Radiographic staging practices of newly diagnosed colorectal cancer vary according to medical specialty.

BACKGROUND: Since 2008, multiple guidelines have endorsed incorporation of chest CT in the radiographic staging assessment of newly diagnosed colorectal cancer (CRC). Radiographic staging practices performed after CRC is detected have not been studied. OBJECTIVE: To evaluate radiographic staging practices for newly diagnosed CRC between gastroenterologists versus non-gastroenterologists. DESIGN: Observational cohort study. SETTING: Single, tertiary-care referral center. PATIENTS: Patients newly diagnosed with a T1 or higher stage CRC at time of colonoscopy between 2008 and 2013. INTERVENTIONS: Radiographic staging. MAIN OUTCOME MEASUREMENTS: Radiographic preoperative staging examinations ordered by gastroenterologists in comparison to those ordered by non-gastroenterology specialists. RESULTS: This study included 277 patients with CRC newly diagnosed by colonoscopy. There were 141 total ordering physicians (68 gastroenterologists and 73 non-gastroenterologists). The majority of preoperative radiographic staging was performed by gastroenterologists (59.2% of patients, n = 164). Colorectal surgeons managed staging in 28.7% of patients (n = 47). Gastroenterologists were more likely to omit a staging chest CT than were non-gastroenterologists (64.6% vs 46.9%; P < .001). Physician practice setting, rectal location of tumor, and advanced endoscopic appearance of tumors were predictors of chest CT inclusion. LIMITATIONS: Single center, moderate sample size of both providers and patients. CONCLUSION: Gastroenterologists more frequently ordered the initial radiographic staging studies in newly diagnosed CRC patients. However, gastroenterologists were less likely to include chest CT in the initial staging of CRC despite current guideline recommendations to do so. If confirmed with further studies, educational efforts to improve compliance and standardization may be needed.

Patient Non-adherence and Cancellations Are Higher for Screening Colonoscopy Compared with Surveillance Colonoscopy.

BACKGROUND: A significant proportion of the eligible population is non-adherent to colonoscopy for colorectal cancer (CRC) screening. AIMS: To define the demographic and clinical variables associated with non-adherence and multiple cancellations to scheduled colonoscopy within 1 year in a CRC screening and adenomatous polyp surveillance population. METHODS: This was an observational cohort study of 617 consecutive patients scheduled to undergo colonoscopy at an outpatient academic tertiary care center for CRC screening or adenomatous polyp surveillance from January 2012 to September 2012. RESULTS: Overall, 551 patients (89.3%) were adherent and 66 (10.7%) were non-adherent to scheduled colonoscopy at 1 year. The relative risk for non-adherence was 5.42 [95% confidence interval (CI) 2.74-10.75] in patients undergoing colonoscopy for screening compared to those for surveillance (16.7 vs. 3.5% non-adherence, respectively, P < 0.001). An indication of screening in comparison with surveillance was associated with non-adherence [odds ratio (OR) 12.69, 95% CI 4.18-38.51] and multiple cancellations (OR 2.33, 95% CI 1.27-4.31) by multiple regression analysis. CONCLUSIONS: Patients undergoing colonoscopy for CRC screening are significantly less likely to attend their scheduled procedure within a year and have more procedure cancellations than those undergoing surveillance colonoscopy.

Hepatitis B vaccination in patients with inflammatory bowel disease.

AIM: To determine the prevalence for hepatitis B virus (HBV) and HBV screening and vaccination practices for inflammatory bowel disease (IBD). METHODS: This study is a retrospective, cross-sectional observational study. A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section. The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic, and that they had a diagnosis of IBD at the time of visit discharge. Once identified, each record was analyzed to determine whether the subject had been infected with HBV in the past, already been vaccinated against HBV, or advised to get vaccinated and followed through with the recommended vaccination. RESULTS: About 254 out of 500 patients (51%) had HBV screening ordered. Among those ordered to have screening tests, 86% followed through with HBV serology. Gastroenterology physicians had significantly different screening ratios from each other (P < 0.001). There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians (0.505 ± 0.023 vs 0.536 ± 0.066, P = 0.66). Of those 220 patients screened, 51% of IBD patients were found not to be immune against HBV. Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV. IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians (0.168 ± 0.019 vs 0.038 ± 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6% of the patients who had serology checked. There was no statistically significant difference in the prevalence of hepatitis B surface antigen (HBsAg) between our study and that reported in previous studies done in Spain (4/220 vs 14/2076 respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159). But, the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not significantly different from that reported in the study in France (7/220 vs 8/315 respectively, P = 0.313). CONCLUSION: The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies. Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.

Commonality and differences of methylation signatures in the plasma of patients with pancreatic cancer and colorectal cancer.

Profiling of DNA methylation status of specific genes is a way to screen for colorectal cancer (CRC) and pancreatic cancer (PC) in blood. The commonality of methylation status of cancer-related tumor suppressor genes between CRC and PC is largely unknown. Methylation status of 56 cancer-related genes was compared in plasma of patients in the following cohorts: CRC, PC and healthy controls. Cross validation determined the best model by area under ROC curve (AUC) to differentiate cancer methylation profiles from controls. Optimal preferential gene methylation signatures were derived to differentiate either cancer (CRC or PC) from controls. For CRC alone, a three gene signature (CYCD2, HIC and VHL) had an AUC 0.9310, sensitivity (Sens) = 0.826, specificity (Spec) = 0.9383. For PC alone, an optimal signature consisted of five genes (VHL, MYF3, TMS, GPC3 and SRBC), AUC 0.848; Sens = 0.807, Spec = 0.666. Combined PC and CRC signature or "combined cancer signature" was derived to differentiate either CRC and PC from controls (MDR1, SRBC, VHL, MUC2, RB1, SYK and GPC3) AUC = 0.8177, Sens = 0.6316 Spec = 0.840. In a validation cohort, N = 10 CRC patients, the optimal CRC signature (CYCD2, HIC and VHL) had AUC 0.900. In all derived signatures (CRC, PC and combined cancer signature) the optimal panel used preferential VHL methylation. In conclusion, CRC and PC differ in specific genes methylated in plasma other than VHL. Preferential methylation of VHL is shared in the optimal signature for CRC alone, PC alone and combined PC and CRC. Future investigations may identify additional methylation markers informative for the presence of both CRC and PC.

Advanced adenoma detection rate is independent of nonadvanced adenoma detection rate.

OBJECTIVES: Adenoma detection rate (ADR) is the accepted rate marker in colonoscopy quality. Advanced adenomas detected at index colonoscopy, while less frequent than nonadvanced adenomas, carry greater risk for future advanced neoplasia during surveillance colonoscopy. This study aimed to determine the effect of the colonoscopist and other factors on advanced ADR and to define the correlation of advanced and nonadvanced ADRs among colonoscopists. METHODS: An observational study of a cohort of patients undergoing first-time colorectal cancer screening colonoscopy was conducted. Patient characteristics and colonoscopic findings were collected. Adenoma, advanced adenoma, and nonadvanced ADRs were calculated. Logistic regression was used to determine variable effects on advanced adenoma detection, and Spearman's rank-order correlation was used to evaluate the relationship between advanced and nonadvanced ADRs. RESULTS: A total of 1,944 patients had first-time screening colonoscopies by 14 colonoscopists. All colonoscopists had adequate (>20%) ADRs. The variability in the colonoscopist ranges of detection was 22.22 to 44.66% for adenomas and 2.00 to 18.18% for advanced adenomas. Logistic regression showed that increasing patient age (odds ratio (OR) 1.16 per 5-year increase, 95% confidence interval (CI) 1.05-1.28, P=0.008) and male gender (OR 2.15, 95% CI 1.51-3.06, P<0.0001) were variables associated with advanced adenoma detection. Colonoscopists were significantly different in detecting advanced adenomas by random effects model (P=0.002), adjusting for patient age, gender, race, year of colonoscopy, gastroenterology fellow participation during colonoscopy, and nonadvanced adenomas. Spearman's rank-order correlation coefficient of -0.42 (95% CI -0.77 to 0.14, P=0.13) was not significant and showed no correlation between advanced and nonadvanced adenoma detection by the group of colonoscopists. CONCLUSIONS: Advanced ADR is variable among colonoscopists with acceptable ADRs. Colonoscopists' advanced ADRs are independent of their nonadvanced ADRs.

Endoscopic mis-sizing of polyps changes colorectal cancer surveillance recommendations.

BACKGROUND: Adenomatous polyps greater than 1 cm are defined as advanced adenomas. Inaccurate size estimation can lead to inappropriate surveillance recommendations of colorectal adenomas. OBJECTIVE: The aim of this study was to determine the impact of endoscopic polyp mis-sizing on colorectal cancer surveillance recommendations. DESIGN: This is a prospective study. SETTING: This study was conducted in a gastroenterology practice at a US academic medical center. PATIENTS: Patients undergoing colorectal cancer screening and surveillance colonoscopies from 2010 to 2011 were included. MAIN OUTCOME MEASUREMENTS: Endoscopic size estimates of polyps 10 to 25 mm were compared with postfixation histopathologic polyp measurements for 15 different gastroenterologists. Only adenomatous polyps removed in entirety by snare polypectomy were included in the analysis. Size variation was defined as (endoscopic estimate - histopathologic size)/(histopathologic size). Clinical mis-sizing was defined as a size variation of >33%. The mean size variation, the percentage of clinical mis-sizing, and the percentage of inappropriate surveillance recommendation due to size variation >33% were reported per endoscopist. RESULTS: : Included for analysis were 4990 procedures from 15 gastroenterologists. A total of 230 polyps from 200 patients met inclusion criteria. The average age was 62.6 years (SD 10.1), and 52% were men. The mean size variation between the endoscopic polyp size estimation and the histopathologic polyp was 73.6% (range of mean size variation, 13%-127%). 62.6% (range, 0%-91%) of included polyps had clinical mis-sizing. Of included polypectomies, 35.2% (range, 0%-67%) resulted in an inappropriate surveillance recommendation due to clinical mis-sizing even after considering histology and synchronous polyps. LIMITATIONS: This was a single-center study. CONCLUSIONS: There is marked variation in endoscopists' ability to accurately size adenomatous polyps. Some endoscopists rarely mis-size adenomas, and their surveillance recommendations are appropriate in regard to sizing. However, other endoscopists inaccurately size adenomas, and this leads to inappropriate surveillance of colorectal polyps. In this study, approximately 1 of 3 included polypectomies yielded inappropriate surveillance recommendations because of clinical mis-sizing.

DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps.

Colorectal cancer (CRC) screening rates are currently suboptimal. Blood-based screening could improve rates of earlier detection for CRC and adenomatous colorectal polyps. In this study, we evaluated the feasibility of plasma-based detection of early CRC and adenomatous polyps using array-mediated analysis methylation profiling of 56 genes implicated in carcinogenesis. Methylation of 56 genes in patients with Stages I and II CRC (N=30) and those with adenomatous polyps (N=30) were compared with individuals who underwent colonoscopy and were found to have neither adenomatous changes nor CRC. Composite biomarkers were developed for adenomatous polyps and CRC, and their sensitivity and specificity was estimated using five-fold cross validation. Six promoters (CYCD2, HIC1, PAX 5, RASSF1A, RB1 and SRBC) were selected for the biomarker, which differentiated CRC patients and controls with 84% sensitivity and 68% specificity. Three promoters (HIC1, MDG1 and RASSF1A) were selected for the biomarker, which differentiated patients with adenomatous polyps and controls with sensitivity of 55% and specificity of 65%. Methylation profiling of plasma DNA can detect early CRC with significant accuracy and shows promise as a methodology to develop biomarkers for CRC screening.

Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells.

Cultured rat hepatocytes and human hepatoma HepG2 cells were used to evaluate the hepatoprotective properties of polyphenolic extracts from the edible part of artichoke (AE). The hepatocytes were exposed to H2O2generated in situ by glucose oxidase and were treated with either AE, or pure chlorogenic acid (ChA) or with the well known antioxidant, N, N'-diphenyl-p-phenilenediamine (DPPD). Addition of glucose oxidase to the culture medium caused depletion of intracellular glutathione (GSH) content, accumulation of malondialdehyde (MDA) in the cultures, as a lipid peroxidation indicator, and cell death. These results demonstrated that AE protected cells from the oxidative stress caused by glucose oxidase, comparable to DPPD. Furthermore, AE, as well as ChA, prevented the loss of total GSH and the accumulation of MDA. Treatment of HepG2 cells for 24 h with AE reduced cell viability in a dose-dependent manner, however, ChA had no prominent effects on the cell death rate. Similarly, AE rather than ChA induced apoptosis, measured by flow cytometric analysis of annexin and by activation of caspase-3, in HepG2 cells. Our findings indicate that AE had a marked antioxidative potential that protects hepatocytes from an oxidative stress. Furthermore, AE reduced cell viability and had an apoptotic activity on a human liver cancer cell line.

Coffee: good, bad, or just fun? A critical review of coffee's effects on liver enzymes.

Coffee consumption is a regular part of daily life throughout the world. Research into the effects of coffee on human health is ongoing, but a recent study suggests that coffee and caffeine consumption can reduce the risk of elevated alanine aminotransferase activity in individuals at high risk for liver disease. This review will analyze the results of that study in light of the current literature.

Antiplatelet agents: current drugs and future trends.

Antiplatelet drugs in clinical use are discussed in terms of their mechanisms of action and the relevancy of that to the physiology of platelets and the pathophysiology of arterial thrombosis. Current clinical usage is outlined in detail for each drug. Experimental antiplatelet drugs also are discussed.

Central obesity and elevated liver enzymes.

Nonalcoholic fatty liver disease is commonly associated with obesity, a growing epidemic worldwide. A new large, population-based investigation has shown a statistically significant association between central adiposity and elevated liver enzymes. This finding adds to the growing research specifically linking central adiposity, and more specifically, visceral adiposity, with adverse health effects.

Hypovitaminosis D-induced pain.

Vitamin D deficiency is a problem of considerable magnitude that has reemerged as a major public health issue in the United States and several other developed countries. Vitamin D plays a crucial role in calcium homeostasis in the body. Hypovitaminosis D leads to osteomalacia and increased risk of fractures, especially in the elderly. Preliminary research suggests that vitamin D can prevent certain types of cancer and autoimmune diseases. A recent large study has shown the association between severe hypovitaminosis D and persistent, non-specific musculoskeletal pain, further suggesting that patients with no apparent cause of pain should be assessed and possibly treated for vitamin D deficiency.

A therapeutic approach to wean total parenteral nutrition in the management of short bowel syndrome: three cases using nocturnal enteral rehydration.

Short bowel syndrome is characterized by severe dehydration and malnutrition and requires total parenteral nutrition (TPN). Prolonged TPN has serious complications. Caloric requirements can be met orally but oral fluid replacement is problematic. Noncompliance and an inability to discontinue TPN earlier increase the likelihood of complications. Discontinuation of parenteral support requires an assessment of gastrointestinal anatomy and absorption capacity. Fluids must be replaced independently of feedings because the osmotic gradients decrease fluid absorption. Nocturnal enteral rehydration is an intervention using oral rehydration solutions through percutaneous endoscopic gastrostomy tubes at night. Patients given nocturnal enteral rehydration discontinued TPN earlier and had improved fluid absorption.

New support for branched-chain amino acid supplementation in advanced hepatic failure.

Nutritional supplementation with branched-chain amino acids (BCAA) has been a topic of considerable debate for more than two decades. Several studies have demonstrated that supplementation with BCAA is associated with improvement of the catabolic state commonly seen in people with cirrhosis, whereas other studies have showed an improvement in portosystemic encephalopathy in patients with liver disease. Some studies have also shown there to be no benefit in BCAA supplementation in advanced cirrhosis. A recent large clinical trial showed that long-term BCAA supplementation may be useful in preventing progressive hepatic failure and improving liver function in some patients.

A critical interaction: leptin and ghrelin.

Continuing research has increased our understanding of regulatory factors involving appetite, food intake, and energy metabolism. There appears to be a complex interaction among insulin, leptin, and ghrelin. A new study explored these interactions and indicates that leptin may regulate ghrelin levels and affect body weight changes.

Finding a place for immunonutrition.

The role of certain nutrients that seem to have pharmacologic effects on immune and inflammatory parameters has been studied over the last two decades. This area of research is called immunonutrition. A recent study administered a combination of immunonutrients perioperatively in well nourished gastrointestinal cancer patients undergoing elective surgery. The rate of infectious complications and length of hospital stay was decreased in those receiving immunonutrients compared with patients receiving no nutritional support. The role of the individual components of this immunonutrition and the clinical trials of similar combinations in surgical gastrointestinal cancer patients are reviewed.

The Metabolic Syndrome: where are we and where do we go?

The Metabolic Syndrome, also known as Syndrome X, refers to a constellation of atherosclerotic risk factors, including insulin resistance, hyperinsulinemia, dyslipidemia, essential hypertension, and abdominal obesity. We review four major published studies involving animals and humans that may be linked together in a unified hypothesis and justify a comprehensive approach in the treatment of this ever-increasing syndrome.

Effects of soybean extract on morphology and survival of Caco-2, SW620, and HT-29 cells.

Soybean consumption may be beneficial to prevention of certain human cancers. Low incidence of colon cancer in Asian countries is associated with consumption of soybean products. A limited number of human and animal studies suggested that soybean consumption might prevent colon cancer; other studies did not support this conclusion. Therefore, it is important to understand the biological effects of soybeans on colon cells. In the present study, cultures of Caco-2, SW620, and HT-29 cells were treated with soybean extract, the soluble fraction of a soybean product. The crude extract contains proteins and many soluble components of soybeans. After incubation with soybean extract (1-6%, vol/vol) for 24 h, most Caco-2 cells were found to contain numerous vacuoles within the cytoplasm and to become very flat. Exposure to > 6% soybean extract resulted in cell death and giant vacuoles. Soybean extract (0.25-2%) induced small vacuoles within the cytoplasm of SW620 cells. SW620 cells detached from culture dishes at > 2% soybean extract. Exposure to 0.5-2% soybean extract produced vacuoles within HT-29 cells similar to those observed in SW620 cells. Soybean extract significantly reduced density of Caco-2, SW620, and HT-29 cells. Reducing protein content of soybean extract reduced but did not abolish its effects on colon cells. Purified genistein (12.5 micrograms/ml) was capable of producing morphological changes similar to those observed after treatment of colon cells with soybean extract. Assays using annexin V-propidium iodide demonstrated that treatment of Caco-2 and SW620 cells with soybean extract increased cell death. Membranes of vacuoles in soybean-treated Caco-2 and SW620 cells were labeled with Texas red-conjugated wheat germ agglutinin, a cytological marker for the Golgi apparatus. Exposure to soybean extract enhanced protein levels of Rab6, a small GTP-binding protein that is involved in regulation of membrane traffic of the Golgi apparatus. Data from this study suggest that exposure to soybean extract or isoflavones affects morphology and survival of colon cancer cells and that the response to soybean extract varies depending on the cell lines examined.

Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants.

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.