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Objectives: To investigate the imaging features of pancreatic ductal adenocarcinoma (PDAC) with histological large duct pattern. Methods: Our study included 37 patients (mean age, 66.5 years; 22 women) with surgically proven PDAC with histological large duct pattern, whose imaging features were classified into four types: Type I, solid mass; Type II, predominantly cystic mass with intracystic solid components; Type III, predominantly solid mass with intratumoral cysts; and Type IV, solid mass with peritumoral retention cysts or pseudocysts. Two radiologists independently analyzed both CT and MRI images for the morphological type, presence of abrupt main pancreatic duct (MPD) cutoff, adjacent vascular invasion, diffusion restriction, and reached consensus. Results: On CT, 26 patients (70.3%) had Type I tumors, five (13.5%) had Type II, three (8.1%) had Type III, and three (8.1%) had Type IV. Among the 26 patients with Type I tumors on CT, 16 had tumors with multiple intratumoral cysts within the solid mass on MRI and were subsequently classified as Type III. Accordingly, 10 patients (27.0%) were classified as Type I, five (13.5%) as Type II, 19 (51.7%) as Type III, and three (8.1%) as Type IV on MRI. Of the 37 patients, 27 (73.0%) had an abrupt MPD cutoff, 15 (40.5%) had adjacent vascular invasion, and 25 (67.6%) had diffusion restriction on MRI. Conclusions: Predominantly solid pancreatic masses with small intratumoral cysts visualized on MRI may be a characteristic imaging finding of PDAC with histological large duct pattern, and differentiate it from conventional PDAC or other cystic pancreatic tumors. Clinical relevance statement: Radiologists should be familiar with the various imaging features of PDAC with histological large duct pattern and should be aware that it may mimic other solid or cystic tumors of the pancreas. Key Points: Imaging features of pancreatic ductal adenocarcinoma with histological large duct pattern can be classified into four types. This pathology more frequently appears as a predominantly solid mass with intratumoral cysts on MRI than on CT. Adding MRI to CT may help identify pancreatic ductal adenocarcinoma with histological large duct pattern. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement. Methods: This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics. Results: R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤.009). Specificity was significantly higher with the 2017 guidelines (p =.043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91). Conclusion: The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines. [ABSTRACT FROM AUTHOR]

This investigation examined the potential pharmacotherapeutic efficacy of emetine, a natural alkaloid, against pancreatic ductal carcinoma, utilizing the PaCa3 cell line as a model. Employing a multifaceted approach, the study explored emetine's impact on cell viability, clonogenic potential, and apoptotic pathways, unravelling its molecular mechanisms. Additionally, an in vivo assessment was conducted to evaluate emetine's antitumor efficacy against PaCa3 xenografts. Under standard conditions, PaCa3 cells were treated with varying emetine concentrations and subjected to MTT, clonogenic, DAPI, AO/EB, Annexin V-FITC/PI, and Western blot assays. In vivo experiments involved the administration of emetine to female nude mice with PaCa3 xenografts, with subsequent measurement of tumor weight and volume. Statistical analyses included Tukey-test and ANOVA. Emetine demonstrated a significant and doseand time-dependent cytotoxic effect on PaCa3 cells, reducing viability from 98% to 8% (***p < 0.001). Clonogenic assay indicated a substantial inhibition of colony formation. DAPI staining revealed nuclear chromatin condensation, while AO/EB staining indicated heightened apoptosis. Annexin V-FITC/PI assay exhibited a dose-dependent decrease in normal cell viability and an increase in apoptotic events. Western blot analysis showed a concentration-dependent downregulation of anti-apoptotic Bcl-2 and the upregulation of pro-apoptotic markers. In vivo experiments illustrated a dose-dependent reduction in tumor weight (5 g to 1.6 g) and volume (2400 mm³ to 844 mm³) with emetine treatment. In conclusion, emetine emerges as a potent anticancer agent against pancreatic ductal carcinoma, exhibiting cytotoxicity, clonogenic inhibition, and apoptotic induction in PaCa3 cells. The in vivo study further highlights its promising therapeutic potential, laying the groundwork for future clinical studies in pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is crucial for clinical implementation. Purpose: To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls. Study Type: Prospective. Population: 15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age‐/sex‐matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC. Field Strength/Sequence: 3‐T, spin‐echo echo‐planar‐imaging, turbo spin‐echo, and fast field echo gradient‐echo. Assessment: Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal‐to‐noise ratio (SNR) was compared between all regimens. MRE repeatability (test–retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions‐of‐interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability. Statistical Tests: Repeated measures analysis of variance, coefficients of variation (CoVs), Bland–Altman analysis, (un)paired t‐test, Mann–Whitney U‐test, and Wilcoxon signed‐rank test. P‐value<0.05 was considered statistically significant. Results: Preparation regimens did not significantly influence MRE‐SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy–nontumor (P = 0.094). Data Conclusion: The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue–tumor and tumor–nontumor. Level of Evidence: 2 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Purpose Clinical prognostic criteria using preoperative factors were not developed for post-neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria. Materials and Methods Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system. Results One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, -0.012 to 0.142). Conclusion "Any degree of decrease in tumor size on CT" and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging. [ABSTRACT FROM AUTHOR]

