Reduce Colon Cancer Mortality Research Articles

Colon Capsule Endoscopy in the Diagnosis of Colon Polyps: Who Needs a Colonoscopy?

Colon screening programs have reduced colon cancer mortality. Population screening should be minimally invasive, safe, acceptably sensitive, cost-effective, and scalable. The range of screening modalities include guaiac or immunochemical fecal occult blood testing and CT colonography and colonoscopy. A number of carefully controlled studies concur that second-generation capsule endoscopy has excellent sensitivity for polyp detection and a high negative predictive value. Colon capsules fulfill the screening expectation of safety, high sensitivity for polyp detection, and patient acceptance, and appear to straddle the divide between occult blood testing and colonoscopy. While meeting these criteria, there remains the challenges of scaling, capsule practitioner training, resource allocation, and implementing change of practice. Like CT colonography, capsule screening presents the clinician with a decision on the threshold for colonoscopy referral. Overall, colon capsules are an invaluable tool in polyp detection and colon screening and offer a filter that determines “who needs a colonoscopy?”.

Beyond Screening: An Interim Report and Analysis of a Multimodal Initiative to Decrease Colon Cancer Mortality.

Colon cancer, a potentially preventable and curable cancer, remains one of the leading causes of cancer-related death in the United States. In 2010 the researchers undertook a multifaceted initiative to reduce colon cancer mortality rates by 50% over 10 years. A baseline literature review of preventable causes of colon cancer mortality and review of 50 deaths from colon cancer in one institution identified a set of care process improvements that could be implemented to decrease colon cancer mortality. In 2017 a second mortality review identified a second set of care process improvements that were subsequently implemented. Compliance with these processes was monitored along with age and gender-adjusted mortality rates. Identified care process improvements included improving the follow-up of patients with rectal bleeding and presumed iron deficiency anemia and improving the reliability of postsurgical surveillance for cancer recurrence, decreasing elapsed time from surgery to chemotherapy, increasing surgical referrals for patients with advanced colon cancer, increasing the upper age limit and overall rate of colon cancer screening, increasing vitamin D and aspirin use, and monitoring and increasing the adenoma detection rate. Compliance with these processes improved for most measures, including screening (73.7% to 79.9%), adenoma detection rates on screening colonoscopy (30% to 36% for women and 42% to 49% for men), and chemotherapy within 35 days of surgery for colon cancer (39.0% to 51.9%). Age- and gender-adjusted mortality decreased from 13.8 per 100,000 in 2009-2011 to 10.5 per 100,000 in 2016-2018. This quality improvement program was feasible to implement, resulted in process improvements, and decreased colon cancer mortality over seven years.

What is the Best Colonoscopy Surveillance for Lynch Syndrome Patients?

Lynch syndrome is the most common form of hereditary colorectal cancer. Screening programs have reduced colon cancer mortality. Despite intensive surveillance, the cumulative risk of developing colorectal cancer is substantial. Identification of modifiable factors has the potential to improve outcome of surveillance. Our article will review current guidelines for Lynch syndrome and how to perform colonoscopy. High-quality surveillance colonoscopy should be performed in an experimented center every 1–2 years, starting at the age of 20–25 years. Colonoscopy should include meticulous inspection and precise removal of all polyps, with special attention to the right colon especially of flat lesions. News endoscopic techniques, such as chromoendoscopy, were developed and recommended to improve the detection of adenomas, particularly of flat adenomas, and minimize the risk of developing interval cancer. Finally, educational intervention in a surveillance program is essential for optimizing screening including adherence.

Endoscopic resection of colorectal lesions: The narrowing divide between East and West.

Colonic polypectomy is an effective way of reducing colon cancer mortality. Multiple techniques now exist for the resection of polyps, and the endoscopist must decide on the appropriate resection approach for individual patients and lesions. This decision should maximize efficacy, safety and cost-effectiveness and provide optimal oncological outcomes while minimizing unnecessary surgical treatment. Advances in endoscopic imaging technology are improving the accuracy of endoscopic diagnosis and allowing more precise risk assessment of colonic lesions. Resection technique can be tailored to the endoscopic findings. Diminutive (≤5 mm) and small polyps (≤9 mm) are best resected primarily by snare techniques. Cold snare polypectomy has proven safety, but efficacy and technique require further study. There is variation in techniques used for polyps 6-20 mm in size and incomplete resection rates for conventional polypectomy may be considerable. Endoscopic mucosal resection (EMR) is well established, safe and effective for lesions without submucosal invasion (SMI); however, recurrence is a key limitation. Endoscopic submucosal dissection (ESD) is well established in the East; however, it is resource intensive and its role in lesions with a low risk of SMI is questionable. ESD in the West remains incompletely defined and is associated with high adverse event rates, but it is becoming increasingly available and successful as experience grows. Emerging full-thickness resection technologies are still in their infancy and remain experimental as a result of the absence of reliable closure devices and techniques. Patient-focused outcomes should guide technique selection.

