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Background: Utilization of minimally-invasive distal pancreatectomy (MIDP) for pancreatic adenocarcinoma has increased. While unplanned conversion to an open procedure during MIDP is associated with inferior short-term outcomes, the long-term consequences of conversion have not been adequately examined., Methods: Patients with pancreatic adenocarcinoma undergoing MIDP were selected from the National Cancer Database (2010-2015) and subdivided based on the occurrence of unplanned conversion. Post-operative outcomes and overall survival (OS) were examined. Conversion was additionally compared to a matched group of planned open resections., Results: Among 592 patients undergoing attempted MIDP, unplanned conversion occurred in 23.1%. Despite increased 90-day mortality among patients experiencing conversion, there was no difference in median OS between groups (25.0 vs 27.8 months, p = 0.095). For patients undergoing conversion, post-operative outcomes and long-term survival were similar when compared to a propensity-matched group of patients undergoing planned open resection. On multivariable analysis, treatment at an academic facility (OR 0.63) and a robotic approach (OR 0.50) were both significantly associated with completed MIDP., Conclusion: Despite inferior post-operative outcomes compared to successful MIDP, unplanned conversion did not result in significantly reduced long term survival. MIDP can be attempted selectively but treatment at experienced centers via a robotic approach should be considered., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Although neoadjuvant therapy is increasingly administered to patients with pancreatic ductal adenocarcinoma (PDAC), the impact of additional adjuvant therapy (AT) following resection is not well defined., Methods: The National Cancer Database (NCDB) was queried for patients who received neoadjuvant therapy followed by R0 or R1 resection for PDAC. Factors influencing survival, including the receipt of AT were evaluated., Results: Of patients receiving neoadjuvant therapy and resection 680 (33.8%) received AT and 1331 (66.2%) did not. For R0 resected patients (n = 1800), lymphovascular invasion (HR 1.24, p = 0.034) and increasing N classification (N1: HR 1.27, p = 0.019; N2: HR 1.51, p = 0.004) were associated with increased risk of death while AT was not associated with improved overall survival (OS) (HR 0.88, p = 0.179). Following R1 resection (n = 211), AT was associated with reduced risk of death (HR 0.57, p = 0.038). Within propensity matched cohorts, median OS for patients receiving and not receiving AT was 32.1 and 30.0 months after R0 resection (p = 0.184), and 23.6 and 20.5 months after R1 resection (p = 0.005)., Conclusion: This analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection., Competing Interests: Conflicts of interest None to declare., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The "classic" CT appearance of pancreatic neuroendocrine tumors (PNETs) is a solid, hypervascular lesion; however, non-PNET diagnoses may appear similar. In addition, some PNETs have a "non-classic" appearance., Methods: Demographic, imaging, endoscopic ultrasound-fine needle aspiration (EUS/FNA) results, and pathology data were analyzed for patients who underwent pancreatectomy for suspected or confirmed diagnosis of PNET from our institutional database., Results: Forty-three patients with a hypervascular lesion on CT had pancreatectomy for a pre-operative diagnosis of PNET. Final pathology revealed PNET in 30 (70%) and non-PNET diagnoses in 13 (30%). EUS/FNA had a sensitivity of 82% for the pre-operative diagnosis of PNET in patients with "classic" CT. Of 13 non-PNET diagnoses, 7 were benign. Among a total of 41 patients with a final diagnosis of PNET, 11 (27%) had "non-classic" CT (5 hypodense solid lesions, 3 isodense solid lesions, and 3 cystic lesions). Among these patients, EUS/FNA had a sensitivity of 100% in diagnosing PNET., Conclusions: Consideration of non-PNET diagnoses is important for patients with hypervascular lesions on CT. Appropriate pre-operative evaluation will optimize treatment plans., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pancreatic cancer is a complex disease accounting for fibrotic tumors and an aggressive phenotype. Gemcitabine (GEM) is used as a standard therapy, which develops chemoresistance leading to poor patient outcome. We have recently developed a superparamagnetic iron oxide nanoparticle (SPION) formulation of curcumin (SP-CUR), which is a nontoxic, bioactive anti-inflammatory/anti-cancer agent for its enhanced delivery in tumors. In this study, we demonstrate that SP-CUR effectively delivers bioactive curcumin to pancreatic tumors, simultaneously enhances GEM uptake and its efficacy. Mechanistic revelations suggest that SP-CUR targets tumor microenvironment via suppression of sonic hedgehog (SHH) pathway and an oncogenic CXCR4/CXCL12 signaling axis that inhibits bidirectional tumor-stromal cells interaction. Increased GEM uptake was observed due to upregulation of the human nucleoside transporter genes (DCK, hCNT) and blocking ribonucleotide reductase subunits (RRM1/RRM2). Additionally, co-treatment of SP-CUR and GEM targets cancer stem cells by regulating