Objectives: To determine the sensitivity of contrast-enhanced computed tomography (CECT) in detecting pancreatic ductal adenocarcinoma (PDAC) and identify factors associated with false negatives (FNs). Methods: Patients diagnosed with PDAC in 2014–2015 were retrospectively identified by a cancer registry. CECTs performed during the diagnostic interval were retrospectively classified as true positive (TP), indeterminate, or FN. Sensitivity TP/(TP+FN) was calculated for all CECTs and the following subgroups: protocol (uniphasic vs. biphasic); tumor size (≤ 2 cm vs. > 2 cm); and resectability (potentially resectable vs. unresectable). Multivariate logistic regression was performed to assess which of the following factors were associated with FN: clinical suspicion of PDAC; size >2 cm; presence of metastases; protocol; isoattenuating tumor; and potentially resectable disease on imaging. Results: In total, 176 CECTs (127 uniphasic; 49 biphasic) in 154 patients (90 men, mean age 72 ± 11 years) were included. Sensitivity was 125/149 (83.9%) overall and 87/106 (82.1%) and 38/43 (88.4%) for uniphasic and biphasic protocols, respectively. Sensitivity was decreased for tumors ≤ 2 cm (45.4% vs. 90.6%), no liver metastases (78.0% vs. 95.9%), and potentially resectable disease (65.3% vs. 93.0%). Factors significantly associated with FN were clinical suspicion (OR, 0.24, 95% CI: 0.07–0.75), size>2 cm (OR, 0.10, 95% CI: 0.02–0.44), absence of liver metastases (OR, 4.94, 95% CI: 1.29–22.99), and potentially resectable disease (OR, 4.13, 95% CI: 1.07–16.65). Conclusions: In our population, the overall sensitivity of CECT to detect PDAC is 83.9%; however, this is substantially lower in several scenarios, including patients with potentially resectable disease. This finding has important implications for patient outcomes and efforts to maximize CECT sensitivity should be sought. Clinical relevance statement: The sensitivity of CECT to detect PDAC is significantly decreased in the setting of sub-2 cm tumors and potentially resectable disease. A dedicated biphasic pancreatic CECT protocol has higher sensitivity and should be applied in patients with suspected pancreatic disease. Key Points: • The sensitivities of contrast-enhanced CT for the detection of PDAC were 87/106 (82.1%) and 38/43 (88.4%) for uniphasic and biphasic protocols, respectively. • The sensitivity of contrast-enhanced CT was decreased for small tumors ≤ 2 cm (45.4% vs. 90.6%), if there were no liver metastases (78.0% vs. 95.9%), and with potentially resectable disease (65.3% vs. 93.0%). • Absence of liver metastases (OR, 4.94, 95% CI: 1.29–22.99) and potentially resectable disease (OR, 4.13, 95% CI: 1.07–16.65) were associated with a false--negative (FN) CT result; suspicion of malignancy on the imaging requisition (OR, 0.24, 95% CI: 0.07–0.75) and size > 2 cm (OR, 0.10, 95% CI: 0.02–0.44) were negatively associated with FN. [ABSTRACT FROM AUTHOR]

PDAC (pancreatic ductal adenocarcinoma) is a highly aggressive malignant tumor. We have previously developed induced tumor-suppressing cells (iTSCs) that secrete a group of tumor-suppressing proteins. Here, we examined a unique procedure to identify anticancer peptides (ACPs), using trypsin-digested iTSCs-derived protein fragments. Among the 10 ACP candidates, P04 (IGEHTPSALAIMENANVLAR) presented the most efficient anti-PDAC activities. P04 was derived from aldolase A (ALDOA), a glycolytic enzyme. Extracellular ALDOA, as well as P04, was predicted to interact with epidermal growth factor receptor (EGFR), and P04 downregulated oncoproteins such as Snail and Src. Importantly, P04 has no inhibitory effect on mesenchymal stem cells (MSCs). We also generated iTSCs by overexpressing ALDOA in MSCs and peripheral blood mononuclear cells (PBMCs). iTSC-derived conditioned medium (CM) inhibited the progression of PDAC cells as well as PDAC tissue fragments. The inhibitory effect of P04 was additive to that of CM and chemotherapeutic drugs such as 5-Flu and gemcitabine. Notably, applying mechanical vibration to PBMCs elevated ALDOA and converted PBMCs into iTSCs. Collectively, this study presented a unique procedure for selecting anticancer P04 from ALDOA in an iTSCs-derived proteome for the treatment of PDAC. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a devastating tumor type where a very high proportion of people diagnosed end up dying from cancer. Surgical resection is an option for only about 20% of patients, where the 5-year survival increase ranges from 10 to 25%. In addition to surgical resection, there are adjuvant chemotherapy schemes, such as FOLFIRINOX (a mix of Irinotecan, oxaliplatin, 5-Fluorouraci and leucovorin) or gemcitabine-based treatment. These last two drugs have been compared in the NAPOLI-3 clinical trial, and the NALIRIFOX arm was found to have a higher overall survival (OS) (11.1 months vs. 9.2 months). Despite these exciting improvements, PDAC still has no effective treatment. An interesting approach would be to drive ferroptosis in PDAC cells. A non-apoptotic reactive oxygen species (ROS)-dependent cell death, ferroptosis was first described by Dixon et al. in 2012. ROS are constantly produced in the tumor cell due to high cell metabolism, which is even higher when exposed to chemotherapy. Tumor cells have detoxifying mechanisms, such as Mn-SOD or the GSH-GPX system. However, when a threshold of ROS is exceeded in the tumor cell, the cell's antioxidant systems are overwhelmed, resulting in lipid peroxidation and, ultimately, ferroptosis. In this review, we point out ferroptosis as an approach to consider in PDAC and propose that altering the cellular ROS balance by combining oxidizing agents or with inhibitors of the main cellular detoxifiers triggers ferroptosis in PDAC. [ABSTRACT FROM AUTHOR]

