for discontinuation of systemic treatment. Conclusions: Triple-drug chemotherapy in a group of patients aged over 65 years with a diagnosis of advanced pancreatic cancer shows similar effectiveness to the general treated population, and with proper medical supervision the severity of side effects is at an acceptable level. [ABSTRACT FROM AUTHOR]

The article offers medical news briefs. Topics include combination of breast-conserving surgery and radiotherapy is superior to mastectomy alone; Urinalysis can detect pancreatic cancer up to two years before diagnosis; and the advantages of E-health, digitization or digital transformation on supportive care in oncology.

Molecularly imprinted polymers MIPs were successfully assembled around quantum dots (QDs), for the detection of the protein biomarker CA19-9 associated to pancreatic cancer (PC). These imprinted materials MIP@QDs were incorporated within the cellulose hydrogel with retention of its conformational structure inside the binding cavities. The concept is to use MIPs which function as the biorecognition elements, conjugated to cadmium telluride QDs as the sensing system. The excitation wavelength was set to 477 nm and the fluorescence signal was measured at its maximum intensity, with an emission range between 530 and 780 nm. The fluorescence quenching of the imprinted cellulose hydrogels occurred with increasing concentrations of CA19-9, showing linearity in the range 2.76 × 10 −2 – 5.23 × 10 2 U/ml, in a 1000-fold diluted human serum. Replicates of the imprinted hydrogel show a linear response below the cut-off values for pancreatic cancer diagnosis (< 23 U/ml), a limit of detection of 1.58 × 10 −3 U/ml and an imprinting factor (IF) of 1.76. In addition to the fact that the imprinted cellulose hydrogel displays good stability and selectivity towards CA19-9 when compared with the non-imprinted controls, the conjugation of MIPs to QDs increases the sensitivity of the system for an optical detection method towards ranges within clinical significance. This fact shows potential for the imprinted hydrogel to be applied as a sensitive, low-cost format for point-of-care tests (PoCTs). [ABSTRACT FROM AUTHOR]

Despite the uniform mortality in pancreatic adenocarcinoma (PDAC), clinical disease heterogeneity exists with limited genomic differences. A highly aggressive tumor subtype termed 'basal-like' was identified to show worse outcomes and higher inflammatory responses. Here, we focus on the microbial effect in PDAC progression and present a comprehensive analysis of the tumor microbiome in different PDAC subtypes with resectable tumors using metagenomic sequencing. We found distinctive microbial communities in basal-like tumors and identified an increasing abundance of Acinetobacter, Pseudomonas and Sphingopyxis to be highly associated with carcinogenesis. Functional characterization of microbial genes suggested the potential to induce pathogen-related inflammation. Host-microbiota interplay analysis provided new insights into the tumorigenic role of specific microbiome compositions and demonstrated the influence of host genetics in shaping the tumor microbiome. Taken together, these findings indicated that the tumor microbiome is closely related to PDAC oncogenesis and the induction of inflammation. Additionally, our data revealed the microbial basis of PDAC heterogeneity and proved the predictive value of the microbiome, which will contribute to the intervention and treatment of disease. Guo, Zhang, Guo et al. investigate microbiome alterations in different molecular subtypes of PDAC and report that distinct signatures exist in basal-like tumours, characterized by an increase in certain bacteria, such as Acinetobacter, Pseudomonas and Sphingopyxis. The authors associate increases in these bacteria with increased inflammation and carcinogenic potential, as suggested by pathway analyses. [ABSTRACT FROM AUTHOR]

Shear wave elastography (SWE) is a technique to non-invasively and quantitatively evaluate tissue stiffness. We aimed to investigate whether we can differentiate pancreatic cancer (PC) from normal pancreatic parenchyma (NPP) by SWE using transabdominal ultrasound. We investigated a total of 106 patients (84 with NPP and 22 with PC) whose pancreatic elastic modulus was measured by two-dimensional SWE (2D-SWE). Intra-rater reliability in this study was examined, and three measurements were sufficiently reliable. There were no differences between the two groups in factors that could affect SWE measurements. The median value of the elastic modulus was 5.70 kPa in the PC patients and 5.66 kPa in the NPP group, which was not significantly different (P = 0.785). On the contrary, the range was 8.64 kPa and 4.72 kPa, with a significantly greater range in the PC patients (P = 0.001). In conclusion, the median elastic modulus measured by 2D-SWE was not significantly different between PC and NPP, and evaluating the obtained elastic modulus itself is not useful in differentiation. However, the variability was significantly greater in PC than in NPP. Evaluating the range of elasticities will provide additional information in SWE, which may be useful in the diagnosis of PC. [ABSTRACT FROM AUTHOR]

To identify a gemcitabine resistance-associated gene signature for risk stratification and prognosis prediction in pancreatic cancer. Pearson correlation analysis was performed with gemcitabine half maximal inhibitory concentration (IC50) data of 17 primary pancreatic cancer lines from Genomics of Drug Sensitivity in Cancer (GDSC) and the transcriptomic data from GDSC and Broad Institute Cancer Cell Line Encyclopedia, followed by risk stratification, expression evaluation, overall survival (OS) prediction, clinical data validation and nomogram establishment. Our biomarker discovery effort identified a 14-gene signature, most of which featured differential expression. The 14-gene signature was associated with poor OS in E-MTAB-6134 (HR 2.37; 95% CI 1.75–3.2; p < 0.0001), pancreatic cancer-Canada (PACA-CA) (HR 1.76; 95% CI 1.31–2.37; p = 0.00015), and 4 other independent validation cohorts: pancreatic cancer-Australia (PACA-AU) (HR 1.9; 95% CI 1.38–2.61; p < 0.0001), The Cancer Genome Atlas (TCGA) (HR 1.73; 95% CI 1.11–2.69; p = 0.014), GSE85916 (HR 1.97; 95% CI 1.14–3.42; p = 0.014) and GSE62452 (HR 1.82; 95% CI 1.02–3.24; p = 0.039). Multivariate analysis revealed that the 14-gene risk score was an independent pancreatic cancer outcome predictor in E-MTAB-6134 (p < 0.001) and TCGA (p = 0.006). A nomogram including the 14-gene was established for eventual clinical translation. We identified a novel gemcitabine resistance gene signature for risk stratification and robust categorization of pancreatic cancer patients with poor prognosis. [ABSTRACT FROM AUTHOR]

