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Medicine » Gastroenterology » "Colonoscopy and Colorectal Cancer Screening - Future Directions", book edited by Marco Bustamante, ISBN 978-953-51-0949-5, Published: February 13, 2013 under CC BY 3.0 license. © The Author(s).

# Issues in Screening and Surveillance Colonoscopy

By Anjali Mone, Robert Mocharla, Allison Avery and Fritz Francois
DOI: 10.5772/53111

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# Issues in Screening and Surveillance Colonoscopy

Anjali Mone1, Robert Mocharla1, Allison Avery1 and Fritz Francois1

## 1. Introduction

Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world. However timely screening and treatment can dramatically impact outcomes. The association with well-defined precancerous lesions and long asymptomatic period provides the opportunity for effective screening and early treatment of CRC. The current options for CRC screening are strongly anchored in evidence demonstrating utility in reducing morbidity and mortality. This chapter will review the epidemiology of CRC, risk stratification, strategies for screening, as well as factors that threaten achieving health equity through appropriate screening programs.

## 2. Epidemiologic trends in colorectal cancer

Worldwide CRC is the third most common cancer and fourth most common cause of death. Interestingly this disease affects men and women almost equally (Haggar and Boushey, 2009). In the United States CRC is the third most commonly diagnosed cancer and constitutes 10% of new cancers in men and women (Society, 2011). In 2011, there were approximately 141,120 new cases and it is estimated that 143,460 Americans will be diagnosed with colorectal cancer in 2012 (NIH, 2009). Furthermore it is estimated up to 30% of new cases are found in the general population without known risk factors for this disease (Imperiale et al., 2000). Although there are still approximately one million new cases of CRC diagnosed each year, incidence has been steadily declining over the past 15 years (Bresalier, 2009; Ferlay et al., 2010; Kohler et al., 2011). In the United States mortality from CRC has also declined with a 7% decrease in men and 12% decrease in women between 1980 and 1990 (Jemal et al., 2008). Since 1990 decreases in CRC incidence and mortality have been even more substantial, and is largely attributable to improvements in screening rates (Lieberman, 2010), especially the growing use of colonoscopy procedures (Edwards et al., 2010). Nevertheless, important trends remain in the worldwide epidemiology of CRC.

### 2.1. Geographic variations in CRC epidemiology

There is significant diversity in colorectal cancer incidence worldwide. Surprisingly industrialized nations have a remarkably greater occurrence of CRC accounting for 63% of all cases. In fact CRC incidence rates range from more than 40 per 100,000 people in the United States, Australia, New Zealand, and Western Europe to less than 5 per 100,000 in Africa and parts of Asia. It is notable that the US is the only country with significantly declining CRC incidence rates for both genders, and this is most likely a reflection of better screening practices and early prevention (Jemal et al., 2011).

While there is substantial disparity in CRC occurrence globally, CRC incidence has been increasing in places previously reporting low rates. For example the number of new CRC diagnoses has been rising in a number of Asian countries that recently transitioned from low-income to high-income economies. Individuals residing in China, Japan, India, Singapore, and Eastern European countries were previously reported to have the lowest rates of CRC. Countries with the highest incidence rates include Australia, New Zealand, Canada, the United States, and parts of Europe, however incidence has started stabilizing and even declining in these regions (Haggar and Boushey, 2009; Jemal et al., 2010).

Interestingly CRC incidence seems to have a close association with location. In fact studies show that migrants rapidly acquire the risk patterns for CRC associated with their new surroundings. For example the incidence rates in Japanese immigrants have been found to significantly increase after moving to the United States. Geographic influence is also evident in a study done in Israel where male Jews of Western descent were found to have a higher likelihood of developing CRC than those born in Africa or Asia. Furthermore environment may be responsible for variations within ethnic groups. This is demonstrated by higher rates of CRC among American Indians living in Alaska than those residing in the Southwest. Incidence rates among black males were found to range from 46.4 cases per 100,000 individuals in Arizona to 82.4 per 100,000 in Kentucky. In white men rates range from 44.4 per 100,000 in Utah to 68.7 per 100,000 in North Dakota (The Centers for Disease Control and Prevention [CDC], 2011).

The importance of location can also be seen by differences in CRC incidence within specific genders. CRC mortality rates for men are lower in Western states excluding Nevada, and higher in Southern and Midwestern states. These differences in CRC rates may be attributable to regional variations in risk factors including diet and lifestyle as well as access to screening and treatment. In fact one study found that up to 43% of colorectal cancers are preventable through diet and lifestyle modifications (Perera P.S., 2012).

### 2.2. Racial and ethnic variations

There is substantial evidence demonstrating racial disparities in CRC risk particularly for black men. In the USA this group has been found to have 20% higher incidence rate and 45% higher mortality rate from colorectal cancer compared to whites (Jemal et al., 2008; Wallace and Suzuki, 2012). There are also significant differences in life expectancy among blacks compared to whites. While there was a 39% reduction in mortality rate for white men between 1960-2005, during the same period there was a dramatic 28% increase in mortality for black men (Soneji et al., 2010). Of note incidence rates among other racial groups including Hispanics, Asian Americans, and American Indians are lower than those among whites. The factors that underlie these differences have not been fully elucidated but most likely encompass both modifiable factors (e.g. smoking, socioeconomic status, body mass index, and cultural beliefs) as well as non-modifiable factors (e.g. race/ethnicity, gender, and genetic predisposition). These findings do suggest there is a need for appropriate risk stratification for CRC and for more aggressive screening in high-risk populations, particularly among blacks in the United States. Such an approach has been recommended by both the American College of Gastroenterology as well as the American Society for Gastrointestinal Endoscopy with the suggestion to start screening blacks at the age of 45 (Cash et al., 2010; Rex et al., 2009).

### 2.3. The gender gap

According to SEER 2012 statistics, the overall prevalence of colorectal cancer does not vary substantially between the genders. The lifetime risk of being diagnosed with CRC is similar for men 5.7% and women 5.2%. The lifetime risk of dying from CRC is also similar; 2.3% and 2.1% for men and women respectively (NIH, 2009). Even though annually the new diagnoses of CRC have roughly been equal in men (187,973) and women (185,983), men have higher age-adjusted CRC incidence rates (Abotchie et al., 2012). Women seem have a delay of approximately 7-8 years in the development of advanced polyps (Jaroslaw Regula, 2012; Lieberman et al., 2005). Additionally age adjusted mortality rates can be up to 35-40% higher in men compared to women (CDC, 2011). Gender related disparities are not completely understood but may be attributable to variations in hormonal exposure (Chlebowski et al., 2004). These biological differences related to sex raise the issue of whether men and women should be screened differently for CRC. However current screening guidelines have not been modified based on gender (Levin et al., 2008).