Background and Aims: Endoscopic ultrasonography‐guided fine‐needle aspiration/biopsy (EUS‐FNA/B) is considered to be a first‐line procedure for the pathological diagnosis of pancreatic cancer owing to its high accuracy and low complication rate. The number of new cases of pancreatic ductal adenocarcinoma (PDAC) is increasing, and its accurate pathological diagnosis poses a challenge for cytopathologists. Our aim was to develop a hyperspectral imaging (HSI)‐based convolution neural network (CNN) algorithm to aid in the diagnosis of pancreatic EUS‐FNA cytology specimens. Methods: HSI images were captured of pancreatic EUS‐FNA cytological specimens from benign pancreatic tissues (n = 33) and PDAC (n = 39) prepared using a liquid‐based cytology method. A CNN was established to test the diagnostic performance, and Attribution Guided Factorization Visualization (AGF‐Visualization) was used to visualize the regions of important classification features identified by the model. Results: A total of 1913 HSI images were obtained. Our ResNet18‐SimSiam model achieved an accuracy of 0.9204, sensitivity of 0.9310 and specificity of 0.9123 (area under the curve of 0.9625) when trained on HSI images for the differentiation of PDAC cytological specimens from benign pancreatic cells. AGF‐Visualization confirmed that the diagnoses were based on the features of tumor cell nuclei. Conclusions: An HSI‐based model was developed to diagnose cytological PDAC specimens obtained using EUS‐guided sampling. Under the supervision of experienced cytopathologists, we performed multi‐staged consecutive in‐depth learning of the model. Its superior diagnostic performance could be of value for cytologists when diagnosing PDAC. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate an automated magnetic resonance imaging (MRI)-based model to preoperatively differentiate pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC). Methods: This retrospective study included patients with surgically resected, histopathologically confirmed PASC or PDAC who underwent MRI between January 2011 and December 2020. According to time of treatment, they were divided into training and validation sets. Automated deep-learning-based artificial intelligence was used for pancreatic tumor segmentation. Linear discriminant analysis was performed with conventional MRI and radiomic features to develop clinical, radiomics, and mixed models in the training set. The models' performances were determined from their discrimination and clinical utility. Kaplan–Meier and log-rank tests were used for survival analysis. Results: Overall, 389 and 123 patients with PDAC (age, 61.37 ± 9.47 years; 251 men) and PASC (age, 61.99 ± 9.82 years; 78 men) were included, respectively; they were split into the training (n = 358) and validation (n = 154) sets. The mixed model showed good performance in the training and validation sets (area under the curve: 0.94 and 0.96, respectively). The sensitivity, specificity, and accuracy were 76.74%, 93.38%, and 89.39% for the training set, respectively, and 67.57%, 97.44%, and 90.26% for the validation set, respectively. The mixed model outperformed the clinical (p = 0.001) and radiomics (p = 0.04) models in the validation set. Log-rank test revealed significantly longer survival in the predicted PDAC group than in the predicted PASC group (p = 0.003), according to the mixed model. Conclusion: Our mixed model, which combined MRI and radiomic features, can be used to differentiate PASC from PDAC. [ABSTRACT FROM AUTHOR]

Introduction. Difficulties in advanced pancreatic ductal adenocarcinoma (PDAC) treatment require a constant search for novel prognostic factors. The aim of this study is to determine the role of various morphological parameters in predicting the prognosis of advanced PDAC during systemic therapy with a FOLFIRINOX regimen. Material and methods. The data of 52 patients, treated with FOLFIRINOX chemotherapy due to metastatic PDAC were analyzed retrospectively in this study. Results. The median time of overall survival (OS) in the group of patients with neutrophil-to-lymphocyte ratio (NLR) ≥3 was 5.8 months, compared to 14.5 months in patients with NLR < 3. Median progression-free survival (PFS) in patients with NLR ≥ 3 was 4.1 months, compared to 8.5 months in patients with NLR < 3. There were no statistically significant differences among patients concerning the lymphocyte-to-monocyte ratio (LMR) and platelets-to-lymphocyte ratio (PLR). Conclusions. Higher NLR is a negative prognostic factor in metastatic PDAC. [ABSTRACT FROM AUTHOR]