Accuracy for computed tomography (CT) diagnosis of extrapancreatic perineural invasion (EPNI) in pancreatic ductal adenocarcinoma (PDAC), which is a significant cause of recurrence, has not been established. The aim of the study was to evaluate the diagnostic accuracy of CT in detecting EPNI preoperatively in resectable PDAC of the pancreatic head. Retrospective study design was approved by institutional review board. Preoperative CT-series of 46 patients with resectable PDAC were evaluated by two independent observers. Plexus Pancreaticus Capitalis-II (PPC-II) was assessed as this area is more susceptible for EPNI. All patients underwent surgery with dedicated histopathology, which served as the reference standard. Histologically EPNI was confirmed in 63.1%. Sensitivity of MDCT was 93.1% (95% confidence interval (CI) 77.23% to 99.15%), specificity 64.7% (95% CI 38.33% to 85.79%) with area under the curve (AUC) 0.789 for the first observer. Positive predictive value (PPV) was 81.82% (95% CI 70.12% to 89.62%), negative predictive value (NPV—84.62% (95% CI 57.98% to 95.64%) with diagnostic accuracy of 82.61% (95% CI 68.58% to 92.18%). Interobserver agreement showed k-value of 0.893 ( p < 0.001 ), which represents very good agreement between observers. Median actual survival in patients without EPNI was 30 months (95% CI 18.284–41.716), in patients with EPNI—13 months (95% CI 12.115–13.885). CT provides sufficient diagnostic information to detect PPC-II invasion in patients with resectable PDAC of the pancreatic head. Preoperative detection of EPNI might be an additional argument to perform neoadjuvant chemotherapy in patients with resectable PDAC. It should be included in preoperative evaluation form of CT-findings. [ABSTRACT FROM AUTHOR]

Inflammation promotes tumor progression, induces invasion and metastatic spread. This retrospective study explored CRP, CA19-9, and routine laboratory values as preoperative prognostic factors in pancreatic cancer patients. Between 2000 and 2016, there were 212 surgically treated pancreatic cancer patients at Helsinki University Hospital, Finland. Out of these, 76 borderline resectable patients were treated with neoadjuvant therapy (NAT); 136 upfront resected patients were matched for age and sex at a 1:2 ratio. We analyzed preoperative CRP, CA19-9, CEA, leukocytes, albumin, bilirubin and platelets. CRP and CA19-9 were combined into a prognostic score: both CRP and CA19-9 below the cut-off values (3 mg/l and 37 kU/l, respectively), either CRP or CA19-9 above the cut-off value, and finally, both CRP and CA19-9 above the cut-off values. Among all patients, median disease-specific survival times were 54, 27 and 16 months, respectively (p < 0.001). At 5 years, among patients with CRP and CA19-9 levels below the cut-off values, 49% were alive and 45% were disease-free. Among NAT patients the corresponding survival rates were 52% and 45% and among those undergoing upfront surgery 45% and 40%, respectively. This novel prognostic score combining CRP and CA19-9 serves as a useful preoperative tool estimating survival. [ABSTRACT FROM AUTHOR]

One epigenetic hallmark of many cancer types is differential DNA methylation occurring at multiple loci compared to normal tissue. Detection and assessment of the methylation state at a specific locus could be an effective cancer diagnostic. We assessed the effectiveness of hypermethylation at the CpG island of ZNF154, a previously reported multi-cancer specific signature for use in a blood-based cancer detection assay. To predict its effectiveness, we compared methylation levels of 3698 primary tumors encompassing 11 solid cancers, 724 controls, 2711 peripheral blood cell samples, and 350 noncancer disease tissues from publicly available methylation array datasets. We performed a single-molecule high-resolution DNA melt analysis on 71 plasma samples from cancer patients and 20 noncancer individuals to assess ZNF154 methylation as a candidate diagnostic metric in liquid biopsy and compared results to KRAS mutation frequency in the case of pancreatic carcinoma. We documented ZNF154 hypermethylation in early stage tumors, which did not increase in most noncancer disease or with respect to age or sex in peripheral blood cells, suggesting it is a promising target in liquid biopsy. ZNF154 cfDNA methylation discriminated cases from healthy donor plasma samples in minimal plasma volumes and outperformed KRAS mutation frequency in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to report on the development of a simple electrochemical nanobiosensor for early detection of pancreatic cancer. The nanobiosensor uses the newly emerged stable micro ribonucleic acid (miR-21) as a cancer-associated biomarker for diagnosis, prognosis or therapy response. Design/methodology/approach: The biosensing practice consists of two main steps: capturing probe immobilization on a working electrode modified with multi-walled carbon nanotubes and gold nanoparticles (MWCNTs-AuNPs) and then sensing the miR-21 interaction electrochemically. Two electrochemical techniques, atomic force microscopy and Fourier-transform infrared spectroscopy, were applied for characterizations. Findings: The nanobiosensor sensitivity exhibited satisfying results to miR-21 and demonstrated a wide dynamic range with a detection limit of just about 3.68 femtomolar using the source measure unit (SMU). Originality/value: Researchers commonly use potentiostats to perform the differential pulse voltammetry (DPV) measurements for the electrochemical biosensing applications. In this study, the SMU was used to perform the DPV to detect the biomarker miR-21 using the MWCNTs-AuNPs screen-printed electrode as the electrochemical system. [ABSTRACT FROM AUTHOR]

The 80% mortality rate of pancreatic-cancer (PC) makes early diagnosis a challenge. Oral fluids (OF) may be considered the ultimate body fluid for non-invasive examinations. We have developed techniques to improve visualization of minor OF proteins thereby overcoming major barriers to using OF as a diagnostic fluid. The aim of this study was to establish a short discriminative panel of OF biomarkers for the detection of PC. Unstimulated OF were collected from PC patients and controls (n = 30). High-abundance-proteins were depleted and the remaining proteins were analyzed by two-dimensional-gel-electrophoresis and quantitative dimethylation-liquid-chromatography-tandem mass-spectrometry. Label-free quantitative-mass-spectrometry analysis (qMS) was performed on 20 individual samples (n = 20). More than 100 biomarker candidates were identified in OF samples, and 21 had a highly differential expression profile. qMS analysis yielded a ROC-plot AUC value of 0.91 with 90.0% sensitivity and specificity for a combination of five biomarker candidates. We found a combination of five biomarkers for PC. Most of these proteins are known to be related to PC or other gastric cancers, but have never been detected in OF. This study demonstrates the importance of novel OF depletion methodologies for increased protein visibility and highlights the clinical applicability of OF as a diagnostic fluid. [ABSTRACT FROM AUTHOR]