pluripotency maintaining stemness factors (Nanog, Sox2, c-Myc and Oct-4), and restricting tumor sphere formation. In an orthotopic mouse model, an enhanced accumulation of SP-CUR was found in pancreas, which potentiated GEM to reduce tumor growth and metastasis. Analysis of tumor tissues suggest that the treatment inhibits tumor stroma (α-SMA, Desmin and Hyluronic Acid) and induces changes in cell stiffness, as measured via Atomic Force Microscopy. This was accompanied by alteration of key cellular proteins of SHH signaling such as SHH, Gli-1, Gli-2, Sufu, and NFĸB-65 as indicated by Immunoblotting and Immunohistochemistry. These results suggest that SP-CUR has a great potential for future clinical use in the management of pancreatic cancer., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Intraductal papillary mucinous neoplasms (IPMN) are currently managed based on imaging characteristics and cyst fluid sampling. This study was designed to determine if MUC13, a glycoprotein aberrantly overexpressed in pancreatic adenocarcinoma, might aid in distinguishing high-risk lesions (high grade dysplasia/invasive disease) from low-grade lesions., Methods: MUC13 immunohistochemical staining was performed on surgically resected formalin-fixed tissue specimens from 49 IPMNs and 23 non-mucinous cysts. Membranous MUC13 expression was measured by H-score, which quantifies staining intensity and the percentage of cells involved (range 0-300)., Results: MUC13 expression was detected in all IPMNs and was significantly greater than in non-mucinous cysts (median 210 vs 40, p < 0.001). MUC13 expression was similar among main (n = 26), branch (n = 15), and mixed (n = 8) duct lesions (median 210, 200, 225, respectively). The highest expression was observed in tumors with intestinal and pancreatobiliary histologic features (both median 225) and the lowest in gastric type lesions (median 200). MUC13 expression was significantly greater in high-risk lesions (n = 21) compared to those with low-grade dysplasia (n = 28) (median 250 vs 195, p < 0.001)., Conclusion: MUC13 expression was significantly greater in high-risk IPMNs in this analysis. The preoperative assessment of MUC13 in cyst fluid samples warrants further investigation., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Minimally invasive pancreatic resection (MIPR) is being increasingly utilized. Outcomes for patients experiencing unplanned conversion to an open procedure during MIPR have been incompletely assessed. We sought to determine the short-term outcomes and factors associated with unplanned conversion during MIPR., Methods: A retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program pancreatectomy-targeted data set was conducted. Successful MIPR was compared with unplanned conversion. Propensity matching was used to separately compare unplanned conversion during MIPR with planned open pancreatectomy., Results: Unplanned conversion occurred in 24.6% of 350 attempted minimally invasive pancreatoduodenectomy (MIPD) and 19.6% of 1174 attempted minimally invasive distal pancreatectomy (MIDP). Conversion was associated with greater overall morbidity and 30-day mortality compared with successful MIPR for both MIPD and MIDP. After matching, unplanned conversion resulted in outcomes equivalent or inferior to open pancreatectomy. Factors significantly associated with unplanned conversion during MIPD included intermediate gland texture, vascular resection, hypertension, disseminated cancer, and chronic steroid use. For MIDP, male sex, hard gland texture, vascular resection, smoking, and recent weight loss were independently associated with conversion. A robotic approach was inversely associated with conversion for MIPD and MIDP., Conclusions: Unplanned conversion during MIPR is associated with greater morbidity and 30-day mortality. Conversion resulted in outcomes that, at best, mimicked those of open pancreatectomy. Several risk factors including the need for vascular resection are associated with unplanned conversion and should be acknowledged when planning an operative approach., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa., Methods: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses., Results: MUC13 expression was detected in 100% pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS = 5.8; AUC >0.8, P < 0.0001), 94.6% of pancreatic ductal adenocarcinoma (PDAC) samples (MCS = 9.7, P < 0.0001) as compared to low expression in tumor adjacent tissues (MCS = 4, P < 0.001) along with faint or no expression in normal pancreatic tissues (MCS = 0.8; AUC >0.8; P < 0.0001). Nuclear MUC13 expression positively correlated with nodal metastasis (P < 0.05), invasion of cancer to peripheral tissues (P < 0.5) and poor patient survival (P < 0.05; prognostic AUC = 0.9). Submicron scale mass density and artificial intelligence based algorithm analyses also elucidated association of MUC13 with greater morphological disorder (P < 0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and poor patient survival., Conclusion: This study provides significant information regarding MUC13 expression/subcellular localization in PanCa samples and supporting the use anti-MUC13 MAb for the development of PanCa diagnostic/prognostic test., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)