### 2.4. Modifiers of the epidemiologic trends

Despite some overall gains, several factors remain that impact the epidemiology of CRC. Advancements in elucidating CRC pathogenesis allow for explanations of the above epidemiologic trends and have the potential for more efficient screening and treatment. It is estimated that up to 70% of CRC cases occur sporadically in individuals with no identifiable risks (Hardy et al., 2000). Factors that predispose individuals to a higher risk for developing CRC include any personal or family history of CRC or adenomatous polyps, inflammatory bowel disease (IBD), and inherited genetic syndromes such as familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC). Guidelines recommend earlier and more aggressive screening for this high-risk population.

As evidenced by the presence of both modifiable and non-modifiable risk factors, the pathogenesis of CRC seems to be influenced by a combination of genetics and the environment. Indeed the disease results from the progressive accumulation of both genetic as well as epigenetic changes in the colonic epithelium. Currently genetic tests are available that identify patients with inherited mutations associated with FAP and HNPCC. While this technology is promising, only 2-6% of CRC cases are attributable to common inherited mutations, suggesting other variables are playing a role in the development of this disease (Winawer et al., 2003).

Some of the environmental influences that have been investigated include the role of Streptococcus Bovis. Although infections are recognized as a major preventable cause in cancer, an infectious etiology has not been identified in cases of sporadic CRC, strongly suggesting that more factors are involved in the development of this disease (Boleij and Tjalsma, 2012). Similar to many other cancers, an important common thread in the pathogenesis of CRC is the presence of chronic inflammation that is thought to increase the probability of mutagenic events that lead to the production of oxidative species and damage DNA causing genomic instability (Zauber et al., 2008). This is demonstrated by patients with inherited genetic mutations who are found on colonoscopic examination to have chronic inflammatory changes that precede tumor development (Terzic et al., 2010). This can also be seen in patients colonized with S. Bovis who are found to have inflammatory changes in the bowel wall (Terzic et al., 2010). Further support for an inflammatory basis is found in recent studies showing aspirin and non-steroidal, anti-inflammatory drugs greatly reduce the risk of CRC (Rothwell et al., 2012).

### 2.5. Impact of screening on the epidemiology of CRC

Numerous studies show favorable CRC outcomes if the cancer is identified and treated at an early stage. In fact the 5-year survival rate is greater than 90% if CRC is identified at an early stage. However if the cancer extends beyond the colon, 5-year survival is less than 10% (Collett et al., 1999). Continuing advances in CRC therapies hold the promise of adequate treatment for advanced stages of the disease. A recent study in Nature suggests the possibility of helping patients with advanced stage CRC with targeted drugs. This study suggests that there are a finite number of genetic pathways in CRC that can be therapeutically targeted. Although these findings are promising much work is still needed before there will be a cure for CRC (Muzny et al., 2012).

Given the limited effective treatment for advanced CRC, prevention through early detection is paramount. CRC is a model disease for routine population screening since it is prevalent, has a long asymptomatic period, and precancerous lesions can be identified and treated (Pezzoli et al., 2007). Compared to other cancers where the primary goal is early detection of neoplasia, CRC can actually be prevented with detection and removal of cancer precursor lesions (Inadomi et al., 2012). It is estimated that 30% of people over the age of 50 with no history of CRC risk factors harbor adenomatous polyps (Alberti et al., 2012; Pezzoli et al., 2007), and the incidence of these polyps increases with age. Early adenoma resection is associated with considerable reductions in CRC (Rex et al., 2009; Winawer et al., 1993b), and has now been demonstrated to have mortality benefit (Zauber et al., 2012).

Although it is difficult to identify precisely which adenomas will undergo neoplastic transformation, there are certain pathologic features that can help predict their level of risk: increased size ≥10 mm, increased number of 3 or more adenomas, villous histology, and high-grade dysplasia (Alberti et al., 2012; Lieberman et al., 2012). Most adenomas undergo a similar progression to invasive cancer termed the adenoma-carcinoma sequence (Levin et al., 2008; Sano et al., 2009). Given that these cancer precursors are often asymptomatic, there is compelling evidence to support early screening for healthy individuals. In fact the average-risk individuals compose 70-75% of the CRC population (Lieberman, 2010). In response to mounting evidence suggesting that screening of average-risk individuals allows for early cancer detection and prevention, CRC guidelines from several organizations were updated in 2008 (USPSTF, 2008).

### 2.6. CRC prevention tests

Colonoscopy allows for the direct visualization of the entire colon and for the potential to remove lesions that are identified. Results from the National Polyp Study confirm that colonoscopy and adenoma removal is associated with decreased rates of developing colon cancer in the future (Winawer S.J., 2006) and reduces mortality (Zauber et al., 2012). The finding that mortality is reduced by polypectomy is of major significance because it suggests that colonoscopy can identify a subset of adenomas which can potentially become aggressive cancers and provides further evidence that colonoscopy is in fact the best screening option because of its added benefit of decreased mortality, particularly in individuals at increased risk. In patients with no lesions detected during a screening colonoscopic examination, the interval for follow-up surveillance can be extended to 10 years compared to 5 years for sigmoidoscopy (which visualizes only the left side of the colon) along with FOBT every 3 years. The known draw backs to colonoscopy include the need for bowel prep, sedation that may be associated with cardiopulmonary risks, higher cost compared to other methods, association with greater risk of bleeding and perforation, and a miss rate of up to 5% for malignant colon lesions.

While colonoscopy remains the gold standard for CRC prevention, economic constraints and patient attitudes may prevent screening with this technique. In an effort to improve participation alternative tests have been endorsed. There are a range of screening methods that are categorized into two major groups, prevention and detection. Prevention tests detect cancer as well as pre-cancerous polyps, and are generally structural exams such as the colonoscopy, flexible sigmoidoscopy, CT colonography, and double-contrast barium enema. Detection tests are only able to identify CRC lesions and consist of fecal tests including the fecal immunochemical test (FIT), fecal occult blood testing (FOBT), and Fecal DNA testing (Rex et al., 2009).