Although serum markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) have been widely used in screening for pancreatic cancer (PC), their sensitivity and specificity are unsatisfactory. Recently, a novel tool of analyzing serum using the short-time Fourier transform (STFT) of free induction decays (FIDs) obtained by 1H-NMR has been introduced. We for the first time evaluated the utility of this technology as a diagnostic tool for PC. Serum was obtained from PC patients before starting any treatments. Samples taken from individuals with benign diseases or donors for liver transplantation were obtained as controls. Serum samples from both groups underwent 1H-NMR and STFT of FIDs. STFT data were analyzed by partial least squares discriminant analysis (PLS-DA) to clarify whether differences were apparent between groups. As a result, PLS-DA score plots indicated that STFT of FIDs enabled effective classification of groups with and without PC. Additionally, in a subgroup of PC, long-term survivors (≥ 2 years) could be discriminated from short-term survivors (< 2 years), regardless of pathologic stage or CEA or CA19-9 levels. In conclusion, STFT of FIDs obtained from 1H-NMR have a potential to be a diagnostic and prognostic tool of PC. [ABSTRACT FROM AUTHOR]

Tumour spheroids have the potential to be used as preclinical chemo-sensitivity assays. However, the production of three-dimensional (3D) tumour spheroids remains challenging as not all tumour cell lines form spheroids with regular morphologies and spheroid transfer often induces disaggregation. In the field of pancreatic cancer, the MiaPaCa-2 cell line is an interesting model for research but it is known for its difficulty to form stable spheroids; also, when formed, spheroids from this cell line are weak and arduous to manage and to harvest for further analyses such as multiple staining and imaging. In this work, we compared different methods (i.e. hanging drop, round-bottom wells and Matrigel embedding, each of them with or without methylcellulose in the media) to evaluate which one allowed to better overpass these limitations. Morphometric analysis indicated that hanging drop in presence of methylcellulose leaded to well-organized spheroids; interestingly, quantitative PCR (qPCR) analysis reflected the morphometric characterization, indicating that same spheroids expressed the highest values of CD44, VIMENTIN, TGF-β1 and Ki-67. In addition, we investigated the generation of MiaPaCa-2 spheroids when cultured on substrates of different hydrophobicity, in order to minimize the area in contact with the culture media and to further improve spheroid formation. [ABSTRACT FROM AUTHOR]

Background: A novel fork-tip fine-needle biopsy (FNB) needle has recently been introduced for endoscopic ultrasound (EUS)-guided sampling. The aim of this study was to compare the performance of fork-tip FNB histology and standard fine-needle aspiration (FNA) cytology in the diagnosis of solid pancreatic masses.Methods: A randomized crossover study was performed in patients referred for EUS-guided sampling. Three passes were taken with each needle in a randomized order. Only samples reported as diagnostic of malignancy were considered positive. The primary end point was the sensitivity of diagnosis of malignancy. Secondary end points included the amount of sample obtained, ease of diagnosis, duration of tissue sampling, pathologist viewing time, and cost.Results: 108 patients were recruited. Median age was 69 years (range 30 - 87) and 57 were male; 85.2 % had a final diagnosis of malignancy. There were statistically significant differences in sensitivity (82 % [95 % confidence interval (CI) 72 % to 89 %] vs. 71 % [95 %CI 60 % to 80 %]), accuracy (84 % [95 %CI 76 % to 91 %] vs. 75 % [95 %CI 66 % to 83 %]), proportion graded as a straightforward diagnosis (69 % [95 %CI 60 % to 78 %] vs. 51 % [95 %CI 41 % to 61 %]), and median pathology viewing time (188 vs. 332 seconds) (P < 0.001) between FNB and FNA needles, respectively. There was no significant difference in cost between an FNB or FNA strategy.Conclusion: The diagnostic performance of the fork-tip FNB needle was significantly better than that of FNA; it was associated with ease of diagnosis, shorter pathological viewing times, and was cost neutral. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is an aggressive tumor associated with poor survival, and early detection is important to improve patient outcomes. In the present study, we examined MIR1246 expression as a biomarker of pancreatic cancer. Total RNA was extracted from serum, urine and saliva samples from healthy subjects (n = 30) and patients with pancreatic cancer (n = 41, stage 0–IV). The MIR1246 level in each fluid was analyzed by quantitative reverse transcription-polymerase chain reaction. Significantly higher MIR1246 expression in serum and urine was observed in patients with cancer than in healthy controls. A significant positive correlation was found between serum and urine MIR1246 expression (r = 0.34). Receiver operating characteristic curves were constructed for MIR1246 in all three body fluids. The area under the curve for serum MIR1246 was 0.87 (sensitivity, 92.3%; specificity, 73.3%), and that for urine MIR1246 was 0.90 (sensitivity, 90.2%; specificity, 83.3%). With a cut-off of the control group's mean plus twice the standard deviation, the sensitivities of MIR1246 in serum and urine for pancreatic cancer were 60.9 and 58.5%, respectively. Combining both serum and urine MIR1246 expression yielded a sensitivity of 85%. These results indicate that MIR246 may be a useful diagnostic biomarker for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Since the beginning of the twenty-first century, people's living standards have been continuously improved, followed by changes in diet structure and living habits. These changes have affected the body's endocrine system, causing lesions in the pancreatic tissue. Among these pancreatic tissue diseases, pancreatic cancer is the most harmful to human health because of its inability to find and high mortality within 1 year. At present, in the diagnosis of pancreatic cancer, medical imaging and pathological puncture are the main methods of diagnosis. These methods have a high diagnostic rate for patients with advanced pancreatic cancer, but it is difficult to apply to the diagnosis of early pancreatic cancer. In response to these problems, this paper proposes a pancreatic cancer diagnosis model based on the fusion of distribution estimation algorithm and genetic algorithm. By collecting pathological data of patients with pancreatic cancer from a hospital oncology, pathological data include clinical manifestations of pancreatic cancer patients, serum tumor markers, etc., after data preprocessing, input models, and then use different machine learning classification algorithms to make pancreatic cancer for diagnosis. By evaluating the diagnosis results of each classification algorithm, an optimal classification algorithm is obtained and applied to the diagnosis model of pancreatic cancer. The results show that compared with other classification algorithms, the model using classification algorithm has the highest accuracy, recall rate and harmonic mean, and the diagnostic performance is the best. The results show that the diagnostic model constructed in this paper has a very high application value in the early auxiliary pre-diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is a malignancy with little/no warning signs before the disease reaches its ultimate stages. Currently early detection of PC is very difficult because most patients have non-specific symptoms leading to postponing the correct diagnosis. In this study, using multiple bioinformatics tools, we integrated various serum expression profiles of miRNAs to find the most significant miRNA signatures helpful in diagnosis of PC and constructed novel miRNA diagnosis models for PC. Altogether, 27 differentially expressed miRNAs (DEMs) showed area under curve (AUC) score >80%. The most promising miRNAs, miR-1469 and miR-4530, were individually able to distinguish two groups with the highest specificity and sensitivity. By using multivariate cox regression analyses, 5 diagnostic models consisting of different combinations of miRNAs, based on their significant expression algorithms and functional properties were introduced. The correlation model consisting of miR-125a-3p, miR-5100 and miR-642b-3p was the most promising model in the diagnosis of PC patients from healthy controls with an AUC of 0.95, Sensitivity 0.98 and Specificity 0.97. Validation analysis was conducted for considered miRNAs on a final cohort consist of the microarray data from two other datasets (GSE112264 & GSE124158). These results provide some potential biomarkers for PC diagnosis after testing in large case-control and cohort studies. [ABSTRACT FROM AUTHOR]

