Multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the ...Medicare program(2014).The United States Preventive Services Task Force(USPSTF) October 2015 draft recommendation for CRC screening included mt-s DNA as an "alternative" screening test that "may be useful in select clinical circumstances",despite its very high sensitivity for early stage CRC.The evidence supporting mt-s DNA for routine screening use is robust.The clinical efficacy of mt-s DNA as measured by sensitivity,specificity,life-years gained(LYG),and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document,especially those requiring annual testing adherence.In a population with primarily irregular screening participation,tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual adherence.This paper reviews the evidence supporting mt-s DNA for routine screening and demonstrates,using USPSTF’s modeling data,that mt-s DNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing,high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening.
Background & Aims: Endoscopic screening of the colon with available instruments requires considerable training, is often painful, and carries a risk of perforation. New instrument platforms for ...endoscopic screening could be useful. The aim of this study was to evaluate the extent of colonic intubation by using a novel self-propelled, self-navigating endoscope (the Aer-O-Scope; GI View Ltd, Ramat Gan, Israel). Methods: Twelve young healthy volunteers underwent complete bowel preparation followed by a nonsedated examination using the novel device. Each examination was followed by a standard colonoscopy for safety evaluation. Cecal intubation was confirmed by endoscopic landmarks and fluoroscopy. Results: In 10 out of 12 subjects (83%) the cecum was successfully reached, whereas in 2 cases the Aer-O-Scope advanced to the hepatic flexure. The time to complete advancement to cecum averaged 14.0 ± 7 minutes, and the driving pressures averaged 34 ± 2.3 milibar. Two subjects requested analgesics during the procedures (in both cases the cecum was reached). Four subjects experienced sweating and a bloating sensation that resolved spontaneously. All subjects were followed up to 48 hours and then for 30 days postprocedure, and no complications were observed. Conclusions: In a preliminary pilot feasibility study of this new instrument, the Aer-O-Scope effectively intubated all or most of the colon. Further clinical studies are warranted.
A
Ciboria
sp. strain (Phylum Ascomycota) was isolated from hydrocarbon-polluted soil of an abandoned oil refinery in Italy. The strain was able to utilize diesel oil as a sole carbon source for ...growth. Laboratory-scale experiments were designed to evaluate the use of this fungal strain for treatment of the polluted soil. The concentration of total petroleum hydrocarbons (TPH) in the soil was 8,538 mg/kg. Mesocosms containing the contaminated soil were inoculated with the fungal strain at 1 or 7%, on a fresh weight base ratio. After 90 days of incubation, the depletion of TPH contamination was of 78% with the 1% inoculant, and 99% with the 7% inoculant. 16S rDNA and ITS metabarcoding of the bacterial and fungal communities was performed in order to evaluate the potential synergism between fungi and bacteria in the bioremediation process. The functional metagenomic prediction indicated
Arthrobacter
,
Dietzia
,
Brachybacerium
,
Brevibacterium
,
Gordonia
,
Leucobacter
,
Lysobacter
, and
Agrobacterium
spp. as generalist saprophytes, essential for the onset of hydrocarbonoclastic specialist bacterial species, identified as
Streptomyces
,
Nocardoides
,
Pseudonocardia
,
Solirubrobacter
,
Parvibaculum
,
Rhodanobacter
,
Luteiomonas
,
Planomicrobium
, and
Bacillus
spp., involved in the TPH depletion. The fungal metabolism accelerated the onset of specialist over generalist bacteria. The capacity of the
Ciboria
sp. to deplete TPH in the soil in treatment was also ascertained.
