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The potential of artificial intelligence (AI) applied to clinical data from electronic health records (EHRs) to improve early detection for pancreatic and other cancers remains underexplored. The Kenner Family Research Fund, in collaboration with the Cancer Biomarker Research Group at the National Cancer Institute, organized the workshop entitled: "Early Detection of Pancreatic Cancer: Opportunities and Challenges in Utilizing Electronic Health Records (EHR)" in March 2021. The workshop included a select group of panelists with expertise in pancreatic cancer, EHR data mining, and AI-based modeling. This review article reflects the findings from the workshop and assesses the feasibility of AI-based data extraction and modeling applied to EHRs. It highlights the increasing role of data sharing networks and common data models in improving the secondary use of EHR data. Current efforts using EHR data for AI-based modeling to enhance early detection of pancreatic cancer show promise. Specific challenges (biology, limited data, standards, compatibility, legal, quality, AI chasm, incentives) are identified, with mitigation strategies summarized and next steps identified.

The superior longitudinal fasciculus (SLF) is a complex associative tract comprising of three distinct subdivisions in the fronto-parietal cortex, each presenting different anatomical connectivity and different functional roles. However, the subdivision of SLF was hampered by limitations of data quality and tractography methods, and many studies on white matter development often consider the SLF as a single entity. The exact anatomical trajectory and developmental status of each sub-bundle of the human SLF in neonatal period remain poorly understood. In this work, we investigated the morphological characteristics and maturation degree of SLF each branch using the diffusion MRI (dMRI) data of 40 healthy term neonates from the Developing Human Connectome Project (dHCP) database. An advanced single shell 3-tissue constrained spherical deconvolution (SS3T-CSD) algorithm was used to ensure the successful separation of the SLF three branches (SLF I, SLF II and SLF III). In addition, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters values of the three subcomponents of SLF were measured quantitatively. The fiber morphology and connectivity of SLF sub-bundles in neonatal brain were nicely revealed in our study. Furthermore, the comparison results of parameters values supported that the maturation of SLF three segments was heterochronic. Further multiple comparison results indicated that the dorsal SLF II was less mature than the ventral SLF III and the former may involve in higher-level cognitive functions. Our findings can provide new anatomical basis for early diagnosis and treatment of related diseases caused by aberrant development of SLF.

Despite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are mostly nonspecific. The premise of improved survival through early detection is that more individuals will benefit from potentially curative treatment. Artificial intelligence (AI) methodology has emerged as a successful tool for risk stratification and identification in general health care. In response to the maturity of AI, Kenner Family Research Fund conducted the 2020 AI and Early Detection of Pancreatic Cancer Virtual Summit (www.pdac-virtualsummit.org) in conjunction with the American Pancreatic Association, with a focus on the potential of AI to advance early detection efforts in this disease. This comprehensive presummit article was prepared based on information provided by each of the interdisciplinary participants on one of the 5 following topics: Progress, Problems, and Prospects for Early Detection; AI and Machine Learning; AI and Pancreatic Cancer-Current Efforts; Collaborative Opportunities; and Moving Forward-Reflections from Government, Industry, and Advocacy. The outcome from the robust Summit conversations, to be presented in a future white paper, indicate that significant progress must be the result of strategic collaboration among investigators and institutions from multidisciplinary backgrounds, supported by committed funders.

