A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density.

PURPOSE: Obesity is a known risk factor for post-menopausal breast cancer and may increase risk for triple negative breast cancer in premenopausal women. Intervention strategies are clearly needed to reduce obesity-associated breast cancer risk. METHODS: We conducted a Phase II double-blind, randomized, placebo-controlled trial of metformin in overweight/obese premenopausal women with components of metabolic syndrome to assess the potential of metformin for primary breast cancer prevention. Eligible participants were randomized to receive metformin (850 mg BID, n = 76) or placebo (n = 75) for 12 months. Outcomes included breast density, assessed by fat/water MRI with change in percent breast density as the primary endpoint, anthropometric measures, and intervention feasibility. RESULTS: Seventy-six percent in the metformin arm and 83% in the placebo arm (p = 0.182) completed the 12-month intervention. Adherence to study agent was high with more than 80% of participants taking ≥ 80% assigned pills. The most common adverse events reported in the metformin arm were gastrointestinal in nature and subsided over time. Compared to placebo, metformin intervention led to a significant reduction in waist circumference (p < 0.001) and waist-to-hip ratio (p = 0.019). Compared to placebo, metformin did not change percent breast density and dense breast volume but led to a numerical but not significant decrease in non-dense breast volume (p = 0.070). CONCLUSION: We conclude that metformin intervention resulted in favorable changes in anthropometric measures of adiposity and a borderline decrease in non-dense breast volume in women with metabolic dysregulation. More research is needed to understand the impact of metformin on breast cancer risk reduction. TRIAL REGISTRATION: ClinicalTrials.gov NCT02028221. Registered January 7, 2014, https://clinicaltrials.gov/ct2/show/NCT02028221.

Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy after Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non-Hodgkin Lymphoma: Final Results of a Phase II Study.

BACKGROUND: Radioimmunotherapy (RIT) is effective in treating relapsed/refractory follicular lymphoma (FL), with durable remissions in first-line consolidation. We hypothesized that RIT with ibritumomab tiuxetan (Zevalin®) would result in durable remissions by eliminating minimal residual disease after cytoreduction. METHODS: Patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) every 28 days, followed by Zevalin 4-6 weeks later if there was no disease progression and bone marrow biopsy showed < 25% involvement. RESULTS: Twenty-eight patients were treated, with a median age of 61 years, median of 3 prior therapies, 49% high-risk disease (Follicular Lymphoma International Prognostic Index, FLIPI), and 39% progressive disease. Three patients did not receive Zevalin due to residual bone marrow involvement. The main toxicities were cytopenias, with 11% febrile neutropenia. The overall response rate (ORR) was 72%, with 45% achieving complete response. With a median follow-up of 73 months, 1-year progression-free survival (PFS) was 38%, and median PFS was 10 months, but median overall survival (OS) was not reached. CONCLUSION: The study did not reach its primary endpoint of a 1-year PFS of 67.3%. Reasons for this could include low accrual, high-risk disease, and inadequate debulking provided by 2 cycles of ESHAP. However, this protocol was associated with tolerable toxicity, high ORR, and high OS. Further studies would optimize debulking and focus on high-risk FL patients.

Kinase-driven metabolic signalling as a predictor of response to carboplatin-paclitaxel adjuvant treatment in advanced ovarian cancers.

BACKGROUND: The biological mechanisms underlying early- and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin-paclitaxel treatment. METHODS: Tumour epithelia were isolated from two independent sets of primary EOC (n=72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection. Reverse phase protein microarrays were used to broadly profile the kinase-driven metabolic signalling of EOC with particular emphasis on the LBK1-AMPK and AKT-mTOR axes. Signalling activation was compared between early and advanced lesions, and carboplatin-paclitaxel-sensitive and -resistant tumours. RESULTS: Advanced EOCs were characterised by a heterogeneous kinase-driven metabolic signature and decreased phosphorylation of the AMPK-AKT-mTOR axis compared to early EOC (P<0.05 for AMPKα T172, AMPKα1 S485, AMPKß1 S108, AKT S473 and T308, mTOR S2448, p70S6 S371, 4EBP1 S65, GSK-3 α/ß S21/9, FOXO1 T24/FOXO3 T32, and FOXO1 S256). Advanced tumours with low relative activation of the metabolic signature and increased FOXO1 T24/FOXO3 T32 phosphorylation (P=0.041) were associated with carboplatin-paclitaxel resistance. CONCLUSIONS: If validated in a larger cohort of patients, the decreased AMPK-AKT-mTOR activation and phosphorylation of FOXO1 T24/FOXO3 T32 may help identify carboplatin-paclitaxel-resistant EOC patients.

