Outcomes in Patients with Left Ventricular Assist Devices, Pacemakers, and Implantable Cardioverter Defibrillators Undergoing Single Balloon Enteroscopy.

OBJECTIVES: Obscure overt gastrointestinal bleeding can be challenging to evaluate in patients with electronic cardiac devices such as continuous flow left ventricular assist devices (LVADs), pacemakers (PPMs), and implantable cardioverter defibrillators (ICDs). Limited data exist on the utility and safety of single balloon enteroscopy (SBE) in patients with cardiac devices. We aimed to evaluate the safety, efficacy, diagnostic, and therapeutic outcomes of the aforementioned devices in patients undergoing SBE. METHODS: A retrospective study was performed using the medical records of 57 patients undergoing SBE at our institution from 2010 to 2014. Patients were divided into two groups: those with cardiac devices and those without. Data on comorbidities, complications, findings, diagnostic, and therapeutic yield were compared. t Test and logistic regression assessed the association between dependent and independent variables. For continuous data, the results were summarized as mean difference and standard deviation. For dichotomous data, the results were summarized as odds ratio and 95% confidence intervals. RESULTS: The overall age in patients with cardiac devices was 67.89 ± 6.96 versus 66.03 ± 11.95 years in the control. The cardiac device group was composed of 42.1% women; the control comprised 21.1% women. There were 19 patients with cardiac devices; 8 (LVAD + ICD), 1 (LVAD + PPM + ICD), 2 (PPM + ICD), 6 (PPM), 2 (ICD); 38 patients were in the control group. Patients with cardiac devices were hospitalized more often than patients without devices; this finding was not statistically significant (odds ratio 1.826, 95% confidence interval 0.544-6.128, P = 0.389). Procedure times were longer in the cardiac device group, 65.16 ± 49.92 minutes, when compared with the control, 57.40 ± 20.42, but it also did not reach statistical significance (mean difference 7.758, 95% confidence interval -11.360 to 26.876, P = 0.049). There was no statistically significant difference in major or minor events between patients with cardiac devices and the control group. Diagnostic and therapeutic yield and rebleeding rates were similar across both groups. CONCLUSIONS: Patients in the cardiac device group did not appear to be at any more significant risk than those without cardiac devices. Furthermore, diagnostic and therapeutic yield and rebleeding rates appear to be similar across both groups. Clinicians may perform SBE in these patients safely and effectively, with good overall outcomes.

Advances in the Endoscopic Diagnosis of Barrett Esophagus.

BACKGROUND: Barrett esophagus (BE) continues to be a major risk factor for developing esophageal adenocarcinoma. METHODS: We review the risk factors, diagnosis, and management of BE, with an emphasis on the most current endoscopic diagnostic modalities for BE. RESULTS: Novel diagnostic modalities have emerged to address the inadequacies of standard, untargeted biopsies, such as dye-based and virtual chromoendoscopy, endoscopic mucosal resection, molecular biomarkers, optical coherence tomography, confocal laser endomicroscopy, volumetric laser endomicroscopy, and endocytoscopy. Treatment of BE depends on the presence of intramucosal cancer or dysplasia, particularly high-grade dysplasia with or without visible mucosal lesions. CONCLUSIONS: Recent advances in endoscopic diagnostic tools demonstrate promising results and help to mitigate the shortcomings of the Seattle protocol. Future research as well as refining these tools may help aid them in replacing standard untargeted biopsies.

Capsule Studies Performed in a Tertiary Care Center Versus Community Referrals Prior to Single-Balloon Enteroscopy: Does It Matter?

BACKGROUND AND AIMS: Within the community, patients with positive capsule endoscopy (CE) are often referred to centers performing balloon-assisted enteroscopy. There is limited data evaluating the concordance and diagnostic/therapeutic yield of CE performed in the community versus CE conducted at institutions experienced with enteroscopy. The primary aim of this retrospective study was to evaluate the concordance between CE and SBE after CE was performed either in the community or at our tertiary care center. METHODS: A total of 141 patients were analyzed after selecting patients undergoing evaluation of obscure GI bleeding from January 2010 to May 2014. Forty-seven CE were performed inside and the remaining 94 CE were performed at outside institutions prior to single-balloon enteroscopy at our institution. Agreement beyond chance was evaluated using kappa coefficient. A p value <5% was considered significant. RESULTS: The most frequent findings on CE were vascular lesions in 39 patients (41.5%) within the referral group and 23 within inside patients (48.9%), followed by active bleeding/clots in 23 patients (24.5%) and in 14 patients (29.8%) respectively. There was a fair degree of concordance in the referral group for vascular lesions 0.23 (0.03-0.42) compared to a good degree in the inside group 0.65 (0.44-0.87). Fair agreement was found looking at ulcers within the referral group 0.29 (0.06-0.65) compared to a moderate agreement in the inside group 0.55 (0.17-0.94). CONCLUSIONS: Degree of concordance for vascular lesions and ulcers was significantly higher for patients undergoing CE at our institution compared to those referred from the community. Patients referred to tertiary care centers for balloon-assisted enteroscopy may benefit from advanced endoscopists re-reading the capsule findings or even potentially repeating CE in hemodynamically stable patients if the study is not available.

Increased Expression of the Glucose Transporter Type 1 Gene Is Associated With Worse Overall Survival in Resected Pancreatic Adenocarcinoma.

OBJECTIVES: There is currently no reliable method to predict the risk of relapse after curative resection of early-stage pancreatic adenocarcinoma. Increased glucose metabolism observed on F-fluorodeoxyglucose positron emission tomography (PET) by malignant cells, the Warburg effect, is a well-known characteristic of the malignant phenotype. We investigated the role of glucose transporter type 1 (GLUT-1) gene expression, a glucose cell plasma membrane transporter, in early-stage pancreatic cancer. METHODS: Associations between GLUT-1 gene expression with PET maximum standardized uptake values and histologic grade were investigated in early-stage pancreatic adenocarcinoma patients. Multivariate analysis was conducted to determine predictors of prognosis. Cox proportional hazard model was used for survival analysis. RESULTS: Sixty-three patients had GLUT-1 gene analysis performed, and 50 patients had both GLUT-1 analysis and PET scan. Patients with high GLUT-1 gene expression had a decreased overall survival by univariate analysis using Cox proportional hazard model (hazard ratio, 2.82; P = 0.001) and remained significant on multivariate analysis (hazard ratio, 2.54; P = 0.03). There was no correlation of GLUT-1 gene expression with histologic grade or PET maximum standardized uptake values. CONCLUSIONS: Increased GLUT-1 gene expression was associated with a decreased overall survival in pancreatic adenocarcinoma. This supports increased GLUT-1 gene expression as a potential prognostic marker in resected pancreatic adenocarcinoma.

Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas.

BACKGROUND: Limited knowledge exists about the effects chronic hepatitis C virus (HCV) infection has in the development of colorectal adenomas (CRA). Data regarding the association between chronic HIV infection and the development of CRA is scarce as well. We aim to determine if there is an association between the development of CRA and chronic infection with HCV and HCV/HIV co-infection. METHODS: From July 1, 2009 to March 31, 2011 a total of 2,051 patients that underwent colonoscopy were included in our study. The population was divided into 2 study groups: those patients who tested positive for HCV, and HCV/HIC; the control groups consisted of patients whose results were negative. Fisher's exact χ(2) test for categorical variables and t-test for continuous variables was used to analyze data between groups. Logistic regression was performed to obtain odds ratios (OR). RESULTS: CRA detection was higher in the HCV than in the control group (26.3% vs. 20.2%; P=1.02); Likewise, the incidence of CRA (25.5% vs. 20.8%; P=0.63) was higher in the co-infection group. However, in both of the study groups this difference was non-statistical. CONCLUSIONS: A higher detection rate of CRP was seen in the HCV population; however, it failed to reach statistical significance. Whether co-infection with HIV/HCV increases the incidence of CRA and/or has a synergistic effect remains to be determined. The small sample population and the retrospective single institution nature of our study, as well as other confounders may have contributed to our negative results. However, our findings question whether HCV and HIV/HCV co-infected patients will benefit from screening colonoscopy at an earlier age. This issue merits further investigation with a large multi-center prospective study.

Timing of single balloon enteroscopy: significant or not?

BACKGROUND: The development of balloon assisted enteroscopy (BAE) has revolutionized diagnostic and therapeutic modalities for small-bowel disorders. Although the role of emergent esophagogastroduodenoscopy and colonoscopy for upper and lower gastrointestinal bleeding is well defined, there is scarce data with regard to emergent BAE for gastrointestinal bleeding. STUDY: We performed a retrospective cohort study including 110 hospitalized patients with obscure gastrointestinal bleeding who underwent single balloon enteroscopy (SBE) between January 2010 and August 2013. Patients were divided into two groups based on procedures performed emergently (within 24 hours) versus non-emergently (greater than 24 hours). Data on patient demographics, hemodynamic characteristics, type of obscure bleed, lesions identified, location of lesions, endoscopic intervention performed, need for further surgical or radiological intervention, diagnostic and therapeutic yield, and adverse events were compared between groups. Independent samples t test and Fisher's exact test were used to assess the association between dependent and independent variables. For continuous data, the results were summarized as mean difference and 95 % confidence intervals (CI), and for binary as odds ratio and 95 %CI. RESULTS: Although patients in the group where enteroscopy was performed within 24 hours had a significantly higher incidence of radiological intervention (10.0 % vs. 0.0 %, P = 0.019), the diagnostic and therapeutic yields between the two groups were not significantly different. Additionally, there were no statistically significant differences between the groups for overt and occult bleeding, transfusion requirements, type and location of lesions, endoscopic intervention performed, or adverse events. Hospital stay was shorter in the patients who had SBE within 24 hours of admission (6.2 vs. 11.3 days, P < 0.001). CONCLUSIONS: Although the diagnostic and therapeutic yields of SBE were not significantly different between patients having the procedure within 24 hours and those having it later, the early SBE group required more interventional radiology procedures. While endoscopists may not necessarily have to perform emergent assessment within 24 hours in patients with obscure gastrointestinal bleeding (OGIB) for greater diagnostic or therapeutic yield, early intervention may allow for earlier stabilization and thus shorter hospital stays. Prospective studies further evaluating these findings are indicated.

The safety and efficacy of single balloon enteroscopy in the elderly.

BACKGROUND: Single balloon enteroscopy (SBE) is an important tool in the management of small bowel disease with limited data available on its performance in the elderly. We aimed to evaluate the safety, efficacy, diagnostic and therapeutic outcomes of SBE in the elderly. METHODS: A retrospective review was performed on 366 patients undergoing 428 SBEs from 2010 to 2014. Patients were divided into different age groups: control <55, 55-64, 65-74 and ⩾75 years. Data on comorbidities, complications, findings, diagnostic and therapeutic yield were compared between groups. RESULTS: Anterograde and retrograde SBE were performed in 340 and 49 patients, respectively, with 63 patients requiring more than 1 procedure. Diagnostic yield was significantly higher for age ⩾75 years compared with <55, 66.3% versus 50%, odds ratio (OR) 1.97 [95% confidence interval (CI) 1.14-3.41]. Therapeutic yield was significantly higher in all three older age groups compared with <55 years, 20.3%: 55-64 years, 44.4%, OR 3.13(95% CI 1.7-5.78); 65-74 years, 42%, OR 2.84 (95% CI 1.59-5.06); and >75 years, 47.5%, OR 3.55 (95% CI 1.96-6.43). No significant difference was seen between age groups in complications or failures. Our overall complication rate was 2.3% with 5 minor and 5 major complications. There was a higher yield of angioectasias in the elderly. Argon plasma coagulation (APC) and multipolar electrocoagulation were used more often in older age groups. CONCLUSION: SBE is safe in elderly patients and delivers higher diagnostic and therapeutic yields compared to younger patients. The elderly are more likely to have angioectasias and undergo APC and electrocoagulation.

Metabolic Activity by 18F-FDG-PET/CT Is Prognostic for Stage I and II Pancreatic Cancer.

PURPOSE: Metabolic activity, as defined by F-FDG uptake on PET, is a prognostic marker for multiple malignancies; however, no study has examined the prognostic value of imaging with FDG PET in stage I and II pancreatic cancer. We examined the value of PET FDG uptake in early-stage pancreatic cancer patients. METHODS: We identified patients with early-stage pancreatic cancer (I-II) who had FDG PET scan performed as part of their preoperative evaluation. The patients were divided into either high or low FDG uptake according to the median primary tumor standard uptake value (SUVmax). Our primary end points were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier estimate was used for survival analysis. Pathologic data were compared using the Fisher exact and χ tests. RESULTS: One hundred five patients were identified: 51 patients with low FDG uptake and 54 patients with high FDG uptake. Eighty-five patients (81%) had PET avid tumors, whereas 20 (19%) patients did not. High FDG uptake correlated with pathologic stage (P = 0.012). Patients with low FDG uptake had significantly better median OS than patients with high FDG uptake (28 vs. 16 months; P = 0.036). Patients with low-FDG uptake had significantly longer median RFS than patients with high FDG uptake (14 vs. 12 months; P = 0.049). CONCLUSIONS: Low FDG uptake in PET scans in patients with stage I and II pancreatic cancer correlates with improved OS and RFS. This supports the concept that glucose metabolic pathways are important in pancreatic cancer biology and that PET scan activity can be used as a prognostic biomarker after pancreatectomy.

Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications.

Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer.

Establishing the link between hepatitis B virus infection and colorectal adenoma.

BACKGROUND: Chronic hepatitis B (CHB) infection has been associated with malignancy, most notably hepatocellular carcinoma. Previous research has shown that hepatitis C is associated with increased colorectal adenomas and neoplasia. Currently, there are no studies on the association of CHB and colorectal adenomas. We aimed to identify a possible link between CHB and colorectal adenoma. METHODS: A retrospective chart review was performed on 588 consecutive patients undergoing screening or diagnostic colonoscopy that were previously screened or diagnosed with hepatitis B. Comparisons between categorical variables were analyzed with Chi Square test and t-test for continuous variables. Unconditional logistic regression was used to generate age-, gender-and race-adjusted odds ratios and their 95% confidence intervals (CI) comparing medication users with non-users. Statistical analyses were performed with SAS 9.3 software. RESULTS: A total of 487 patients were analyzed in the control group vs. 71 in the hepatitis B group. The adenoma detection rate was 23.9% in hepatitis B vs. 15.9% in the non-hepatitis B group for all cause colonoscopy; however this did not reach statistical significance. There was a significantly higher number of adenomas present in the distal colon compared to control (OR =2.16; 95% CI, 1.06-4.43; P=0.04). There were no significant findings between hepatitis B infection with size, multiplicity or presence of proximal adenomas. There was a significant difference noted in regards to smoking history, BMI and age between two groups. CONCLUSIONS: Although the adenoma detection rate was higher in hepatitis B population vs. the non-hepatitis B group this did not reach statistical significance. However, we did find an association between CHB infection and the presence of distal colorectal adenomas. Larger prospective studies are needed to strengthen our findings along with future studies examining hepatitis B virus (HBV) and mechanisms inducing colorectal carcinogenesis.

Annexin A8 Is a Prognostic Marker and Potential Therapeutic Target for Pancreatic Cancer.

OBJECTIVES: We investigated whether annexin A8 (A-A8), a Ca-binding protein overexpressed in pancreatic cancer, plays a role in cell growth and migration and investigated its association with pancreatic cancer prognosis. METHODS: Clinicopathological features and associations between increased A-A8 expression (determined by immunohistochemistry) and histologic grade were studied in a tissue microarray of 90 patients with resected stage I/II pancreatic cancer. We investigated A-A8's effect on cell migration, proliferation, and colony formation in 2 pancreatic cancer cells (BXPC-3 and Panc-1). Statistical analyses included Fisher exact test, t test, analysis of variance, and survival analysis. RESULTS: Western blot showed increased A-A8 expression in human pancreatic cancer cells, with A-A8 knockdown in BXPC-3 and Panc-1 cells demonstrating decreased cell viability (P = 0.017 and P = 0.001), migration (2.5 vs 0.9 mm and 1.6 vs 1 mm at 96 hours; P = 0.048 and P = 0.004), and colony formation (approximately 75% and 40% from scramble; P ≤ 0.01), respectively. In our tissue microarray, A-A8 expression increased 5.9-fold (r = 0.31; P = 0.019) from low- to high-grade tumors, correlating with tumor grade (r = 0.23; P = 0.027). In addition, high A-A8 expression was associated with a decreased 5-year survival (P = 0.042). CONCLUSIONS: Our study is the first showing that increased A-A8 expression is associated with poor prognosis in early-stage pancreatic cancer, thus supporting its further investigation as a future therapeutic target and prognostic marker.

Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma.

The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC) are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment decision-making process. To derive a prognostic gene signature for patients with early stage PDAC, a PDAC cohort from Moffitt Cancer Center (n = 63) was used with overall survival (OS) as the primary endpoint. This was further evaluated using an independent microarray cohort dataset (Stratford et al: n = 102). Technical validation was performed by NanoString platform. A prognostic 15-gene signature was developed and showed a statistically significant association with OS in the Moffitt cohort (hazard ratio [HR] = 3.26; p<0.001) and Stratford et al cohort (HR = 2.07; p = 0.02), and was independent of other prognostic variables. Moreover, integration of the signature with the TNM staging system improved risk prediction (p<0.01 in both cohorts). In addition, NanoString validation showed that the signature was robust with a high degree of reproducibility and the association with OS remained significant in the two cohorts. The gene signature could be a potential prognostic tool to allow risk-adapted stratification of PDAC patients into personalized treatment protocols; possibly improving the currently poor clinical outcomes of these patients.

Ethnic disparities in the risk of colorectal adenomas associated with lipid levels: a retrospective multiethnic study.

BACKGROUND: Although data exists showing that uncontrolled lipid levels in white and black patients is associated with colorectal adenomas, there are currently no studies looking only at the Hispanic population. PURPOSE: With the rapid increase in the Hispanic population, we aimed to look at their risk of colorectal adenomas in association with lipid levels. METHODS: We retrospectively analyzed 1473 patients undergoing colonoscopy from 2009 to 2011 at a community hospital. Statistical analysis was performed using Chi-squared for categorical variables and t test for continuous variables with age-, gender-, and race-adjusted odds ratios. Unconditional logistic regression model was used to estimate 95 % confidence intervals (CI). SAS 9.3 software was used to perform all statistical analysis. RESULTS: In our general population, there was an association with elevated triglyceride levels greater than 150 and presence of multiple colorectal adenomas with odds ratio (OR) 1.60 (1.03, 2.48). There was an association with proximal colon adenomas and cholesterol levels between 200 and 239 with OR 1.57 (1.07, 2.30), and low-density lipoprotein (LDL) levels of greater than 130 with OR 1.54 (1.04, 2.30). There was no association between high-density lipoproteins (HDL) levels and colorectal adenomas. The Hispanic population showed no statistical correlation between elevated triglycerides, cholesterol, or LDL with the presence, size, location, or multiplicity of colorectal adenomas. CONCLUSIONS: We found a significant correlation between elevated lipid levels and colorectal adenomas in white and black patients; however, there was no such association in the Hispanic population. This finding can possibly be due to environmental factors such as dietary, colonic flora, or genetic susceptibility, which fosters further investigation and research.

Low bone mineral density linked to colorectal adenomas: a cross-sectional study of a racially diverse population.

BACKGROUND: Epidemiologic studies suggest that lower bone mineral density (BMD) is associated with an increased risk for colorectal adenoma/cancer, especially in postmenopausal women. The aim of this study is to investigate the association between osteopenia and/or osteoporosis and colorectal adenomas in patients from a New York community hospital. METHODS: We performed a cross-sectional observational study on 200 patients who underwent screening colonoscopies and bone density scan (dual-energy X-ray absorptiometry) at Nassau University Medical Center from November 2009 to March 2011. Among these, 83 patients were identified as osteoporosis (T score of -2.5 or below) and 67 were osteopenia (T score between -1.0 and -2.5). Logistic regression model was performed to assess the association between osteopenia and/or osteoporosis and colorectal adenomas. RESULTS: Among the patients with osteopenia and osteoporosis, the mean ages were 59.1 years [standard deviation (SD) =8.9] and 61.5 (SD =8.9), respectively. There were 94.0%, 85.1% and 74.7% women, respectively, in normal BMD, osteopenia and osteoporosis groups. The prevalence of colorectal adenomas was 17.9% and 25.3% in the osteopenia and osteoporosis groups, respectively, and 18.0% in the normal BMD group. After adjustment for potential confounders including age, sex, race, body mass index (BMI), tobacco use, alcohol use, history of diabetes, hypertension, or dyslipidemia, osteoporosis was found to be associated with presence of colorectal adenomas more than 2, compared to the normal BMD group. No significant associations were found for the prevalence, size, and location of adenomas. CONCLUSIONS: Our study suggests that osteoporosis is significantly associated with the presence of multiple colorectal adenomas. Prospective studies with a larger sample size are warranted in the future.

Ethnic disparities in the risk of colorectal adenomas associated with aspirin and statin use: a retrospective multiethnic study.

BACKGROUND: Although data on the inverse association between colorectal adenomas (CRA) and daily aspirin or statin therapy exists in white and black patients, scarce data exists on these associations in the Hispanic population. With a rapidly increasing Hispanic population in the United States, defining the association in Hispanics is crucial. METHODS: The study sample included 1,843 consecutive patients who underwent a colonoscopy (screening or diagnostic) from 2009 to 2011 at a community hospital in East Meadow, New York. Data was then extracted from patient charts regarding aspirin and/or statin use. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were calculated to assess the association between colonoscopy findings and aspirin, statin, or aspirin/statin use. RESULTS: In our total population including all races, aspirin user had an increased risk for having two or more adenomas (OR =1.73, 95% CI: 1.00, 2.99, P=0.05) and presence of an adenoma in the proximal colon (OR =1.66, 95% CI: 1.07, 2.58, P=0.02). In the total study population, those who used both statin and aspirin had an increased risk for having two or more adenomas (OR =2.56, 95% CI: 1.21, 5.39, P=0.01). In the Hispanic population, users of both medications had an increased risk for having two or more adenomas (OR =19.04, 95% CI: 1.30, 280.09, P=0.03), adenoma present in the distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01) and largest adenoma in distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01). CONCLUSIONS: Aspirin use and aspirin/statin use was associated with abnormal colonoscopy findings, particularly in the Hispanic population. These findings may be due to environmental factors such as dietary, colonic flora, or genetic susceptibility. The findings warrant further investigational research, particularly in Hispanics.