Cyclic Phosphatidic Acid Stimulates cAMP Production and Inhibits Growth in Human Colon Cancer Cells

Colon cancer is a malignancy that develops in colon and rectal tissues. The prognosis for metastatic colon cancer remains poor, and novel therapeutic options are required to reduce colon cancer mortality. Recently, intracellular cAMP levels have been suggested to influence the behavior of cancer cells. Intriguingly, cyclic phosphatidic acid (cPA) and its structural analogs inhibit growth in many cancer cell lines, and our previous work has suggested that cPA increases cAMP production. Phosphodiesterase (PDE) type 3 isoforms PDE3A and PDE3B are expressed mainly in cardiovascular tissue and adipose tissue, respectively. Moreover, increase in intracellular cAMP levels has been associated with the inhibition of growth in colon cancer cells. These findings suggest that cPA could be used in colon cancer therapy. In this study, we found that cPA inhibited the growth of HT-29 cells, which express high levels of PDE3B, but not the growth of DLD-1 cells, which express low levels of PDE3B. Furthermore, cPA inhibited the phosphorylation of Akt in HT-29 cells in a dose-dependent fashion. Our results suggest that PDE3B expression and intracellular cAMP levels are correlated with the proliferation of colon cancer cells. These findings demonstrate for the first time that cPA may serve as a useful a molecule in targeted therapy for colon cancer.

Interval colon cancer in a Lynch syndrome patient under annual colonoscopic surveillance: a case for advanced imaging techniques?

BackgroundLynch syndrome confers increased risk for various malignancies, including colorectal cancer. Colonoscopic surveillance programs have led to reduced incidence of colorectal cancer and reduced mortality from colorectal cancer. Colonoscopy every 1–2 years beginning at age 20–25, or 10 years earlier than the first diagnosis of colorectal cancer in a family, with annual colonoscopy after age 40, is the recommended management for mutation carriers. Screening programs have reduced colon cancer mortality, but interval cancers may occur.Case presentationWe describe a 48-year-old woman with Lynch syndrome who was found to have an adenoma with invasive colorectal cancer within one year after a normal colonoscopy.ConclusionOur patient illustrates two current concepts about Lynch syndrome: 1) adenomas are the cancer precursor and 2) such adenomas may be “aggressive,” in the sense that the adenoma progresses more readily and more rapidly to carcinoma in this setting compared to usual colorectal adenomas. Our patient’s resected tumor invaded only into submucosa and all lymph nodes were negative; in that sense, she represents a success for annual colonoscopic surveillance. Still, this case does raise the question of whether advanced imaging techniques are advisable for surveillance colonoscopy in these high-risk patients.

Oral supplementation of silibinin prevents colon carcinogenesis in a long term preclinical model

Chemoprevention through dietary intervention is an emerging option to reduce colon cancer mortality. β-catenin plays an important role in the Wnt signaling cascade that is most commonly dysregulated in colorectal cancer. Our aim was to explore the modulatory effect of silibinin on β-catenin expression employing 1,2-dimethylhydrazine (DMH) induced colon cancer in male Wistar rats as an experimental model during the different stages of carcinogenesis. Colon tissues were analyzed for the expression of β-catenin, proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer regions by using immunohistochemistry and silver staining. Immunoblotting was employed to study cyclin D1 expression. Glutathione (GSH) and glutathione related enzymes were assayed by spectrophotometric analysis. Silibinin inhibited DMH-induced colon cancer by decreasing tumor incidence and multiplicity. Silibinin supplementation to DMH-treated rats restored the levels of GSH-dependent enzymes and decreased the levels of β-catenin, PCNA, argyrophilic nucleolar organizer regions and cyclin D1. Mechanistically silibinin inhibits DMH-induced colon carcinogenesis by modulating the Wnt/β-catenin pathway and glutathione redox system. Since colon cancer is highly sensitive to dietary intervention adults who may have preneoplastic lesions in their colon may be benefited by silibinin.

