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WATER II (80-150 mL) procedural outcomes.
Desai, M, Bidair, M, Bhojani, N, Trainer, A, Arther, A, Kramolowsky, E, Doumanian, L, Elterman, D, Kaufman, RP, Lingeman, J, et al
BJU international. 2019;(1):106-112
Abstract
OBJECTIVES To present early safety and feasibility data from a multicentre prospective study (WATER II) of aquablation in the treatment of symptomatic men with large-volume benign prostatic hyperplasia (BPH). METHODS Between September and December 2017, 101 men with moderate-to-severe BPH symptoms and prostate volume of 80-150 mL underwent aquablation in a prospective multicentre international clinical trial. Baseline demographics and standardized postoperative management variables were carefully recorded in a central independently monitored database. Surgeons answered analogue scale questionnaires on intra-operative technical factors and postoperative management. Adverse events up to 1 month were adjudicated by an independent clinical events committee. RESULTS The mean (range) prostate volume was 107 (80-150) mL. The mean (range) operating time was 37 (15-97) min and aquablation resection time was 8 (3-15) min. Adequate adenoma resection was achieved with a single pass in 34 patients and with additional passes in 67 patients (mean 1.8 treatment passes), all in a single operating session. Haemostasis was achieved using either a Foley balloon catheter placed in the bladder under traction (n = 98, mean duration 18 h) or direct tamponade using a balloon inflated in the prostate fossa (n = 3, mean duration 15 h). No patient required electrocautery for haemostasis at the time of the primary procedure. The mean length of stay after the procedure was 1.6 days (range same day to 6 days). The Clavien-Dindo grade ≥2 event rate observed at 1 month was 29.7%. Bleeding complications were recorded in 10 patients (9.9%) during the index procedure hospitalization prior to discharge, and included six (5.9%) peri-operative transfusions. CONCLUSIONS Aquablation is feasible and safe in treating men with men with large prostates (80-150 mL). The 6-month efficacy data are being accrued and will be presented in future publications (ClinicalTrials.gov number, NCT03123250).
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Detection rates of premalignant polyps during screening colonoscopy: time to revise quality standards?
Ross, WA, Thirumurthi, S, Lynch, PM, Rashid, A, Pande, M, Shafi, MA, Lee, JH, Raju, GS
Gastrointestinal endoscopy. 2015;(3):567-74
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Abstract
BACKGROUND Standards for the detection of adenomas during screening colonoscopy are widely used to measure examination quality. No such standards exist for sessile serrated adenomas (SSAs). OBJECTIVE To measure both the adenoma detection rate (ADR) and SSA detection rate (SSADR) during screening colonoscopy before and after quality improvement/financial incentive measures. DESIGN Retrospective determination of baseline ADR/SSADR by the endoscopist, followed by prospective collection of data after informing physicians of baseline detection rates. SETTING Tertiary cancer center with a large cancer screening program. PATIENTS A total of 2833 average-risk colorectal cancer screening patients 50 to 75 years of age undergoing initial colonoscopy. DATA COLLECTION Electronic medical records for indication and demographics, endoscopy report, and pathology report. MAIN OUTCOME MEASUREMENTS Detection rates of adenomas and SSAs by sex. RESULTS The overall ADR in male and female patients was 50.6% and 36.6%, respectively. The overall detection rate of advanced adenomas in male and female patients was 12.4% and 6.5%, respectively. The overall SSADR in male and female patients was 10.1% and 7.1%, respectively. In 108 patients (3.8% of entire group), SSAs were the only premalignant lesions found. Detection rates of both types of premalignant polyps improved over time but did not reach statistical significance. LIMITATIONS Single-center experience with limited sample size and small group of endoscopists. CONCLUSION ADRs far in excess of current standards are achievable. Cecal withdrawal time is associated with the ADR. Prevalence of SSA rivals that of advanced adenomas and is greater than current medical literature suggests. The combination of monitoring and financial incentives did not result in statistically significant improvement in ADRs.
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Relationship between detection of adenomas by flexible sigmoidoscopy and interval distal colorectal cancer.