When performing paediatric pancreatic cancer (PC) diagnosis, magnetic resonance imaging (MRI) will be interfered by many factors, resulting in poor diagnosis. In order to improve the diagnostic effect of MRI on PC, this study is based on machine learning and combines SVM (support vector machine) and MRI detection with the support of image processing technology and improves the diagnostic accuracy of MRI for PC by the computer‐assisted method. At the same time, in the research, this study combines the characteristics of MRI detection to construct an MRI detection model based on SVM. In addition, this study obtains test samples through data collection, analyses the performance of the algorithm model through actual cases, and combines image processing to improve the detection effect. Studies have shown that the algorithm model proposed in this study can effectively improve the accuracy of MRI diagnosis of PC and provide a theoretical reference for subsequent related research. [ABSTRACT FROM AUTHOR]

Pancreatic tumours are the fourth most common cause of cancer-related deaths in the world. Czech Republic has long been amongst countries with the highest incidence of pancreatic carcinoma. Mortality closely reflects incidence, because even at present time, we often fail to diagnose this disease in a timely and correct manner. Isoattenuating tumours that cannot be visualised on CT is one of the major diagnostic problems. In addition to CT, other imaging methods, such as abdominal ultrasonography, magnetic resonance imaging, endoscopic ultrasonography and positron emission tomography, play a crucial role in the diagnosis of pancreatic cancer. The article summarises essential information about pancreatic adenocarcinoma imaging and its distinction from other tumours. Among the most common neoplasms mentioned in its differential diagnosis are neuroendocrine tumours, solid pseudopapillary tumour, lymphoma and metastases into the pancreas. Although pancreatic adenocarcinoma forms the majority share of the number of solid pancreatic masses, it is important to think of other more rare lesions that can imitate this malignant disease. These include, for example, some congenital conditions, fatty infiltrationreplacement, peripancreatic lesions, other uncommon tumours or pancreatic sarcoidosis. The distinction of pancreatic adenocarcinoma from tumour-like chronic pancreatitis also deserves a separate chapter. [ABSTRACT FROM AUTHOR]

Purpose: Deep learning is an emerging technique that allows us to capture imaging information beyond the visually recognizable level of a human being. Because of the anatomic characteristics and location, on-board target verification for radiation delivery to pancreatic tumors is a challenging task. Our goal was to use a deep neural network to localize the pancreatic tumor target on kV x-ray images acquired using an on-board imager for image guided radiation therapy.Methods and Materials: The network is set up in such a way that the input is either a digitally reconstructed radiograph image or a monoscopic x-ray projection image acquired by the on-board imager from a given direction, and the output is the location of the planning target volume in the projection image. To produce a sufficient number of training x-ray images reflecting the vast number of possible clinical scenarios of anatomy distribution, a series of changes were introduced to the planning computed tomography images, including deformation, rotation, and translation, to simulate inter- and intrafractional variations. After model training, the accuracy of the model was evaluated by retrospectively studying patients who underwent pancreatic cancer radiation therapy. Statistical analysis using mean absolute differences (MADs) and Lin's concordance correlation coefficient were used to assess the accuracy of the predicted target positions.Results: MADs between the model-predicted and the actual positions were found to be less than 2.60 mm in anteroposterior, lateral, and oblique directions for both axes in the detector plane. For comparison studies with and without fiducials, MADs are less than 2.49 mm. For all cases, Lin's concordance correlation coefficients between the predicted and actual positions were found to be better than 93%, demonstrating the success of the proposed deep learning for image guided radiation therapy.Conclusions: We demonstrated that markerless pancreatic tumor target localization is achievable with high accuracy by using a deep learning technique approach. [ABSTRACT FROM AUTHOR]

Importance: Pancreatic cancer is an uncommon cancer with an age-adjusted annual incidence of 12.9 cases per 100 000 person-years. However, the death rate is 11.0 deaths per 100 000 person-years because the prognosis of pancreatic cancer is poor. Although its incidence is low, pancreatic cancer is the third most common cause of cancer death in the United States. Because of the increasing incidence of pancreatic cancer, along with improvements in early detection and treatment of other types of cancer, it is estimated that pancreatic cancer may soon become the second-leading cause of cancer death in the United States.Objective: To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for pancreatic cancer.Evidence Review: The USPSTF reviewed the evidence on the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treatment of screen-detected or asymptomatic pancreatic cancer.Findings: The USPSTF found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves disease-specific morbidity or mortality, or all-cause mortality. The USPSTF found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small. The USPSTF found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate. The USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms.Conclusions and Recommendation: The USPSTF recommends against screening for pancreatic cancer in asymptomatic adults. (D recommendation). [ABSTRACT FROM AUTHOR]

Importance: Pancreatic adenocarcinoma is the third most common cause of cancer death among men and women in the United States.Objective: To systematically review benefits and harms of screening for pancreatic adenocarcinoma to inform the US Preventive Services Task Force.Data Sources: MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials, from January 2002 through April 27, 2018; surveillance through March 22, 2019.Study Selection: Studies of adults with or without risk factors for pancreatic adenocarcinoma (eg, family history of pancreatic cancer, personal history of new-onset diabetes) undergoing imaging-based screening; studies of treatment for adults with screen-detected or asymptomatic pancreatic adenocarcinoma. Included study designs were randomized clinical trials, nonrandomized controlled intervention studies, diagnostic accuracy studies with a reference standard, cohort studies, and case-control studies (for evaluation of harms only). Studies consisting entirely of populations with known genetic syndromes associated with pancreatic cancer were excluded.Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and rated included studies for quality; data were quantitatively analyzed to calculate a pooled diagnostic yield and narratively synthesized.Main Outcomes and Measures: Mortality, morbidity, or quality of life; diagnostic accuracy of screening tests; any harm of screening or treatment.Results: Thirteen fair-quality prospective cohort screening studies (N = 1317) conducted predominantly in populations at high familial risk for pancreatic adenocarcinoma were included. No studies reported on the effect of screening on morbidity or mortality or on the effectiveness of treatment for screen-detected pancreatic adenocarcinoma. Although no studies evaluated the diagnostic accuracy of screening tests, all 13 studies reported the diagnostic yield. Yields ranged from 0 to 75 cases per 1000 persons in studies using endoscopic ultrasound, magnetic resonance imaging, and/or computed tomography-based screening. In total, 18 cases of pancreatic adenocarcinoma were detected in 1156 adults at increased familial risk and 0 cases were detected in 161 average-risk adults. In 8 studies (n = 675) assessing procedural harms of screening, no serious harms from initial screening were reported. Two studies (n = 271) found no evidence of psychosocial harms related to screening. Evidence of surgical harms was limited.Conclusions and Relevance: Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma with limited evidence of minimal harms. However, the effect of screening on morbidity and mortality in groups at high familial risk has not been studied, and no data are available in average-risk populations. There is limited evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

