COVID-19-Associated Portal Vein Thrombosis Post-Cholecystitis.

This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.

Randomized intervention to assess the effectiveness of an educational video on organ donation intent among Hispanics in the New York metropolitan area.

BACKGROUND: The Hispanic community has a high demand for organ donation but a shortage of donors. Studies investigating factors that could promote or hinder organ donation have examined emotional video interventions. Factors acting as barriers to organ donation registration have been classified as: (1) Bodily integrity; (2) medical mistrust; (3) "ick"-feelings of disgust towards organ donation; and (4) "jinx"-fear that registration may result in one dying due to premeditated plans. We predict that by providing necessary information and education about the donation process via a short video, individuals will be more willing to register as organ donors. AIM: To determine perceptions and attitudes regarding barriers and facilitators to organ donation intention among Hispanic residents in the New York metro politan area. METHODS: This study was approved by the Institutional Review Board at Northwell Health. The approval reference number is No. 19-0009 (as presented in Supplementary material). Eligible participants included Hispanic New York City (NYC) residents, 18 years of age and above, who were recruited voluntarily through Cloud Research and participated in a larger randomized survey study of NYC residents. The survey an 85-item Redcap survey measured participant demographics, attitudes, and knowledge of organ donation as well as the intention to register as an organ donor. Attention checks were implemented throughout the survey, and responses were excluded for those who did fail. Participants were randomly assigned two-between subject conditions: To view a short video on organ donation and then proceed to complete the survey (i.e., video first) and view the same video at the end of the survey (video last). No intra-group activities were conducted. This study utilized an evidenced-based emotive educational intervention (video) which was previously utilized and was shown to increase organ donation registration rates at the Ohio Department of Motor Vehicles. Results were analyzed using Jamovi statistical software. Three hundred sixty-five Hispanic individuals were included in the analysis. Once consent was obtained and participants entered the survey (the survey sample is presented in Supplementary material), participants were asked to report on demographic variables and their general impression of organ donation after death. The video depicted stories regarding organ donation after death from various viewpoints, including from the loved ones of a deceased person who died waiting for a transplant; from the loved ones of a deceased person whose organs were donated upon death; and, from those who were currently waiting for a transplant. RESULTS: Using a binomial logistic regression, the analysis provides information about the relationship between the effects of an emotive video and the intention to donate among Hispanic participants who were not already registered as donors. The willingness to go back and register was found to be significantly more probable for those who watched the emotive video before being asked about their organ donation opinions (odds ratio: 2.05, 95% confidence interval: 1.06-3.97). Motivations for participation in organ donation were also captured with many stating the importance of messages coming from "people like me" and a message that highlights "the welfare of those in need". Overall, the findings suggest that using an emotive video that addresses organ donation barriers to prompt organ donation intentions can be effective among the Hispanic populous. Future studies should explore using targeted messaging that resonates with specific cultural groups, highlighting the welfare of others. CONCLUSION: This study suggests that an emotive educational intervention is likely to be effective in improving organ donation registration intent among the Hispanic population residing in NYC.

Colorectal cancer screening and surveillance strategy for patients with Diamond Blackfan anemia: Preliminary recommendations from the Diamond Blackfan Anemia Registry.

Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by red cell failure, congenital anomalies, poor linear growth, and cancer predisposition. Two previous analyses from the Diamond Blackfan Anemia Registry have quantified DBA as a cancer predisposition syndrome of moderate cancer penetrance. Patients with DBA have a 4.8-fold higher relative risk of developing cancer with an overall cumulative incidence of 13.7% by age 45 years. The two most prevalent solid tumors are colorectal cancer (CRC) and osteogenic sarcoma. Current and evolving data support the institution of cancer screening and surveillance strategies for CRC in DBA.

Early Onset Colorectal Cancer: An Emerging Cancer Risk in Patients with Diamond Blackfan Anemia.

Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome, the founding member of a class of disorders known as ribosomopathies. Most cases result from loss of function mutations or deletions in 1 of 23 genes encoding either a small or large subunit-associated ribosomal protein (RP), resulting in RP haploinsufficiency. DBA is characterized by red cell hypoplasia or aplasia, poor linear growth and congenital anomalies. Small case series and case reports demonstrate DBA to be a cancer predisposition syndrome. Recent analyses from the Diamond Blackfan Anemia Registry of North America (DBAR) have quantified the cancer risk in DBA. These studies reveal the most prevalent solid tumor, presenting in young adults and in children and adolescents, to be colorectal cancer (CRC) and osteogenic sarcoma, respectively. Of concern is that these cancers are typically detected at an advanced stage in patients who, because of their constitutional bone marrow failure, may not tolerate full-dose chemotherapy. Thus, the inability to provide optimal therapy contributes to poor outcomes. CRC screening in individuals over the age of 50 years, and now 45 years, has led to early detection and significant improvements in outcomes for non-DBA patients with CRC. These screening and surveillance strategies have been adapted to detect familial early onset CRC. With the recognition of DBA as a moderately penetrant cancer risk syndrome a rational screening and surveillance strategy will be implemented. The downstream molecular events, resulting from RP haploinsufficiency and leading to cancer, are the subject of significant scientific inquiry.

A Randomized Intervention to Assess the Effectiveness of an Educational Video on Organ Donation Intent.

Background: The primary objective of this study was to evaluate the effectiveness of an emotive educational video on organ donation intent in New York City. The secondary study objective was to determine if the educational video affected various factors associated with organ donation. Methods: New York City residents were recruited via a crowdsourcing online platform and randomized to one of two groups, with exposure to viewing (1) an educational video before completing an 81 question survey on organ donation ("video first" condition) or (2) after completing the survey ("video last" condition). Logistic regression analysis compared organ donation intent (i.e., "how likely are you to become an organ donor") between the two groups. Additional variables related to organ donation (e.g., religious beliefs, financial incentives) were also evaluated between the two groups. Analyses were adjusted for organ donation registration status. Results: In total, 1905 participants were randomized. We observed a statistically significant increased odds of organ donation intent among those randomized to the video first condition compared with those randomized to the video last condition (odds ratio [OR], 1.70; 95% confidence interval [95% CI], 1.29 to 2.24). Differences regarding both educational effect on nondonors and racial differences such that there was a decreased odds of organ donation intent among those who identified as Black compared with those who were White (OR, 0.66; 95% CI, 0.47 to 0.92). Black participants were also more likely to report bodily integrity and differential treatment by doctors compared with White participants. Conclusion: Our findings suggest that future interventions to increase organ donation registration among ethnically diverse populations could be effective if sufficient information is presented before decision making to addresses potential concerns.

Increased Risk of Colorectal Cancer Tied to Advanced Colorectal Polyps: An Untapped Opportunity to Screen First-Degree Relatives and Decrease Cancer Burden.

Advanced adenomas represent a subset of colorectal polyps that are known to confer an increased risk of colorectal neoplasia to the affected individual and their first-degree relatives (FDRs). Accordingly, professional guidelines suggest earlier and more intensive screening for FDRs of those with advanced adenomas similar to FDRs of those with colorectal cancer (CRC). Although the risk to family members is less clear among patients with advanced serrated polyps, they are often considered in the same category. Unfortunately, there is a growing concern that patients, endoscopists, and primary care providers are unaware of the familial risk associated with these polyps, leaving a wide gap in screening these high-risk individuals. Herein, we propose a standardized language around advanced colorectal polyps and present a detailed review of the literature on associated familial risk. We outline the challenges to implementing the current screening recommendations and suggest approaches to overcome these limitations, including a proposed new colonoscopy quality metric to capture communication of familial CRC risk. Improving screening in these high-risk groups has the potential to substantially reduce the burden of CRC.

Time-Effect of Donor and Recipient Characteristics on Graft Survival after Kidney Transplantation.