Flexible Sigmoidoscopy remains an acceptable alternative to colonoscopy for colorectal cancer screening (Levin et al., 2008; USPSTF, 2008; Winawer et al., 2003; Winawer et al., 1997). Although both screening techniques are similar, sigmoidoscopy requires more frequent screenings at 5–year intervals and the benefits are confined to the distal colon only. In addition the USPSTF recommends screening with FOBT every 3 years (USPSTF, 2008). Prior studies have demonstrated a significant mortality benefit for the section of the colon examined (Wilkins and Reynolds, 2008). A recent study in the NEJM confirmed this data showing that flexible sigmoidoscopy decreases CRC incidence and mortality (Schoen et al., 2012). The advantages of sigmoidoscopy include lower cost, lower risk profile, and need for less bowel preparation compared to colonoscopy. However a major setback for this alternative is that polyp visualization is limited to the distal colon. Studies have shown that up to 30% of patients with distal colon cancer also have synchronous proximal lesions that will be missed by sigmoidoscopy (Francois et al., 2006; Imperiale et al., 2000; Lieberman et al., 2000). As such individuals with polyps in the distal colon should undergo follow up with colonoscopy given the increased prevalence of synchronous right-sided lesions. Screening only 50% of colon will preclude detection of the lesions in the portion of the colon not within reach of the sigmoidoscope. This test would also not be an appropriate screening tool for women, patients over the age of 60, patients with HIV, and African Americans who have a higher likelihood of harboring proximal polyps (Bini et al., 2006; Lieberman et al., 2000; Lieberman et al., 2005; Schoenfeld et al., 2005).

Double contrast Barium enema allows for visualization of the entire colon and must be completed every 5 years. Its high polyp miss rate (as high as 23%), lack of therapeutic intervention (another procedure is needed to remove detected polyps), and concerns regarding radiation exposure, have limited its use (Toma et al., 2008; Wilkins and Reynolds, 2008).

CT colonography is able to provide information about the entire colon and has been proposed as a possible screening option for patients who decline conventional colonoscopy. This test is less invasive compared to conventional colonoscopy, is associated with decreased risk of perforation and does not require sedation (Lieberman, 2010). Not only are detection rates far superior to the barium enema, but CT colonography (CTC) has comparable sensitivity to colonoscopy for polyps 10mm or greater in size (Johnson et al., 2008). However relative to other options, this modality is costly, and has poor sensitivity for polyps less than 7mm (Lieberman, 2010). Due to insufficient evidence for performance metrics this test is currently not supported by established guidelines. The United States Preventive Services Task Force expresses additional concern about the impact and extra costs related to following-up extra-colonic findings (USPSTF, 2008). In fact an estimated 27% to 69% of tests performed uncover abnormal extra-colonic findings (Lieberman, 2010). More studies are needed to assess this procedure’s benefits and risks, particularly to determine whether this method may be missing significant lesions.

Capsule Endoscopy provides direct visualization of the colonic mucosa via an ingestible capsule with video cameras at both ends that wireless transmits images to a receiver. Given that bowel motility significantly affects results, this test is not performed regularly and is not supported by current guidelines.

### 2.7. CRC detection tests

Fecal occult blood testing (FOBT) is an annual stool test that detects cancer at an early stage. The USPSTF now specifically recommends the high-sensitivity guaiac-based testing (Hemoccult Sensa) over the standard guaiac-based testing (Hemoccult II) (USPSTF, 2008). Based on the premise that colon cancer intermittently bleeds, the FOBT tests for blood by detecting the peroxidase activity of heme (Lieberman, 2010). Not only is the test economical and convenient, patients with a positive test result have an almost 4 fold increased likelihood having cancer (Winawer et al., 2003). In fact studies have found FOBT reduces mortality by approximately 33% over a 10-year period (Lieberman, 2010). Another study reported approximately 20% reduction in mortality when FOBT was compared to controls over an 18-year period (Lieberman, 2010). Supporters of the FOBT question whether invasive measures such as the colonoscopy are harmful given that computer simulated modeling shows similar life-years gained in both tests (Zauber et al., 2008). Furthermore advocates assert that FOBT has the greatest potential for impact at the population level because it is directed at healthy people (Harvard Medical School, 2012). Additionally asymptomatic people may be more willing to participate in a less invasive and generally less inconvenient test.

While a case can be made that FOBT has some quantifiable mortality benefits, evidence suggests that colonoscopy is still the superior screening option. FOBT has many disadvantages. One major drawback of this modality is the high false positive rate because the test is not specific for human blood. In fact the test will not be accurate if patients consume red meat or any other peroxidase containing substances. Additionally three-stool sample are required on separate days (Lieberman, 2010). Single sample FOBT is estimated to miss 95% of CRC (Wilkins and Reynolds, 2008). Furthermore the test must be repeated annually to be effective. In addition to these drawbacks, this test only detects potentially high-risk individuals which means that abnormal test results require subsequent follow up with colonoscopy. Compliance with all of the aforementioned recommendations is unknown making the effectiveness of the test uncertain. In fact one survey found that up to 30% of doctors recommended inappropriate forms of follow up rendering the FOBT not useful (Nadel et al., 2005). Despite these drawbacks the FOBT sampling test is still preferable to the no screening option.

Fecal immunochemical testing (FIT) is a newer test that is easier to use and specific for humans. This means that the FIT is less susceptible to interference by diet or drugs. This modality uses antibodies to detect human blood components such as hemoglobin and albumin in stool samples (School, 2012). This alternative is appealing because it is less invasive than colonoscopy but potentially more accurate than the FOBT. Studies show over 50% sensitivity for cancer after using as small an amount as one stool sample (Lieberman, 2010). FIT may be superior to the FOBT given that one study showed higher participation in the FIT group. Participation is key for fecal tests making the previously mentioned study clinically relevant. However no randomized trials have shown that FIT decreases mortality (Wilkins and Reynolds, 2008).

Given that participation may be negatively impacted by hesitation to undergo colonoscopy screening, a recent study investigated whether FIT can serve as a valid screening alternative and no significant differences were found between FIT and colonoscopy in terms of participation (Quintero et al., 2012). Furthermore colonoscopy still detected substantially higher numbers of cancerous polyps. It is difficult from this study to declare that FIT testing is non-inferior because of colonoscopy’s mortality benefit.