CRC development is a multi-step process that spans 10 to 15 years, thereby providing an opportunity for early detection and even prevention. The poor survival rate of advanced CRC has prompted the ...emphasis on prevention of this disease. CRC screening and removal of adenomas is an effective intervention, and is the cornerstone of prevention. However, screening efforts have had limited impact due to less than optimal compliance with guidelines. Chemoprevention involves the long-term use of a variety of oral agents that can delay, prevent or even reverse the development of adenomas in the large bowel, thus interfering with the multi-step progessing from adenoma to carcinoma. This effect is of particular importance to individuals with a hereditary prediposition to colorectal neoplasia and to those who are especially susceptile to the environmental causes of CRC. NSAIDs have drawn the most attention as chemoprevention agents. Sulindac and celecoxib are effective in promoting poly regression in high risk individuals with Familial Adenomatous Polyposis (FAP). In the more common sporadic setting the APROVe (refecoxib), APC and PreSAP (Celecoxib) trials have shown a significant reduction in adenoma recurrence but important concerns exist regarding cardiovascular toxicity associated with selective COX-2 inhibitors. These landmark studies are very important, as they provide a proof of concept that we can prevent high risk adenomas that can lead to CRC development. The ideal chemopreventive agent remains to be discovered with great emphasis on need not to harm. Possibly, combinations of agents will maximize effectiveness while limiting drug toxicity. Finally, personalized approaches will include the ability to predict risk and toxicity.
This year, for the first time, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening, an ...annual review of the most significant clinical research presented or published over the past year across all cancer types. ASCO embarked on this project to provide the public, patients, policymakers, and physicians with an accessible summary of the year's most important research advances. While not intended to serve as a comprehensive review, this report provides a year-end snapshot of research that will have the greatest impact on patient care. As you will read, there is much good news from the front lines of cancer research. These pages report on new chemotherapy regimens that sharply reduce the risk of recurrence for very common cancers; the "coming of age" of targeted cancer therapies; promising studies of drugs to prevent cancer; and improvements in quality of life for people living with the disease, among many other advances. Survival rates for cancer are on the rise, increasing from 50% to 64% over the last 30 years. Cancer still exacts an enormous toll, however. Nearly 1.4 million Americans will be diagnosed this year, and some 570,000 will die of the disease. Clearly, more research is needed to find effective therapies for the most stubborn cancer types and stages. We need to know more about the long-term effects of newer, more targeted cancer therapies, some of which need to be taken over long periods of time. And we need to devote far greater attention to tracking and improving the care of the nearly 10 million cancer survivors in the United States today. Despite these and other challenges, the message of this report is one of hope. Through the dedicated, persistent pursuit of clinical research and participation in clinical trials by people with cancer, we steadily uncover new and better ways of treating, diagnosing, and preventing a disease that touches the lives of so many. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report, and I hope you find it useful.
In the present study, an Ascomycete fungal strain, Lambertella sp., isolated from environmental polluted matrices, was tested for the capacity to reduce the contamination and the toxicity of ...intermediate and old landfill leachates. Batch tests in flasks, under co-metabolic conditions, were performed with two different old leachates, with suspended and immobilized Lambertella sp. biomass, resulting in a soluble chemical oxygen demand depletion of 70% and 45%, after 13 and 30 days, respectively. An intermediate landfill leachate was treated in lab-scale reactors operating in continuous conditions for three months, inoculated with immobilized Lambertella sp. biomass, in absence of co-substrates. The Lambertella sp. depleted the corresponding total organic carbon by 90.2%. The exploitability of the Lambertella sp. strain was evaluated also in terms of reduction of phyto-, cyto-, and mutagenicity of the different Landfill Leachates at the end of the myco-based treatment, resulting in an efficient depletion of leachate clastogenicity.
Background Accurate measures of the total polyp burden in familial adenomatous polyposis (FAP) are lacking. Current assessment tools include polyp quantitation in limited-field photographs and ...qualitative total colorectal polyp burden by video. Objective To develop global quantitative tools of the FAP colorectal adenoma burden. Design A single-arm, phase II trial. Patients Twenty-seven patients with FAP. Intervention Treatment with celecoxib for 6 months, with before-treatment and after-treatment videos posted to an intranet with an interactive site for scoring. Main Outcome Measurements Global adenoma counts and sizes (grouped into categories: <2 mm, 2-4 mm, and >4 mm) were scored from videos by using a novel Web-based tool. Baseline and end-of-study adenoma burden results were summarized by using 5 models. Correlations between pairs of reviewers were analyzed for each model. Results Interobserver agreement was high for all 5 measures of polyp burden. Measures that used both polyp count and polyp size had better interobserver agreement than measures based only on polyp count. The measure in which polyp counts were weighted according to diameter, calculated as (1) × (no. of polyps <2 mm) + (3) × (no. of polyps 2-4 mm) + (5) × (no. of polyps >4 mm) had the highest interobserver agreement (Pearson r = 0.978 for two gastroenterologists, 0.786 and 0.846 for the surgeon vs each gastroenterologist). Treatment reduced the polyp burden by these measurements in 70% to 89% of patients ( P < .001). Limitations Phase II study. Conclusion This novel, Web-based polyp scoring method provides a convenient and reproducible way to quantify the global colorectal adenoma burden in FAP patients and a framework for developing a clinical staging system for FAP.