ImportanceThe outbreak of highly contagious COVID-19 has posed a serious threat to human health, especially for those with underlying diseases. However, Impacts of COVID-19 epidemic on HD center and HD patients have not been reported.ObjectiveTo summery an outbreak of COVID-19 epidemic in HD center.Design, Setting, and ParticipantsWe reviewed the epidemic course from the first laboratory-confirmed case of COVID-19 infection on January 14 to the control of the epidemic on March 12 in the HD center of Renmin Hospital of Wuhan University. Total 230 HD patients and 33 medical staff were included in this studyExposuresCOVID-19.Main Outcomes and MeasuresEpidemiological, clinical, laboratory, and radiological characteristics and outcomes data were collected and analyzed. 19 COVID-19 HD patients, 19 non-COVID-19 HD patients and 19 healthy volunteers were enrolled for further study about the effect of SARS-CoV-2 infection on host immune responses.Results42 out of 230 HD patients (18.26%) and 4 out of 33 medical staffs (12.12%) were diagnosed with COVID-19 from the outbreak to March 12, 2020. 13 HD patients (5.65%), including 10 COVID-19 diagnosed, died during the epidemic. Only 2 deaths of the COVID-19 HD patients were associated with pneumonia/lung failure. Except 3 patients were admitted to ICU for severe condition (8.11%), including 2 dead, most COVID-19 diagnosed patients presented mild or none-respiratory symptoms. Multiple lymphocyte populations in HD patients were significantly decreased. HD patients with COVID-19 even displayed more remarkable reduction of serum inflammatory cytokines than other COVID-19 patients.Conclusions and RelevanceHD patients are the highly susceptible population and HD centers are high risk area during the outbreak of COVID-19 epidemic. HD Patients with COVID-19 are mostly clinical mild and unlikely progress to severe pneumonia due to the impaired cellular immune function and incapability of mounting cytokines storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of COVID-19 epidemic on HD patients.

Oral squamous cell carcinomas (OC) are life-threatening diseases emerging as major international health concerns. Development of an efficient clinical strategy for early diagnosis of the disease is a key for reducing the death rate. Biomarkers are proven to be an effective approach for clinical diagnosis of cancer. Although mechanisms underlying regulation of oral malignancy are still unclear, microRNAs (miRNAs) as a group of small non-coded RNAs may be developed as the effective biomarkers used for early detection of oral cancer. A literature search was conducted using the databases of PubMed, Web of Science, and the Cochrane Library. The following search terms were used: miRNAs and oral cancer or oral carcinoma. A critical appraisal of the included studies was performed with upregulated miRNAs and downregulated miRNAs in oral cancer. In this review, we summarize the research progress made in miRNAs for diagnosis of oral cancer. The involvement of miRNAs identified in signal transduction pathways in OC, including Ras/MAPK signaling, PI3K/AKT signaling, JAK/STAT signaling, Wnt/β-catenin signaling, Notch signaling, and TGF-β/SMAD signaling pathway. A number of studies demonstrated that miRNAs may be developed as an ideal set of biomarkers used for early diagnosis and prognosis of cancers because of the stability in human peripheral blood and body fluids and availability of non-invasive approaches being developed for clinical utility. Clinical relevance: These findings suggest that miRNAs as biomarkers may be useful for diagnosis of OC.

We describe a rare and unique case of extramammary Paget disease in the genitals with concomitant histological features of herpes virus infection. This is a very rare and interesting association that has only been reported in 1 article in the literature so far.

A diagnosis of pancreatic cancer is devastating owing to its poor prognosis, with a 5-year survival rate of only 9%. Currently, most individuals are diagnosed at a late stage when treatment options are limited. Early detection of pancreatic cancer provides the greatest hope for making substantial improvements in survival. The Kenner Family Research Fund in partnership with the American Pancreatic Association has sponsored a series of fora to stimulate discussion and collaboration on early detection of pancreatic cancer. At the first forum in 2014, "Early Detection of Sporadic Pancreatic Cancer Summit Conference," a strategic plan was set forth by an international group of interdisciplinary scientific representatives and subsequently The Strategic Map for Innovation was generated. The current conference report is the third forum in the series, "Early Detection of Pancreatic Cancer: The Role of Industry in the Development of Biomarkers," which was held in Boston, Massachusetts, on October 27, 2016. This report provides an overview of examples of innovative initiatives by industry and confirms the critical need for collaboration among industry, government, research institutions, and advocacy groups in order to make pancreatic cancer more easily detectable in its earlier stages, when it is more treatable.

The implementation of effective early detection programs has significantly improved treatment, prognosis, and life expectancy in breast, prostate, and colorectal cancers. Early-detection methods need to be developed for pancreatic ductal adenocarcinoma (PDAC), where progress during the past decades has remained slow. Addressing this need, the forum “Early Detection: Lessons Learned from Other Cancers” was held in November 2015 and presented by the Kenner Family Research Fund in partnership with the American Pancreatic Association. Leading experts from breast, prostate, and colorectal cancers described the development of early detection methods in their respective fields. Emerging opportunities for scientific advancement were subsequently identified that hold the greatest promise for the future of early detection in PDAC, including a 4-part strategic map of necessary actionable items. Knowledge from other fields must be applied to achieve large-scale change within the arena of PDAC. A major breakthrough in early detection of PDAC will occur only through a definitive interdisciplinary collaborative effort involving a critical mass of committed academic research institutions, government agencies, industry leaders, and philanthropies.