Background: Endoscopic ultrasound-guided puncture aspiration biopsy (EUS-FNA) of pancreatic ductal adenocarcinoma (PDAC) is highly diagnostic, but it is difficult to distinguish from benign disease. Our objective was to determine the usefulness of maspin staining, in addition to conventional p53 staining, in the diagnosis of PDAC by EUS-FNA. Methods: Of the patients who underwent EUS-FNA and were diagnosed with PDAC, we retrospectively identified 90 cases in which both maspin and p53 staining were performed. In addition, we identified 28 cases of benign pancreatic disease diagnosed using EUS-FNA and these were selected as a control group. For analysis of EUS-FNA specimens, Cohen's Kappa (κ) coefficient and the prevalence and bias adjusted Kappa statistic (PABAK) were applied to assess the significance of sensitivity and specificity, comparing p53, maspin, p53+maspin. Results: The sensitivity and specificity of p53 staining were 48.9% and 100%. The κ coefficient was 0.31 (95%CI 0.18–0.44) (p < 0.01) and the PABAK coefficient was 0.22 (95%CI 0.03–0.40). The results for maspin staining were 88.9% and 92.9%. The κ coefficient was 0.72 (95%CI 0.54–0.90) (p < 0.01) and the PABAK coefficient was 0.78 (95%CI 0.64–0.88). The results for the combination of maspin and p53 staining were 94.4% and 92.2%. The κ coefficient was 0.82 (95%CI 0.64–1.00) (p < 0.01) and the PABAK coefficient was 0.86 (95%CI 0.74–0.94). Conclusion: Adding maspin staining to p53 staining showed high sensitivity and specificity. Our results demonstrated the usefulness of their combined use that might contribute to the improvement of tissue diagnostic performance of PDAC by EUS-FNA. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential role of MR findings and DWI parameters in predicting small regional lymph nodes metastases (with short-axis diameter < 10 mm) in pancreatic ductal adenocarcinomas (PDACs). Methods: A total of 127 patients, 82 in training group and 45 in testing group, with histopathologically diagnosed PDACs who underwent pancreatectomy were retrospectively analyzed. PDACs were divided into two groups of positive and negative lymph node metastases (LNM) based on the pathological results. Pancreatic cancer characteristics, short axis of largest lymph node, and DWI parameters of PDACs were evaluated. Results: Univariate and multivariate analyses showed that extrapancreatic distance of tumor invasion, short-axis diameter of the largest lymph node, and mean diffusivity of tumor were independently associated with small LNM in patients with PDACs. The combining MRI diagnostic model yielded AUCs of 0.836 and 0.873, and accuracies of 81.7% and 80% in the training and testing groups. The AUC of the MRI model for predicting LNM was higher than that of subjective MRI diagnosis in the training group (rater 1, P = 0.01; rater 2, 0.008) and in a testing group (rater 1, P = 0.036; rater 2, 0.024). Comparing the subjective diagnosis, the error rate of the MRI model was decreased. The defined LNM-positive group by the MRI model showed significantly inferior overall survival compared to the negative group (P = 0.006). Conclusions: The MRI model showed excellent performance for individualized and noninvasive prediction of small regional LNM in PDACs. It may be used to identify PDACs with small LNM and contribute to determining an appropriate treatment strategy for PDACs. [ABSTRACT FROM AUTHOR]

Objective: Most patients with pancreatic ductal adenocarcinoma receive chemo‐radiotherapy as first approach, some of them with the future hope to undergo surgery. Methodology: The aim of the study was to estimate the probabilities to receive surgery, to experience tumour progression or post‐operative recurrence. We performed a competing‐risk approach to estimate competing events of disease progression and surgery, as well as post‐operative recurrence and death without recurrence. Results: Of 96 enrolled patients, 49 received chemotherapy because they were judged borderline resectable, 21 were locally advanced and 7 had liver‐only limited metastatic disease. Competing‐risk analyses showed that resectability status at diagnosis not only determines future probabilities of surgery, but also tumour progression and post‐operative recurrence (p <.05 in all cases). CA19‐9 decrease ≥50% predicted surgery (p =.032), whereas CA19‐9 ≥ 300 U/mL predicted post‐operative recurrence (p =.001). Younger age also predicted surgery (p =.001) and margin status predicted recurrence (p =.047). The combination of the competing events suggested that the best outcomes since diagnosis depended not only on resectability and final surgical margin, but also on the combination of relative decrease of CA19‐9 and its absolute value after therapy. Conclusions: The combination of CA19‐9 decrease, added to resectability criteria, can be used to optimise the selection of surgical candidates. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis because it is often detected at an advanced stage, and drug resistance interferes with treatment. However, the mechanism underlying drug resistance in PDAC remains unclear. Here, we investigated metabolic changes between a parental PDAC cell line and a gemcitabine (GEM)-resistant PDAC cell line. We established a GEM-resistant cell line, MIA-G, from MIA-PaCa-2 parental (MIA-P) cells using continuous therapeutic-dose GEM treatment. MIA-G cells were also more resistant to 5-fluorouracil in comparison to MIA-P cells. Metabolic flux analysis showed a higher oxygen consumption rate (OCR) in MIA-G cells than in MIA-P cells. Notably, OCR was suppressed by GEM treatment only in MIA-G cells. GEM treatment increased mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS) in MIA-P cells, but not in MIA-G cells. Glutamine uptake and peroxidase levels were elevated in MIA-G cells. The antioxidants N-acetyl-L-cysteine and vitamin C increased the sensitivity to GEM in both cell lines. In MIA-G cells, the expression of the mitochondrial transcription factor A also decreased. Furthermore, rotenone reduced the sensitivity of MIA-P cells to GEM. These findings suggest that the suppression of oxidative phosphorylation contributes to GEM resistance by reducing ROS production. Our study provides a new approach for reducing GEM resistance in PDAC. [ABSTRACT FROM AUTHOR]

The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 ( https://jrct.niph.go.jp/ ). [ABSTRACT FROM AUTHOR]

Background: Limited English proficiency has been shown to negatively affect health outcomes. However, as of now, little is known about survival rates of patients with limited English proficiency (LEP) and pancreatic ductal adenocarcinoma (PDAC) when compared to patients with English proficiency (EP) in an urban, non-safety net setting. We aimed to compare survival rates between patients with LEP and those with EP who had a diagnosis of PDAC. Methods: A single-institution retrospective propensity-matched cohort study of patients with biopsy-proven PDAC was undertaken. Demographics, clinical characteristics, and language information were collected for all participants. Patients were classified as having LEP or EP based on their preferred speaking language at the time of admission and matched on baseline characteristics using propensity scores. Survival analysis methods were used to study survival rates in patients with PDAC based on their EP status. Results: Of 739 included patients, 71 (9.48%) had LEP, mean age was 68.4 ± 10.9, and 51.8% were female. Both groups of patients were comparable for age, gender, marital status, and time to treatment. LEP status was associated with higher odds of death in both unmatched (HR 1.65, 95% CI 1.22–2.22) and matched (HR 1.60, 95% CI 1.03–2.47) analyses. Additionally, patients with LEP had significantly decreased odds of receiving cancer-directed treatment and increased odds of advanced stage cancer at presentation. Conclusions: In this cohort of patients with PDAC, LEP predicted worse survival. The results of this study suggest that, after accounting for interpreter use, other factors contribute to this disparity. Such factors, as yet unmeasured, may include health literacy and cultural expectations, for which further investigation is warranted to better understand and limit this survival disparity. [ABSTRACT FROM AUTHOR]