The kidney allocation system (KAS) is based on quality-based "longevity matching" strategies that provide only a momentary snapshot of expected outcomes at the time of transplantation. The purpose of our study was to define on a continuous timeline the relative and mutual interactions of donor and recipient characteristics on graft survival. Total 39,108 subjects who underwent kidney transplant between October 25, 1999 and January 1, 2007 were identified in the United Network for Organ Sharing dataset. Our primary outcome was graft survival. Time-dependent receiver operating characteristic (ROC) curves and area under time-dependent ROC curve (AUC) were used to compare the predictive ability of the two allocation systems. During the first year after transplantation, both donor and recipient models showed identical relevance. From the first to the sixth years, although the two ROC curves were nearly identical, the donor model outweighed the recipient model. Both models intersected again at the sixth year. From that time onward, the ROC curve for recipient characteristics model predominated over the ROC curve for donor characteristics model. The predictive value of the recipient model (AUC = 0.752) was greater than that of the donor model (AUC = 0.673) We hope that this model will provide additional guidance and risk stratification to further optimize organ allocation based on the dynamic interaction of both donor and recipient characteristics over time.

Phase II Feasibility Study of a Weight Loss Intervention in Female Breast and Colorectal Cancer Survivors (SWOG S1008).

OBJECTIVE: This study aimed to test the feasibility of a 12-month weight loss intervention using telephone-based counseling plus community-situated physical activity (PA) in female breast cancer (BC) and colorectal cancer (CRC) survivors. METHODS: This multisite cooperative group study enrolled sedentary, female, postmenopausal BC and CRC survivors with BMI ≥ 25 kg/m2 to receive 12-month fitness center memberships and telephone counseling encouraging 150 min/wk of PA and a 500-kcal/ddecrease in energy intake. Feasibility criteria included accrual, adherence, and retention. Target weight loss was ≥ 5%. RESULTS: Among 25 BC survivors, median baseline BMI was 37.2 (range: 27.7-54.6), accrual occurred in 10 months, 60% and 28% met diet and exercise goals, 80% provided 12-month measures, and average weight loss was 7.6% (95% CI: -3.9%, 19.2%). Among 23 CRC survivors, median BMI was 31.8 (range: 26.4-48.7), accrual occurred in 24 months, 61% and 17% met diet and exercise goals, 87% provided measures, and average weight loss was 2.5% (95% CI: -8.2%, 13.3%). CONCLUSIONS: It is feasible to recruit and retain BC survivors in a cooperative group diet and PA weight loss trial. BC survivors achieved clinically meaningful weight loss but did not meet a priori adherence goals. In CRC survivors, recruitment was more difficult, and the intervention was less effective.

Trends in Obesity Prevalence in Adults With a History of Cancer: Results From the US National Health Interview Survey, 1997 to 2014.

PURPOSE: Obesity after a diagnosis of specific cancers has been associated with worse prognosis. We examined the trend in obesity prevalence among cancer survivors in the United States in the past two decades and compared trends with those of adults without a history of cancer. PATIENTS AND METHODS: This was a population-based nationally representative sample of 538,969 noninstitutionalized US adults 18 to 85 years old with and without a history of cancer who participated in annual cross-sectional National Health Interview Surveys from 1997 to 2014. Obesity was defined as body mass index ≥ 30 kg/m(2) for non-Asians and body mass index ≥ 27.5 kg/m(2) for Asians. RESULTS: Among 32,447 cancer survivors identified, the most common cancer diagnoses were breast (n = 6,948), prostate (n = 3,984), and colorectal (n = 2,546). From 1997 to 2014, the prevalence of obesity increased from 22.4% to 31.7% in cancer survivors and from 20.9% to 29.5% in adults without a history of cancer (P for trend < .001, both groups). Over this period, the estimated rate of annual increase in obesity prevalence was higher in women and men with a history of cancer compared with those without a history of cancer (all P for interaction < .001). The estimated rate of annual increase in obesity prevalence was 3.1% in female and 3.7% in male colorectal cancer survivors, 3.0% in breast cancer survivors, and 2.1% in prostate cancer survivors (all P < .001). In subgroup analyses, populations with the highest rates of increasing obesity burden were colorectal cancer survivors, breast cancer survivors, and non-Hispanic blacks. CONCLUSION: From 1997 to 2014, obesity increased more rapidly among adult cancer survivors compared with the general population. Colorectal and breast cancer survivors and non-Hispanic blacks were identified as being at the highest risk for obesity.

Survivorship care plans and adherence to lifestyle recommendations among breast cancer survivors.