We report an unusual intrasinusoidal growth pattern of an intraabdominal diffuse large B-cell lymphoma both clinically and histologically mimicking a metastatic adenocarcinoma. A 66-year-old woman presented with a high-grade distal biliary stricture with multiple enlarged abdominal lymph nodes. Frozen section at the time of pancreatoduodenectomy ("Whipple") demonstrated cohesive nests of large atypical cells within a totally effaced lymph node presenting a diagnostic challenge. Immunohistochemistry proved this to be a diffuse large B-cell lymphoma extensively involving the sinusoids. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is a digestive system tumor that is highly malignant, with an increasing incidence rate, poor prognosis, and a low 5-year survival rate. The overwhelming majority of patients with PC are in an advanced stage at the time of diagnosis and have lost the opportunity for radical surgery. The efficacy of radiotherapy and chemotherapy for PC is very poor. Therefore, it is of great significance to explore the mechanisms of PC development and new therapeutic targets. Exosomes are extracellular vesicles that mediate the exchange of substances and information between cells. In recent years, exosomes have been shown to play a key role in the development and progression of PC and might be useful for both its diagnosis and treatment. This article reviews the composition and function of exosomes and their roles in the development, diagnosis, and treatment of PC. [ABSTRACT FROM AUTHOR]

In tumour cells, macropinocytosis functions as an amino acid supply route and supports cancer cell survival and proliferation. Initially demonstrated in oncogenic KRAS-driven models of pancreatic cancer, macropinocytosis triggers the internalization of extracellular proteins via discrete endocytic vesicles called macropinosomes. The incoming protein cargo is targeted for lysosome-dependent degradation, causing the intracellular release of amino acids. These protein-derived amino acids support metabolic fitness by contributing to the intracellular amino acid pools, as well as to the biosynthesis of central carbon metabolites. In this way, macropinocytosis represents a novel amino acid supply route that tumour cells use to survive the nutrient-poor conditions of the tumour microenvironment. Macropinocytosis has also emerged as an entry mechanism for a variety of nanomedicines, suggesting that macropinocytosis regulation in the tumour setting can be harnessed for the delivery of anti-cancer therapeutics. A slew of recent studies point to the possibility that macropinocytosis is a pervasive feature of many different tumour types. In this review, we focus on the role of this important uptake mechanism in a variety of cancers and highlight the main molecular drivers of macropinocytosis in these malignancies. [ABSTRACT FROM AUTHOR]

FAM64A, a marker of cell proliferation, has been investigated as a potential biomarker in several cancers. In the present study, we examined the value of FAM64A expression in the diagnosis and prognosis of pancreatic cancer through bioinformatics analysis of data obtained from The Cancer Genome Atlas (TCGA) database. The diagnostic value of FAM64A expression in pancreatic cancer tissue was deteremined through receiver operating characteristic (ROC) curve analysis, and based on the obtained cut-off value, patients were divided into two groups (high FAM64A expression and low FAM64A expression). Chi-square and Fisher exact tests were applied to identify associations between FAM64A expression and clinical features. Moreover, the effect of FAM64A expression in the survival of pancreatic cancer patients was observed by Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Our results showed that high FAM64A expression in pancreatic cancer was associated with survival status, overall survival (OS), and recurrence. The area under the ROC curve was 0.736, which indicated modest diagnostic value. Patients with higher FAM64A expression had significantly shorter OS and recurrence-free survival (RFS) times. Multivariate survival analysis demonstrated that high FAM64A expression was an independent risk factor for OS and RFS. GSEA identified mitotic spindles, myc targets, MTORC1 signaling, G2M checkpoint, E2F targets, DNA repair, glycolysis and unfolded protein response as differentially enriched with the high FAM64A expression phenotype. In conclusion, high FAM64A mRNA expression is an independent risk factor for poor prognosis in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic cancer is the 4th most common cause of cancer death in Japan and exhibits a 5-year overall survival rate of approximately 7%. The accurate diagnosis of pancreatic cancer is important for determining the optimal management strategy. Fludeoxyglucose-positron emission tomography (FDG PET) integrated with computed tomography (18F-FDG PET/CT) has emerged as a powerful imaging tool for detecting and evaluating various cancers, and it is used for staging, detecting local recurrence and distant metastasis, measuring therapeutic effects, and predicting prognosis in pancreatic cancer patients. Lately, FDG PET/CT-derived parameters, such as standardized uptake values (SUV), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG), have been suggested as prognostic factors for various types of cancer, including pancreatic cancer. However, there is no consensus regarding the best parameters for evaluating patient prognosis, operability, etc. The purpose of this study was to examine the differences between operable and non-operable pancreatic cancer using FDG PET/CT-derived parameters, and to investigate whether volumetric parameters (TLG and the MTV) are superior to SUV-based parameters for predicting infiltration status/determining operability. Materials and methods: We conducted a retrospective study of the cases of 48 patients with clinically proven pancreatic adenocarcinoma, who underwent FDG PET/CT imaging before treatment. In the operable group, the surgical specimens were subjected to histopathological examinations, and the cases were separated into those exhibiting less and greater infiltration. SUVmax, SUVpeak, the tumor background ratio (TBR), TLG, and the MTV were compared between these groups as well as between the operable and non-operable groups. Results: Venous infiltration showed significant associations with several metabolic parameters (SUVmax, SUVpeak, and the TBR). However, it did not display any significant associations with volumetric parameters, such as TLG or the MTV. None of the FDG PET/CT-derived parameters exhibited significant associations with lymphatic or neural infiltration. Significant differences in volumetric parameters, such as the MTV and TLG, were detected between the operable and non-operable subgroups. Conclusions: Metabolic 18F-FDG PET/CT-derived parameters, such as SUVmax, SUVpeak, and the TBR, are useful for predicting venous infiltration status in patients with operable pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the current study was to compare CT-signs of portal venous confluence infiltration for actual histopathological infiltration of the vein or the tumor/vein interface (TVI) in borderline resectable pancreatic ductal adenocarcinoma (PDAC). Methods and materials: 101 patients with therapy-naïve, primarily resected PDAC of the pancreatic head without arterial involvement were evaluated. The portal venous confluence was assessed for contour irregularity (defined as infiltration) and degree of contact. The sensitivity and specificity of contour irregularity versus tumor to vein contact >180° as well as the combination of the signs for tumor cell infiltration of the vessel wall or TVI was calculated. Overall survival (OS) was compared between groups. Results: Sensitivity and specificity of contour irregularity for identification of tumor infiltration of the portal venous confluence or the TVI was higher compared to tumor to vessel contact >180° for tumor cell infiltration (96%/79% vs. 91%/38% respectively, p<0.001). The combination of the signs increased specificity to 92% (sensitivity 88%). Patients with contour irregularity/ tumor to vein contact >180°/ both signs had significantly worse overall survival (16.2 vs. 26.5 months/ 17.9 vs. 37.4 months/ 18.5 vs. 26.5 months respectively, all p<0.05). Conclusion: Portal venous confluence contour irregularity is a strong predictor of actual tumor cell infiltration of the vessel wall or the TVI and should be noted as such in radiological reports. [ABSTRACT FROM AUTHOR]