A Phase II Exploratory Study of PXD-101 (Belinostat) Followed by Zevalin in Patients with Relapsed Aggressive High-Risk Lymphoma.

OBJECTIVE: Aggressive lymphomas (aNHL) including diffuse large B-cell lymphoma (DLBCL) have poor outcomes in relapsed refractory patients. Prior studies have demonstrated that loss of major histocompatibility complex class II (MHCII) expression in DLBCL is associated with poor survival. The objective of this single-arm phase II study was to evaluate if PXD-101 would increase MHCII expression, synergize with Zevalin, and improve clinical outcomes. METHODS: This was a single-center open-label phase II trial (NCT01686165) geared toward heavily pretreated patients with CD20-positive aNHL. The primary endpoint was overall response rate (ORR) in aNHL patients treated with 2 cycles of PXD-101 followed by restaging CT and 1 cycle of Zevalin. RESULTS: Five patients were enrolled, and all were heavily pretreated. Therapy was well tolerated, with nausea and vomiting being the most frequent adverse events. All patients progressed after receiving therapy; the study did not achieve the required ORR to proceed to the next stage. CONCLUSION: The pleotropic effects of histone deacetylase inhibition and lack of clinical biomarkers have precluded a priori identification of responding patients. Thus, while we report a negative trial of PXD-101 in combination with Zevalin, this study highlights the importance of a clinically feasible biomarker.

Randomized controlled trial of Qigong/Tai Chi Easy on cancer-related fatigue in breast cancer survivors.

BACKGROUND: Many breast cancer survivors experience fatigue, mood, and sleep disturbances. PURPOSE: This study aims to compare a meditative movement practice, Qigong/Tai Chi Easy (QG/TCE) with sham Qigong (SQG), testing effects of meditation/breath aspects of QG/TCE on breast cancer survivors' persistent fatigue and other symptoms. METHODS: This double-blind, randomized controlled trial tested 12 weeks of QG/TCE versus SQG on fatigue, depression, and sleep among 87 postmenopausal, fatigued breast cancer survivors, stages 0-III, age 40-75. RESULTS: Fatigue decreased significantly in the QG/TCE group compared to control at post-intervention (p = 0.005) and 3 months follow-up (p = 0.024), but not depression and sleep quality. Improvement occurred over time for both interventions in depression and sleep quality (all p < 0.05). CONCLUSIONS: QG/TCE showed significant improvement over time compared to SQG for fatigue, but not depression or sleep. Both QG/TCE and SQG showed improvement for two prevalent symptoms among breast cancer survivors, depression and sleep dysfunction.

A comparison of the prehospital motor component of the Glasgow coma scale (mGCS) to the prehospital total GCS (tGCS) as a prehospital risk adjustment measure for trauma patients.