This paper aimed to assess the physiological effects of p53 on glucose homeostasis in vivo.A recombinant adenoviral p53 (rAd-p53) vector was administered to insulin-resistant diabetic mice. Intraperitoneal glucose tolerance test was performed in all groups of mice. Changes in fasting blood glucose, serum triglycerides, C-peptide, and insulin concentrations in treated and untreated mice were measured. Analyses of the target genes related to glucose metabolism were performed.Treatment with the rAd-p53 improved glucose control in a dose- and time-dependent manner and lowered significantly the fasting blood glucose, the serum triglycerides, and improved tolerance test of glucose as compared to control. Lowered blood glucose was associated with up-regulation of genes in the glycogenesis pathways, and down-regulation of genes in the gluconeogenesis pathways in the liver. Overexpressions of GLUT2, GK, PPAR-γ, and insulin receptor precursor were also observed in the liver and the pancreas of treated animals.Activation of p53-mediated glucose metabolism led to insulin-like antidiabetic effect in the mouse model especially by changing hepatic insulin sensitivity in the diabetic mouse model.

Obesity-related conditions including heart disease, stroke, and type 2 diabetes are leading causes of preventable death. Recent evidence suggests that altered myocellular lipid metabolism in obesity may lead to increased insulin resistance (IR) that predisposes to these disorders. To test the hypothesis that muscles rich in type I vs. type II muscle fibers would exhibit similar changes in intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) content in obesity, we utilized a new four-dimensional multi echo echo-planar correlated spectroscopic imaging technique that allows separate determination of IMCL and EMCL content in individual calf muscles in obese vs. normal healthy human subjects. Calf muscles were scanned in 32 obese and 11 healthy subjects using a 3T MRI/MRS scanner, and IR in the obese subjects was documented by glucose tolerance testing. In obese subjects, elevation of both IMCL and EMCL content was observed in the gastrocnemius and tibialis anterior muscles (with mixed type I and II fiber content), while a significant increase in only IMCL content (+48%, p

Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer.

In Chinese hospitals, each patient is checked regularly during their night time. This happens to confirm that there are no emergency situations in which a patient is in need of immediate help. Because the regular checking can be very annoying for patients who are sleeping due to noise, we are looking for a solution to solve this problem using technology. The focus lies on non-obtrusive sensing technologies and on the social relation between patient and doctor. Two prototypes were developed, tested and evaluated on their usability to monitor patients from the central nurse station without disturbing them. The first prototype consists of a piezoelectric sensor with filtering circuit which measures the heartbeats. The second consists of a capacitive sensor capable of sensing the presence of a patient in the bed. Both sensors are placed under the mattress of the patient with as a result that they are not bothered while being monitored.

The Hirshberg Foundation for Pancreatic Cancer Research was founded by Agi Hirshberg in 1997, following her husband Ronald Hirshberg’s 8-month, 7-day battle with the disease. (http://www.pancreatic.org/). At the time, the Hirshberg family viewed pancreatic cancer as the ‘‘unknown enemy’’ (http:// www.pancreatic.org/site/c.htJYJ8MPIwE/b.8276835/k.66CB/ Agi_Hirshbergs_Story.htm). In the years since Ronald Hirshberg’s death, Agi Hirshberg has made it her mission to unmask the unknown for others facing the same enemy. When patients present with a new diagnosis of pancreatic cancer, most are already in an advanced stage of the disease. Pancreatic cancer is resistant to most chemotherapeutic agents and radiotherapy. These factors combine to make pancreatic cancer a highly lethal disease, and according to the National Cancer Institute (NCI) 2013 estimates, pancreatic cancer was diagnosed in approximately 45,220 US citizens, and some 38,460 died of the disease. 1 The Annual Report to the Nation on the Status of Cancer, 1975Y2009, shows that overall cancer death rates continued to decline in the United States among both men and women, among all major racial and ethnic groups, and for all of the many common cancer sites, including lung, colon and rectum, female breast, and prostate. However, this trend does not hold true for pancreatic cancer. The report demonstrates that death rates continued to increase during the latest time period (2000 through 2009) for pancreatic cancer. 2 Only about 23% of patients with cancer of the pancreas will still be living 1 year after diagnosis, and only about 4% will survive 5 years. Even for those diagnosed with pancreatic cancer that has not spread to other organs or systems, the overall 5-year survival rate approaches only 15%. The Hirshberg Foundation’s vision is to advance pancreatic cancer research and provide information, resources, and support to pancreatic cancer patients and their families. The mission of the Foundation is as follows: & To find a cure for pancreatic cancer in honor of Ron Hirshberg and the thousands of people who are diagnosed with this disease each year. & To create a premier Pancreatic Cancer Center where all needs of pancreatic cancer patients can be met in one location with the most advanced treatment options. & To be recognized as a patient support reference source for