Metabolic changes induced by pancreatic cancer were investigated by 1H NMR spectroscopy of plasma samples of patients and healthy controls. The acquired data were submitted to multivariate statistical analysis providing clear discrimination between both groups. The most significant differences were found in levels of 3-hydroxybutyrate and lactate. The obtained results (100% sensitivity, 90% specificity) clearly show the potential of 1H NMR spectroscopy in pancreatic cancer diagnosis. Therefore, the NMR-based metabolomics may contribute to the early diagnosis, prevention and/or therapy of diseases in the future. On the other hand, the number of samples in the presented pilot study is limited and has to be significantly increased in the future in order to obtain solid statistical models and to confirm the current findings. [ABSTRACT FROM AUTHOR]

Effective treatment for pancreatic cancer remains challenging, particularly the treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than 95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and radiotherapy are all too common, and many patients die soon after diagnosis. Here, we make the case for the increased use of molecular imaging in PDAC preclinical research and in patient management. [ABSTRACT FROM AUTHOR]

Purpose: To reveal the prevalence of small (≤ 20 mm) pancreatic ductal carcinomas with enhanced rims on triple-phase contrast-enhanced CT and correlate the CT images with the pathologic findings.Materials and methods: Between April 2005 and April 2016, 45 patients underwent preoperative triple-phase contrast-enhanced CT and were pathologically diagnosed with small pancreatic ductal carcinoma. CT images were independently reviewed by two radiologists. The attenuation values of the enhanced rims, internal areas of the tumors, and surrounding pancreatic parenchyma were compared using Mann-Whitney U test. These areas were also correlated with the pathologic findings. Tumor invasiveness was compared between the tumors with and without enhanced rims using Fisher’s exact test.Results: Enhanced rims were identified in 18 tumors (40%) by consensus between the two reviewers. The enhanced rims showed significantly higher mean attenuation values compared with the internal areas of the tumors (p < 0.001) and surrounding pancreatic parenchyma (p < 0.0086), and were most clearly visualized on equilibrium phase. The enhanced rims pathologically reflected the abundant fibrotic stroma with cancer cells in all tumors. There was no statistically significant difference in tumor invasiveness between the tumors with and without enhanced rims (anterior peripancreatic invasion, p = 0.137; posterior peripancreatic invasion, p = 0.758; portal vein invasion, p = 0.639; and lymph node metastases, p = 0.359).Conclusions: Enhanced rims were detected at a rate of 40% in small pancreatic ductal carcinomas and could be an important finding for diagnosis on CT images, but did not suggest a less aggressive nature. [ABSTRACT FROM AUTHOR]

Abstract Fucosylation is one of the most important glycosylations involved in cancer and inflammation. Many studies have reported significant increases in serum fucosylated haptoglobin (Fuc-Hpt) in a variety of cancer patients. In this study, we measured Fuc-Hpt using a lectin-antibody enzyme-linked immunosorbent assay (ELISA) or a novel ELISA system that used a glycan antibody for Fuc-Hpt. Hpt is known to be divided into three phenotypes (Hpt1–1, Hpt2–1, and Hpt2–2), depending on its genetic background. Normal levels of serum Hpt are different in each Hpt phenotype and these phenotypes are associated with the incidence of several human diseases. Here, we investigated how Hpt phenotype affected measurements of Fuc-Hpt, using two kinds of ELISA. Interestingly, we found that serum Fuc-Hpt levels were dramatically lower in the Hpt1–1 phenotype for both types of ELISA. For Hpt2–1 and Hpt2–2, we observed significantly increased serum Fuc-Hpt levels in patients with pancreatic cancer. When cases of the Hpt1–1 phenotype were depleted, our receiver operating characteristic (ROC) curve analyses showed that the area under the curve (AUC) value for pancreatic cancer diagnosis increased in each ELISA. Taken together, our results indicate that Hpt phenotype is a critical for the clinical application of Fuc-Hpt as a cancer biomarker. Highlights • Fucosylated haptoglobin (Fuc-Hpt) is a novel glyco-biomarker for pancreatic cancer. • We measured serum Fuc-Hpt levels with two kinds of ELISA kit, which we established. • Fuc-Hpt levels and Hpt phenotype are related in pancreatic cancer patients. • In both ELISA kits, the Hpt1–1 phenotype had much lower Fuc-Hpt levels. • Except Hpt1–1, Fuc-Hpt measures improved AUC values in pancreatic cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background. CA 19-9 and carcinoembryonic antigen (CEA) are widely used for the diagnosis of pancreatic cancer. The purpose of the present study was to compare the diagnostic value of CA 19-9 with CEA for pancreatic cancer. Methods. The studies were obtained from electronic searches conducted in PubMed, Embase, and Cochrane Library databases until December 2017. The keywords included diagnosis of pancreatic cancer, CA 19-9, and CEA. The ratio of sensitivity, the specificity, the diagnostic odds ratio (DOR), and the summary of the receiver operating characteristic (SROC) with regard to CA 19-9 and CEA were measured using the random effects model. The current study included 13 studies that comprised 4,537 participants and 1,277 patients with pancreatic cancer. Results. The levels of CA 19-9 for use for the detection of pancreatic cancer were associated with higher sensitivity (ratio of sensitivity: 1.54; 1.31–1.81; P<0.001), DOR (DOR: 3.50; 95% CI: 2.24–5.45; P<0.001), and AUC (ratio of AUC: 1.24; 95% CI: 1.15–1.33; P<0.001) compared with the variable CEA, while no significant difference between CA 19-9 and CEA was noted with regard to specificity (ratio of specificity: 0.97; 95% CI: 0.89–1.06; P=0.517). The findings of the subgroup analyses suggested that different cutoff values of CA 19-9 and CEA might affect the diagnostic value. Conclusions. The findings of the present study indicated that CA 19-9 levels were associated with higher sensitivity, DOR, and AUC compared with the corresponding levels of CEA with regard to the diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: A contrast‐enhancing agent is imperative for the accurate target delineation of pancreatic tumors. This study demonstrates the potential use of treatment planning for patients with pancreatic tumors based on the water density image (WDI) generated by dual‐energy computed tomography (DECT). Methods: Tissue characterization and multi‐energy phantom scanning were performed through DECT and the physical characteristics of the WDI and a virtual monochromatic image (VMI) were assessed. The measured and the corresponding theoretical electron density relative to water (RED) and mass density (MD) were compared. Treatment plans based on the WDI (TPWDI) and VMI (TPVMI) were compared for 22 pancreatic cancer patients who underwent contrast‐enhanced DECT scan. Results: The total absolute difference in the HU value between the conventional 120 kVp images and the VMI was the smallest at the energy level of 77 keV (3.3 HU), and the VMI at 77 keV was used for subsequent analysis. The difference between the measured and theoretical values of RED and MD for iodine using the VMI (>15%) was larger than that using WDI (<4%). In clinical cases, the maximum difference in the dosimetric parameters between TPWDI and TPWDI for the planning target volume was 3.0% when the doses were calculated using AXB, and for the duodenum, it was 1.7%. Conclusions: The WDI estimated the RED and MD accurately and could form the basis for a new treatment planning approach for pancreatic cancer using contrast‐enhancing agent. [ABSTRACT FROM AUTHOR]