OBJECTIVE: This study compared the prehospital motor component subscale of the Glasgow Coma Scale (mGCS) to the prehospital total GCS (tGCS) score for its ability to predict the need for intubation, survival to hospital discharge, and neurosurgical intervention in trauma patients. METHODS: This is a retrospective analysis of an urban level 1 trauma registry. All trauma patients presenting to the trauma center emergency department via emergency medical services from July 2008 through June 2010 were included. The area under the receiver operating characteristics curve (AUC) analysis was used to compare the predictive ability of the prehospital mGCS to tGCS for three outcomes: intubation, survival to hospital discharge, and neurosurgical intervention. Two subgroups (patients with injury severity score [ISS] ≥ 16 and traumatic brain injury [TBI] [head abbreviated injury score (AIS) ≥ 3]) were analyzed. An a priori statistically significant absolute difference of 0.050 in AUC between mGCS and tGCS for these clinical outcomes was used as a clinically significant difference. Multiple imputation was used for missing prehospital GCS data. RESULTS: There were 9,816 patients, of which 4% were intubated, 3.8% had neurosurgical intervention, and 97.1% survived to hospital discharge. The absolute difference in AUC (prehospital tGCS minus mGCS) for all cases was statistically significant for all three outcomes but did not reach the clinical significance threshold: survival = 0.010 (95% CI: 0.002-0.018), intubation = 0.018 (95% CI: 0.011-0.024), and neurosurgical intervention = 0.019 (95% CI: 0.007-0.029). The difference in AUC between tGCS and mGCS for the subgroups ISS ≥ 16 (n = 1,151) and TBI (n = 1,165) did not reach clinical significance for the three outcomes. The discriminatory ability of the prehospital mGCS was good for survival (AUC: all patients = 0.89, ISS ≥ 16 = 0.84, traumatic brain injury = 0.86) excellent for intubation (AUC: all patients = 0.95, ISS ≥ 16 = 0.91, traumatic brain injury = 0.91), and poor for neurosurgical intervention (AUC: all patients = 0.67, ISS ≥ 16 = 0.57, traumatic brain injury = 0.60). CONCLUSION: The prehospital mGCS appears have good discriminatory power and is equivalent to the prehospital tGCS for predicting intubation and survival to hospital discharge in this trauma population as a whole, those with ISS ≥ 16, or TBI.

Oesophageal sensation in response to high PCO(2) and acidic solutions in nonerosive reflux disease.

BACKGROUND: Heartburn is commonly associated with the presence of acid in the oesophageal lumen. However, in patients with nonerosive reflux disease (NERD), the mechanism by which acid traverses the mucosa is not clear. We hypothesized that the luminal acid signal traverses the oesophageal epithelium in the form of the highly permeant gas CO(2) , which then is reconverted to H(+) in the submucosa. MATERIALS AND METHODS: Ten patients with heartburn, normal upper endoscopy and increased oesophageal acid exposure (NERD patients) and 10 healthy subjects were enrolled. Perceptual responses to intraoesophageal acid (0·1 N HCl solution) and a high PCO(2) solution were determined using a randomized cross over design. Stimulus-response functions to perfusions were quantified by three parameters: lag time to symptom perception, intensity rating and perfusion sensitivity score. RESULTS: In NERD patients, the difference in lag time to typical symptom perception, intensity rating and perfusion sensitivity score between high PCO(2) and acid perfusions was statistically significant (P = 0·02, 0·01 and 0·02, respectively). However, the difference in the same perfusion parameters between acid and high PCO(2) perfusions was nonsignificant in healthy controls. When NERD and controls were compared, the difference between the different perfusion variables was nonsignificant (adjusted to age). CONCLUSIONS: In NERD subjects, acid perfusion reliably evoked heartburn symptoms of greater intensity than in healthy controls. Nevertheless, a high PCO(2) perfusion failed to produce symptoms in either group.

Randomized Crossover Trial Evaluating Detoxification of Tobacco Carcinogens by Broccoli Seed and Sprout Extract in Current Smokers.