Guanylyl Cyclase C Prevents Colon Cancer Metastasis by Regulating Tumor Epithelial Cell Matrix Metalloproteinase-9

Matrix metalloproteinase-9 (MMP-9) produced by colorectal cancer cells is a critical determinant of metastatic disease progression and an attractive target for antimetastatic strategies to reduce colon cancer mortality. Cellular signaling by cyclic GMP (cGMP) regulates MMP-9 dynamics in various cell systems, and the bacterial enterotoxin receptor guanylyl cyclase C (GCC), the principle source of cGMP in colonocytes, which is overexpressed in colorectal cancers, inhibits tumor initiation and progression in the intestine. Here, we show that ligand-dependent GCC signaling through cGMP induces functional remodeling of cancer cell MMP-9 reflected by a compartmental redistribution of this gelatinase, in which intracellular retention resulted in reciprocal extracellular depletion. Functional remodeling of MMP-9 by GCC signaling reduced the ability of colon cancer cells to degrade matrix components, organize the actin cytoskeleton to form locomotory organelles and spread, and hematogenously seed distant organs. Of significance, GCC effects on cancer cell MMP-9 prevented establishment of metastatic colonies by colorectal cancer cells in the mouse peritoneum in vivo. Because endogenous hormones for GCC are uniformly deficient in intestinal tumors, reactivation of dormant GCC signaling with exogenous administration of GCC agonists may represent a specific intervention to target MMP-9 functions in colon cancer cells. The notion that GCC-mediated regulation of cancer cell MMP-9 disrupts metastasis, in turn, underscores the unexplored utility of GCC hormone replacement therapy in the chemoprevention of colorectal cancer progression.

How Much Does Colonoscopy Reduce Colon Cancer Mortality?

In this issue, Baxter and colleagues report an association between complete colonoscopy and CRC mortality reduction of 0.33 for left-sided lesions but 0.99 for right-sided lesions. These results hi...

Mailings timed to patients' appointmentsA controlled trial of fecal occult blood test cards

<h2>Abstract</h2><h3>Background</h3> Fecal occult blood testing (FOBT) programs cost-effectively reduce colon cancer mortality. To improve the rate of colon cancer screening with FOBT, we tested the effect of mailing FOBT cards timed to appointments on the rates of completion of FOBT. <h3>Design</h3> Controlled trial. <h3>Setting/participants</h3> A total of 119 patients with primary care appointments scheduled in May or June 2000 for an urban, public hospital clinic that serves predominantly low-income, African Americans with chronic diseases. The patients in the study were selected by linking a quality improvement registry, the appointment system database, and an FOBT database to generate a list of clinic patients who had not completed an FOBT in the preceding year. <h3>Intervention</h3> Subjects were assigned to either a system of mailing FOBT cards and reminders 2 weeks prior to a scheduled appointment or usual care. <h3>Main outcome measures</h3> The primary outcomes were the rate of screening at the index appointment and during the year beginning with the date of the index appointment. <h3>Results</h3> The rate of return of the FOBT cards during the year beginning with the index appointment was 40.7% for the intervention group compared to 5% for the usual care group (odds ratio [OR]=13.0, <i>p</i> <0.001). The difference was accounted for largely by increases in screening at the index appointment (35.6% compared to 3.3%, OR=16.0, <i>p</i> <0.001). <h3>Conclusions</h3> Using computer databases to generate a list of patients due for FOBT and then mailing FOBT cards timed to a scheduled appointment significantly increased the rate of colon cancer screening. This may be an efficient approach to increasing colon cancer screening with FOBT.

Mailings timed to patients' appointments: A controlled trial of fecal occult blood test cards

Background Fecal occult blood testing (FOBT) programs cost-effectively reduce colon cancer mortality. To improve the rate of colon cancer screening with FOBT, we tested the effect of mailing FOBT cards timed to appointments on the rates of completion of FOBT. Design Controlled trial. Setting/participants A total of 119 patients with primary care appointments scheduled in May or June 2000 for an urban, public hospital clinic that serves predominantly low-income, African Americans with chronic diseases. The patients in the study were selected by linking a quality improvement registry, the appointment system database, and an FOBT database to generate a list of clinic patients who had not completed an FOBT in the preceding year. Intervention Subjects were assigned to either a system of mailing FOBT cards and reminders 2 weeks prior to a scheduled appointment or usual care. Main outcome measures The primary outcomes were the rate of screening at the index appointment and during the year beginning with the date of the index appointment. Results The rate of return of the FOBT cards during the year beginning with the index appointment was 40.7% for the intervention group compared to 5% for the usual care group (odds ratio [OR]=13.0, p <0.001). The difference was accounted for largely by increases in screening at the index appointment (35.6% compared to 3.3%, OR=16.0, p <0.001). Conclusions Using computer databases to generate a list of patients due for FOBT and then mailing FOBT cards timed to a scheduled appointment significantly increased the rate of colon cancer screening. This may be an efficient approach to increasing colon cancer screening with FOBT.