Carcinosarcoma of the pancreas is a rare entity with poor prognosis. Here, we report a case of pancreatic carcinosarcoma in a 68-year-old male patient who underwent a pancreatoduodenectomy for a unilocular cystic mass in the head of the pancreas. Histologically, the lesion showed a biphasic tumor with a carcinoma component and a spindle cell sarcomatous component, which were intimately intermingled. Most of the carcinoma components are well-differentiated ductal adenocarcinoma with small areas of moderately to poorly differentiated ductal adenocarcinoma. The sarcomatous component is a high-grade highly cellular spindle cell tumor with frequent mitosis and apoptosis. Immunohistochemical studies demonstrated that the carcinomatous component was positive for epithelial markers and cyclin D1, and the sarcomatous component was negative for these markers while positive for vimentin, p16, and DOG1 with patchy positivity for S100. Other markers, including SOX10, CD117, Melan A, HMB45, actin, desmin, myogenin, beta-catenin, TLE1, and p53, were negative in both components. Molecular studies demonstrated that the tumor was microsatellite stable. Whole exome next generation sequencing analysis was performed and no pathogenic alterations in the genes were identified. [ABSTRACT FROM AUTHOR]

Background: The outcomes of minimally invasive pancreaticoduodenectomy have not been adequately compared with those of open pancreaticoduodenectomy in patients with pancreatic ductal adenocarcinoma. We performed a meta‐analysis to compare the perioperative and oncological outcomes of these two pancreaticoduodenectomy procedures specifically in patients with pancreatic ductal adenocarcinoma. Methods: Before this study was initiated, a specific protocol was designed and has been registered in PROSEPRO (ID: CRD42020149438). Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, PubMed, EMBASE, Web of Science, Cochrane Central Register, and ClinicalTrials.gov databases were systematically searched for studies published between January 1994 and October 2019. Overall survival, disease-free survival, and time to commencing adjuvant chemotherapy were the primary endpoint measurements, whereas perioperative and short-term outcomes were the secondary endpoints. Results: The final analysis included 9 retrospective cohorts comprising 11,242 patients (1377 who underwent minimally invasive pancreaticoduodenectomy and 9865 who underwent open pancreaticoduodenectomy). There were no significant differences in the patients' overall survival, operative time, postoperative complications, 30-day mortality, rate of vein resection, number of harvested lymph nodes, or rate of positive lymph nodes between the two approaches. However, disease-free survival, time to starting adjuvant chemotherapy, length of hospital stay, and rate of negative margins in patients who underwent minimally invasive pancreaticoduodenectomy showed improvements relative to those in patients who underwent open surgery. Conclusions: Minimally invasive pancreaticoduodenectomy provides similar or even improved perioperative, short-term, and long-term oncological outcomes when compared with open pancreaticoduodenectomy for patients with pancreatic ductal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objectives: To retrospectively examine US, CT, and MR imaging examinations of missed or misinterpreted pancreatic ductal adenocarcinoma (PDAC), and identify factors which may have confounded detection or interpretation. Methods: We reviewed 107 examinations in 66/257 patients (26%, mean age 73.7 years) diagnosed with PDAC in 2014 and 2015, with missed or misinterpreted imaging findings as determined by a prior study. For each patient, images and reports were independently reviewed by two radiologists, and in consensus, the following factors which may have confounded assessment were recorded: inherent tumor factors, concurrent pancreatic pathology, technical limitations, and cognitive biases. Secondary signs of PDAC associated with each examination were recorded and compared with the original report to determine which findings were missed. Results: There were 66/107 (62%) and 49/107 (46%) cases with missed and misinterpreted imaging findings, respectively. A significant number of missed tumors were < 2 cm (45/107, 42%), isoattenuating on CT (32/72, 44%) or non-contour deforming (44/107, 41%). Most (29/49, 59%) misinterpreted examinations were reported as uncomplicated pancreatitis. Almost all examinations (94/107, 88%) demonstrated secondary signs; pancreatic duct dilation was the most common (65/107, 61%) and vascular invasion was the most commonly missed 35/39 (90%). Of the CT and MRIs, 28 of 88 (32%) had suboptimal contrast dosing. Inattentional blindness was the most common cognitive bias, identified in 55/107 (51%) of the exams. Conclusion: Recognizing pitfalls of PDAC detection and interpretation, including intrinsic tumor features, secondary signs, technical factors, and cognitive biases, can assist radiologists in making an early and accurate diagnosis. Key Points: • There were 66/107 (62%) and 49/107 (46%) cases with missed and misinterpreted imaging findings, respectively, with tumoral, technical, and cognitive factors leading to the misdiagnosis of pancreatic ductal adenocarcinoma. • The majority (29/49, 59%) of misinterpreted cases of pancreatic ductal adenocarcinoma were mistaken for pancreatitis, where an underlying mass or secondary signs were not appreciated due to inflammatory changes. • The most common missed secondary sign of pancreatic ductal adenocarcinoma was vascular encasement, missed in 35/39 (90%) of cases, indicating the importance of evaluating the peri-pancreatic vasculature. [ABSTRACT FROM AUTHOR]