Consumption of cruciferous vegetables, rich in the isothiocyanate glucoraphanin, is associated with reduced risk of tobacco-related cancers. Sulforaphane, released by hydrolysis of glucoraphanin, potently induces cytoprotective phase II enzymes. Sulforaphane decreased the incidence of oral cancer in the 4NQO carcinogenesis model. In residents of Qidong, China, broccoli seed and sprout extracts (BSSE) increased detoxification of air pollutants benzene and acrolein, also found in tobacco smoke. This randomized, crossover trial evaluated detoxification of tobacco carcinogens by the BSSE Avmacol® in otherwise healthy smokers. Participants were treated for 2 weeks with both low and higher-dose BSSE (148 µmol vs. 296 µmol of glucoraphanin daily), separated by a 2-week washout, with randomization to low-high vs. high-low sequence. The primary endpoint was detoxification of benzene, measured by urinary excretion of its mercapturic acid, SPMA. Secondary endpoints included bioavailability, detoxification of acrolein and crotonaldehyde, modulation by GST genotype, and toxicity. Forty-nine participants enrolled, including 26 (53%) females with median use of 20 cigarettes/day. Low and higher-dose BSSE showed a mean bioavailability of 11% and 10%, respectively. Higher-dose BSSE significantly upregulated urinary excretion of the mercapturic acids of benzene (p = 0.04), acrolein (p < 0.01), and crotonaldehyde (p = 0.02), independent of GST genotype. Retention and compliance were high resulting in early study completion. In conclusion, BSSE significantly upregulated detoxification of the tobacco carcinogens benzene, acrolein, and crotonaldehyde in current tobacco smokers.

Clinical Study of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers.

The chemopreventive effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on lung cancer risk is supported by epidemiologic and preclinical studies. Zileuton, a 5-lipoxygenase inhibitor, has additive activity with NSAIDs against tobacco carcinogenesis in preclinical models. We hypothesized that cyclooxygenase plus 5-lipoxygenase inhibition would be more effective than a placebo in modulating the nasal epithelium gene signatures of tobacco exposure and lung cancer. We conducted a randomized, double-blinded study of low-dose aspirin plus zileuton vs. double placebo in current smokers to compare the modulating effects on nasal gene expression and arachidonic acid metabolism. In total, 63 participants took aspirin 81 mg daily plus zileuton (Zyflo CR) 600 mg BID or the placebo for 12 weeks. Nasal brushes from the baseline, end-of-intervention, and one-week post intervention were profiled via microarray. Aspirin plus zilueton had minimal effects on the modulation of the nasal or bronchial gene expression signatures of smoking, lung cancer, and COPD but favorably modulated a bronchial gene expression signature of squamous dysplasia. Aspirin plus zileuton suppressed urinary leukotriene but not prostaglandin E2, suggesting shunting through the cyclooxygenase pathway when combined with 5-lipoxygenase inhibition. Continued investigation of leukotriene inhibitors is needed to confirm these findings, understand the long-term effects on the airway epithelium, and identify the safest, optimally dosed agents.

Early assessment of biophysical parameters predicts lesion formation during RF energy delivery in vitro.

BACKGROUND: There is no currently available technology to accurately predict ablation lesion size within seconds of onset of delivery of radiofrequency (RF) energy. METHODS: Changes in several biophysical characteristics of cardiac tissue in vitro within 5-15 seconds of the onset of RF energy were evaluated to predict lesion formation at 120 seconds. RF energy was applied with a 50% duty cycle to measure heating and cooling behavior of the electrode temperature sensor. Changes in impedance, phase angle, and the resulting resistance and capacitance, power, and electrode temperature variation during RF ablation were analyzed. RESULTS: A combination of electrical-based parameters measured online as early as 5, 10, and 15 seconds after onset of RF energy in vitro was found to explain 63, 75, and 76% of variability (R(2) ) of lesion volume. These correlations were better than any single parameter, particularly impedance and target temperature. CONCLUSIONS: A combination of electrical-based parameters provides better correlation with lesion formation than a single parameter and may be useful to predict lesion size during RF ablation in vivo. These parameters appear to represent changes in the tissue during heating.

Optimal surgical intervention for achalasia: laparoscopic or robotic approach.

