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Contrast-enhanced endoscopic ultrasound for differentially diagnosing autoimmune pancreatitis and pancreatic cancerBackground/Aims: Differentially diagnosing focal-type autoimmune pancreatitis (f-AIP) and pancreatic cancer (PC) is challenging. Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) may provide information for differentiating pancreatic masses. In this study, we evaluated the usefulness of CEH-EUS in differentiating f-AIP from PC. Methods: Data were collected prospectively and analyzed on patients who underwent CEH-EUS between May 2014 and May 2015. Eighty consecutive patients were diagnosed with f-AIP or PC. PC and f-AIP were compared for enhancement intensity, contrast agent distribution, and internal vasculature. Results: The study group comprised 53 PC patients and 27 f-AIP patients (17 with type-1 AIP [15 definite and two probable], two with probable type-2 AIP, and eight with AIP, not otherwise specified). Hyper- to iso-enhancement in the arterial phase (f-AIP, 89% vs PC, 13%; p<0.05), homogeneous contrast agent distribution (f-AIP, 81% vs PC, 17%; p<0.05), and absent irregular internal vessels (f-AIP, 85% vs PC, 30%; p<0.05) were observed more frequently in the f-AIP group. The combination of CEH-EUS and enhancement intensity, absent irregular internal vessels improved the specificity (94%) in differentiating f-AIP from PC. Conclusions: CEH-EUS may be a useful noninvasive modality for differentially diagnosing f-AIP and PC. Combined CEH-EUS findings could improve the specificity of CEH-EUS in differentiating f-AIP from PC. Copyright 2018 Editorial Office of Gut and Liver. All rights reserved.
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Use and assessment of a Palliative Care Nurse Practitioner on a Pancreatic Cancer Web SitePatients with pancreatic cancer and their families struggle with physical and emotional issues. They could benefit from palliative care services, but may not have access to them. The Internet has become an important source of health information and a link between patients, families and health care providers. The purpose of this capstone project was to 1) determine if patients and their families would use a Web page where they could access a palliative care nurse practitioner (PCNP); 2) to identify the palliative care needs of the patients and families who accessed the PCNP; and 3) to determine the helpfulness of the Web page. Participants were recruited to the PCNP Web page from the Johns Hopkins Pancreatic Cancer Research Center’s (JHPCRC) Web site. A mixed method design was used to determine 1) the volume of participation with the PCNP Web page, 2) patient and family member needs, and 3) the usefulness of the Web page. Participants could post their questions to the public comments section of the PCNP Web or send the PCNP a private email. There also was a link to an online survey to gather demographic and evaluative information. The PCNP Web page was visited 650 times by 395 unique individuals over an 8-week period. Participants spent an average of 4 minutes and 4 seconds on the PCNP Web page. Half, 49%, came from a link posted on the discussion board of the JHPCRC Web site. Forty-eight participants posted a total of 55 questions or sent individual emails to the PCNP. The majority were from female family members of patients with pancreatic cancer. The majority of questions (66%) fell into one of the eight domains of palliative care. Of these, most of the questions, 42%, asked about physical aspects of pancreatic cancer with the next largest domain, 11%, being psychological concerns about the illness and the risks of developing it. The other third of questions had to do with non-palliative aspects of pancreatic cancer and its treatment. Twenty participants (5% of total visitors) completed the online survey. Most survey respondents were female, family members, middle-aged, white, and college-educated. Although statistical significance was not achieved, most survey respondents found the PCNP website helpful. It was considered easy to use and participants found information and support there and recommended that the PCNP page should be an on-going resource. Access to a PCNP is an important resource for patients with pancreatic cancer and their family members. The Internet can be used to offer information, support and advice to patients and families dealing with a life-threatening illness.
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Water Soluble Polymer Drug Therapies for Targeted Delivery to Pancreatic CancerCurrent therapies of advanced staged pancreatic cancer are limited by poor response and high toxicity of chemotherapeutics. As the molecular basis of pancreatic cancer has become better understood the need for a targeted therapy could help provide an increase in therapeutic response while also limiting side effects. N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer drug conjugates have demonstrated their potential use as carriers of small molecule drugs to improve cancer therapies. The overall goal of this research was to develop a polymer peptide drug conjugate based on HPMA copolymers, which can increase the therapeutic index of pancreatic cancer chemotherapy. Previous investigation of the uMUC1 receptor, which is a glycoprotein overexpressed on the surface of pancreatic tumors, has lead to the development of EPPT1, a small peptide has been found to have a strong binding affinity to uMUC1, (Kd=20uM). Our hypothesis HPMA copolymer with an active target EPPT1 to the uMUC1 receptor will enhance therapeutic action of a cancer chemotherapeutic drug such as gemcitabine. In this study, we were successful in the synthesis and characterization of a series of HPMA copolymer-EPPT1-Gemcitabine conjugates. Using model pancreatic cancer cell lines, the binding efficiency, internalization and mechanisms of cellular uptake were evaluated with polymer EPPT1 conjugates. Polymer gemcitabine conjugates were evaluated for efficacy against free gemcitabine. The optimized polymer peptide drug conjugates were evaluated for efficacy and drug release. Results during synthesis and characterization indicated that copolymer yield, solubility and performance were influenced by each incorporation of peptide and drug. Flow cytomentry determined that polymer peptide conjugates were able to bind with Capan-2 and Panc-1 cell lines. Confocal microscopy verified that polymer peptide conjugates were not only getting internalized into the cytoplasm but also routing to the lysosome. Using endocytosis inhibitors, confirmed that polymer peptide conjugates use clathrin mediated endocytosis pathways when getting internalized into the cell. Drug release studies revealed that gemcitabine will detached from the polymer in lysosomal conditions. Polymer drug conjugates compared to free gemcitabine alone against pancreatic cancer cells in MTT assay had equal efficacy. Attachment of the active targeting moiety EPPT1, exhibited that polymer peptide drug conjugates were superior in killing cells to free gemcitabine alone.