Background Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions. Methods and Results In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms ( P =0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P CI 1.51–1.90, P Conclusions In a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 00403767.

Scutellaria baicalensis Georgi (Chinese Skullcap) is a member of the Lamiaceae family and has been used in China and Japan for centuries to treat inflammation, respiratory, and gastrointestinal bacterial and viral infections. It is known to the Chinese as Huang-Qin and to the Japanese as Ogon and is a major component of several herbal medicine products.1 Recent studies on animal models have demonstrated that Scutellaria baicalensis (SB) or its major active constituent baicalin exhibits multiple activities against severe acute pancreatitis,2 obesity,3 metabolic disorders,4 and cancer.5, 6 The most abundant bioactive component in Scutellaria baicalensis root extract is baicalin (5, 6, 7-trihydetroxyflavone-7-β-D-glucuronide or baicalein-7-O-glucuronide; BG). Other flavones identified are wogonoside (wogonin-7-O-glucuronide; WG), oroxylin A-7-O-glucuronide (OAG) and their aglycones, baicalein (B), wogonin (W), and oroxylin A (OA)7 (Figure 1). There have been a number of pharmacokinetics studies to investigate absorption of BG and B.8–11 Akao et al compared in vivo absorption of BG and B in regular rats to that in germ-free rats and suggested that BG underwent intestinal conversion to B, which is absorbed rapidly and converted back to BG in the systemic circulation.11 An in situ absorption experiment revealed the existence of double-site absorption of BG. The first absorption site was in upper intestine and might be due to the directly absorption of BG and the second site was in colon in the form of aglygone.10 In rat plasma glucuronic acid conjugates were the predominant forms, the result of first-pass metabolism.11–14 A few recent pharmacokinetics studies identified and quantified rat plasma OA, a 6-O-methylated B.1, 15 Hou et al reported the distribution of B and W and their conjugates in the lung, liver, kidney, and brain of rats to which a decoction of SB roots at 2.0 g/4 mL/kg three times daily for 7 doses was administered via gastric gavage. We are unaware of any report of tissue absorption and distribution after long-term oral administration of SB in animal models. Figure 1 Chemical structures of major flavonoids found in Scutellaria baicalensis. Our research team has demonstrated that B induces apoptosis in human pancreatic cancer BxPC-3, HPAF-II, Panc-1 and MicPaCa-2 cell lines which is mediated through the inhibition of Mcl-1 activity.16 Furthermore, we have shown that a diet containing an extract from the root of SB inhibited the growth of pancreatic tumor xenograft in a mouse in vivo model after a long-term oral administration (unpublished data). To exert its biologic activity, BG must be sufficiently absorbed in the gastrointestinal tract and reach pharmacological concentrations in the target tissue. In order to understand how BG is absorbed and metabolized in mice, we investigated uptake of BG and presence of metabolites in pancreas and tumor tissue, and in the respiratory and gastrointestinal organs including lung, colon, small intestine, as well as in liver, kidney, and prostate in xenograft-bearing mice. In addition, we examined metabolic stability of BG in the tissues sampled.