Fecal DNA testing detects a finite number of gene mutations in stool samples associated with colon neoplasia (Alberti et al., 2012). One large prospective trial found stool DNA testing to have greater sensitivity for cancer than standard FOBT (Imperiale et al., 2004). Furthermore patients were found to prefer fecal DNA testing to both FOBT and colonoscopy (Wilkins and Reynolds, 2008). However this option is not recommended by current guidelines because of insufficient evidence. Also there have been other studies comparing stool DNA testing to FOBT that suggest this fecal DNA testing does not measure up in terms of cost or efficacy (Lansdorp-Vogelaar et al., 2010).

### 2.8. Which screening test should be done?

Each of the aforementioned screening options has strengths and setbacks, however patient adherence to CRC screening remains more critical than the specific method chosen (Vijan et al., 2001). Simply put, the best test is the one that the patient accepts and complies with. Despite mounting evidence that screening is life saving, screening rates remain surprisingly low for this preventable cancer. In fact awareness of the importance of CRC screening has only recently started to approach that of other cancers. Statistics indicate only 24% of Americans have completed the FOBT within the past few years and only 57.1% have ever had a sigmoidoscopy or colonoscopy (Wilkins and Reynolds, 2008). Data from the NHIS, a national survey of the general population, shows that only 58.3% of the US population met recommendations for CRC screening in 2010 (Shapiro et al., 2012). This is increased from 54.5% in 2008. Although there has been progress in the use of CRC testing, 40-50% of individuals over the age of 50 still are not receiving routine screening for colorectal cancer.

It is apparent from these suboptimal screening rates that there is a demand for novel screening strategies that are not only effective but also economical and non-invasive. Continued research in this field is ongoing and in a fascinating study published in Gut, Citarda et al (Citarda et al., 2001) took steps towards attempting to find this desired formula. Their study is evidence of the increasing knowledge about the molecular properties of cancer. Based on the theory that a specific cancer smell exists, they found that a trained labrador retriever could detect the presence of colorectal cancer with 91% sensitivity and 99% specificity in breath samples and 97% sensitivity and 99% specificity in watery stool samples. Surprisingly the study dog’s ability to detect cancer was not confounded by benign colorectal disease, inflammatory bowel disease, or smoking. Even though the routine use of canines for cancer screening is not practical, this study suggests there is potential for future screening tests based on cancer-specific chemical compounds.

### 4.4. Evidence based approach to ending screening

The USPSTF currently recommends that colon cancer screening via colonoscopy be terminated at age 75 (USPSTF, 2008). This recommendation is based upon a Decision Analysis published in 2008. Again, using two simulation models, the authors examined the average life-years gained and the number of colonoscopies that would be required based upon the age at which colonoscopy screening was stopped (and assuming a 10-year interval screening method in average-risk individuals). The authors primarily tested ceasing colonoscopy at age 75 vs 85. In essence, they found that by stopping screening at age 75, they decreased the number of life-years gained by only 2-5/1000 people. However, the number of colonoscopies needed decreased by 348-398/1000 people. The ranges given signify the results from both simulation models. While some may argue that adding 2-5 life-years per 1000 people should take paramount importance, this unfortunately cannot be the case given the limited resources as discussed above. Until resources are infinite, it is necessary to funnel finances and medical staff toward the population that will most benefit from screening. Distributing the additional 348-398 colonoscopies to a younger population will result in more life-years gained, lives saved, and far fewer complications. Therefore, for the time being, it seems that ceasing colonoscopy screening at age 75 is both responsible and in the best interest of society.

### 4.5. Surveillance after late stage cancer diagnosis

Lastly, it is important to recognize that not all colonoscopies will be performed for strictly screening purposes. Ultimately, the goal of colonoscopy is early diagnosis and curative treatment by either polypectomy or bowel resection. However, as colon cancer is unfortunately still such a large cause of mortality in the United States and the screening rate is not 100%, many individuals will still be diagnosed with late-stage and unresectable colon cancer. This then poses the question, what is the utility in surveillance colonoscopy in these individuals?

To date, limited data exists concerning this topic. The primary treatment for patients with diagnosed Stage IV inoperable colon cancer is palliative chemotherapy. Occasionally, chemotherapy may be able to shrink the tumor(s) to an operable state, but this is more often not the case among late-stage diagnoses due to multiple metastases. Studies have analyzed prognostic indicators among patients with inoperable disease and found that performance status, ASA-class, CEA level, metastatic load, extent of primary tumor, and chemotherapy were the only independent variables affecting prognosis in these patients (Stelzner et al., 2005). While the initial diagnostic colonoscopy can provide valuable tissue data and information regarding depth of invasion, at this time surveillance colonoscopy does not appear to play a role in the management beyond initial diagnosis. Given that there is no clear benefit to surveillance colonoscopy after diagnosis of inoperable colon cancer and there are a multitude of risks associated with the procedure, surveillance colonoscopy is not indicated in these patients.

## 5. Factors that impact effective screening

Colonoscopy is an accurate and effective screening technique that is endorsed by many societies including the American Cancer Society, U.S. Multi-society Task Force, American College of Radiology, and American College of Gastroenterology (ACG) (Levin et al., 2008; Rex et al., 2009; USPSTF, 2008). While it may seem that screening for CRC is a well-established and accepted standard of care, screening rates for CRC have only recently started to approach that of other cancers. Increasing interest in the issue of best practice for CRC screening is attributable to updates to screening guidelines as a result of recent studies indicating significant mortality benefits. In addition to changes in the actual screening guidelines, the goal of screening has shifted to focus on cancer prevention by removing polyps rather than simply cancer detection (USPSTF, 2008). Important factors exist that impact the effectiveness of available screening modalities for CRC, and these originate from physicians, patients, as well as from society. While current recommendations support initiation of screening at age 50 for all average risk men and women, earlier initiation is advocated for those at higher risk including African American men and women. Knowledge about these guidelines can impact screening practice. Consideration must also be given to the modality of CRC screening. The ACG recommends colonoscopy as the preferred mode of screening, and the gold standard given it diagnostic and therapeutic potential (Rex et al., 2009). Studies demonstrate that most physicians overwhelmingly prefer colonoscopy as the test of choice (Guerra et al., 2007). In fact, 70% of PCPs strongly believe colonoscopy is the best available colorectal cancer-screening test. Furthermore, a large proportion of physicians are concerned over lawsuits if they do not offer screening colonoscopies. The fear of facing a lawsuit over colonoscopy complications can be outweighed by the fear of being sued if the procedure is not offered at all (McGregor et al., 2010; Varela et al., 2010). While CRC screening saves lives, the use of colonoscopy and other available options, remains suboptimal. Pinpointing the reasons why people are not getting screened, either by choice or by circumstance, is essential in order to increase screening outcomes and compliance. There are unquestionably many barriers to effective healthcare delivery in the US, let alone being able to appropriately screen for CRC (Hoffman et al., 2011). Barriers can be sorted into a few main categories: physician, patient, societal related factors. This section will touch on some of these obstacles.