Purpose: Intraductal papillary mucinous neoplasms (IPMNs) are radiographically visible precursor lesions of pancreatic cancer. Despite standard criteria for assessing risk, only 18% of cysts are malignant at resection. Thus, a large number of patients undergo unnecessary invasive surgery for benign disease. The ability to identify IPMNs with low or high risk of transforming into invasive cancer would optimize patient selection and improve surgical decision‐making. The purpose of this study was to investigate quantitative CT imaging features as markers for objective assessment of IPMN risk. Methods: This retrospective study analyzed pancreatic cyst and parenchyma regions extracted from CT scans in 103 patients to predict IPMN risk. Patients who underwent resection between 2005 and 2015 with pathologically proven branch duct (BD)‐IPMN and a preoperative CT scan were included in the study. Expert pathologists categorized IPMNs as low or high risk following resection as part of routine clinical care. We extracted new radiographically inspired features as well as standard texture features and designed prediction models for the categorization of high‐ and low‐risk IPMNs. Five clinical variables were also combined with imaging features to design prediction models. Results: Using images from 103 patients and tenfold cross‐validation technique, the novel radiographically inspired imaging features achieved an area under the receiver operating characteristic curve (AUC) of 0.77, demonstrating their predictive power. The combination of these features with clinical variables obtained the best performance (AUC = 0.81). Conclusion: The present study demonstrates that features extracted from pretreatment CT images can predict the risk of IPMN. Development of a preoperative model to discriminate between low‐risk and high‐risk IPMN will improve surgical decision‐making. [ABSTRACT FROM AUTHOR]

Pancreatic cancer, also known as exocrine pancreatic carcinoma or pancreatic ductal adenocarcinoma, is one of the most challenging tumor entities worldwide, which is characterized as a highly aggressive disease with dismal overall prognosis. Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy, and radiotherapy. In many cases, surgical resection is not possible due to the advanced stage at diagnosis and poor responses to current treatments, therefore, treatment alternatives have to be performed. However, brachytherapy through radioactive 125I seeds (RIS) implantation into pancreatic cancer has been first applied in unresectable carcinoma and made accuracy curative effects. Therapeutic procedures of RIS implantation for pancreatic carcinoma were not identical in domestic medical centers, making it hard to achieve homogeneity and affecting the efficacy seriously at last. To maximize the benefits of RIS for patients with pancreatic cancer, Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee and Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, Radioactive Seed Therapy Branch organized and helped establish China expert consensus on RIS implantation for the treatment of pancreatic cancer, to provide a reference for clinical practices. [ABSTRACT FROM AUTHOR]

Pancreatic cancer ranks the fifth leading cause of cancer-related death， while the incidence has increased in the recent years. Although available diagnosis and treatment have failed to significantly improve patients′ outcome, some advances have been made along with the understanding of the new concepts from oncology over the past several years. Pancreatic Cancer Committee of Chinese Anti-Cancer Association worked out this latest edition of “The Clinical Practice Guidelines for Pancreatic Cancer (version 2018)” based on current situation to standardize and improve the diagnosis and treatment of pancreatic cancer in China. This guideline shows algorithms for the diagnosis involving classification and staging, the systematic treatment including surgical resection, systemic chemotherapy and radiation therapy, and the whole-course management model for patients with pancreatic cancer. Different from previous consensus, this guideline contains the discussions and recommendations of 19 hot-issues in the clinical practice for pancreatic cancer in a question-oriented form, such as selection of biopsy and specimen sites, clinical diagnostic criteria for pancreatic cancer, assessment of resectable pancreatic cancer, indications and methods of preoperative biliary drainage, application of laparoscopic surgery, effect of expanding resection on patients′ outcomes, dissection of group 16th lymph node in standard pancreaticoduodenectomy, prognostic value of serum tumor markers, and neoadjuvant therapy in patients with resectable pancreatic cancer, etc. This guideline aims to raise a better comprehensive understanding of the diagnosis and treatment of pancreatic cancer for specialists, and further improving and standardizing the clinical practice in different medical institutions. [ABSTRACT FROM AUTHOR]