Sympathetic hyperactivity has an important role in cardiovascular mortality in patients with type 2 diabetes (T2D). Thyrotropin-releasing hormone (TRH)-containing fibers innervate autonomic motor and premotor nuclei of the brainstem and spinal cord that regulate cardiovascular functions. We compared cardiovascular responses to application of TRH-analog in the brainstem of Wistar and T2D Goto-Kakizaki (GK) rats. GK rats exhibited basal systolic hypertension (152±2 mm Hg) and had a significantly potentiated, dose-related hypertensive response to intracisternal (i.c.) injection of the TRH-analog RX77368 (10-60 ng). In GK rats only, i.c. RX77368 (30-60 ng) markedly increased heart rate (HR; +88 b.p.m.) and induced acute cardiac mortality (100%), concurrent with extreme hyperglycemia (>26 mmol l(-1)), increased plasma H(2)O(2) and 8-isoprostane, and enhanced heart expression of NADPH oxidase 4 and vascular cell adhesion molecule-1 mRNAs. GK rats also had elevated basal plasma epinephrine, higher adrenal gene expression of tyrosine hydroxylase and dopamine β-hydroxylase (DβH), and greater plasma catecholamine and adrenal DβH responses to i.c. TRH-analog, compared with Wistar rats. In GK rats, hexamethonium blocked i.c. RX77368-induced hypertensive and tachycardic responses, and reduced mortality by 86%, whereas phentolamine abolished the hypertensive response but enhanced tachycardia (+160 b.p.m.), and reduced mortality by 50%. The angiotensin II type 1 receptor antagonist irbesartan prevented i.c. RX77368-induced increases in blood pressure, HR and mortality. In conclusion, sympathetic overactivation triggered by brainstem TRH contributes to the mechanism of cardiovascular morbidity and mortality in T2D, which involves heightened cardiac inflammation and peripheral oxidative stress responses to sympathetic drive, and a mediating role of the renin-angiotensin system.

OBJECTIVES This supplement represents the proceedings of a panel of investigators whose goal was to assess the quality of evidence pertaining to current therapeutic approaches in the management of neuroendocrine tumors (NETs). It will examine the differences in opinions between expert faculty and community physicians. METHODS The Neuroendocrine Tumors Summit convened in December 2009 to address 6 statements prepared by panel members that reflect important questions in the management of NETs. RESULTS Panel members were polled on their acceptance of each statement, and those results were compared with community-based oncologists, gastroenterologists, and endocrinologists. CONCLUSIONS More education regarding the treatment of NETs, including pertinent studies, is needed for physicians. Additional multicenter, prospective, placebo-controlled trials are necessary to demonstrate the benefits of somatostatin analogs, including their ability to control symptoms and affect tumor growth, and their synergistic effect with other therapies. New trials should be reported consistently and include time to tumor progression and progression-free survival as primary or secondary end points.

In this review, we focus on the use of biochemical markers for the diagnosis of neuroendocrine tumors and exclusion of conditions that masquerade as neuroendocrine tumors. In addition, we outline the use of biochemical markers for follow-up, response to intervention, and determination of prognosis. Previous publications have focused only on markers specific to certain tumor types, but the uniqueness of this chapter is that it presents a new approach ranging from biochemical markers that relate to symptoms to the use of markers that facilitate decision making with regard to optimizing the choices of therapy from the complex arrays of intervention, The sequence of presentation in this chapter is first to provide the usual view, that is, biochemical markers of each tumor type and thereafter the diagnosis of the underlying condition or exclusion thereof and finally the algorithm for their use from the clinical presentation to the suspected diagnosis and the biochemical markers to monitor progression and therapeutic choice. There is also a specific description of the properties of the most important biochemical markers and 2 complications, bone metastasis and carcinoid heart disease, from the biochemical point of view.

Background. Despite recent advances in cancer survivorship knowledge and care, most medical schools lack a comprehensive survivorship curriculum, potentially leaving students ill-prepared for caring of survivors. Methods. A total of 211 students and 22 oncology fellows in 3 institutions completed a questionnaire assessing knowledge and experience in survivorship care. Results. Medical students and oncology fellows lack knowledge in key survivorship issues. Students were exposed to cancer survivors frequently in medical school but only half received instruction or practiced critical components of survivorship care. Conclusions. Improvement of both undergraduate and postgraduate training in survivorship care is urgently warranted.