### 5.1. The role of the physician in CRC screening

Physician recommendations play a crucial role in the decision to get screened for CRC (Zapka et al., 2011). A mere discussion of CRC screening at the time of an office visit may be sufficient and motivate patients to complete CRC screening. Given the prominence of the physician factor it is important to consider elements that impact physician recommendation of colonoscopy to their patients. Collegial norms, patient preferences, and published evidence including guidelines from the ACS and USPSF have been identified as important elements. Physicians in the US favor endoscopy and often fail to adequately present alternatives such as stool testing. One study found that 50% of the patients surveyed did not receive the test they requested, and most underwent a colonoscopy instead (Hawley et al., 2012). However, since all screening tests have some benefit, even if they are not on par with colonoscopy, physicians need to be sensitive and attuned to patient preferences. Techniques other than colonoscopy may be more suitable for specific patients, given their individual circumstances. For example, a recent study published in Cancer found that wealthy patients frequently opt for colonoscopy while lower socioeconomic groups tended to choose at home stool testing over endoscopy (Bandi et al., 2012). Patient preference varies by ethnicity as well, with African Americans less likely to choose endoscopy than Caucasians (Dimou et al., 2009). From their trial data, Inadomi and colleagues (Inadomi et al., 2012) predict that if colonoscopy were the only option offered, fewer patients would be screened. It is evident that the choice of screening test should take into consideration not only the physician’s, but also the patient’s perspective because some form of screening still remains superior to no screening at all. Considering the evidence above, physicians should recommend one best option to their patients using evidence-based medicine and taking into account patient specific factors. CRC screening guidelines are complicated and offering multiple options still requires shared decision making in practice (Zapka et al., 2011).

Although Medicare coverage has lessened these concerns, many physicians reported that health insurance remains very influential for screening recommendations (White et al., 2012). Of note, individuals of lower socioeconomic classes have expressed concerns that they experience a lack of screening offers from doctors. This is supported by physicians who admit they do not recommend colonoscopy, if patients do not have insurance or ready access. Another interesting difference in physician screening recommendation was the age of the physician, with younger physicians recommending the test more. Although this is merely speculation, younger physicians may be more comfortable ordering this newer test (Zapka et al., 2011).

In practice, physicians often fail to mention CRC screening because of limited time, competing issues, and forgetfulness. At times the many pressing issues that need to be addressed, preclude the lengthy discussion about available cancer screening tests. Additionally, many patients only go to a clinic to address urgent issues. These clinics are often overbooked and the main focus is to stabilize the acute problem. Some patients lack health insurance or are unwilling to wait for appointments (Guerra et al., 2007). At best, some physicians may recommend a follow up health maintenance visit. In addition, one national survey suggested that the primary care physicians may not adequately discuss all test options available with average risk patients because they are under the assumption that this will be addressed in more depth by specialists. Screening rates suffer from lack of coordination between specialists and PCPs (Doubeni et al., 2010). Physician forgetfulness and unfamiliarity with guidelines is a preventable obstacle to screening (White et al., 2012). The screening and surveillance recommendations differ significantly for a subset of CRC patients with hereditary syndromes. There is a marked lack of knowledge about screening guidelines for high-risk populations based on family history and also ethnicity. Primary care physician recommendations are often inconsistent with published guidelines. Among those most intimate with guidelines, the gastroenterologists, only a fraction recommended genetic counseling, which is also a part of appropriate screening (White et al., 2012).

Studies have suggested that physicians may not be fully aware of patient’s attitudes and values towards screening. Physicians underestimated test discomfort and did not recognize the importance of helping patients make informed decisions for screening. In addition, several studies have shown that PCPs recommendations are affected by their demography including age, sex and ethnicity. For example, non-Caucasian physicians are less likely to recommend cancer screening compared to Caucasian doctors. Hispanic physicians in the US were found to be less likely to recommend CRC screening. In a study in Australia, general practitioners of Middle Eastern ethnicity estimated CRC incidence to be lower in immigrants compared to patients born in Australia, which may have resulted in lower recommendations of CRC screening for immigrants (Koo et al., 2012). Thus in general, primary care physicians need greater awareness about CRC rates and screening.

While patients cite physician recommendation as the number one motivator for screening, other factors might impact compliance. Research demonstrates that providing excessive choices can be overwhelming subsequently leading to confusion and indecision. Selection of one preferred alternative may help simplify the discussion about screening (Inadomi et al., 2012). Studies that target physician recommendations have been shown to be more effective than those that focus only on the patient (Guerra et al., 2007). In contrast, others argue that options are needed because every CRC screening modality has its own strengths and limitations. Additionally, there does not seem to be a clear consensus among patients about preferred methods. Thus, an important question arises: would patients be more willing to participate in screening, if they are given the opportunity to choose? Engaging patients in the decision-making process can improve satisfaction by taking into account each patient’s unique needs. A patient-centered approach improves screening compliance (Inadomi et al., 2012).

### 5.2. Patient-based factors in CRC screening

At the center of the discussion related to screening is the patient’s participation in completing the process. While low participation rates in screening related to infrequent or lack of follow-up is a difficult barrier to overcome, other factors are also important. It is notable that most of the data about reasons for screening non-compliance comes from direct physician report (Hoffman et al., 2011). Physicians reported offering screening to all of their high risk and most of their average risk patients, and most were surprised at the low adherence rates. Through their interactions with patients, physicians believed barriers to screening were fear of the test, embarrassment, lack of insurance, and lack of knowledge about cancer and screening. Interestingly, when patients were asked the same questions, they did not feel that discomfort or embarrassment kept them from undergoing the procedure. Patients reported lack of physician recommendation as one of the main factors for not getting tested, along with lack of symptoms that might suggest a colon neoplasm (Jones et al., 2010). Of course these studies are limited in terms of the particular patient population sampled and may not be applicable to all patients; however, it is important to note that patients place great importance on the conversation with primary care providers about CRC screening (Fenton et al., 2011). Furthermore, this is directly linked to patient’s knowledge about CRC and screening. Misconceptions continue to prevail as barriers to CRC screening, indicating a continued need for brief, direct encouragement from providers to educate patients about screening, particularly in the absence of symptoms or family history of CRC. Physicians can have great impact on CRC screening, particularly with lifesaving colonoscopy, which is greatly underutilized in the US.

In a questionnaire investigating the patient barriers to CRC screening, hesitation about screening was highest among never-screened respondents, intermediate among ever-screened respondents who were overdue for testing, and lowest among the people adherent with guidelines suggesting that different obstacles exist within each target group. The only difference between those groups of patients is prior screening status. These results also demonstrate that people who have undergone screening are less fearful of the test itself, this could be attributed to the fact that they have first hand experience instead of false information or misconceptions. Patients who are more educated are likely to be aware of the risks and benefits of CRC screening (Winterich et al., 2011).

#### 5.2.1. Patient attitudes, beliefs, and knowledge of CRC

Low compliance for CRC screening by patients can be attributed to several factors including lack of insurance, cost, lack of knowledge of cancer and screening, not seeing a need for testing, embarrassment, lack of symptoms or health problems, fear of perceived pain, and anxiety of testing. This is in addition to failure by recommendation from a physician (Jones et al., 2010). Studies have suggested that many patients dread getting ready for and having the test and also worry about the test results. Additional research has found that the participants did not understand the purpose of screening for cancer, were not able to distinguish between screening tests from any other tests and did not realize that screening is performed when a person feels well (Shokar et al., 2005).

Lack of knowledge is a major barrier to screening, particularly for immigrants, ethnic minorities, and underserved populations because of challenges in effective communication, as will be discussed later. Studies looking into lack of knowledge about colon cancer screening identified many other knowledge gaps including low health literacy. Some individuals did not have a basic understanding of human anatomy and were not able to identify the location of the colon nor its purpose. A subset of these individuals did not believe colon cancer existed. Furthermore, a surprising amount of educated individuals could not accurately describe the colon’s function, confusing it with the rectum and anus (Francois et al., 2009; Winterich et al., 2011).

Those that had some fundamental knowledge of colon anatomy lacked an adequate understanding about the causes and risk factors of colon cancer. Many individuals without symptoms or family history do not feel concerned about this disease. Some are under the impression that causes of colon cancer center around food and thought that bowel cleansing was a good way to maintain or re-establish health. Others cited that they did not get screened because they did not smoke, drink, eat unhealthy foods, or participate in anal sex, all of which they perceived to be high-risk behaviors (Francois et al., 2009).

In addition to poor understanding about colon cancer, many misperceptions about colonoscopy itself were identified. One study captured the reasons some people did not like colonoscopy including that the preparation was “inconvenient”, “uncomfortable”, and involved a “compromising position”. Men of all races and levels of educational attainment shared the male specific gender barrier that they were turned off by the invasive nature of the colonoscopy. While males and females have similar screening rates, men expressed more initial hesitation about screening because of the fear that it threatens their masculinity. Men who associated their masculinity with these exams experienced them more negatively (Winterich et al., 2011). Interestingly, Winterich et al. (Winterich et al., 2011) found that as education increased, men’s negative views of colonoscopy also seemed to increase. Most individuals of a low-educational attainment generally described the colonoscopy as a “good” test because of the culturally dominant view that medical care is important (Winterich et al., 2011).

#### 5.2.2. Racial and ethnic disparities in CRC screening

As mentioned earlier, screening rates differ based on race and ethnic groups. The National Health Interview Survey reported that racial disparities seen with CRC screening are related to socioeconomic status, however, racial disparities persist despite coverage for CRC screening in a Medicare population (Wilkins et al., 2012). Compared to whites, blacks and Hispanics are less likely to be screened. Overall rates of CRC screening are estimated to be 50% and it is even lower for minorities. Screening rates vary even within a racial or ethnic group, e.g among Asians, Koreans and Vietnamese have lower rates of screening; among whites, those living in Appalachia have lower screening rates. Minority populations and low socioeconomic status are considered to be factors resulting in low CRC screening rates (Linsky et al., 2011). Research studies also suggest that immigrants may experience unique barriers such as language and cultural differences with their health care providers which can lead to poorer communication about the importance of screening (Goel et al., 2003).

#### 5.2.3. The language divide

Patients who do not speak English are less likely to be screened (Linsky et al., 2011). According to the 2005-2007 American Community Survey, minorities comprise 26% of the population, and nearly 20% of Americans speak a language other than English at home. By 2050, minorities could make up about half of the US population, with a similar increase in individuals speaking a language other than English at home. Spanish speaking Hispanics are 43% less likely to receive CRC screening. Communication problems when discussing cancer screening are also documented with Vietnamese Americans (Linsky et al., 2011). Additionally, for Creole speaking Haitian Americans the language barrier may also be a factor in communicating with physicians (Francois et al., 2009). While patient-physician language discordance presents a barrier, it is possible to address it through initiatives such as translation services so that disparities in screening rates can be reduced.

#### 5.2.4. Cultural chasms

Cultural beliefs can result in lower screening rates, for example, Italian- Australians, Macedonian-Australians and Greek- Australians were found to believe that nothing can be done to treat ‘malignant’ cancers and that in fact, treatment of cancers may hasten death (Severino et al., 2009). They also believe that consumption of ‘unnaturally’ grown foods, eating foods sprayed with pesticides or experiencing strong emotions may cause cancer. Studies with African Americans have indicated that the lack of CRC knowledge, lack of physician recommendation, and a distrust of the health care system and providers impede screening; as well as a fatalistic belief (beliefs that screening and treatments are ‘futile’ since it is in “God’s hands”) which has also been reported as a barrier for CRC screening (James et al., 2002). A subset of individuals connected colon cancer with “someone putting a curse on you” (Francois et al., 2009). Studies in Latino population suggest that fatalistic attitudes and fear of cancer are barriers to cancer screening and misconceptions about the causes of cancer as well as perceived discomfort and embarrassment (Walsh et al., 2004).

