scholarly journals Establishing a Living Biobank of Patient-Derived Organoids of Intraductal Papillary Mucinous Neoplasms of the Pancreas

2020 ◽  
Author(s):  
Francisca Beato ◽  
Dayana Reverón ◽  
Kaleena B. Dezsi ◽  
Antonio Ortiz ◽  
Joseph O. Johnson ◽  
...  

AbstractPancreatic cancer (PaCa) is the third leading cause of cancer-related deaths in the United States. There is an unmet need to develop strategies to detect PaCa at an early, operable stage and prevent its progression. Intraductal papillary mucinous neoplasms (IPMNs) are cystic PaCa precursors that comprise nearly 50% of pancreatic cysts detected incidentally via cross-sectional imaging. Since IPMNs can progress from low- and moderate-grade dysplasia to high-grade dysplasia and invasion, the study of these lesions offers a prime opportunity to develop early detection and prevention strategies. Organoids are an ideal preclinical platform to study IPMNs, and the objective of the current investigation was to establish a living biobank of patient-derived organoids (PDO) from IPMNs. IPMN tumors and adjacent normal pancreatic tissues were successfully harvested from 15 patients with IPMNs undergoing pancreatic surgical resection at Moffitt Cancer Center & Research Institute (Tampa, FL) between May of 2017 and March of 2019. Organoid cultures were also generated from cryopreserved tissues. Organoid count and size were determined over time by both Image-Pro Premier 3D Version 9.1 digital platform and Matlab application of a Circular Hough Transform algorithm, and histologic and genomic characterization of a subset of the organoids was performed using immunohistochemistry and targeted sequencing, respectively. The success rates for organoid generation from IPMN tumor and adjacent normal pancreatic tissues were 81% and 87%, respectively. IPMN organoids derived from different epithelial subtypes showed different morphologies in vitro, and organoids recapitulated histologic and genomic characteristics of the parental IPMN tumor. In summary, this pre-clinical model has the potential to provide new opportunities to unveil mechanisms of IPMN progression to invasion and to shed insight into novel biomarkers for early detection and targets for chemoprevention.

Diagnostics ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 18 ◽  
Author(s):  
Atsushi Kanno ◽  
Atsushi Masamune ◽  
Keiji Hanada ◽  
Masataka Kikuyama ◽  
Masayuki Kitano

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. PDAC is the fourth leading cause of death in the United States and Japan based on epidemiological data. Early detection of PDAC is very important to improve the prognosis of PDAC. Early detection of pancreatic ductal adenocarcinoma (PDAC) requires further examination after selecting cases with risk factors for the condition, such as family history, hereditary pancreatic carcinoma syndrome, intraductal papillary mucinous neoplasms, or chronic pancreatitis. The Japan Study Group on the Early Detection of Pancreatic Cancer has investigated and clarified the clinicopathological features for the early diagnosis of PDAC. In Japan, an algorithm for the early diagnosis of PDAC, which utilized the cooperation of local clinics and regional general hospitals, has been a breakthrough in the detection of early-stage PDAC. Further approaches for the early diagnosis of PDAC are warranted.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Koen de Jong ◽  
Marco J. Bruno ◽  
Paul Fockens

Although little is known on the true prevalence of pancreatic cysts, physicians are currently more frequently confronted with pancreatic cysts because of the increasing use of sophisticated cross-sectional abdominal imaging. Cystic lesions of the pancreas comprise of a heterogeneous group of diagnostic entities, some of which are benign such as inflammatory pseudocysts or serous cystadenomas and do not require resection when asymptomatic. Others like mucinous cysts or intraductal papillary mucinous neoplasms (IPMN) have a malignant potential and in these cases surgical resection is often indicated. For this reason an adequate distinction between the various cysts is crucial to optimize management strategy. Different diagnostic methods that could be of value in the differentiation include radiologic imaging techniques such as CT, MR, and endosonography. In addition, fluid aspiration for cytopathology, tumormarkers or molecular analysis is widely used. Different guidelines are available but so far no optimal diagnostic algorithm exists. We summarize the epidemiology, classification, clinical presentation, diagnostics, management, and future perspectives.