The present study focused on the roles of members of the Hedgehog (Hh) signaling pathway in the maintenance of malignant biological characteristics, such as tumorigenesis, similar to that of pancreatic tumor cells. Cluster of differentiation (CD)44+CD24+/CD44-CD24- cells were isolated from three different pancreatic cancer cell lines by flow cytometry. Among the three pancreatic cancer cell lines, the SW1990 cell line exhibited the highest percentage of CD44+CD24+ cells, which accounted for 39.9% of the total. The expression of members of the Hh signaling pathway in CD44+CD24+/CD44-CD24- cells was detected using reverse transcription‑polymerase chain reaction and western blot analysis. The results demonstrated that members of the Hh signaling pathway were differentially expressed in CD44+CD24+ cells compared with CD44-CD24-, normal pancreatic duct cells and unsorted SW1990 cells. In addition, lentiviral expression vectors expressing Smoothened (Smo) small interfering RNA (siRNA) were constructed. Following transfection with the lentiviral expression vectors, Smo expression was markedly reduced in CD44+CD24+ cells. The present study represents a preliminary investigation into the biological characteristics of CD44+CD24+ pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Aim To assess the correlation between the magnetic resonance imaging (MRI) characteristics and histopathology in pancreatic intraductal papillary mucinous neoplasms (IPMNs) associated with invasive carcinoma. Materials and methods Thirty-two patients with pancreatic IPMN associated with invasive carcinoma treated at a regional hospital in Dezhou were enrolled and the MRI findings were analysed retrospectively. The patients were assigned to one of two groups based on the invasive component: invasive component of <50% (IPMC-I; group A; n= 17) and invasive component of ≥50% (pancreatic ductal adenocarcinoma-associated IPMN [PDAC-IPMN]; group B; n= 15). The MRI findings between the groups were compared. Results The groups did not significantly differ in lesion location, radiological type, apparent diffusion coefficient (ADC) value, main pancreatic duct diameter, mural nodule size, early arterial phase signal enhancement ratio (SER EAP), lymphatic metastasis, etc.; however, lesion size and tumour classifications significantly differed between the groups (p< 0.05). Moreover, the positive enhancement integral (PEI), late arterial phase signal enhancement ratio (SER LAP), early portal venous phase signal enhancement ratio (SER EVP), late portal venous phase signal enhancement ratio (SER LVP), and delay phase signal enhancement ratio (SER DP) values were significantly greater in group A than in group B (p< 0.05). Conclusion Thus, the MRI features differed between IPMC-I and PDAC-IPMN. In particular, dynamic enhancement on preoperative MRI could be used for diagnosis and clinicopathological classification of pancreatic IPMN associated with invasive carcinoma. Highlights • The first study to compare the diagnostic performance of MRI. • The first study to predicte the malignant potential of pancreatic IPMNs. • Enhanced-MRI can determine the degree of invasion and preoperative classification. • Enhanced-MRI can guide the clinical development of a more complete treatment plan. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of combining non-enhanced magnetic resonance imaging (MRI) and non-enhanced endoscopic ultrasonography (EUS) for assessing the malignant potential of lesions in patients with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Material and methods: Data from 38 patients histopathologically diagnosed with IPMN adenomas or IPMN adenocarcinomas were retrospectively analysed. Preliminary univariate and multivariate analyses were conducted to identify statistically significant associations. Three blinded radiologists evaluated the image sets to assess the diagnostic performance of combined use of non-enhanced MRI and EUS as opposed to non-enhanced MRI alone in distinguishing malignant from benign lesions. Observer performance and interobserver variability were determined using receiver-operating-characteristic curve analysis and weighted κ statistics. Results: Multivariate analyses identified a significant difference between the abrupt change in the main pancreatic duct (MPD) calibre with distal pancreatic atrophy and the signal intensity of lesion-to-spinal cord ratio on MRI; a significant difference was observed in MPD size on EUS. Diagnostic performance assessments of the image sets did not differ significantly between the blinded radiologists. Conclusions: The clinical utility of non-enhanced EUS may be attributive in evaluating IPMN that has already been evaluated by non-enhanced MRI. [ABSTRACT FROM AUTHOR]

One hallmark of pancreatic cancer (PC) is the high prevalence of pancreatic cancer-associated diabetes mellitus (PC-DM), but the mechanisms remain to be elucidated. Patients with PC who are diagnosed with new-onset diabetes/prediabetes have recently been shown to display significantly lower levels of glucose-dependent insulinotropic peptide (GIP) secreted mainly by enteroendocrine cells. We hypothesized that PC-derived exosomes are responsible for the decreased levels of incretins in patients with PC-DM. In this study, exosomes were successfully isolated from PANC-1, MIA PaCa-2 and SW620 cells and characterized. Only the exosomes from MIA PaCa-2 cells (Exo-Mia) reduce the production of GIP and glucagon-like peptide-1 (GLP-1) from STC-1 cells in vitro in a concentration- and time-dependent manner. Moreover, Exo-Mia increased the levels of the Gip and proglucagon mRNAs and decreased the expression of proprotein convertase subtilisin/kexin type 1/3 (PCSK1/3), which is responsible for the post-translational processing of Gip and proglucagon. Furthermore, differentially expressed exosomal miRNAs (miR-6796-3p, miR-6763-5p, miR-4750-3p and miR-197-3p) were identified and considered to be responsible for the inhibitory effects on GIP and GLP-1 production. To further determine the approach of cancer-derived exosomes reaching enteroendocrine cells, we analyzed the uptake and distribution of exosomes in animal model. It was observed that exosomes infused into the intestinal cavity were more easily internalized by the intestinal epithelium than exosomes injected into blood. In conclusion, pancreatic cancer-derived exosomes (Exo-Mia) suppress the synthesis of GIP and GLP-1 from STC-1 cells in vitro by down-regulating the PCSK1/3. Moreover, it may be the pancreatic juice that transport cancer-derived exosomes to target cells (K and L cells) in the gut. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly metastatic cancer with an exceptionally poor prognosis. Despite development of different drugs and combined therapies, advances in survival rate still remain low and slow, mainly due to the invasiveness and late diagnosis. Therefore, it is crucial to find an effective treatment for invasiveness. The first-line therapy for pancreatic cancer is gemcitabine. Everolimus is another drug with benefits in gemcitabine-refractory metastasis. Rgs16 has a role in inhibition of pancreatic cancer migration and invasion. Accordingly, we aimed to investigate to which extent a combination of everolimus and gemcitabine is effective in killing highly metastatic pancreatic cancer cells and alter the expression of Rgs16 indicating its usefulness in invasiveness. Gemcitabine, everolimus, and a combination of both drugs were added to cultured Panc-1 cells. The cell killing effects of the drugs were tested through alamar blue assay and cell count. The expression of Rgs16 gene and protein was measured by qPCR and Western blotting. This study showed that a combination of everolimus and gemcitabine is more potent than everolimus, which is more effective than gemcitabine, in killing pancreatic cancer cells. However, Rgs16 as a marker of invasion was very low in Panc-1 cells and the drugs were not effective in altering Rgs16 gene expression or protein level. Although this may suggest that Panc-1 is a very invasive cell line and these drugs are not effective in highly metastatic cases, the cell line might be resistant to Rgs16 expression due to its specific mutations. [ABSTRACT FROM AUTHOR]