Mixed carcinoma of the pancreas is defined as the concurrent existence of pancreatic ductal carcinoma, acinar cell carcinoma, and/or islet cell carcinoma within the same neoplasm. We herein report a rare case of mixed ductal-acinar cell carcinoma in a 74-year-old man who was undergoing treatment for hypertension and diabetes at another hospital. After an abrupt worsening of his blood glucose control, the patient was referred to our hospital for further evaluation. Abdominal contrast-enhanced computed tomography and magnetic resonance imaging revealed a tumor with a multilocular cystic lesion in the head of the pancreas. Endoscopic retrograde cholangiopancreatography revealed obstruction of the main pancreatic duct and dilation of the dorsal pancreatic duct; in addition, adenocarcinoma was detected in the pancreatic juice cytology. Based on the abovementioned findings, the patient was diagnosed with carcinoma of the pancreatic head and underwent subtotal stomach-preserving pancreaticoduodenectomy. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with mixed ductal-acinar cell carcinoma. The patient was prescribed TS-1 as postoperative adjuvant chemotherapy upon discharge. However, treatment was discontinued 2 months later due to marked general malaise, and the patient succumbed to tumor recurrence in the residual pancreas 12 months after the surgery. [ABSTRACT FROM AUTHOR]

• The tilted r-DWI provided higher subjective image quality scores compared with f-DWI. • In all patients, no aliasing artifacts were observed in tilted r-DWI. • The CNR of tilted r-DWI was significantly higher than that of f-DWI. Modified reduced FOV diffusion-weighted imaging (DWI) using spatially-tailored 2D RF pulses with tilted excitation plane (tilted r-DWI) has been developed. The purpose of this study was to evaluate the impact on image quality and quantitative apparent diffusion coefficient (ADC) values of tilted r-DWI for pancreatic ductal adenocarcinomas (PDAC) in comparison to conventional full-FOV DWI (f-DWI). This retrospective study included 21 patients (mean 70.7, range 50–85 years old) with pathologically confirmed PDAC. All MR images were obtained using 3 T systems. Two radiologists evaluated presence of blurring or ghost artifacts, susceptibility artifacts, and aliasing artifacts; anatomic visualization of the pancreas; interslice signal homogeneity; overall image quality; and conspicuity of the PDAC. For quantitative analysis, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), signal-intensity ratio (SIR) and ADC values were measured using regions of interest. All image quality scores except aliasing artifacts in tilted r-DWI were significantly higher than those in f-DWI (p < 0.01). The CNR and SIR of PDAC were significantly higher in tilted r-DWI than in f-DWI (6.7 ± 4.4 vs. 4.7 ± 3.9, 2.02 ± 0.72 vs. 1.72 ± 0.60, p < 0.01). Conversely, the SNR of PDAC in tilted r-DWI was significantly lower than that in f-DWI (56.0 ± 33.1 vs. 113.6 ± 67.3, p < 0.01). No significant difference was observed between mean ADC values of the PDAC calculated from tilted r-DWI (tilted r-ADC) and those from f-DWI (f-ADC) (1225 ± 250 vs. 1294 ± 302, p = 0.11). The r-DWI using 2D RF techniques with a tilted excitation plane was shown to significantly improve the image quality and CNR and reduce image artifacts compared to f-DWI techniques in MRI evaluations of PDAC without significantly affecting ADC values. [ABSTRACT FROM AUTHOR]

Objectives: To assess the interreader agreement and reader performance in the evaluation of patients with pancreatic cancer (PC) in two classification systems of local resectability status prior to initiation of therapy, namely the National Comprehensive Cancer Network (NCCN) and Karolinska classification system (KCS).Methods: In this ethics review board-approved retrospective study, six radiologists independently evaluated pancreatic CT-examinations of 30 patients randomly selected from a tertiary referral centre's multidisciplinary tumour board database. Based on well-defined criteria of tumour-vessel relationship, each patient was assigned to one of three NCCN and six KCS categories. We assessed the intraclass correlation coefficient (ICC) and compared the percentages of correct tumour classification of the six readers in both systems (Chi-square test; a P-value <0.05 was considered significant). The standard of reference was a consensus evaluation of CT-examinations by three readers not involved in the image analysis.Results: The ICC for NCCN and KCS was 0.82 and 0.84, respectively (very strong agreement). The percentages of correct tumour classification at NCCN and KCS were 53-83% and 30-57%, respectively, with no statistically significant differences in the overall reader comparison per classification system. In pair-wise comparison between readers for NCCN/KCS, there were statistically significant differences between reader 5 vs. readers 4 (P = 0.012) and 3 (P = 0.045)/ reader 5 vs. reader 4 (P = 0.037).Conclusion: Interreader agreement in both PC classification systems is very strong. NCCN may be advantageous in terms of reader performance compared to KCS. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic potential of intravoxel incoherent motion (IVIM) DWI for differentiating metastatic and non-metastatic lymph node stations (LNS) in pancreatic ductal adenocarcinoma (PDAC).Methods: 59 LNS histologically diagnosed following surgical resection from 15 patients were included. IVIM DWI with 12 b values was added to the standard MRI protocol. Evaluation of parameters was performed pre-operatively and included the apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f). Diagnostic performance of ADC, D, D* and f for differentiating between metastatic and non-metastatic LNS was evaluated using ROC analysis.Results: Metastatic LNS had significantly lower D, D*, f and ADC values than the non-metastatic LNS (p< 0.01). The best diagnostic performance was found in D, with an area under the ROC curve of 0.979, while the area under the ROC curve values of D*, f and ADC were 0.867, 0.855 and 0.940, respectively. The optimal cut-off values for distinguishing metastatic and non-metastatic lymph nodes were D = 1.180 × 10-3 mm2/s; D* = 14.750 × 10-3 mm2/s, f = 20.65 %, and ADC = 1.390 × 10-3 mm2/s.Conclusion: IVIM DWI is useful for differentiating between metastatic and non-metastatic LNS in PDAC.Key Points: • IVIM DWI is feasible for diagnosing LN metastasis in PDAC. • Metastatic LNS has lower D, D*, f, ADC values than non-metastatic LNS. • D-value from IVIM model has best diagnostic performance, followed by ADC value. • D* has the lowest AUC value. [ABSTRACT FROM AUTHOR]