In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the ...detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average‐risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps and a screening test that primarily is effective at early cancer detection. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.
Purpose: Demographic, behavioral, and environmental factors have been associated with increased risk of colorectal cancer (CRC). We reviewed the published evidence and explored associations between ...risk factors and CRC incidence. Methods: We identified 12 established non-screening CRC risk factors and performed a comprehensive review and meta-analyses to quantify each factor's impact on CRC risk. We used random-effects models of the logarithms of risks across studies: inverse-variance weighted averages for dichotomous factors and generalized least squares for dose–response for multi-level factors. Results: Significant risk factors include inflammatory bowel disease (RR = 2.93, 95 % CI 1.79–4.81); CRC history in first-degree relative (RR = 1.80, 95 % CI 1.61–2.02); body mass index (BMI) to overall population (RR = 1.10 per 8 kg/m² increase, 95 % CI 1.08–1.12); physical activity (RR = 0.88, 95 % CI 0.86–0.91 for 2 standard deviations increased physical activity score); cigarette smoking (RR = 1.06, 95 % CI 1.03–1.08 for 5 pack-years); and consumption of red meat (RR = 1.13, 95 % CI 1.09–1.16 for 5 servings/week), fruit (RR = 0.85, 95 % CI 0.75–0.96 for 3 servings/day), and vegetables (RR = 0.86, 95 % CI 0.78–0.94 for 5 servings/day). Conclusions: We developed a comprehensive risk modeling strategy that incorporates multiple effects to predict an individual's risk of developing CRC. Inflammatory bowel disease and history of CRC in first-degree relatives are associated with much higher risk of CRC. Increased BMI, red meat intake, cigarette smoking, low physical activity, low vegetable consumption, and low fruit consumption were associated with moderately increased risk of CRC.
Objective The use of risk prediction models grows as electronic medical records become widely available. Here, we develop and validate a model to identify individuals at increased risk for colorectal ...cancer (CRC) by analyzing blood counts, age, and sex, then determine the model’s value when used to supplement conventional screening.
Materials and Methods Primary care data were collected from a cohort of 606 403 Israelis (of whom 3135 were diagnosed with CRC) and a case control UK dataset of 5061 CRC cases and 25 613 controls. The model was developed on 80% of the Israeli dataset and validated using the remaining Israeli and UK datasets. Performance was evaluated according to the area under the curve, specificity, and odds ratio at several working points.
Results Using blood counts obtained 3–6 months before diagnosis, the area under the curve for detecting CRC was 0.82 ± 0.01 for the Israeli validation set. The specificity was 88 ± 2% in the Israeli validation set and 94 ± 1% in the UK dataset. Detecting 50% of CRC cases, the odds ratio was 26 ± 5 and 40 ± 6, respectively, for a false-positive rate of 0.5%. Specificity for 50% detection was 87 ± 2% a year before diagnosis and 85 ± 2% for localized cancers. When used in addition to the fecal occult blood test, our model enabled more than a 2-fold increase in CRC detection.
Discussion Comparable results in 2 unrelated populations suggest that the model should generally apply to the detection of CRC in other groups. The model’s performance is superior to current iron deficiency anemia management guidelines, and may help physicians to identify individuals requiring additional clinical evaluation.
Conclusions Our model may help to detect CRC earlier in clinical practice.
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