Among other factors, family recommendations and cultural norms weighed heavily on perceptions about cancer and colonoscopy. For example, studies with Mexican and Hispanic communities have cited the need for strategies to distribute the information without causing any stigma or embarrassment. Privacy is highly valued in Mexican culture and thus individualized educational sessions are a good approach. On the other hand, Hispanic communities prefer group educational workshops. Emphasis on family and being healthy to provide for the family was effective, as well as convincing women within families of the importance of screening. Latinos also tend to see doctors only when sick and combine traditional and home healing with physician prescribed medications. Religion and spirituality seem to impact the willingness to accept CRC screening, as does low income and less education (Getrich et al., 2012).

In a study of Haitian immigrants, preventive care was not emphasized by the community. Haitians make one of the largest immigrant groups in US and have the lowest percentage of insurance coverage. Instead of having a primary physician they seem to rely on emergency rooms and do not see a doctor unless there is something wrong, there is not an operating concept valuing ‘check ups’. Undocumented persons, seek help only in an emergency situation and instead rely on home remedies. These individuals expressed that they simply did not want to know if there was something wrong with them, because finding one problem might lead to other ones (Francois et al., 2009).

#### 5.2.5. Health literacy and educational outreach in CRC screening

Efforts to empower patients to become involved in their own care have proven to be effective. Health literacy campaigns in New York City have improved CRC screening rates. Community education is required to promote screening and public education campaigns are shown to be effective. For example Mr. Polyp ads, a public service announcement from the American Cancer Society, led many to ask their doctors about colonoscopies (Guerra et al., 2007). Population based interventions aimed at increasing the demand for screening include, reminders and incentives, mass and small media, group and one-on-one education. Bilingual verbal communication and ‘word of mouth’ are also potentially very effective modalities. Blumenthal et al. (Blumenthal et al., 2010) tested three interventions intended to increase the rate of CRC screening among African Americans. They concluded that group education doubled screening rates and reduced out of pocket expenses. Furthermore, differences in attitudes and perceived barriers among ethnic and minority population may need culturally tailored interventions. Focus groups with Hispanics identified fear of finding cancer and fear of embarrassment from the examination, as screening obstacles. With this information, Varela et al. (Varela et al., 2010) developed targeted educational materials to promote colonoscopies among Hispanics. Similar educational materials could tap into faith-based programs like the successful Witness Project for breast cancer.

#### 5.2.6. Patient navigators and customized CRC screening

As previously mentioned, ethnic and cultural differences can pose a great barrier to effective cancer screening. Patient advocates who help coordinate care provide an option for tackling screening disparities. Termed patient navigators, these individuals are laypersons from the community who help patients navigate the intricacies of the health care system (Lasser et al., 2011). They can better address the unique needs of a patient and are responsible for almost anything such as helping patients get insurance, finding transportation to doctors’ appointments, healthcare education, and emotional support. For example, patients that require interpreters are found to be less compliant with screening recommendations. Providing patients with a healthcare ambassador who speaks their preferred language has proven to be a simple yet extremely powerful intervention. In a randomized controlled trial, recently published in the Archives of Internal Medicine, researchers found quantifiable benefits from assigning black and non-English speaking patients with a healthcare navigator. These patients had a greater likelihood of being screened by FOBT than control subjects (33.6% vs 20.0%; P<.001) and were also more likely to undergo colonoscopy (26.4% vs 13.0%; P,.001). Moreover, these patients had more adenomas detected (8.1% vs 3.9%; P<.06) and more cases of CRC prevented (Lasser et al., 2011). This study highlights the importance of a multidisciplinary approach to medicine. The impact of patient navigators, especially on urban and racial minorities, is demonstrated by numerous studies (Chen et al., 2008; Lasser et al., 2011; Lasser et al., 2009; Ma et al., 2009; Myers et al., 2008; Nash et al., 2006). A recent study found patient navigators to be effective for Creole or Portuguese speaking patients. This model can be observed in practice in Boston where Partners in Health routinely trains paramedical personnel to assist in providing customized care for patients with HIV and TB in Haiti and Rwanda.

The benefit of a team approach to healthcare is further evidenced by studies demonstrating that the use of nurse practitioners and physicians assistants further streamlines healthcare delivery and improves screening compliance. Moreover, telephone counseling and printed materials can help improve follow up and overall quality of life in colorectal cancer survivors. Clouston et al. (Clouston et al., 2012) performed a study to evaluate use of a website and telephones on CRC screening rates and concluded that both increased compliance significantly. However, a strong and trusting family physician-patient relationship must be maintained; otherwise, patients will experience a fundamental disconnect in the patient-physician relationship that may discourage screening. The team-based approach does not look to replace the physician, but can enhance patient-physician discourse.

Customized programs targeted to specific individuals may help improve patient participation rates. Tailored screening guidelines have been advocated for certain groups based on noted prevalence and anatomic location of colonic lesions in these populations. For example, women are known to have an increased risk of right-sided polyps and cancer (Chu et al., 2011), while African Americans tend to develop colorectal cancer at an earlier age (Agrawal et al., 2005). The recommendation for tailored screening guidelines as suggested by the ACG have the potential to help address existing disparities in CRC but must be balanced by ease of implementation as well as healthcare financing concerns.

### 5.3. Public policies, outreach, and CRC screening

Although screening rates for CRC remain suboptimal, there has been an overall upward trend. Endorsement from various recommending organizations helped promote awareness of CRC screening in the medical community. Supported by population-based studies, gastroenterology organizations have promoted screening with colonoscopy as the best screening test. The healthcare policy to support CRC screening through Medicare reimbursement was impactful in developing further acceptance. Medicare’s decision to support screening colonoscopy had a significant impact on the popularity of this modality as other payers followed suit. With insurance companies willing to pay, doctors were more inclined to recommend screening and free to choose their preferred modality, colonoscopy. In fact, gastroenterologists report they are now performing many more colonoscopies than before. Some spend 50% to 80% of their time performing this one procedure, a dramatic increase from before (Ransohoff, 2005).

Public perception and support has greatly impacted the implementation of screening, especially colonoscopy. All of the aforementioned factors are geared at gaining strong popular support, a necessary ingredient for any widespread screening practice. For example, prostate cancer screening became widely practiced on the basis of popular support, even without evidence of mortality reduction. Arguably the most influential aspect of colon cancer and screening awareness was the increasing presence of colonoscopy in the media. Famous people affected by colon cancer include Ronald Reagan, Audrey Hepburn, and Daryl Strawberry to name a few. Public interest in colonoscopy reached a turning point in March of 2000, the first colon cancer awareness month. This initiative was spearheaded by news icon Katie Couric, who advocated for CRC screening on the national stage by televising her own colonoscopy after her husband’s death (Cram et al., 2003). Similar appearances of colonoscopy in the media impacted CRC screening practices in the United States. Most recently, Dr. Oz underwent a colonoscopy on his eponymous television show. An editorial featured in the New York Times entitled “Going the distance-the case for true colorectal-cancer screening” garnered further support for colonoscopies stating that sigmoidoscopy, that only screens part of the colon, is comparable to mammography for only one breast. Numerous editorials and front page articles have featured colonoscopies (Ransohoff, 2005). For example a newspaper ad made the assertion, “your golden years deserve the gold standard of colon cancer screening” (American College of Gastroenterology [ACG], 2012). Additional marketing on the web has helped improve awareness among the public who increasingly use the web for health information (Cohen and Adams, 2011).

#### 5.3.1. Healthcare access

For patients to consider screening, it is important that to have insurance coverage, access to healthcare or both. Only 24% of uninsured Americans, who do not have a usual source of health care and are eligible, participate in CRC screening (Shapiro et al., 2012). Patients with higher incomes are likely to have health insurance and tend to have a consistent source of care. A recent systemic review reported that lower socioeconomic status was correlated with a higher incidence and mortality rate (Wilkins et al., 2012). Subramanian et al. (Subramanian et al., 2010) argue that when budgets are tight, options other than colonoscopies are better for screening, basing this on the premise that some form of screening is better than no screening at all. This study asserts that state and federal agencies have screening programs for the uninsured and underinsured that may not be able to support colonoscopy in their limited budget. However efficacy of the guaiac based fecal blood test depends on 100% compliance. This is often not practical and the study’s authors admit that colonoscopy is still a better screening test if annual testing is not feasible.

In addition to financial access, geographic access can pose a problem for individuals in rural areas. In New York City and other urban centers, most hospitals and many private practices will offer colonoscopy; however, this is not the case in every part of the country. Several studies have found lower screening rates in rural versus nonrural areas (Wilkins et al., 2012). Geographic distance is a factor and individuals are less likely to be screened if the nearest colonoscopy-offering center is over an hour away. The rural countries in the study by Wilkins et al. (Wilkins et al., 2012) had higher poverty rates, lower educational level, limited access to doctors, and less insurance coverage.

#### 5.3.2. National programs

The benefits of a team approach to healthcare is further evidenced by national programs that help promote patient awareness and education about CRC screening. Health policy initiatives need to underscore the importance of screening programs to improve quality of cancer screening. Cancer registries may be of use to identify and monitor the incidence, stage of cancer and screening rate across regions. A CRC screening registry similar to Breast Cancer Surveillance Consortium could be established to monitor rates of screening, overuse, quality and complications. An ideal monitoring system should be able to estimate rates of screening regardless of patient’s insurance status and demographic characteristics, assess use, appropriateness and outcomes. Efforts should be made to support expansion, analysis and collaboration of existing data sources and databases such as Clinical Outcome Research Initiative (CORI) endoscopy data base, the Cancer Research Network (CRN) and the Computed Tomography Colonography Registry.

#### 5.3.3. Communication via current technologies

The use of systems strategies can improve physician delivery of healthcare. Systems strategies employ patient and physician screening reminders, performance reports of screening rates, and electronic medical records (Yabroff et al., 2011). Given time constraints, remembering to perform all routine screenings for every patient is difficult. The increasing use of electronic medical records (EMR) has helped physicians overcome this obstacle. Pop-up reminders can help minimize forgetfulness, as well as the added pressure of remembering individualized guidelines. These electronic prompts have the additional advantage of flexibility, which allows for screening to account for the patient’s personal and family history. In one retrospective survey, the physicians that utilized this technology, which automatically provided appointments for CRC screening at a certain age, had the highest screening rates (Fenton et al., 2011).

In addition to physician prompts, organized screening programs make use of patient reminders to improve screening compliance. These programs reach out to all members of the population due for CRC screening via mailed reminders (Levin et al., 2011). In addition to outreach mailings, the Task Force on Community Preventive Services of the Centers for Disease Control and Prevention recommend performance reports for doctors. Monetary incentive from insurance companies for completing age-appropriate screening is effective. Additionally, better reimbursements are needed to encourage spending time on preventive medicine (Guerra et al., 2007). Brouwers (Brouwers et al., 2011) conducted a systemic review that included 66 randomized controlled studies and a cluster of randomized controlled trials. They concluded that client reminders, small media and provider audit and feedback appear to increase screening rates significantly. Despite evidence that systems strategies are effective, relatively few physicians report using a comprehensive plan to promote cancer screening (Yabroff et al., 2011).

#### 5.3.4. Health insurance coverage for colonoscopy

Ensuring health insurance coverage and usual source of care will most likely increase use among those who have never been screened. Following Medicare’s example, private insurance coverage of CRC screening will be a step towards resolving the cost issue for physicians and patients. Asking patients to pay thousands of out of pocket expenses to undergo a colonoscopy, will not help increase the rates of this life saving procedure. In a step to increase testing accessibility and affordability, the Affordable Care Act will ask insurers to cover screening colonoscopies. This will include not only colonoscopy, but the use of anesthesia (e.g. propofol) as opposed to conscious sedation (e.g., midazolam, fentanyl). Providing increased options for sedation is likely to remove the patient barrier related to discomfort and make it more likely that individuals will comply with colonoscopy as a life-saving screening modality (Liu et al., 2012).

## 6. Conclusion

This chapter has summarized the current body of knowledge related to colorectal cancer screening and surveillance recommendations in the context of addressing risk stratification, when to start and stop screening, as well as factors that impact screening rates. Overall, screening, detection, and removal of precancerous lesions allow for the prevention of CRC. It is notable that although strong evidence now exists for the mortality benefits of CRC screening, significant disparities remain in the disease thus giving rise to opportunities to address physician, patient, as well as societal factors that can improve screening rates.

## Acknowledgements

We thank the Office of Diversity Affairs at the New York University School of Medicine for its support.

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