Objectives: Recent guidelines suggest that imaging surveillance be conducted for 5 years for patients with at most one high-risk feature. If there were no significant changes, surveillance is stopped. We sought to validate this follow-up strategy.Methods: In study 1, data were analysed for 392 patients with intraductal papillary mucinous neoplasms (IPMNs) and at most one high-risk feature who were periodically followed up for more than 1 year with imaging tests. In study 2, data were analysed for 159 IPMN patients without worsening high-risk features after 5 years (stop surveillance group).Results: In study 1, pancreatic cancer (PC) was identified in 12 patients (27.3%) in the endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) indication group and none in the non-EUS-FNA indication group (P < 0.01). In the EUS-FNA indication group, 11 patients (25%) died, whereas 29 (8.3%) died in the non EUS-FNA indication group (P < 0.01). In study 2 (stop surveillance group), PC was identified in three patients (1.9%) at 84, 103 and 145 months.Conclusions: PC risk and mortality for IPMNs not showing significant change for 5 years is likely to be low, and the non-EUS-FNA indication can provide reasonable decisions. However, three patients without worsening high-risk features for 5 years developed PC. The stop surveillance strategy should be reconsidered.Key Points: • The AGA guidelines provide reasonable clinical decisions for the EUS-FNA indication. • In stop surveillance group, PC was identified in 3 patients (1.9%). • In stop surveillance group, 2 of 3 PC patients died from PC. • Risk of pancreatic cancer in "stop surveillance" group is not negligible. [ABSTRACT FROM AUTHOR]

Adjuvant chemotherapy (AC) can prolong overall survival (OS) after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, fitness for AC may be influenced by postoperative recovery. We aimed to investigate if serious (Clavien-Dindo grade ≥ IIIa) postoperative complications affected AC rates, disease recurrence and OS. Data were extracted from the Recurrence After Whipple's (RAW) study (n = 1484), a retrospective study of PD outcomes (29 centres from eight countries). Patients who died within 90-days of PD were excluded. The Kaplan-Meier method was used to compare OS in those receiving or not receiving AC, and those with and without serious postoperative complications. The groups were then compared using univariable and multivariable tests. Patients who commenced AC (vs no AC) had improved OS (median difference: (MD): 201 days), as did those who completed their planned course of AC (MD: 291 days, p < 0.0001). Those who commenced AC were younger (mean difference: 2.7 years, p = 0.0002), more often (preoperative) American Society of Anesthesiologists (ASA) grade I-II (74% vs 63%, p = 0.004) and had less often experienced a serious postoperative complication (10% vs 18%, p = 0.002). Patients who developed a serious postoperative complication were less often ASA grade I-II (52% vs 73%, p = 0.0004) and less often commenced AC (58% vs 74%, p = 0.002). In our multicentre study of PD outcomes, PDAC patients who received AC had improved OS, and those who experienced a serious postoperative complication commenced AC less frequently. Selected high-risk patients may benefit from targeted preoperative optimisation and/or neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Pancreatic acinar cell carcinoma (ACC) is a rare tumor that is difficult to diagnose preoperatively. The aim of this study was to evaluate and describe the computed tomography (CT) features of ACC and compare the results with pancreatic ductal adenocarcinoma (DAC) for improving preoperative diagnosis. The control group consisted of 34 patients with DAC collected from the pathology electronic database. The CT imaging from nine patients with pathologically confirmed ACC was retrospectively reviewed. Two radiologists independently assessed the tumor location, size, texture, and enhancement patterns. We found that 64.3% (9/14) of ACC tumors were homogeneous and 35.7% (5/14) had necrosis. The percentage of common bile duct and pancreatic ductal dilation was 14.3% (2/14) and 7.1% (1/14), respectively. The mean size of ACC was 50.1±24.2 mm. The mean attenuation of ACC was 35.4±3.9 Hounsfield unit (HU) before enhancement, 73.1±42.9 HU in arterial phase, and 71.8±15.6 HU in port venous phase. It is difficult to distinguish ACC from DAC preoperatively only based on CT findings. However, compared with DAC, we found that ACC tumors are likely to be larger and contain more heterogeneous intratumoral necrotic hypovascular regions, and less pancreatic ductal and common biliary dilation. [ABSTRACT FROM AUTHOR]