Ethnic issues in endoscopy

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text. In preparing this guideline, a search of the medical literature was performed by using PubMed. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When few or no data exist from well-designed prospective trials, emphasis is placed on results from large series and reports from recognized experts. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations are based on reviewed studies and are graded on the quality of the supporting evidence (Table 1). The strength of individual recommendations is based on both the aggregate evidence quality and an assessment of the anticipated benefits and harms. Weaker recommendations are indicated by phrases such as "we suggest," whereas stronger recommendations are typically stated as "we recommend." This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient's condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from this guideline.

Screening/early detection model for colorectal cancer. Why screen?

Colon cancer is a leading cause of cancer death in the United States, causing approximately 60,000 deaths each year. Ideal screening would identify high risk patients and screen them with sensitive tests. Most cancers evolve from adenomatous polyps. There is now evidence that detection and removal of adenomas can prevent cancer. Unfortunately, our ability to identify high risk patients is limited. Screening of asymptomatic, average-risk individuals has been advocated, with the goal of reducing colon cancer mortality by detecting cancers at an early, curable stage or preventing cancer by detecting and removing adenomatous polyps. Recent data have suggested that screening populations older than age 50 with sigmoidoscopy and fecal occult blood tests can reduce colon cancer mortality. These reports are encouraging but also highlight significant limitations of this form of screening. Screening itself is designed merely to identify something that, once identified, needs further evaluation. Therefore, any discussion of colon screening must include consideration of how physicians will approach positive test results. The strategies for dealing with positive test results are costly and invariably lead to further surveillance. Current data suggest that patients with large polyps (> 1 cm) or villous adenomas have a high risk of colon cancer and are likely to benefit from full colonoscopy and subsequent surveillance. The benefits are far less clear for patients with small polyps. The subject of colon screening becomes even more complicated as consideration is given to when to start and stop screening, and how often to perform screening exams. There is clearly a need to improve upon the ability to identify patients most likely to develop colon cancer and design strategies to prevent cancer in this group. In the future, it may be possible to identify the high risk patient with some precision using genetic or biologic markers.

Screening Colonoscopy: Has the Time Come?

Although current screening with flexible sigmoidoscopy and fetal occult blood test likely reduce colon cancer mortality, it is costly and probably not as effective as one-time screening with colonoscopy for detecting and preventing cancer, as well as risk stratification for further testing and surveillance. Ideal screening would target sensitive tests at high-risk individuals. It is possible that the identification of genetic or biologic markers in the future will enable us to target screening at high-risk individuals with precision.

Screening for colon malignancy with colonoscopy.

Screening of asymptomatic individuals for colon malignancy has been advocated for the past 20 yr in the hopes of reducing colon cancer mortality. Although sigmoidoscopy is an important element of current screening recommendations, the sensitivity of this test in asymptomatic subjects has never been studied. The purpose of this study was to determine the prevalence and location of polyps and cancers in an asymptomatic population by performing full colonoscopy. We wished to assess the sensitivity of screening flexible sigmoidoscopy to 60 cm by determining how many patients with adenomas or cancer had "index" adenomatous polyps in the distal 60 cm. One hundred five healthy male outpatients, over 50 yr old, with negative examinations for occult blood in stools and no prior history of colon pathology, had full colonoscopy. Careful examination of the distal 60 cm was performed, followed by a full colon examination to the cecum. Forty-three patients (41%) had adenomatous polyps, and only 19 of these patients had an index adenomatous polyp in the distal 60 cm. Therefore, the sensitivity of sigmoidoscopy was 44%. The prevalence of adenomas increased with age. Patients were assigned to one of three groups based on the findings in the distal 60 cm. Group 1 (n = 65) had no polyps in the distal 60 cm, but 18 of these patients (28%) had adenomatous polyps in the proximal colon. Among 21 patients with only hyperplastic polyps in the distal 60 cm (group 2), six patients (29%) had proximal adenomas. In group 3, eight of 19 patients (42%) with adenomas in the distal 60 cm also had proximal adenomatous polyps. We conclude that adenomatous polyps are common in asymptomatic men who have negative tests for fecal occult blood. Sigmoidoscopy to 60 cm had a sensitivity of only 44% in this patient population, suggesting that this is an insensitive test for the detection of patients with adenomatous polyps.