Laparoscopic esophageal myotomy is the standard surgical intervention for achalasia. Compared to standard laparoscopic techniques, use of the robot has theoretical advantages of improved visualization and dexterity. We evaluated the University of Arizona's experience with the two alternatives to compare outcomes. Patients who underwent either laparoscopic or robot-assisted myotomy were identified from a retrospective database from 1/1/2006 to 12/31/2015. Patient demographics, prior treatment, intra-operative complications, operative time, post-operative length of stay and complications, and long-term results were compared between the two groups. We identified 35 laparoscopic and 37 robot-assisted Heller myotomies performed by multiple surgeons. Patient demographics were similar between the two groups with no statistical difference in age, gender, previous operations, pre-operative Botox or dilation treatment, or pre-op Eckardt score. In univariate analysis, the patients with the robotic procedure received a longer myotomy (5.85 cm vs. 5.56 cm for esophageal and 2.92 cm vs. 2.68 cm for gastric) and had a lower post-operative Eckardt score (0.51 vs. 1.09). A trend toward lower incidence of recurrent achalasia symptoms was found in the robotic group (0 patient vs. 4 patients) compared with those who had laparoscopic surgery (p < 0.05). Multivariate analysis showed that a longer gastric myotomy was associated with a lower recurrence rate (p = 0.0002). Both laparoscopic and robot-assisted Heller myotomy can provide definitive treatment of achalasia with good results and few complications. The mechanical advantage provided by the robotic approach may improve outcomes by providing a more complete myotomy and durable long-term result.

Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial.

A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blinded study in current heavy smokers to compare modulating effects of intermittent versus continuous low-dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Low-dose ASA suppressed urinary prostaglandin E2 metabolite (PGEM; change of -4.55 ± 11.52 from baseline 15.44 ± 13.79 ng/mg creatinine for arms combined, P = 0.02), a surrogate of COX-mediated ARA metabolism, but had minimal effects on nasal gene expression of nasal or bronchial gene-expression signatures associated with smoking, lung cancer, and chronic obstructive pulmonary disease. Suppression of urinary PGEM correlated with favorable changes in a smoking-associated gene signature (P < 0.01). Gene set enrichment analysis (GSEA) showed that ASA intervention led to 1,079 enriched gene sets from the Canonical Pathways within the Molecular Signatures Database. In conclusion, low-dose ASA had minimal effects on known carcinogenesis gene signatures in nasal epithelium of current smokers but results in wide-ranging genomic changes in the nasal epithelium, demonstrating utility of nasal brushings as a surrogate to measure gene-expression responses to chemoprevention. PGEM may serve as a marker for smoking-associated gene-expression changes and systemic inflammation. Future studies should focus on NSAIDs or agent combinations with broader inhibition of pro-inflammatory ARA metabolism to shift gene signatures in an anti-carcinogenic direction.

Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas.

BACKGROUND: Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). PATIENTS AND METHODS: Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment. Rituximab 375 mg/m2 intravenous (IV) day 1, cladribine 4 mg/m2 IV days 1 to 5, and bortezomib 1.3 mg/m2 IV days 1 and 4 were administered every 28 days for 6 cycles. RESULTS: Twenty-four patients were enrolled onto the study with a median follow-up of 38.5 months. Median age was 66.5 years, and 46% had MCL. The most common adverse events were hematologic, with febrile neutropenia in 3 patients. Neuropathy was noted in 17% of patients, of which 8% was grade 3 or above. The overall response rate was 92%. For the entire cohort, and for MCL patients, the median progression-free survival and the median overall survival were not reached. The 2-year progression-free survival was 82% for the MCL group and 54% for the iNHL group; it was 80% for treatment-naive patients and 57% for R/R patients. CONCLUSION: VCR is effective in MCL and iNHL. Although hematologic toxicity can be an issue, this study demonstrates a high response rate to a novel combination and provides an alternative option in transplant-ineligible R/R MCL and iNHL.

Baseline dietary fiber intake and colorectal adenoma recurrence in the wheat bran fiber randomized trial.