Background: miR-23a, which participates in invasion of pancreatic ductal adenocarcinoma cells into the mesothelial barrier, is a critical regulator in many cancers. It, however, is still unknown whether miR-23a regulates pancreatic cell proliferation and apoptosis or not. Aims: We sought to investigate the role of miR-23a in regulation of pancreatic cell proliferation and apoptosis. Methods: miRNA, mRNA, and protein expressions were determined by qRT-PCR and Western blot, respectively. Dual-luciferase reporter assay was used in detection for binding ability of miR-23a to APAF1. Ectopic miR-23a and APAF 1 were introduced to pancreatic cells, and their roles in proliferation and apoptosis were detected by MTT, colony formation, and apoptosis assays, respectively. Results: Up-regulation of miR-23a and down-regulation of APAF 1 were found in pancreatic ductal cancer, respectively. miR-23a significantly inhibited the luciferase activity by targeting APAF 1 3′UTR. Ectopic miR-23a significantly suppressed the APAF 1 gene expression in pancreatic cancer cells. Similar to siAPAF1, miR-23a significantly promoted pancreatic cancer cell proliferation and repressed apoptosis. Furthermore, miR-23a inhibitor and exogenous APAF 1 could recover the effects. Conclusions: It is suggested that miR-23a, acting as an oncogenic regulator by directly targeting APAF 1 in pancreatic cancer, is a useful potential biomarker in diagnosis and treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: To establish a prognostic stratification model for predicting prognosis in patients with pancreatic ductal adenocarcinoma (PDAC) after curative resection based on preoperative contrast-enhanced computed tomography (CECT) findings.Method: From January 2014 to June 2020, 126 patients with radically resected PDAC were reviewed and divided into a development cohort (n = 90) and a validation cohort (n = 36). In the development cohort, clinicopathological parameters and preoperative CECT findings associated with recurrence-free survival (RFS) and overall survival (OS) were identified by using univariate and multivariate analyses. Nomograms were constructed based on Cox proportional hazards regression models. New prognostic nomograms were certificated in the validation cohort. Model performance was evaluated based on calibration, discrimination, and clinical utility.Results: Tumor size >4 cm, adjacent organs invasion, suspicious lymph nodes, and rim enhancement were independently associated with worse RFS and OS (all P values were < 0.05). In the validation cohort, the nomograms based on pancreatic CECT showed good discrimination capability and outperformed the TNM staging system in outcomes prediction. Patients were stratified into low- and high-risk groups based on nomograms, and RFS and OS rates in the low-risk group were significantly higher than those in the high-risk group (P < 0.001 and <0.01, respectively).Conclusions: Nomograms based on preoperative pancreatic CECT findings can predict RFS and OS for PDAC patients after curative resection and facilitate further prognostic stratification. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of this study was to evaluate the expression of Krebs yon den Lundgen-6/Mucin 1 (KL-6/MUC1) in pancreatic ductal carcinoma and its potential relationship with β-catenin in tumor progression. Main methods: The expressions of KL-6/MUC1 and β-catenin in 18 cases of pancreatic ductal carcinoma were detected by immunohistochemical staining. To determine the impact of KL-6/MUC1 down-regulation on pancreatic ductal carcinoma progression, siRNA targeting MUC1 was used to knockdown KL-6/MUC1 expression. The down-regulation of KL-6/MUC1 expression was confirmed by reverse transcription-polymerase chain reaction and immunofluorescence staining. E-cadherin and E-cadherin/β-catenin complex expressions were determined by immunoprecipitation. The expressions of KL-6/MUC1, β-catenin, cyclin D1 and c-myc were detected by Western blot. Cell proliferation, apoptosis and invasive abilities were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, Annexin V-FITC apoptosis detection kit and invasion assay. Key findings: Positive KL-6/MUC1 staining was observed in the cancer tissues of all the 18 pancreatic ductal carcinoma cases (100.0%), and high nuclear β-catenin expression was seen in 12 cancers (66.7%). Reverse transcription-polymerase chain reaction and immunofluorescence staining showed that both KL-6/MUC1 mRNA and protein were effectively silenced by MUC1 siRNA. After KL-6/MUC1 knockdown, E-cadherin and E-cadherin/β-catenin complex expressions were increased, while the nuclear β-catenin, cyclin D1, and c-myc expressions were decreased. Down-regulation of KL-6/MUC1 also resulted in slower proliferation, increased apoptosis and decreased invasive ability. Significance: This study indicated that KL-6/MUC1 played a complex role in regulating pancreatic ductal carcinoma cell proliferation, apoptosis, and invasion, and also supported the hypothesis that there is a functional link between KL-6/MUC1 expression and β-catenin subcellular localization. [Copyright &y& Elsevier]

Abstract: Beclin-1 has emerged as an autophagy gene in a variety of human carcinomas. The aim of this study was to evaluate beclin-1 expression and to determine its prognostic significance in patients with pancreatic ductal adenocarcinoma (PDA). We performed immunohistochemical staining for beclin-1 in 63 cases of PDA. We investigated whether beclin-1 expression correlated with clinicopathologic characteristics and patient outcomes. Beclin-1 expression was absent in normal pancreatic islet cells, acinar cells, and ductal epithelial cells. In contrast, in PDA, beclin-1 showed positive immunoreactivity in 14 of 63 (22.2%) PDA cases, while the remaining 49 (77.8%) PDA cases exhibited negative beclin-1 expression. We found significant associations between increased beclin-1 expression and the absence of lymphatic invasion (P =0.032) and low rate of distant metastasis (P =0.001). Univariate analysis of survival showed that the median distant metastasis-free survival of beclin-1-negative PDA patients (10 months) was significantly shorter than that of beclin-1-positive PDA patients (21 months; P =0.031). Our results suggest that increased beclin-1 expression plays a role in the inhibition of PDA progression. [Copyright &y& Elsevier]