2017 ◽  
Vol 35 (34) ◽  
pp. 3800-3806 ◽  
Author(s):  
Christopher P. Childers ◽  
Kimberly K. Childers ◽  
Melinda Maggard-Gibbons ◽  
James Macinko

Purpose In the United States, 3.8 million women have a history of breast (BC) or ovarian cancer (OC). Up to 15% of cases are attributable to heritable mutations, which, if identified, provide critical knowledge for treatment and preventive care. It is unknown how many patients who are at high risk for these mutations have not been tested and how rates vary by risk criteria. Methods We used pooled cross-sectional data from three Cancer Control Modules (2005, 2010, 2015) of the National Health Interview Survey, a national in-person household interview survey. Eligible patients were adult females with a history of BC and/or OC meeting select 2017 National Comprehensive Cancer Network eligibility criteria on the basis of age of diagnosis and family history. Outcomes included the proportion of individuals reporting a history of discussing genetic testing with a health professional, being advised to undergo genetic testing, or undergoing genetic testing for BC or OC. Results Of 47,218 women, 2.7% had a BC history and 0.4% had an OC history. For BC, 35.6% met one or more select eligibility criteria; of those, 29.0% discussed, 20.2% were advised to undergo, and 15.3% underwent genetic testing. Testing rates for individual eligibility criteria ranged from 6.2% (relative with OC) to 18.2% (diagnosis ≤ 45 years of age). For OC, 15.1% discussed, 13.1% were advised to undergo, and 10.5% underwent testing. Using only four BC eligibility criteria and all patients with OC, an estimated 1.2 to 1.3 million individuals failed to receive testing. Conclusion Fewer than one in five individuals with a history of BC or OC meeting select National Cancer Comprehensive Network criteria have undergone genetic testing. Most have never discussed testing with a health care provider. Large national efforts are warranted to address this unmet need.


2019 ◽  
Vol 43 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Davide Ausili ◽  
Claudio Barbaranelli ◽  
Barbara Riegel

Measuring self-care behaviors is crucial in diabetes research worldwide. Having a common measure of self-care represents an unmet need limiting the development of the science. The Self-Care of Diabetes Inventory was developed to address limitations of previous tools that were not theoretically grounded, strong in psychometrics, and clinically validated. However, the generalizability and comparability of the Self-Care of Diabetes Inventory has not been tested across cultures and languages. The aim of this study was to test the invariance of the Self-Care of Diabetes Inventory measurement model between Italy and the United States. Data from two multicenter cross-sectional studies were used. Two diabetes clinics and two hospitals in Italy and the United States were involved. We enrolled 200 adults in Italy and 226 in the United States, all with a confirmed diagnosis of type 1 or type 2 diabetes. The Self-Care of Diabetes Inventory was used to measure self-care maintenance, monitoring, and management behaviors as described in the middle range theory of self-care of chronic illness. Configural, metric, scalar, and strict invariance were tested for each scale. Three of the four measurement equivalence levels were supported in the three Self-Care of Diabetes Inventory Scales, whereas strict invariance—the highest level—was reached only by the Self-Care Maintenance and Self-Care Monitoring Scales. Clear support for the use of the Self-Care of Diabetes Inventory in diabetes research was provided. Cross-national comparisons of self-care between groups of Italian and U.S. patients are supported, based on the invariance of the measurement model. Aggregation of research data obtained using the Self-Care of Diabetes Inventory across countries could support knowledge development in the field of diabetes self-care.


2019 ◽  
Vol 28 (4) ◽  
pp. 495-501 ◽  
Author(s):  
Filipe Vilas-Boas ◽  
Guilherme Macedo

Pancreatic cystic lesions are very prevalent, especially in elderly patients and are increasingly being diagnosed because of the massive use of cross sectional imaging. Our knowledge about the natural history of these lesions is limited, especially in the case of intraductal papillary mucinous neoplasms. This fact explains why scientific societies guidelines statements are based on evidence graded as very low quality and helps the understanding of some of the different guidelines recommendations. Several guidelines have been recently revised to incorporate the new evidence published in the literature with the aim to help clinicians make the best decisions. American Gastroenterological Association guidelines, a revision of the International Consensus Guidelines, the American College of Gastroenterology and the European Study Group guidelines are the most recent. Herein we review the current guidelines on pancreatic cysts and focus our discussion on controversies and updates about the best imaging modalities, the indications for endoscopic ultrasound guided fine needle aspiration, cyst fluid analysis, indications for resection and surveillance strategies.


Endoscopy ◽  
2013 ◽  
Vol 46 (01) ◽  
pp. 22-29 ◽  
Author(s):  
Ken Kamata ◽  
Masayuki Kitano ◽  
Masatoshi Kudo ◽  
Hiroki Sakamoto ◽  
Kumpei Kadosaka ◽  
...  

2018 ◽  
Vol 1 (1) ◽  
pp. 106-119
Author(s):  
Griffin McNamara ◽  
Karla Ali ◽  
Shraddha Vyas ◽  
Tri Huynh ◽  
Monica Nyland ◽  
...  

Pancreatic cancer (PC), a leading cause of cancer-related deaths in the United States, is typically diagnosed at an advanced stage. To improve survival, there is an unmet need to detect pre-malignant lesions and early invasive disease. Prime populations to study for early detection efforts include cohorts of high risk individuals (HRI): those with increased risk to develop pre-malignant pancreatic cysts and PC because of a familial or hereditary predisposition to the disease and those in the general population of sporadic cases who are incidentally found to harbor a pre-malignant pancreatic cyst. The objective of this study was to describe the characteristics and clinical outcomes of cohorts of HRI identified at Moffitt Cancer Center. We set out to determine the uptake of screening, the prevalence and characteristics of solid and cystic pancreatic lesions detected via screening or as incidental findings, and the age at which lesions were detected. Of a total of 329 HRI, roughly one-third were found to have pancreatic lesions, most of which constituted pre-malignant cysts known as intraductal papillary mucinous neoplasms. Individuals with the highest genetic risk for PC were found to have smaller cysts at a much earlier age than sporadic cases with incidental findings; however, many individuals at high genetic risk did not have abdominal imaging reports on file. We also identified a subset of HRI at moderate genetic risk for PC that were found to have cystic and solid pancreatic lesions as part of a diagnostic work-up rather than a screening protocol. These findings suggest the pancreatic research community should consider expanding criteria for who should be offered screening. We also emphasize the importance of continuity of care between cancer genetics and gastrointestinal oncology clinics so that HRI are made aware of the opportunities related to genetic counseling, genetic testing, and screening.


2021 ◽  
Vol 19 (2) ◽  
Author(s):  
Youssef A. Alqahtani ◽  
Ayed A. Shati ◽  
Ahmad A. Alhanshani ◽  
Bayan M. Hanif ◽  
Eman S. Salem ◽  
...  

Background: Food allergy (FA) is increasingly recognized with the highest prevalence in preschool children; there has been a significant increase in hospital admissions for systemic allergic diseases with anaphylaxis and food allergies. Hospital admissions for food allergy were noticed to rise from 6 to 41 per million between 1990 and 2000 worldwide . The prevalence of food allergy is increasing over time with significant geographic variations. It is estimated to affect 6% of children in the United States (USA); according to a study conducted in Makkah, by AL Mokarmah, the prevalence of FA among children attending the well-baby clinic was 22.5% and in Riyadh is 6% among children who visit the allergy clinic at King Khalid University Hospital. FA in children is usually caused by milk (2.5%), egg (1.3%), peanut (0.8%), tree nuts (0.2%), fish (0.1%), as well as shellfish (0.1%), with an overall prevalence of 6%. Methods: In this cross-sectional study, a self-administered questionnaire was used in the data collection. After data were collected, they were entered in the Statistical Software IBM SPSS version 22. Descriptive and inferential statistics were obtained. Results: Out of 980 mothers, 49% were suffering from food allergy, while 28.6% of their children were suffering from food allergy. Shellfish was the most common cause of food allergy (38%). Conclusion: The management of FA in children is improving through the acquisition of new knowledge in diagnosis and treatment. Education of physicians and food-allergic patients about FA and its treatment is becoming recognized as an unmet need. Key words: Food allergy, mother, children, knowledge, prevalence, factors


2016 ◽  
Vol 24 (1) ◽  
pp. 145-152 ◽  
Author(s):  
David L Masica ◽  
Marco Dal Molin ◽  
Christopher L Wolfgang ◽  
Tyler Tomita ◽  
Mohammad R Ostovaneh ◽  
...  

Objective: Our objective was to develop an approach for selecting combinatorial markers of pathology from diverse clinical data types. We demonstrate this approach on the problem of pancreatic cyst classification. Materials and Methods: We analyzed 1026 patients with surgically resected pancreatic cysts, comprising 584 intraductal papillary mucinous neoplasms, 332 serous cystadenomas, 78 mucinous cystic neoplasms, and 42 solid-pseudopapillary neoplasms. To derive optimal markers for cyst classification from the preoperative clinical and radiological data, we developed a statistical approach for combining any number of categorical, dichotomous, or continuous-valued clinical parameters into individual predictors of pathology. The approach is unbiased and statistically rigorous. Millions of feature combinations were tested using 10-fold cross-validation, and the most informative features were validated in an independent cohort of 130 patients with surgically resected pancreatic cysts. Results: We identified combinatorial clinical markers that classified serous cystadenomas with 95% sensitivity and 83% specificity; solid-pseudopapillary neoplasms with 89% sensitivity and 86% specificity; mucinous cystic neoplasms with 91% sensitivity and 83% specificity; and intraductal papillary mucinous neoplasms with 94% sensitivity and 90% specificity. No individual features were as accurate as the combination markers. We further validated these combinatorial markers on an independent cohort of 130 pancreatic cysts, and achieved high and well-balanced accuracies. Overall sensitivity and specificity for identifying patients requiring surgical resection was 84% and 81%, respectively. Conclusions: Our approach identified combinatorial markers for pancreatic cyst classification that had improved performance relative to the individual features they comprise. In principle, this approach can be applied to any clinical dataset comprising dichotomous, categorical, and continuous-valued parameters.


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