Although pressure therapy is the mainstay of treatment for hypertrophic scars, its actual mechanism remains unknown. An in vitro study was designed to investigate the effects of positive pressure on the growth of human scar-derived fibroblasts through its transforming growth factor beta1 (TGF-beta1) secretion. A pneumatic pressure system connecting to a cell culture chamber was designed. Six-well cultured plates with fibroblasts implanted were treated with different pressure settings. Cells were treated with constant pressure 20 mm Hg above atmosphere pressure (group A n = 18) or with 40 mm Hg above atmosphere pressure (group B n = 18) daily for nine successive days. Cells without pressure were treated as the control study (group C n = 6). Each experimental group was divided into daily pressure applied at 24 hours (n = 6), 18 hours (n = 6), and 12 hours (n = 6). Cell counting was performed on the 2nd, 4th, 7th, 9th, 11th, and 14th day after implantation. On day 4, the concentration of transforming growth factor beta1 was measured, and cell doubling time was calculated. Compared with the control group, there was a significant decrease in cell count and the concentration in the 18-hour and 24-hour 20 mm Hg or 40 mm Hg pressure treated group. The cell doubling time was significantly increased in the 24-hour 20 mm Hg or 40 mm Hg pressure treated groups, and the 18-hour 40 mm Hg pressure treated group. (P < .05) Pressure inhibits the growth and activity of human scar fibroblasts, and a higher pressure application can shorten the daily application period. There should be an optimal pressure level corresponding to a daily application period to achieve the most effective results on pressure therapy for scars.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.

Although a potential role for estrogen receptors (ER) in pancreatic tumors has been debated for many years, the importance of the receptors in these neoplasms remains unknown. Even the expression of the 2 ER isoforms, ER-alpha and ER-beta, in histological subtypes of pancreatic neoplasms is controversial. The aim of the present study was to systematically review the available literature about ER expression in pancreatic tumors and to discuss the potential importance of estrogen signaling in them.We performed a comprehensive literature search and analyzed the results regarding ER expression in pancreatic tumors, with special emphasis on the specificity of the antibodies used for immunohistochemistry.Many articles have been published investigating the expression of ERs in pancreatic tumors, but the results are inconsistent. Moreover, most studies used antibodies that detected only ER-alpha, not ER-beta. Thus, the expression pattern of ER-beta in pancreatic neoplasm remains especially unclear.The lack of detailed studies evaluating the expression of both ER-alpha and ER-beta receptors using isoform-specific antibodies likely contributes to the inconsistency of published results concerning ER expression in pancreatic tumors. Available published evidence suggests that a thorough reexamination of the potential role of ERs in pancreatic neoplasms is warranted.

The secretion of carcinoembryonic antigen-like (CEA-like) material into the gastrointestinal tract of 28 fasting normal men was quantified by using intestinal perfusion techniques. CEA-like material was recovered from all levels of the gastrointestinal tract. The highest secretory rate was in the colon (mean +/- SE, 2.41 +/- 2.0 mug/minute per colon), followed by pancreatobiliary secretion and pancreatic secretion. The secretory rate from the stomach, duodenum, jejunum, and ileum was less than 20 ng/minute. After perchloric acid extraction, the CEA-like material from the colon had the same chromatographic and radioimmunologic properties as [125I] CEA. These data suggest that the CEA-like material is normally secreted into the gastrointestinal tract and particularly into the colon.

OBJECTIVE Insulin-induced hypoglycemia activates neurons in hypothalamic and brain medullary nuclei involved in central autonomic regulation. We investigated whether these central neuronal activations relates to a deficiency of glucose supply. METHODS Three groups of non-fasted, conscious rats received intravenous (iv) saline infusion (control), a hyperinsulinemic/hypoglycemic clamp, or a hyperinsulinemic/euglycemic clamp for 120 minutes and then the brains were collected for Fos immunohistochemistry. RESULTS The number of Fos positive cells significantly increased in the paraventricular nucleus of the hypothalamus (PVN, 191 +/- 63 versus 66 +/- 18), pontine locus coeruleus (LC, 53 +/- 19 versus 5 +/- 2), brain medullary dorsal motor nucleus of the vagus (DMV, 26 +/- 4 versus 1 +/- 0), and nucleus tractus solitarii (NTS, 38 +/- 3 versus 10 +/- 35) in rats with hyperinsulinemic/hypoglycemic clamp compared with the controls. Maintaining blood glucose levels within physiological range by hyperinsulinemic/euglycemic clamp prevented insulin infusion-induced Fos expression in the PVN, DMV, and NTS. The numbers of Fos positive cells in these nuclei were significantly lower (-87%, -75%, and -51%, respectively) than that in the hypoglycemic rats. CONCLUSION These results indicate that neuronal activation in hypothalamic and medullary autonomic regulatory nuclei induced by insulin administration is caused by hypoglycemia rather than a direct action of insulin. In addition, certain neurons in the medullary DMV and NTS respond to declines in glucose levels within physiological range.

The practice of medicine, including health promotion and disease prevention, is on the verge of being revolutionized once again as the scientific and medical community transitions from evidence-based medicine to genomic medicine. Evidence-based medicine entails the systematic approach of formulating a question, developing literature search strategies, and evaluating and applying evidence to establish clinical practice guidelines. In 1982, when the National Research Council published the first comprehensive review of diet and cancer, the literature was primarily based on epidemiological studies, comparing dietary patterns between countries of low and high incidence for particular cancers. The American Institute for Cancer Research conducted an evidence-based review of the world literature and issued its first report in 1997, and the National Cancer Institute followed with evidence-based overviews of cancer prevention. The World Health Organization International Agency for Research on Cancer recently published a series of handbooks on cancer prevention in relation to dietary factors. The expert recommendations stemming from this extensive evidence subsequently influenced the clinical practice of medicine. In 2001, the complete sequencing of the human genome signified the beginning of the postgenomic era, in which new approaches and technologies are causing a shift in biomedical research. A widening understanding of the complex interactions among genotype, diet, lifestyle, and environment has evoked a change in clinical medical practice, where the evidence- and population-based protocol is evolving into a more personalized system that includes the analysis of individual genotype and phenotype. The implications of this evolution are considerable, because genomic medicine has the potential to give rise to personalized nutrition recommendations and specialized medical treatment.

BACKGROUND & AIMS: Current guidelines recommend empirical, noninvasive approaches to manage dyspeptic patients without alarm symptoms, but concerns about missed lesions persist; the cost savings afforded by noninvasive approaches must be weighed against treatment delays. We investigated the prevalence of malignancies and other serious abnormalities in patients with dyspepsia and the cost of detecting these by endoscopy. METHODS: We studied 2741 primary-care outpatients, 18-70 years in age, who met Rome II criteria for dyspepsia. Patients with alarm features (dysphagia, bleeding, weight loss, etc) were excluded. All patients underwent endoscopy. The cost and diagnostic yield of an early endoscopy strategy in all patients were compared with those of endoscopy limited to age-defined cohorts. Costs were calculated for a low, intermediate, and high cost environment. RESULTS: Endoscopies detected abnormalities in 635 patients (23%). The most common findings were reflux esophagitis with erosions (15%), gastric ulcers (2.7%), and duodenal ulcers (2.3%). The prevalence of upper gastrointestinal malignancy was 0.22%. If all dyspeptic patients 50 years or older underwent endoscopy, 1 esophageal cancer and no gastric cancers would have been missed. If the age threshold for endoscopy were set at 50 years, at a cost of $500/endoscopy, it would cost $82,900 (95% CI, $35,714-$250,000) to detect each case of cancer. CONCLUSIONS: Primary care dyspeptic patients without alarm symptoms rarely have serious underlying conditions at endoscopy. The costs associated with diagnosing an occult malignancy are large, but an age cut-off of 50 years for early endoscopy provides the best assurance that an occult malignancy will not be missed.

Objective: Although weight management is an important component in the treatment of type 2 diabetes, there has been concern about the use of liquid meal replacements (MRs) in treating obese patients with type 2 diabetes because of the sugar content of the MRs. The goal of this study was to evaluate the safety and feasibility of using MRs for weight loss in obese patients with type 2 diabetes. Research Methods and Procedures: Seventy-five subjects with type 2 diabetes, treated only with oral agents, were recruited for this 12-week clinical study. Subjects were randomized into three groups using either a MR containing lactose, fructose, and sucrose, a MR in which fructose and sucrose were replaced with oligosaccharides (sugar-free Slim-Fast), or an exchange diet plan (EDP) using the proportion of macronutrients recommended by the American Diabetes Association. Results: Fifty-seven patients (41 MR and 16 EDP) finished the study. None developed serious adverse effects, including major hypoglycemic reactions. Weight losses in the MR 1 and MR 2 groups were comparable (6.4% and 6.7%, respectively) and greater than the weight loss in the EDP group (4.9%). Fasting glucose level was significantly reduced in the MR group compared with the EDP group (p = 0.012). There was a significant reduction in the MR group in total cholesterol and low-density lipoprotein cholesterol that was not seen in the EDP group. Discussion: We have shown that liquid MRs are a safe and effective weight loss tool for obese subjects with type 2 diabetes, and can result in improvements in body weight, glucose, insulin, hemoglobin A1c and lipid levels.

The relation between insulin-leptin-visceral fat axis during weight loss has not been studied previously.To evaluate the insulin, leptin, and abdominal adiposity relation during weight loss in patients with upper body obesity.Twenty volunteers (7 men, 13 women) with mean age 50.6+/-6.3 (SD) and upper body obesity (weight 105.4+/-12.3 kg, BMI 35.9+/-2.5 kg/m2) were recruited. Participants were enrolled in a one-arm clinical study using a calorie-deficient diet and an escalating dose regimen of sibutramine, starting with 5 mg daily and increasing in 5-mg increments to 20 mg per day. Body weight, insulin, leptin, glucose, lipids, abdominal computed tomography (CT), and total body electrical conductance (TOBEC) were measured serially at weeks 0, 4, 8, 12, and 24.Eighteen patients completed the 6-month study: one man and one woman discontinued because of adverse events. With diet and sibutramine, body weight was significantly and continuously reduced throughout the 6-month study. There was a 16.0% (p = 0.0001) reduction in body weight (p0.001) and 22.5% (p = 0.0001) decrease in total body fat mass. Abdominal CT scans showed a 28.3% (p = 0.0001) reduction in total abdominal fat, a 26.0% (p = 0.0001) reduction in subcutaneous fat (p0.001), and a 31.0% (p = 0.0003) reduction in visceral fat (p0.001). There was a 32.0% (p = 0.0008) reduction in leptin levels and 37.9% (p = 0.0001) reduction in insulin levels between baseline and week 4, but no further significant reduction in leptin and insulin levels was observed for the duration of the study. There was a significant correlation between insulin and leptin concentrations throughout the study (p = 0.0001). Leptin was presented as a function of insulin measured at the same time. Significant associations between visceral abdominal fat, subcutaneous fat, and leptin were also observed.In this study, we found that leptin and insulin were related in weight loss. The data suggest that insulin may act as a strong regulator of leptin secretion during weight loss and that circulating leptin levels can be predicted by insulin level. Using sibutramine in conjunction with hypocaloric diet reduced body weight and decreased fat mass significantly. Visceral and subcutaneous abdominal fat depots were shown to decrease. Whether sibutramine exerts any selective reduction of visceral abdominal fat as opposed to total body fat mass will require further clinical investigation.

We tested the hypothesis that stimulation of intestinal mucosal afferent nerves produces an increase in superior mesenteric artery (SMA) but a decrease in mesenteric adipose tissue (MAT) blood flow. In anesthetized rats, blood flow in the SMA (pulsed Doppler flowmetry) and MAT (hydrogen gas clearance) was measured simultaneously before and after administration of 0.9% saline, 640 μM capsaicin, or 5% dextrose into the intestinal lumen. The changes in the SMA were 3.8 ± 3.0, 15.9 ± 4.0, and 18.8 ± 7.6%; and those in the MAT, 4.7 ± 4.0, −11.5 ± 3.4, and −0.07 ± 3.4% of baseline, respectively. The data indicate that exposure of the intestinal lumen to an afferent nerve stimulant or nutrient induced a dichotomous pattern of blood flow changes, an increase in the SMA and a reduction in MAT. The capsaicin-sensitive afferent nerves may be instrumental in mediating these energy responses.