Rogal, SS, Pinsky, PF, Schoen, RE
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2013;(1):73-8
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BACKGROUND & AIMS Low rates of adenoma detection by colonoscopy have been associated with increased rates of interval colorectal cancer. We evaluated the relationship between the rate of adenoma detection by flexible sigmoidoscopy and interval distal colorectal cancer. METHODS We analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer screening trial, which used flexible sigmoidoscopy as a colorectal cancer screening modality (46,835 subjects; 66,711 examinations by 93 examiners). An adenoma detection rate was defined for each examiner as the number of examinations that identified adenomas (confirmed by pathology analysis) divided by the total number of screening examinations. Interval cancers were defined as cancers presumed detectable but not detected, which was based on the stage at diagnosis and the elapsed time from screening to diagnosis. RESULTS The Prostate, Lung, Colorectal, and Ovarian Cancer study identified 32 interval distal cancers. The incidence of interval cancer for individuals screened by examiners in the lowest quartile of distal adenoma detection (2.0%-7.2%) was 9.0/10,000 examinations, whereas the incidence of interval cancers was lower among individuals whose examiners were in higher quartiles of adenoma detection, ranging from 3.0 to 5.4/10,000 examinations. The odds of interval distal cancer were significantly increased for patients of examiners in the lowest quartile of distal adenoma detection (<7.2%), with an adjusted odds ratio of 2.4 (95% confidence interval, 1.1-5.0; P = .02). CONCLUSIONS Lower levels of adenoma detection by flexible sigmoidoscopy increase the risk for interval distal cancer. Detection of distal adenomas is a marker of the performance quality of flexible sigmoidoscopy.
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Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention.
Thompson, P, Roe, DJ, Fales, L, Buckmeier, J, Wang, F, Hamilton, SR, Bhattacharyya, A, Green, S, Hsu, CH, Chow, HH, et al
Cancer prevention research (Philadelphia, Pa.). 2012;(12):1381-93
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COX inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women, ages 40 to 80 years, were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 μg daily as selenized yeast), or double placebo. The trial was initiated in November 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared with placebo, as determined by surveillance colonoscopy conducted three to five years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n = 1,621) was completed in November 2008. A further 200 patients with one or more advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n = 1,824) was completed in January 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; body mass index (BMI) 29.1 ± 5.1; 47% taking low-dose aspirin while on trial; 20% with three or more adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type II diabetes will also be reported.
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Potential role for retinoic acid in patients with Cushing's disease.
Pecori Giraldi, F, Ambrogio, AG, Andrioli, M, Sanguin, F, Karamouzis, I, Corsello, SM, Scaroni, C, Arvat, E, Pontecorvi, A, Cavagnini, F
The Journal of clinical endocrinology and metabolism. 2012;(10):3577-83
Abstract
CONTEXT Cushing's disease, i.e. cortisol excess due to an ACTH-secreting pituitary adenoma, is a rare disorder with considerable morbidity and mortality but no satisfactory medical treatment as yet. Experimental data have recently shown that retinoic acid restrains ACTH secretion by tumoral corticotropes. OBJECTIVE Our objective was to evaluate the efficacy and safety profile of retinoic acid treatment in patients with Cushing's disease. DESIGN This is a prospective, multicenter study. Seven patients with Cushing's disease (three men, four postmenopausal women) were started on 10 mg retinoic acid daily and dosage increased up to 80 mg daily for 6-12 months. ACTH, urinary free cortisol (UFC), and serum cortisol as well as clinical features of hypercortisolism and possible side effects of retinoic acid were evaluated at baseline, during retinoic acid administration, and after drug withdrawal. RESULTS A marked decrease in UFC levels was observed in five patients; mean UFC levels on retinoic acid were 22-73% of baseline values and normalization in UFC was achieved in three patients. Plasma ACTH decreased in the first month of treatment and then returned to pretreatment levels in responsive patients whereas no clear-cut pattern could be detected for serum cortisol. Blood pressure, glycemia, and signs of hypercortisolism, e.g. body weight and facial plethora, were ameliorated to a variable extent on treatment. Patients reported only mild adverse effects, e.g. xerophthalmia and arthralgias. CONCLUSIONS Long-term treatment with retinoic acid proved beneficial and well tolerated in five of seven patients with Cushing's disease. This represents a novel, promising approach to medical treatment in Cushing's disease.
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Usefulness of an intensive bowel cleansing strategy for repeat colonoscopy after preparation failure.