BACKGROUND: The Wheat Bran Fiber (WBF) trial was a double-blind, high-fiber versus low-fiber phase III intervention trial in which participants were randomly assigned to receive a cereal fiber supplement of either 2.0 g/day or 13.5 g/day to assess whether a high-fiber supplement could decrease risk of recurrent colorectal adenomas. Although no effect of the supplement on polyp recurrence was observed, participants consumed a baseline average of 17.5 grams of fiber per day, which may have been sufficient to protect against adenoma recurrence. Therefore, we examined whether baseline fiber intake affected colorectal adenoma recurrence or modified the effect of treatment group in the WBF trial participants. METHODS: Quartiles of baseline fiber intake were calculated on the basis of the distribution in the study population. Odds ratios (ORs) for adenoma recurrence were calculated using the lowest quartile of fiber intake as the reference. The effect of fiber from specific food sources on adenoma recurrence was also assessed. All statistical tests were two-sided. RESULTS: Adjusted ORs (95% confidence intervals) for adenoma recurrence were 0.79 (0.56 to 1.12), 0.76 (0.54 to 1.08), and 0.83 (0.57 to 1.19) for the second, third, and fourth quartiles, respectively. Fiber from the three primary food sources (fruits; breads, cereals and crackers; and vegetables) had no appreciable effect on adenoma recurrence. Baseline fiber intake also had little effect on adenoma recurrence when the population was stratified by treatment group. In addition, there was no interaction between treatment group and quartile of baseline fiber intake. CONCLUSIONS: No association was found between amount of fiber consumed at baseline and adenoma recurrence in the WBF trial participants. The baseline fiber intake, whether considered as a whole or from specific sources, did not modify the effect of treatment group.

The use of a video laryngoscope by emergency medicine residents is associated with a reduction in esophageal intubations in the emergency department.

OBJECTIVES: The purpose of this investigation was to compare the incidence of esophageal intubations (EIs) when emergency medicine (EM) residents used a direct laryngoscope (DL) versus a video laryngoscope (VL) for intubation attempts in the emergency department (ED). METHODS: Prospectively collected continuous quality improvement data on tracheal intubations performed by EM residents in an academic ED over a 6-year period were retrospectively analyzed. Following each intubation, EM residents completed a data form with patient, intubation, and operator characteristics. Data collected included the method of intubation, drugs used, device(s) used, number of attempts, outcome of each attempt, occurrence of EIs, and occurrence of adverse events (hypoxemia, aspiration, dysrhythmia, hypotension, and cardiac arrest). The incidence of EI was compared between intubation attempts with a DL and with a VL (GlideScope(®) or C-MAC(®) ). Propensity score matching and conditional logistic regression were used to analyze the association between the intubation device (DL vs. VL) and EI. RESULTS: Over the 6-year period, 2,677 patients underwent 3,425 intubation attempts by EM residents with a DL or a VL. A DL was used in 1,530 attempts (44.7%) and a VL was used in 1,895 attempts (55.3%). There were 96 recognized EIs (2.8%). The incidence of EI when using a DL was 78 of 1,530 attempts (5.1%; 95% confidence interval [CI] = 4.1% to 6.3%) and when using a VL was 18 of 1,895 attempts (1.0%; 95% CI = 0.6% to 1.5%). Based on the propensity score matched analysis, the odds ratio for the occurrence of an EI for DL versus VL was 6.9 (95% CI = 3.3 to 14.4). Patients who had inadvertent EIs had a higher incidence of adverse events (49.5%; 95% CI = 38.9% to 60.0%) than patients in which EI did not occur (19.8%; 95% CI = 18.3% to 21.4%). CONCLUSIONS: The use of a VL by EM residents during an intubation attempt in the ED was associated with significantly fewer EIs compared to when a DL was used. Patients who had inadvertent EIs had significantly more adverse events than those who did not have EIs. EM residency training programs should consider using VLs for ED intubations to maximize patient safety when EM residents are performing intubation.

Intake of supplemental and total fiber and risk of colorectal adenoma recurrence in the wheat bran fiber trial.