PURPOSE: The effectiveness of survivorship care plans has not been widely tested. We evaluated whether a one-time brief lifestyle consultation as part of a broader survivorship care plan was effective at changing diet and lifestyle patterns. METHODS: A diverse sample of women with stage 0-III breast cancer were randomized to control or intervention groups within 6 weeks of completing adjuvant treatment. Both groups received the National Cancer Institute publication, "Facing Forward: Life after Cancer Treatment." The intervention group also met with a nurse (1 h) and a nutritionist (1 h) to receive personalized lifestyle recommendations based upon national guidelines. Diet, lifestyle, and perceived health were assessed at baseline, 3 and 6 months. Linear regression analyses evaluated the effects of the intervention adjusted for covariates. RESULTS: A total of 126 women completed the study (60 control/66 intervention, 61 Hispanic/65 non-Hispanic). At 3 months, the intervention group reported greater knowledge of a healthy diet (P = 0.047), importance of physical activity (P = 0.03), and appropriate use of dietary supplements (P = 0.006) and reported lower frequency of alcohol drinking (P = 0.03) than controls. At 6 months, only greater knowledge of a healthy diet (P = 0.01) persisted. The intervention was more effective among non-Hispanics than Hispanics on improving attitude towards healthy eating (P = 0.03) and frequency of physical activity (P = 0.006). CONCLUSIONS: The intervention changed lifestyle behaviors and knowledge in the short-term, but the benefits did not persist. IMPLICATIONS FOR CANCER SURVIVORS: Culturally competent long-term behavioral interventions should be tested beyond the survivorship care plan to facilitate long-term behavior change among breast cancer survivors.

High use of complementary and alternative medicine among a large cohort of women with a family history of breast cancer: the Sister Study.

Use of complementary and alternative medicine (CAM) is high among U.S. women, yet information is limited on use among women at increased breast cancer risk. We analyzed CAM use among women with a family history of breast cancer. CAM use was analyzed among women enrolled 2003-2009 in the Sister Study cohort. Eligible women were aged 35-74, U.S. or Puerto Rican residents, no personal history of breast cancer, and had ≥1 sister with breast cancer. Baseline data on CAM use in the past year were available for 49,734 women. Logistic regression models examined the association between CAM use and Gail Model breast cancer risk score. Results were compared to female participants in the 2007 National Health Interview Survey (n = 7965). Among Sister Study participants, there was high use of vitamin/mineral supplements (79 %), mind-body practices (41 %), manipulative/body-based practices (32 %), and botanicals (23 %). Overall use was higher than the U.S. female population. No association was observed between familial breast cancer risk and CAM use. Black women were more likely to use spirituality/meditation-based CAM modalities, while non-Hispanic white and Asian women were high users of dietary supplements. In a cohort of women with increased breast cancer risk due to family history, CAM use is higher than women in the general U.S. population and is associated with race/ethnicity. Use was not associated with breast cancer risk. Given the high prevalence of CAM use among women at risk for breast caner, research on the effectiveness of CAM use for disease prevention is needed.

Recipient Criteria Predictive of Graft Failure in Kidney Transplantation.

Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables. This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics. All U.S. kidney transplant recipients between October 25,1999 and January 1, 2007 were reviewed. Cox proportional hazards regression was used to model time until graft failure. Death-censored and nondeath-censored graft survival models were generated for recipients of live and deceased donor organs. Recipient age, gender, body mass index (BMI), presence of cardiac risk factors, peripheral vascular disease, pulmonary disease, diabetes, cerebrovascular disease, history of malignancy, hepatitis B core antibody, hepatitis C infection, dialysis status, panel-reactive antibodies (PRA), geographic region, educational level, and prior kidney transplant were evaluated in all kidney transplant recipients. Among the 88,284 adult transplant recipients the following groups had increased risk of graft failure: younger and older recipients, increasing PRA (hazard ratio [HR],1.03-1.06], increasing BMI (HR, 1.04-1.62), previous kidney transplant (HR, 1.17-1.26), dialysis at the time of transplantation (HR, 1.39-1.51), hepatitis C infection (HR, 1.41-1.63), and educational level (HR, 1.05-1.42). Predictive criteria based on recipient characteristics could guide organ allocation, risk stratification, and patient expectations in planning kidney transplantation.

Physical activity, sedentary behavior, and vitamin D metabolites.