Ibáñez, M, Parra-Blanco, A, Zaballa, P, Jiménez, A, Fernández-Velázquez, R, Fernández-Sordo, JO, González-Bernardo, O, Rodrigo, L
Diseases of the colon and rectum. 2011;(12):1578-84
Abstract
BACKGROUND No consensus exists regarding the optimal bowel preparation regimen for patients with poor bowel cleansing at a previous colonoscopy. OBJECTIVE We investigated the usefulness of an intensive cleansing regimen for repeat colonoscopy after previous failure of bowel preparation. DESIGN AND SETTING A prospective observational study was performed in patients undergoing colonoscopy at a university-based, tertiary referral hospital. PATIENTS AND INTERVENTION Outpatients with inadequate preparation at an index colonoscopy were offered a repeat colonoscopy and instructed to follow an intensive preparation regimen consisting of a low-fiber diet for 72 hours, liquid diet for 24 hours, bisacodyl (10 mg) in the evening of the day before the colonoscopy, and a split dose of polyethylene glycol (1.5 L in the evening before and 1.5 L in the morning on the day of the colonoscopy). MAIN OUTCOME MEASURES The adequacy of bowel cleansing was assessed according to the Boston Bowel Preparation Scale (0 or 1 on any colon segment = inadequate bowel preparation). Procedural variables, detection rates for polyps and adenomas, compliance, and tolerability of the regimen were assessed. Satisfaction with the regimen was assessed with a 10-point visual analog scale. RESULTS Of 83 patients with inadequate bowel preparation at colonoscopy, 51 underwent a second colonoscopy and were analyzed; 46 patients (90.2%) had adequate bowel cleansing at the second colonoscopy, with a mean (SD) total Boston Bowel Preparation Scale score of 7.43 (1.5) and scores of 2.31 (0.6) for the right colon, 2.49 (0.6) for the transverse colon, and 2.63 (0.6) for the left colon. Polyps, flat lesions, or flat lesions proximal to the splenic flexure were found in significantly more patients at the second colonoscopy than at the index colonoscopy. The global satisfaction score was 6.6 (2.7). LIMITATIONS The study was limited because of its open observational design, possible patient learning effect for bowel preparation at the repeat colonoscopy, and the inclusion of only outpatients. CONCLUSIONS An intensive regimen consisting of a low-fiber diet, bisacodyl, and a split dose of polyethylene glycol can achieve good colon preparation with an improved detection rate for polyps and adenomas in most patients who have had poor bowel cleansing at a previous colonoscopy.
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Iron homeostasis and distal colorectal adenoma risk in the prostate, lung, colorectal, and ovarian cancer screening trial.
Cross, AJ, Sinha, R, Wood, RJ, Xue, X, Huang, WY, Yeager, M, Hayes, RB, Gunter, MJ
Cancer prevention research (Philadelphia, Pa.). 2011;(9):1465-75
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Red meat consumption has been positively associated with colorectal cancer; however, the biological mechanism underlying this relationship is not understood. Red meat is a major source of iron, which may play a role in colorectal carcinogenesis via increased crypt cell proliferation, cytotoxicity, and endogenous N-nitrosation. In a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we prospectively evaluated multiple iron exposure parameters, including dietary intake and serum measures of iron, ferritin, transferrin, total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) in relation to incident colorectal adenoma in 356 cases and 396 matched polyp-free controls. We also investigated variation in eight key genes involved in iron homeostasis in relation to colorectal adenoma in an additional series totaling 1,126 cases and 1,173 matched controls. We observed a positive association between red meat intake and colorectal adenoma [OR comparing extreme quartiles (OR(q4-q1)) = 1.59, 95% CI = 1.02-2.49, P(trend) = 0.03]. Serum TIBC and UIBC were inversely associated with colorectal adenoma (OR(q4-q1) = 0.57, 95% CI = 0.37-0.88, P(trend) = 0.03; and OR(q4-q1) = 0.62, 95% CI = 0.40-0.95, P(trend) = 0.04, respectively). Colorectal adenoma was not associated with serum ferritin, iron, or transferrin saturation or with polymorphisms in genes involved in iron homeostasis. Serum TIBC and UIBC, parameters that have a reciprocal relationship with overall iron load, were inversely related to colorectal adenoma, suggesting that individuals with lower iron status have a reduced risk of developing colorectal adenoma.
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Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma.
Pufulete, M, Al-Ghnaniem, R, Khushal, A, Appleby, P, Harris, N, Gout, S, Emery, PW, Sanders, TA
Gut. 2005;(5):648-53
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BACKGROUND AND AIMS A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia. The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a randomised, double blind, placebo controlled, parallel design. METHODS Subjects were randomised to receive either 400 microg/day folic acid supplement (n = 15) or placebo (n = 16) for 10 weeks. Genomic DNA methylation, serum and erythrocyte folate, and plasma homocysteine concentrations were measured at baseline and post intervention. RESULTS Folic acid supplementation increased serum and erythrocyte folate concentrations by 81% (95% confidence interval (CI) 57-104%; p<0.001 v placebo) and 57% (95% CI 40-74%; p<0.001 v placebo), respectively, and decreased plasma homocysteine concentration by 12% (95% CI 4-20%; p = 0.01 v placebo). Folic acid supplementation resulted in increases in DNA methylation of 31% (95% CI 16-47%; p = 0.05 v placebo) in leucocytes and 25% (95% CI 11-39%; p = 0.09 v placebo) in colonic mucosa. CONCLUSIONS These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid.
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Risk of prostate cancer in a randomized clinical trial of calcium supplementation.
Baron, JA, Beach, M, Wallace, K, Grau, MV, Sandler, RS, Mandel, JS, Heber, D, Greenberg, ER
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2005;(3):586-9
Abstract
BACKGROUND In some studies, high calcium intake has been associated with an increased risk of prostate cancer, but no randomized studies have investigated this issue. METHODS We randomly assigned 672 men to receive either 3 g of calcium carbonate (1,200 mg of calcium), or placebo, daily for 4 years in a colorectal adenoma chemoprevention trial. Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses. Subject reports were verified by medical record review. Serum samples, collected at randomization and after 4 years, were analyzed for 1,25-(OH)2 vitamin D, 25-(OH) vitamin D, and prostate-specific antigen (PSA). We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels. RESULTS After a mean follow-up of 10.3 years, there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [unadjusted rate ratio, 0.83; 95% confidence interval (95% CI), 0.52-1.32]. Most cases were not advanced; the mean Gleason's score was 6.2. During the first 6 years (until 2 years post-treatment), there were significantly fewer cases in the calcium group (unadjusted rate ratio, 0.52; 95% CI, 0.28-0.98). The calcium risk ratio for conversion to PSA >4.0 ng/mL was 0.63 (95% CI, 0.33-1.21). Baseline dietary calcium intake, plasma 1,25-(OH)2 vitamin D and 25-(OH) vitamin D levels were not materially associated with risk. CONCLUSION In this randomized controlled clinical trial, there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect.
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Gene-specific methylation and subsequent risk of colorectal adenomas among participants of the polyp prevention trial.
Woodson, K, Weisenberger, DJ, Campan, M, Laird, PW, Tangrea, J, Johnson, LL, Schatzkin, A, Lanza, E
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2005;(5):1219-23
Abstract
Hypermethylation of tumor suppressor and other regulatory genes is thought to play an important role in colorectal neoplasia and tumorigenesis. This study examined the association between gene methylation status in baseline adenomas and subsequent adenoma recurrence in a randomized dietary intervention study, the Polyp Prevention Trial. The methylation status of four genes [CDKN2A (p16), PTGS2 (COX2), ESR1 (ER-alpha), and PGR(PR)] was determined by MethyLight in 284 baseline adenomas from 196 trial participants. The association of gene methylation with recurrence was determined using logistic regression models. Gene methylation was evaluated as percent of methylated reference, a measure of methylation of each gene relative to control DNA. ESR1methylation status was inversely associated with adenoma recurrence, odds ratio = 0.36 (95% confidence interval, 0.15-0.88; P = 0.02) for the highest compared with the lowest quartile of the ESR1methylation. Further, ESR1 methylation status was inversely associated with the recurrence of multiple adenomas, advanced adenomas, and the recurrence of adenomas in the proximal but not distal bowel. No association between CDKN2A, PTGS2, or PGR methylation and adenoma recurrence was observed. These data suggest that ESR1 methylation may play a role in subsequent adenoma recurrence.