The Wheat Bran Fiber (WBF) trial was a double-blind Phase III clinical trial in which participants were randomized to a cereal fiber supplement of either 13.5 or 2.0 g/day. No protective effect for adenoma recurrence was observed for those randomized to the high-fiber group as compared with those in the low-fiber group. However, the high-fiber group had significantly lower adherence to the supplement as assessed by cereal box counts. The aim of this study was to determine whether reported supplemental and total fiber intake affected colorectal adenoma recurrence in the WBF trial population, regardless of treatment group assignment. A total of 1208 participants who completed the WBF trial had a colonoscopy before the date of the last cereal box count and/or at least one colonoscopy within 90 days after it and, thus, were eligible for the current analyses. Statistical analyses were done using multivariate logistic regression models that included potentially confounding variables. Compared with individuals consuming less than 1.8 g/day of supplemental fiber, the adjusted odds ratio (95% confidence interval) for adenoma recurrence for those consuming greater than 11.0 g/day was 0.94 (0.66-1.33). The odds ratio (95% confidence interval) for participants whose total fiber intake was greater than 30.3 g/day was 0.98 (0.68-1.42) compared with those whose intake was less than 17.9 g/day. The results of this study show that neither fiber intake from a wheat bran supplement nor total fiber intake affects the recurrence of colorectal adenomas, thus lending further evidence to the body of literature indicating that consumption of a high-fiber diet, especially one rich in cereal fiber, does not reduce the risk of colorectal adenoma recurrence.

Dietary change in an intervention trial of wheat bran fiber and colorectal adenoma recurrence.

PURPOSE: The objectives of this study were to determine whether participants in the Wheat Bran Fiber (WBF) trial exhibited changes in diet over time, and whether these changes were differential by assigned treatment group. METHODS: The WBF trial was a randomized trial with participants assigned to one of two groups: a low-fiber (2.0 g/d) or high-fiber (13.5 g/d) wheat bran fiber cereal supplement. A total of 685 participants from both treatment groups completed the Arizona Food Frequency Questionnaire (AFFQ) at baseline, year one, and year three of the trial. Means were calculated for nutrient intake, change in nutrient intake, number of food group servings, and change in number of food group servings. RESULTS: For both treatment groups combined, significant increases were observed for most micronutrients and vitamins at years one and three, while fat intake significantly decreased. Participants from both groups significantly increased their consumption of cereals, breads, and crackers, but decreased the number of servings from the meat, poultry, and egg group, the fats group, and the salty snacks group. The only differential changes in intake between the treatment groups were for sugar and iron, which increased to a lesser extent among those assigned to the high-fiber treatment as compared with the low-fiber group. CONCLUSIONS: Although differential dietary intake was not appreciable in the WBF trial, participants exhibited longitudinal changes. Future intervention studies should carefully monitor dietary changes during the trial with multiple dietary assessment tools to assess potential secular and treatment-related diet changes.

Wheat bran fiber supplementation and bone loss among older people.

OBJECTIVE: The purpose of this study was to investigate the effect of wheat bran fiber (WBF) supplementation on bone loss in older people. METHODS: Two hundred thirty-seven men and women ages 40 to 80 y were included in this study. They constituted a subgroup of participants from a 3-y WBF intervention trial for preventing recurrence of colorectal adenomas. These participants were randomized into a high (13.5 g/d) or a low (2 g/d) WBF supplementation group. Bone mineral density at the forearm was measured by single photon absorptiometry at baseline and yearly during the intervention to monitor possible toxic effects of fiber supplementation on bone metabolism. RESULTS: Baseline characteristics of this subgroup of participants from the WBF trial were similar between the high and low supplementation groups. The annual amounts of bone loss at the radial third site were -0.017 +/- 0.018 g/cm2 and -0.013 +/- 0.021 g/cm2, respectively, for the low and high WBF groups; and the annual bone losses at the ultra-distal site were was -0.005 +/- 0.020 g/cm2 and -0.006 +/- 0.027 g/cm2, respectively, for the low and high WBF groups. After controlling for confounding factors, we found no significant differences in bone loss between groups (P > 0.05). CONCLUSION: WBF supplementation at the level given in this study may not have a significant effect on bone loss among older people.