Physical activity is associated with circulating 25-hydroxyvitamin D (25(OH)D). However, the influence of activity and/or sedentary behavior on the biologically active, seco-steroid hormone 1α,25-dihydroxyvitamin D (1,25(OH)2D) is unknown. We conducted a cross-sectional analysis among ursodeoxycholic acid (UDCA) randomized trial participants (n=876) to evaluate associations between physical activity, sedentary behavior, and circulating vitamin D metabolite concentrations. Continuous vitamin D metabolite measurements and clinical thresholds were evaluated using multiple linear and logistic regression models, mutually adjusted for either 1,25(OH)2D or 25(OH)D and additional confounding factors. A statistically significant linear association between 1,25(OH)2D and moderate-vigorous physical activity per week was strongest among women (ß (95% CI): 3.10 (1.51-6.35)) versus men (ß (95% CI): 1.35 (0.79-2.29)) in the highest tertile of activity compared to the lowest (p-interaction=0.003). Furthermore, 25(OH)D was 1.54ng/ml (95% CI 1.09-1.98) higher per hour increase in moderate-vigorous activity (p=0.001) and odds of sufficient 25(OH)D status was higher among physically active participants (p=0.001). Sedentary behavior was not significantly associated with either metabolite in linear regression models, nor was a statistically significant interaction by sex identified. The current study identified novel associations between physical activity and serum 1,25(OH)2D levels, adjusted for 25(OH)D concentrations. These results identify the biologically active form of vitamin D as a potential physiologic mechanism related to observed population-level associations between moderate-vigorous physical activity with bone health and chronic disease risk. However, future longitudinal studies are needed to further evaluate the role of physical activity and vitamin D metabolites in chronic disease prevention.

Suppression of Proinflammatory and Prosurvival Biomarkers in Oral Cancer Patients Consuming a Black Raspberry Phytochemical-Rich Troche.

Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and noninvolved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of prosurvival genes (AURKA, BIRC5, EGFR) and proinflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated grade 3-4 toxicities or adverse events, and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark antiapoptotic and proinflammatory molecular biomarkers were overexpressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. As these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention.

Concentrations of the vitamin D metabolite 1,25(OH)2D and odds of metabolic syndrome and its components.

AIM: Few epidemiological studies have investigated the association between circulating concentrations of the active vitamin D metabolite 1,25(OH)2D and metabolic syndrome. We sought to determine whether blood levels of 1,25(OH)2D are associated with metabolic syndrome and its individual components, including waist circumference, triglycerides, blood pressure, and glucose, and high-density lipoprotein. We also investigated these associations for the more abundant precursor vitamin D metabolite, 25(OH)D. METHODS: Participants from two completed clinical trials of colorectal neoplasia with available metabolic syndrome data and blood samples for measurement of 1,25(OH)2D (n=1048) and 25(OH)D (n=2096) were included. Cross-sectional analyses of the association between concentrations of 1,25(OH)2D, 25(OH)D, metabolic syndrome, and its components were conducted. RESULTS: A statistically significant inverse association was observed for circulating concentrations of 1,25(OH)2D and metabolic syndrome, with adjusted ORs (95% CIs) of 0.73 (0.52-1.04) and 0.52 (0.36-0.75) for the second and third tertiles of 1,25(OH)2D, respectively (p-trend <0.001). Significant inverse relationships were also observed between 1,25(OH)2D and high triglycerides (p-trend <0.001), and low high-density lipoprotein (p-trend <0.001). For 25(OH)D concentrations, significant inverse associations were found for metabolic syndrome (p-trend <0.01), high waist circumference (p-trend <0.04) and triglyceride levels (p-trend <0.01). Participants with 25(OH)D ≥30 ng/ml and in the highest tertile of 1,25(OH)2D demonstrated significantly lower odds of metabolic syndrome, with an OR (95% CI) of 0.38 (0.19-0.75) compared to those in the lowest category for both metabolites. CONCLUSION: These results provide new evidence that the relatively rarely-studied active hormonal form of vitamin D, 1,25(OH)2D, is associated with metabolic syndrome and its components, and confirm prior findings for 25(OH)D. The finding that 1,25(OH)2D is related to high-density lipoprotein, while 25(OH)D is not, suggests that there may be an independent mechanism of action for 1,25(OH)2D in relation to metabolic dysregulation.

