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Development of potential cancer chemopreventive drugs involves the systematic evaluation of these drugs in preliminary Phase I and II studies in human beings to identify the optimal drug dose, drug toxicity, and surrogate end point biomarker modulation. Objectives: We tested the hypothesis that aspirin, at a single, once-daily 81-mg dose, will reduce colonic mucosal concentration of prostaglandin estradiol (E2) in individuals at high risk for colorectal cancer development similar to our prior observations in a young normal-risk population. Methods: Aspirin was administered at a dose of 81 mg once daily for 28 days in a cohort of 92 matched high-risk and normal-risk colorectal cancer subjects. Prostaglandin E2 and cyclooxygenase expression were assayed from distal sigmoid biopsies from all of the subjects before and after treatment. Results: The mean prostaglandin E2 for normal-risk subjects before aspirin treatment was 11.3 ± 1.7 pg/μg (mean ± SE) tissue protein and after aspirin treatment was 4.9 ± 0.91 pg/μg tissue protein (P & 0.0001). In high-risk subjects, mean pretreatment prostaglandin E2 was 14.4 ± 1.7 pg/μg tissue protein and after aspirin treatment was 4.7 ± 0.70 pg/μg tissue protein (P & 0.0001). Aspirin treatment did not alter cyclooxygenase-1 protein expression. Conclusions: Aspirin treatment at a dose of 81 mg reduces colorectal mucosal prostaglandin E2 concentration after 28 daily doses. Risk for colorectal carcinoma did not modify colorectal mucosal baseline or post-aspirin prostaglandin E2, or cyclooxygenase expression. Colorectal mucosal prostaglandin concentration may be used as a "drug-effect surrogate biomarker," that is, a surrogate to assess sufficient delivery and tissue effect of a chemopreventive agent.

Background. We quantitated proinflammatory and thrombopoietic cytokines in reactive thrombocytosis (RT) and clonal thrombocytosis (CT) to identify a cytokine profile that might aid in the distinction of these two disorders. Methods. Serum levels of cytokines relevant to platelet biology - interleukins 3, 6, 11, and 1β; thrombopoietin; tumor necrosis factor α; and C-reactive protein (CRP) - were measured by enzyme-linked immunosorbent assay in healthy subjects and in patients with CT and RT. Results. Interleukin-6 and CRP levels were higher in RT patients than in controls or CT patients. Interleukin 1β levels were higher in the RT group than in the CT and control groups. Conclusions. In RT, IL-6, IL-1β, and CRP levels are elevated. In both RT and CT, IL-11 is elevated, but thrombopoietin levels are not.

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Much has been learned about the role of NSAIDs as cancer preventives through epidemiologic and experimental studies. The pathways of carcinogenesis in the gastrointestinal tract are initiated by many different genetic, environmental, infective, and lifestyle factors. It is possible that the final common pathway of all these malignancies may have some common features. It is conceivable that head and neck, esophageal, gastric, and colorectal epithelial carcinogenesis all are influenced by or require COX-2 up-regulation as a step toward transformation. Intuitively, it is possible that selective COX-2 inhibitors may have a preventive role in all these epithelial malignancies. Today's challenge is to translate this information into clinical trials to define what role, if any, COX inhibition might play in the prevention of these malignancies.

Peripartum cardiomyopathy is an uncommon complication of human pregnancy that threatens both the mother and fetus with maternal congestive heart failure. Clinicians must be aware of this problem in order to provide prompt diagnosis and effective treatment that will insure a favorable return of normal left ventricular function.

OBJECTIVES: Hypercalcemia of malignancy confers a poor prognosis. This systematic review evaluated published cases of hypercalcemia of malignancy presenting with acute pancreatitis (AP), in terms of clinical presentation and outcomes. METHODS: A comprehensive review of PubMed and Embase until March 18, 2020, was conducted. Studies were included if they reported on patients with hypercalcemia of malignancy and AP with attempts to exclude other etiologies of hypercalcemia and AP. Two independent reviewers selected and appraised studies using the Murad tool. RESULTS: Thirty-seven cases were identified. Mean (standard deviation) age was 44.8 (2.46) years. Mean (standard deviation) presenting corrected calcium was 14.5 (0.46) mg/dL. Parathyroid carcinoma (21.6%) and multiple myeloma (21.6%) were the most common malignancies. Cases were classified as severe (37.8%), mild (21.6%), and moderately severe (18.9%), whereas 21.6% did not report severity. Necrotizing pancreatitis developed in 21.6% of cases. Most cases were treated with intravenous hydration and bisphosphonates or calcitonin/calcitonin analogues. Mortality was 32.4% during the same presentation of AP. Among mortality cases, 10 of 12 had severe AP, and 5 of 12 had necrotizing pancreatitis. Degree of hypercalcemia did not influence mortality. CONCLUSION: Acute pancreatitis associated with hypercalcemia of malignancy is rare. One in 3 patients with this presentation may not survive AP.

Aims: We aim to determine the influence of lower gastrointestinal bleeding (LGIB) on mortality, morbidity, length of hospital stay and resource utilisation in end-stage renal disease (ESRD) patients. Material and Methods: The National Inpatient Sample database (2016 &2017) was used for data analysis using the International Classification of Diseases, Tenth Revision codes to identify the patients with the principal diagnosis of ESRD and LGIB. We assessed the all-cause in-hospital mortality, morbidity, predictors of mortality, length of hospital stay (LOS) and total costs between propensity-matched groups of ESRD patients with LGIB versus ESRD patients. Results: We identified 2 187 954 ESRD patients, of whom 242 075 has LGIB, and 1 945 879 were ESRD patients. The in-hospital mortality was higher in ESRD with LGIB (OR 2.5, 95% CI 1.5-2.2; P =.00). ESRD with LGIB has higher odds of mechanical ventilation (OR 1.4, 95% CI 6.4-16.4; P =.00), and shock requiring vasopressor (OR 1.2, 95% CI 4.9-5.4; P =.002). Advanced age (OR 1.02 CI 1.02-1.03 P =.00), anaemia (OR 1.04 CI 1.59-1.91 P =.006), acute coronary syndrome (OR 1.8 CI 1.6-2.1, P =.00), acute respiratory failure (OR 1.29 CI 2.0-2.6, P =.00), mechanical ventilation (OR 1.9, CI 3.5-4.4, P =.00) and sepsis (OR 1.5, CI 4.1-5.08, P =.00) were identified as predictors of mortality in ESRD with LGIB. Mean LOS (10.8 ± 14.9 vs 6.3 ± 8.5, P <.01) and mean total charges (37 054 $ vs 18 080 $, P <.01) were also higher. Conclusions: In this propensity-matched analysis, ESRD with LGIB was associated with higher odds of in-hospital mortality, mechanical ventilation and shock requiring vasopressor. Mean LOS and resource utilisation were also higher.