Sedentary behavior is associated with colorectal adenoma recurrence in men.

PURPOSE: The association between physical activity and colorectal adenoma is equivocal. This study was designed to assess the relationship between physical activity and colorectal adenoma recurrence. METHODS: Pooled analyses from two randomized, controlled trials included 1,730 participants who completed the Arizona Activity Frequency Questionnaire at baseline, had a colorectal adenoma removed within 6 months of study registration, and had a follow-up colonoscopy during the trial. Logistic regression modeling was employed to estimate the effect of sedentary behavior, light-intensity physical activity, and moderate-vigorous physical activity on colorectal adenoma recurrence. RESULTS: No statistically significant trends were found for any activity type and odds of colorectal adenoma recurrence in the pooled population. However, males with the highest levels of sedentary time experienced 47% higher odds of adenoma recurrence. Compared to the lowest quartile of sedentary time, the ORs (95% CIs) for the second, third, and fourth quartiles among men were 1.23 (0.88, 1.74), 1.41 (0.99, 2.01), and 1.47 (1.03, 2.11), respectively (p(trend) = 0.03). No similar association was observed for women. CONCLUSIONS: This study suggests that sedentary behavior is associated with a higher risk of colorectal adenoma recurrence among men, providing evidence of detrimental effects of a sedentary lifestyle early in the carcinogenesis pathway.

Associations between circulating 1,25(OH)2D concentration and odds of metachronous colorectal adenoma.

Cellular-level studies demonstrate that the availability of the secosteroid hormone 1α,25-dihydroxyvitamin D [1,25(OH)2D] to colon cells promotes anti-carcinogenic activities. Although epidemiological data are relatively sparse, suggestive inverse trends have been reported between circulating 1,25(OH)2D concentration and colorectal neoplasia. We therefore sought to evaluate the relationship between circulating 1,25(OH)2D concentrations and odds for metachronous colorectal adenomas among 1,151 participants from a randomized trial of ursodeoxycholic acid for colorectal adenoma prevention. No relationship between 1,25(OH)2D and overall odds for metachronous lesions was observed, with ORs (95% CIs) of 0.80 (0.60-1.07) and 0.81 (0.60-1.10) for participants in the second and third tertiles, respectively, compared with those in the lowest (p-trend = 0.17). However, a statistically significant inverse association was observed between circulating 1,25(OH)2D concentration and odds of proximal metachronous adenoma, with an OR (95% CI) of 0.71 (0.52-0.98) for individuals in the highest tertile of 1,25(OH)2D compared with those in the lowest (p-trend = 0.04). While there was no relationship overall between 1,25(OH)2D and metachronous distal lesions, there was a significantly reduced odds for women, but not men, in the highest 1,25(OH)2D tertile compared with the lowest (OR 0.53; 95% CI 0.27-1.03; p-trend = 0.05; p-interaction = 0.08). The observed differences in associations with proximal and distal adenomas could indicate that delivery and activity of vitamin D metabolites in different anatomic sites in the colorectum varies, particularly by gender. These results identify novel associations between 1,25(OH)2D and metachronous proximal and distal colorectal adenoma, and suggest that future studies are needed to ascertain potential mechanistic differences in 1,25(OH)2D action in the colorectum.

A phase Ib study of the effects of black raspberries on rectal polyps in patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer. FAP is treated by colectomy followed by lifelong removal of rectal polyps. This study determined whether black raspberries (BRBs) might regress rectal polyps in patients with FAP. Fourteen patients with FAP were treated with BRBs daily for 9 months. Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime. The other 7 received an oral placebo plus the suppositories. Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment. Polyps and adjacent normal tissue were collected at both time points. The burden (P = 0.036) but not number (P = 0.069) of rectal polyps was significantly decreased. No benefit was noted with the addition of oral BRBs. Three patients were nonresponders. BRBs significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation, but not promoter methylation of the Wnt pathway antagonists, SFRP2 and WIF1, in rectal polyps (adenomas) from responders but not from nonresponders. The MBD-seq assay revealed more demethylated transcription start sites (TSS), including those for miRNAs, in BRB-treated adenomas from the responders. In conclusion, BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP.