Scott R. Steele, MD
Chief, Colon & Rectal Surgery, Madigan Army Medical Center
Assistant Professor of Surgery, Uniformed Services University
Fort Lewis, WA
Endoscopic technology has undergone dramatic improvements since Philipp Bozzini (1773-1809), a urologist from Frankfurt, Germany, developed the lichtleiter in 1806--a light-conducting system that featured a candle and system of prisms to inspect the rectum, bladder and esophagus of patients.  Along the way, multiple different physicians and scientists such as Nitze, Mikulicz, Waye, and Shinya have allowed this modality to evolve from a rigid device able to look into the bladder and stomach to a fully flexible endoscope capable of evaluating the entire gastrointestinal tract. Modern endoscopic equipment allows the direct visualization and treatment of many diseases ranging from colorectal polyps, carcinoma, inflammatory bowel disease, intestinal ischemia, diarrhea, diverticular disease, and lower gastrointestinal bleeding.
Additionally, auxiliary devices ranging from biopsy forceps, snares, injection needles, various knives, baskets and balloon dilators have been developed to expand the ability of surgeons and gastroenterologists alike to manage complex pathology through the use of endoscopes. This update will briefly review some of the emerging advances, evolving parameters and their impact on clinical practice.
Time of withdrawal
Colon cancer remains the second leading cause of cancer-related deaths in the United States, with an estimated 49,380 deaths during 2011 alone, despite multiple efforts aimed at early detection through screening, and evidence that routine screening reduces mortality. [2-5] Multiple studies have demonstrated that when compared to flexible sigmoidoscopy and air-contrast barium enemas, colonoscopy is the most effective screening tool to detect colon cancer. [6-7] These dramatic results, in part, prompted Medicare in July 2001 to provide coverage for screening colonoscopy; which, along with technological advances, dramatically increased its overall use.  Despite the success of colonoscopy to not only identify polyps, but also intervene on them, the rate of “missed” polyps appears to have reached a plateau in most major series. Large studies that include physicians with extensive experience have demonstrated missed polyp rates from 6-29%, with the variation primarily depending on the size of the lesion.  Not surprisingly, missed detection rates have uniformly been significantly lower rates for larger lesions. Pooled analysis of tandem colonoscopies has revealed a failure to detect polyps of any size is as much as 22% of cases (95%CI; 19-26%). In this systematic review, when further stratified by size, adenoma miss rates were 2.1% for > 1cm lesions, 13% for those 5-10 mm, and 26% for polyps 1-5mm.  Others have reported similar results, with miss rates for all polyps at 28%, adenomas (20%), polyps < 5mm (12%), > 5mm (9%) and advanced adenomas (11%).  When accounting for other factors such as the concomitant presence of a sub-optimal bowel preparation, these rates have been reported to be higher than 40% for any size polyp, and even up to 36% with advanced adenomas. 
One factor that has more recently come to light as playing a role in overall polyp detection rates is colonoscopy withdrawal time. In 2002, a U.S. Multi-Society Task Force on Colorectal Cancer recommended that the withdrawal time for colonoscopies should average 6-10 minutes. Interestingly, this was based originally, in part, on a single small series of only 10 consecutive colonoscopies performed by two experienced endoscopists with vastly different withdrawal practices that found different adenoma miss rates.  Following confirmatory studies, practice guidelines have since recommended that endoscopists spend a minimum of 6-10 minutes examining the colonic mucosa during the withdrawal phase of colonoscopy to optimize the diagnostic yield of polyps. In many instances, this has evolved to become a metric tracked by hospital administrators to assess the quality of colonoscopies.  The response was initially positive, with adherence to the benchmark backed by findings in studies including one of approximately 11,000 colonoscopies showing a direct association between longer withdrawal times and higher polyp detection rates (r=0.76; P<0.0001). While this association was overall a strong one, it dropped significantly as polyp size increased (r=0.19 for polyps 6-9mm; r=0.28 for polyps 10-19mm, r=0.02 for polyps > 20mm).  Small variations on this theme were subsequently reported, with others finding overall time (which included the consent and sedation periods and not just withdrawal time) correlated with increased rates of polyp detection (r=0.64; OR 1.4, CI 1.19-1.64 for polyps >1cm; OR 1.03, CI 0.74-1.43 for polyps >2cm).  In one of the sentinel papers, Barclay and associates published a study in the NEJM with 7,882 colonoscopies using 6 minutes as the minimum length of time to allow for “adequate inspection” during withdrawal.  In this study of 12 gastroenterologists, rates of polyp detection ranged widely when measured either by number (0.1 - 1.05 mean number per patient) or percentage with adenomas (9.4% - 32.7%) as well as times of withdrawal (3.1 - 16.8 min for procedures with no polyps removed). When specifically using a cutoff of 6 minutes, those with longer withdrawal times had a significantly higher rate of detection of any neoplasia (28.3% vs. 11.8%, P<0.001), as well as advanced lesions (6.4% vs. 2.6%, P=0.005). Since then, multiple authors have confirmed average withdrawal times of 6 minutes or longer to be correlated with increased adenoma detection rates, including a quality assurance review of 15,955 patients over 49 ambulatory centers, 17 states and 315 gastroenterologists where longer withdrawals had a1.8-fold higher rate of polyp detection.  In this large review, factors that were found to be the strongest predictors of withdrawal time of >6 minutes have included presence of carcinoma [odds ratio (OR)=3.7], adenoma (OR=2), and number of polyps visualized (OR=1.7). Whether the study is performed in a private practice or academic environment, the relationship between longer withdrawal times and higher rates of overall polyp detection, or adenomas per patient (0.09-0.82), has been consistent. 
Yet this has not been met with complete agreement. Several authors have demonstrated no difference in polyp detection rates, despite compliance with meeting withdrawal guidelines improving from 65% to near 100%.  Others argue that colonoscopy rarely misses polyps >1cm, regardless of the time spent during the withdrawal phase. Still others have agreed that withdrawal time is associated with higher rates of polyp detection, but point out that longer withdrawal times have not been associated with ultimately changes in rates in neoplasia at subsequent follow-up colonoscopies, including a recent VA Cooperative Studies Group analysis.  Similarly, published reports cite that after a monitoring and feedback program was instituted that focused on withdrawal times, polyp detection rates and patient satisfaction, there was an increase in mean withdrawal time (6.6 to 8.1 minutes, P<0.0001) and overall polyp detection rate (33.1% to 38.1%, P=0.04), but again without an increase in neoplasia detection rate from the initial to the post-intervention time periods (19.6 to 22.7%; P=0.17). 
Despite this, withdrawal time has evolved into a quality metric indicator in many centers for determining the adequacy of colonoscopy. As such, this has led to some changes in clinical practice--both positive and negative. Some authors have reported improved rates of longer withdrawal times to comply with these guidelines, simply knowing that this quality measure was being recorded, but without using that time to perform the corresponding evaluation. To combat this, practices such as vetting through bystander observation and video recording have been attempted, though without a significant increase in polyp detection.  Other authors have shifted focus in attempt to further clarify other reasons to account for variations in polyp detection rate. Factors such as number of procedures, mean patient age, percentage of women, and mean procedure time have all been evaluated (in addition to polyp size) with only procedure time being significantly associated with polyp detection rate in a study of 2,665 screening colonoscopies.  Multiple other patient and physician-related factors have also been identified as causes for higher miss rates including experience of the endoscopist, larger folds, morphology of polyp, and polyp location (i.e, blind spots at the flexures). [11, 24]
Multiple other variables have been considered as potential factors for affecting both the overall quality of colonoscopy performance and adenoma detection rates, one of which is physician fatigue. This was based on prior data demonstrating that afternoon colonoscopies have higher failure rates than morning colonoscopies, with higher overall incompletion rates (6.5% vs. 4.1%, P=0.013) and higher rates of inadequate bowel preparation (15.4% in a.m. vs. 19.7% in p.m.).  When using cecal intubation rates as the endpoint, success was again lower in the afternoon (93.5% vs. 95%, P=0.02), although gender, age and bowel preparation were felt to play a role in these differences.  Yet, adenoma detection rates have also varied based on the time of day the colonoscopy is performed, with one study reporting rates of 29.3% in the morning versus 25.3% in the afternoon (P=0.008), which independent of factors such as poor bowel preparation, withdrawal time, or partial evaluation.  To further clarify this, authors have compared results in providers that perform a full day of scopes with those limited to half-day blocks. Adenoma detection rates in those only working half days have showed no significant difference between early and late procedures within that time period (27.6% vs. 26.6%, OR 1.05; CI 0.88-1.26, P=0.56), while those in the same practice with full-day blocks reporting higher detection rates in the morning (26.1% vs. 21%; P=0.02), suggesting that the additional time, and subsequent fatigue, plays a role for this difference.  This provider fatigue culminates in lack of focus or acumen, and translates into lower rates of “successful” colonoscopies as time progresses. Interestingly, polyp detection rates have also been shown to decline as time passes during an endoscopist’s schedule, regardless of time of day, or number of prior procedures, as each elapsed hour in their work schedule was associated with a 5.6% reduction in polyp detection (P=0.005); again suggesting that physician fatigue can progress more rapidly in certain cases. 
Regardless of the metric proposed, proper training remains a major factor in becoming and staying proficient in any endeavor. Historically, intra-procedural quality indicators for colonoscopy have focused primarily on physician-related factors such as cecal intubation rates, terminal ileal intubation, number of polyps detected, number of polyps retrieved, size of polyps detected, time to reach the cecum, (and more recently) withdrawal time. Guided by principles such as the United Kingdom Department of Health Global Rating Scale for endoscopy, emphasis has shifted more on defining quality experience through patient-driven metrics including appropriateness of the intervention, proper information/consent, overall safety, patient comfort, and providing timely results.  Use of colonoscopy-based virtual-simulator models has been one major way to bridge the training that is often underachieved in residencies, and improve both the trainee experience and end result. Multiple studies have demonstrated that following intervention with 3-D simulators, many of these aforementioned traditional metrics such as cecal intubation rates, overall times, and need for further medication interventions all significantly improved.  On the other hand, it remains to be seen how these newer quality metrics will be evaluated, and possibly more concerning, enforced.
Endoscopic mucosal resection (EMR) and Endoscopic submucosal dissection (ESD)
Endoscopic mucosal resection (EMR) was first described in 1990 by Inoue and Endo in Japan,  and subsequently followed by Soehendra and colleagues in Hamburg, Germany in 1997.  In the esophagus and stomach, as well as the colon, EMR allows removal of superficial tumors of the gastrointestinal tract. Unlike polypectomy that removes the tumor at the base of the mucosa, the plane of resection during EMR occurs in the middle or deeper submucosal layer. Yet, drawbacks of piecemeal excision are difficulty with proper staging, histological diagnosis, and definitive evaluation of the margins. [34, 35] Furthermore, unlike the stomach, the colonic wall is much thinner and curvy, leading to a somewhat more technically difficult procedure. Indications for EMR currently include adenomas or small well-differentiated carcinomas confined to the mucosa or with minimal invasion into the submucosa, those more than 1/3rd of the lumenal diameter, or flat/depressed polyps. In essence, EMR enables select lesions to be removed that would potentially require colectomy.  It is important that these early carcinomas do not have any lymphovascular invasion, due to the risk of lymph node metastases. As this technique is currently performed more commonly in Japan, the Japanese Society for Cancer of the Colon and Rectum’s current criteria for curative endoscopic resection are: a submucosal invasion of less than 1000 μm, moderate or well-differentiated lesion characteristics, and the absence of vascular invasion.  Local recurrence has been reported in 6.9-13.4% of cases of EMR, with higher rates reported following piecemeal excision, cancers, and rates up to 39% for lesions >2cm.  Median times for recurrence are typically within the first 6 months, signifying the importance of follow-up endoscopic evaluation between 3-6 months and at one year.  In patients with larger polyps or those with dysplasia or cancer, it is recommended to undergo more high intensity surveillance. [40, 41] Other reported risk factors for recurrence include a granulous appearance of the lesion, and distal rectal lesions. Incomplete (R1) resections and those with deep positive margins should be considered for surgery.
Outcomes for EMR are, in general, very good, as most patients are highly selected. Less than 3% are referred for surgical resection, and 44-60% are performed en bloc, with the remaining lesions undergoing piecemeal removal.  In sample series, complications involve procedural (10-13%) and late (0-1%) bleeding, post-polypectomy syndrome (2-3%) and perforations (1-2%).  In attempting to identify those polyps up front that contain cancer in order to decide if EMR would be appropriate, malignancy has been in higher rates with sessile polyps and those > 3cm [42, 43] Although these are not an absolute contraindication to EMR, it is typically more difficult to remove tumors larger than 2cm by en bloc resection using EMR, with reported rates of ~30%, and decisions should be made on an individual basis. [44-46]
Endoscopic submucosal dissection (ESD) is primarily used to help with resecting larger tumors and aid in achieving higher rates of en-bloc resection of superficial tumors in the gastrointestinal tract than EMR. While still primarily performed in select centers and lacking widespread use, the goals of ESD remain 1) treating mucosal cancer; 2) achieving an R0 resection; 3) meeting quality standards; and 4) ensuring that procedures are performed by surgeons trained in this technique or under institutional review board approval.  ESD is more commonly indicated when a snare is unlikely to be successful in enabling en bloc resection with EMR. ESD is also indicated when tumors are diagnosed as carcinomas with intramucosal to shallow submucosal invasion, as well as lesions with submucosal fibrosis that cannot be removed by EMR, even if less than 20mm in size. Others have proposed that this technique is suitable for all large polyps, early colorectal cancer, and those lesions that cannot be accessed by transanal or TEMS routes in those who wish to avoid major resection. Using different techniques, successful en-bloc resection occurs in up to 85-89% of cases and piece-meal resection in the remaining 10-15%. [48-52] [REF] Clear lateral and deep margins (ie, complete resections) have been reported in up to 79-86% of cases. [53, 54] As previously stated, because it is difficult to perform en-bloc resection by EMR for lesions larger than 20 mm, ESD may be more suitable for these lesions. Having the ability to predict depth of invasion up to decide whether to pursue EMR, ESD or formal resection remains somewhat difficult. Similar to EMR studies, predictors of submucosal versus mucosal invasion include poor-differentiation and the absence of background adenoma. [42, 43]
Briefly the technique of ESD involves an initial bowel preparation to remove residual feces. An endoscope with a single channel is used along with a high-frequency generator. After identification of a lesion, a mixture of 1% hyaluronic acid solution and 10% glycerin solution is injected around the lesions to elevate the submucosa.  Specialized knives in various shapes and sizes help to perform the dissection and resection. The border of the tumor is initially marked by indigo carmine dye and with approximately 1 cm margins. Following a mucosal incision, and depending on the physician preference, a partial or circumferential incision is made along with injection of hyaluronic acid solution into the submucosa, and the dissection is carried down to the deep submucosa. This process is continued around the tumor until the entire lesion is resected en bloc, when possible.
Perforation rates occur in ESD in 1.4-10.4%, with the majority <2%,  and are classically higher than that of EMR secondary to the depth of dissection, and in cases involving a significant amount of fibrosis.  When perforation occurs, endoscopic clips are often utilized to close the site when it is small.  In more severe cases or those that cannot be closed endoscopically, more definitive procedures should be performed either open or through a minimally invasive approach. Rare cases of delayed perforation occur in <1%, often thought to be secondary to thermal injury.  Postoperative hemorrhage rates are reported between 0-12%, comparable to that with EMR, and the majority are self-limiting.  One complication unique to this procedure is the inability to complete the procedure secondary to restlessness from abdominal distension and pain (12-32%), requiring additional conscious sedation or even general anesthesia. Other more rare complications include obstruction, fever, and pain. [60,61] Most importantly, residual disease has been reported in 2-3% with ESD.  In one of the few series comparing ESD with EMR, 145 colorectal tumors were treated by ESD and another 228 treated by EMR. ESD was associated with a longer procedure time (108 min vs. 29; P< 0.0001), higher en bloc resection rate (84 vs. 33%; P < 0.0001) and larger resected specimens (37 vs. 28 mm; P = 0.0006).  There were three (2%) recurrences in the ESD group and 33 (14%) in the EMR group requiring additional EMR (P < 0.0001). Complication rates were similar (perforation 6.2% ESD vs. 1.3% EMR; delayed bleeding 1.4% ESD vs. 3.1% EMR; P = NS). Although both of these techniques are currently isolated to select centers, emerging literature and advances in technology may provide the impetus for more widespread use in select patients.
In general terms, a polyp refers to the elevation of tissue above the gastrointestinal epithelium. Colon polyp types range widely from hyperplastic, hamartomatous, and inflammatory varieties to neoplastic adenomatous lesions. Although these lesions are all “benign,” up to one-quarter of patients over 60 years old will have “pre-malignant” adenomatous polyps. Traditionally, polyps have been classified most commonly by their histology (ie, lymphatic, tubular, tubulovillous, etc), location, and physical description—with pedunculated and sessile being the most common descriptive classes. Yet since their first description in 1985,  flat adenomas are increasingly more common and represent one of the “high-risk” categories along with adenomas larger than 1cm, those with dysplasia, those associated with IBD, villous or tubulovillous adenomas, and patients with multiple adenomas (typically >3). Similarly, serrated adenomas are believed to represent a unique pathway in the adenoma-carcinoma sequence.
Flat Polyps and Serrated Adenomas
Although there was initial hesitancy and controversy as to the impact and importance of flat adenomas in “Western” cultures, other “Eastern” cultures have believed differently. The Japanese Research Society Classification (Kudo classification of adenomas) describes flat lesions as those with a height that is less than one half the diameter ; while the Paris classification uses protruding and non-protruding divisions.  Increasingly, these lesions are recognized for their role in malignancy as well as difficulty with identification.  Serrated polyps represent another type of lesion that has been reported to be more difficult to diagnosis. Originally described following evaluation of hyperplastic polyposis syndrome patients, these lesions have a characteristic serrated architecture and can occur either as a traditional serrated adenoma (classically seen as a polypoid lesion), or as a sessile serrated adenoma (flat, slightly raised, right-sided >left). Though historically often diagnosed as a variant of hyperplastic polyps, these lesions are found in ~7% of all colonoscopies, and are now more properly classified as their own distinct entity. They are also believed to have a higher risk of malignancy that occurs apart from the traditional adenoma to carcinoma sequence. [68-69]
The traditional polyp-cancer sequence has been established since Muto and colleagues described it in 1975.  Adenocarcinoma of the colon can arise via multiple different pathways, with the most common described by genetic alterations that result in micro-satellite stable carcinomas.  Approximately 1/3rd, however, will arise along the serrated pathway, developed from the precursor lesion known as the sessile serrated adenoma (SSA). This is caused from an extensive methylation at the CpG island promotor site, which may demonstrate microsatellite instability. While controversy exits, it has been reported that SSAs are precursor lesions to micro-satellite unstable carcinomas; though limited data on the rate of progression currently exists.  In their pre-malignant state, these polyps show features between those of hyperplastic polyps and adenomas. On a molecular level, they have a high proportion of the BRAF mutation and DNA methylation. BRAF, a member of the RAF family of serine/threonine kinases, mediates cellular responses to growth signals, and BRAF mutations have been strongly associated with mixed-match repair-deficient colorectal cancer.  Methylation and inactivation of the DNA repair genes MLH1 and MGMT (06 methylguanine-DNA methyltransferase) similar to that in HNPCC, are felt to be the critical steps that lead to this instability.  It has also previously been found that patients with micro-satellite unstable cancers demonstrate an increased serrated polyp to adenoma ratio compared with stable cancers. Therefore when encountering patients that have more serrated polyps than adenomas in colonoscopy, cancers in these patients may more often demonstrate MSI and should be considered for appropriate testing.  Risk factors for the development of sessile serrated adenomas include greater than 20 pack-year smoking history (OR 7.31 CI 3.9-13.6), and, to a smaller extent, diabetes and obesity. 
Unfortunately, there continues to be inconsistencies in the literature regarding the ultimate prognosis and malignant potential both of these lesions possess. Even large series comparing flat lesions with polypoid have found that the size of the lesion has a much greater propensity than the morphology for the development of malignancy. Furthermore, the incidence of high-grade dysplasia or cancer in flat neoplasias was found to be similar to that of polypoid neoplasias (5.4 percent vs. 4.6 percent, P = 0.36).  [ref] While still somewhat controversial, what seems increasingly clear is that while further information is required to determine the exact context of these lesions for malignant potential, there is evidence to suggest these lesions portend a higher risk profile and should be followed accordingly until this process is better understood.
There is little doubt that colonoscopy is a highly specific and sensitive test or the defection of colonic lesions. However, differentiating early colon cancer from polyps can be more difficult. Factors that are associated with the presence of malignancy in a colonic polyp include villous architecture, increasing size, presence of multiple polyps and sessile lesions.  To further help in distinguishing benign from cancerous lesions, Kudo and colleagues in 1994 reported on differences in mucosal pit patterns of various colorectal polyps.  In this classification system, staining patterns that are often seen in hyperplastic polyps or normal mucosa differ from an unstructured surface architecture more commonly identified with malignancy. Pit patterns were classified into seven principal types: 1) normal round pit; 2) small round pit; 3) small asteroid pit; 4) large asteroid pit; 4) oval pit; 6) gyrus-like pit; and 7) non-pit. The authors found that there was a correlation between pit patterns and the histology of the cells in the gland. The authors further went on to categorize these seven principle types into 5 pit patterns: I) normal round pit; II) small and large asteroid pits; III) small round pit (IIIL, oval pit); IV) gyrus-like pit; and V) non-pit pattern. By using this schema, types I, II are non-neoplastic and III, IV, and V are neoplastic, with accuracy rates reported as high as 90%.  Chromoendoscopy and narrow band imaging (NBI) use these differences in pit pattern to help detect and differentiate polyps.
In chromoendoscopy, a dye such as indigo carmine can further enhance the surface structure of epithelial lesions with the aid of magnifying endoscopy.  Pit patterns become more recognizable, and outlining the borders of polyps is reported to be more accurate. Accuracy rates have been reported as high as 87-100% and 76-99.8% in diagnosing non-neoplastic and neoplastic polyps, respectively.  Furthermore, this technique has been shown to be beneficial for helping detect small lesions and decreasing the missed polyp rate, with diagnostic accuracies of 95% with magnification chromoendoscopy for lesions < 5mm compared to 76% with traditional colonoscopy [83, 84] A recent update of the Cochrane review comparing chromoendoscopy versus conventional endoscopy for polyps containing 5 studies showed that chromoendoscopy has a overall detection rates of at least one neoplastic lesion (OR 1.67, CI 1.29-2.15), and >3 neoplastic lesions (OR 2.55, CI 1.49-4.36).  Although still not widely used, especially in the U.S., chromoendoscopy also has been cited to reduce the time, cost and risk with biopsy/polypectomy, once the initial learning curve associated with dye application is complete.
Narrow band imaging
Narrow band imaging (NBI) is an imaging technique that also relies on better definition of capillary pattern to improve the contrast between adenomas and surrounding normal mucosa. Adenomas, like malignancy have a characteristic angiogenesis that various wavelengths penetrate to a different degree.  The theory behind it lies in its ability to contrast the “normal” mucosa from that of adenomatous tissue to a greater degree than standard white light colonoscopy by selecting out specific wavelengths through optical filters that “narrow” the bandwidth of light. Developed by Gono and associates (and originally described on the vascular pattern and adjacent mucosa of the underside of the human tongue), it uses the reflected light to visualize the superficial structure and enhance the vasculature within the mucosal layers.  Unlike chromoendoscopy, which relies on sprays and specialized equipment, NBI is readily available on most colonoscopes and does not require additional imaging. The data on it, however, remains somewhat conflicting. In a pilot study by Machida and associates, NBI had a 93.4% diagnostic accuracy, equivalent to chromoendoscopy with magnification, and higher than that of conventional colonoscopy.  In one randomized trial during screening colonoscopies, patients randomized to white light (N=108) and NBI (n=103) had adenoma detection rates of 58.3 and 57.3 (P=0.88), respectively. However, when the authors further evaluated only flat adenomas, a lesion believed to be best defined by NBI, the detection rates were 9.3% for traditional colonoscopy and 21.4% for NBI (P=0.019).  Other randomized data including 1,256 patients comparing NBI technology to white light with associated high definition video found no difference in overall adenoma detection rates (33% vs. 34%), total number of lesions (200 vs. 216), or any other subgroups of adenomas to include flat lesions.  In this study, only hyperplastic polyps were found more commonly in NBI. Several other authors have found NBI did not improve the colorectal neoplasm miss rate compared to traditional methods,  or even those of small and flat adenomas with the use of high-definition colonoscope. 
On the contrary, there are studies that do report improvements in distinguishing neoplastic from non-neoplastic lesions using NBI, with accuracy rates higher than that of colonoscopy and equivalent to chromoendoscopy (80-82% low magnification NBI; 85% low magnification chromoendoscopy; 87-90% high magnification NBI; 92-92% high magnification chromoendoscopy; standard colonoscopy (67-68%).  Other authors have found sensitivity of 90-96% and specificity of 85-89% in differentiation of neoplastic versus non-neoplastic lesions, comparable to that of chromoendoscopy. Furthermore, accuracy rates were even higher with the addition of magnifying endoscopy, up to 94% for neoplastic and 89% for non-neoplastic lesions. [93, 94] Similar to chromoendoscopy, however, the ultimate role this will have relies on the long-term data, ability to lower costs, and proper training of endoscopists prior to incorporation into everyday and widespread use.
References Core Subjects
- Morgenthal CB, Richards WO, Dunkin BJ, Forde KA, Vitale G, Line; SAGES Flexible Endoscopy Committee. The role of the surgeon in the evolution of flexible endoscopy. Surg Endosc 2007; 21: 838-53.
- Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328: 1365-71.
- Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348: 1472-7.
- Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992; 326 653-7.
- Newcomb PA, Norfleet RG, Storer BE, Surawicz TS, Marcus PM. Screening sigmoidscopy and colorectal cancer mortality. J Natl Cancer Inst 1992; 84: 1572-5.
- Lieberman DA, Weiss DG, Bond JH, Ahnen DJ, Garewal H, Chejfec G. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med 2000; 343: 162-8.
- Imperiale TF, Wagner DR, Lin CY, Larkin GN, Rogge JD, Ransohoff DF. Risk of advanced proximal neoplasms in asymptomatic adults according to the distal colorectal findings. N Engl J Med 2000; 343: 169-74.
- Harewood GC, Lieberman DA. Colonoscopy practice patterns since introduction of Medicare coverage for average-risk screening. Clin Gastroenterol Hepatol 2004; 2: 72-7.
- Rex DK, Cutler CS, Lemmel GT et al. Colonoscopic miss rates of adenomas determined by back to back colonoscopies. Gastroenterology 1997;112:24-28.
- van Rijn JC, Reitsma JB, Stoker J, Bossuyt PM, van Deventer SJ, Dekker E. Polyp miss rate determined by tandem colonoscopy: a systematic review. Am J Gastroenterol 2006;101:343-50.
- Heresbach D, Barioz T, Lapalus MG, et al. Miss rate of colorectal neoplastic polyps: a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 2008; 40: 284-90.
- Lebwohl B, Kastrinos F, Glick M, Rosenbaum AJ, Wang T, Neugut AI. The impact of suboptimal bowel preparation on adenoma miss rates and the factors associated with early repeat colonoscopy. Gastrointest Endosc. 2011 Apr 7. [Epub ahead of print]
- Rex D. Colonoscopic withdrawal technique is associated with adenoma miss rates. Gastrointest Endosc 2000; 51: 33-6.
- Sawhney MS, Cury MS, Neeman N, et al. Effect of institution-wide policy of colonoscopy withdrawal time > or = 7 minutes on polyp detection. Gastroenterology 2008; 135: 1892-8.
- Simmons DT, Harewood GC, Baron TH, et al. Impact of endoscopist withdrawal speed on polyp yield: implications for optimal colonoscopy withdrawal time. Aliment Pharacol Ther 2006; 24: 965-71.
- Sanchez ZW, Harewood GC, Petersen BT. Evaluation of polyp detection in relation to procedure time of screening or surveillance colonoscopy. Am J Gastroenterol 2004; 99: 1941-5.
- Barclay RL, Vicari JJ, Doughty AS, Johanson JF, Greenlaw RL. Colonoscopic Withdrawal Times and Adenoma Detection during Screening Colonoscopy. N Engl J Med 2006;355:2533-41.
- Overholt BF, Brooks-Belli L, Grace M, et al. Withdrawal times and associated factors in colonoscopy: a quality assurance multicenter assessment. J Clin Gastroenterol 2010; 44: e80-6.
- Benson ME, Reichelderfer M, Said A, Gaumnitz EA, Pfau PR. Variation in colonoscopic technique and adenoma detection rates at an academic gastroenterology unit. Dig Dis Sci. 2010; 55: 166-71.
- Gellad ZF, Weiss DG, Ahnen DJ, Lieberman DA, Jackson GL, Provenzale D. Colonoscopy withdrawal time and risk of neoplasia at 5 years: results from VA Cooperative Studies Program 380. Am J Gastroenterol 2010;105:1746-52.
- Lin OS, Kozarek RA, Arai A, et al. The effect of periodic monitoring and feedback on screening colonoscopy withdrawal times, polyp detection rates, and patient satisfaction scores. Gastrointest Endosc 2010; 71: 1253-9.
- Taber A, Romagnuolo J. Effect of simply recording colonoscopy withdrawal time on polyp and adenoma detection rates. Gastrointest Endosc 2010; 71: 782-6.
- Imperiale TF, Glowinski EA, Juliar BE, Azzouz F, Ransofoff DF. Variation in polyp detection rates at screening colonoscopy. Gastrointest Endosc 2009; 69; 1288-95.
- Warneke J, Petrelli N, Herrera L, Nava H. Accuracy of colonoscopy for the detection of colorectal polyps. Dis Colon Rectum 1992; 35:981-5.
- Sanaka MR, Shah N, Mullen KD, Ferguson DR, Thomas C, McCullough AJ. Afternoon colonoscopies have higher failure rates than morning colonoscopes. AM J Gastroenterol 2006; 1010: 2726-30.
- Wells CD, Heigh RI, Sharma VK, et al. Comparison of morning versus afternoon cecal intubation rates. BMC Gastroentrol 2007; 7:19.
- Sanaka MR, Deepinder F, Thota PN, Lopez R, Burke CA. Adenomas are detected more often in the morning than in afternoon colonoscopy. Am J Gastroenterol 2009; 104: 1659-64.
- Gurudu SR, Ratuapil SK, Leighton JA, Heigh RI, Crowell MD. Adenoma detection rate is not influenced by the timing of colonoscopy when performed in half-day blocks. Am J Gastroenterol 2011 Apr 19. [Epub ahead of print]
- Lee A, Iskander JM, Gupta N, et al. Queue position in the endoscopic schedule impacts effectiveness of colonoscopy. Am J Gastroenterol 2011 March 29. [Epub ahead of schedule]
- GRS Global Rating Scale [Internet]. Available from www.grs.nhs.uk.
- Kaltenbach T, Leung C, Wu K, Yan K, Briedland S, Soetikno R. Use of the colonoscope training model with the colonoscope 3d imaging probe improved trainee colonoscopy performance: a pilot study. Dig Dis Sci 2001; 56: 1496-1502.
- Inoue H, Endo M. Endoscopic esophageal mucosal resection using a transparent tube. Surg Endosc 199; 4: 198-201.
- Soehendra N, Binmoeller KF, Bohnacker S, et al. Endoscopic snare mucosectomy in the esophagus without any additional equipment: a simple technique for resection of flat early cancer. Endoscopy 1997; 29: 380-3.
- Hurlstone DP, Sanders DS, Cross SS, et al. Colonoscopic resection of lateral spreading tumours: a prospective analysis of endoscopic mucosal resection. Gut 2004; 53: 1334-1339.
- Tanaka S, Oka S, Chayama K. Colorectal endoscopic submucosal dissection: present status and future perspective, including its differentiation from endoscopic mucosal resection. J Gastroenterol 2008; 43: 641-651.
- Repici A, Pellicano R, Strangio G, Danese S, Fagoonee S, Malesci A. Endoscopic mucosal resection for early colorectal neoplasia: pathologic basis, procedures, and outcomes. Dis Colon Rectum 2009; 52:1502-15.
- Kitajima K, Fujimori T, Fujii S, et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol 2004; 39: 534-543.
- Brooker JC, Saunders BP, Shah SG, Thapar CJ, Suzuki N, Williams CB. Treatment with argon plasma coagulation reduces recurrence after piecemeal resection of large sessile colonic polyps: a randomized trial and recommendations. Gastrointest Endosc 2002; 55: 371-375.
- Seitz U, Bohnacker S, Seewald S, Thonke F, Soehendra N. Long-term results of endoscopic removal of large colorectal adenomas. Endoscopy 2003; 35: S41-S44.
- Lin OS. Clinical update: postpolypectomy colonoscopy surveillance. Lancet 2007; 370: 1674-1676.
- Arebi N, Swain D, Suzuki N, Fraser C, Price A, Saunders BP. Endoscopic mucosal resection of 161 cases of large sessile or flat colorectal polyps. Scand J Gastroenterol 2007; 42: 859-866.
- Ferrara F, Luigiano C, Ghersi S, et al. Efficacy, safety and outcomes of 'inject and cut' endoscopic mucosal resection for large sessile and flat colorectal polyps. Digestion 2010; 82:213-20.
- Luigiano C, Consolo P, Scaffidi MG, et al. Endoscopic mucosal resection for large and giant sessile and flat colorectal polyps: a single-center experience with long-term follow-up. Endoscopy 2009; 41:829-35.
- Tanaka S, Haruma K, Oka S, et al. Clinicopathologic features and endoscopic treatment of superficially spreading colorectal neoplasms larger than 20 mm. Gastrointest Endosc 2001; 54: 62-66.
- Saito Y, Fukuzawa M, Matsuda T, et al. Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumorsas determined by curative resection. Surg Endosc 2010; 24: 343-352.
- Iishi H, Tatsuta M, Iseki K, et al. Endoscopic piecemeal resection with submucosal saline injection of large sessile colorectal polyps. Gastrointest Endosc 2000; 51: 697-700.
- Deprez PH, Bergman JJ, Meisner S, et al. Current practice with endoscopic submucosal dissection in Europe: position statement from a panel of experts. Endoscopy 2010; 42:853-8.
- Tanaka S, Oka S, Kaneko I, et al. Endoscopic submucosal dissection for colorectal neoplasia: possibility of standardization. Gastrointest Endosc 2007; 66: 100-107.
- Saito Y, Uraoka T, Matsuda T, et al. Endoscopic treatment of large superficial colorectal tumors: a case series of 200 endoscopic submucosal dissections (with video). Gastrointest Endosc 2007; 66: 966-973.
- Fujishiro M, Yahagi N, Kakushima N,. Outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms in 200 consecutive cases. Clin Gastroenterol Hepatol 2007; 5: 678-683.
- Tamegai Y, Saito Y, Masaki N,. Endoscopic submucosal dissection: a safe technique for colorectal tumors. Endoscopy 2007; 39: 418-422.
- Yoshida N, Naito Y, Sakai K, et al. Outcome of endoscopic submucosal dissection for colorectal tumors in elderly people. Int J Colorectal Dis 2010; 25: 455-46.
- Kim MN, Kang JM, Yang JI, et al. Clinical features and prognosis of early colorectal cancer treated by endoscopic mucosal resection. J Gastroenterol Hepatol 2011 Apr 22. IEpud ahead of print]
- Nishiyama H, Isomoto H, Yamaguchi N, et al. Endoscopic submucosal dissection for colorectal epithelial neoplasms. Dis Colon Rectum 2010; 53:161-8.
- Yamamoto H, Kawata H, Sunada K, et al. Successful en-bloc resection of large superficial tumors in the stomach and colon using sodium hyaluronate and small caliber-tip transparent hood. Endoscopy 2003; 35: 690-694.
- Yoshida N, Yagi N, Naito Y, Yoshikawa T. Safe procedure in endoscopic submucosal dissection for colorectal tumors focused on preventing complications. World J Gastroenterol 2010; 16: 16888-1695.
- Matsumoto A, Tanaka S, Oba S, et al Outcome of endoscopic submucosal dissection for colorectal tumors accompanied by fibrosis. Scand J Gastroenterol. 2010; 45:1329-37.
- Uraoka T, Kawahara Y, Kato J, Saito Y, Yamamoto K. Endoscopic submucosal dissection in the colorectum: present status and future prospects. Dig Endosc 2009; 21 Suppl 1: S13-S16.
- Isomoto H, Nishiyama H, Yamaguchi N, et al. Clinicopathological factors associated with clinical outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms. Endoscopy 2009; 41: 679-683.
- Yoshida N, Kanemasa K, Sakai K, et al. Experience of endoscopic submucosal dissection (ESD) to colorectal tumor-especially about clinical course of cases with perforation (Japanese literature with English abstract). Gastroenterol Endosc 2008; 50: 1472-1483.
- Park SY, Jeon SW. Acute intestinal obstruction after endoscopic submucosal dissection: report of a case. Dis Colon Rectum 2008; 51: 1295-1297.
- Oka S, Tanaka S, Kanao H, Ishikawa H, et al. Current status in the occurrence of postoperative bleeding, perforation and residual/local recurrence during colonoscopic treatment in Japan. Dig Endosc 2010; 22:376-80.
- Saito Y, Fukuzawa M, Matsuda T, et al. Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative resection. Surg Endosc 2010; 34: 343-52.
- Anderson JC. Risk factors and diagnosis of flat adenomas of the colon. Expert Rev Gastroenterol Hepatol 2011; 5: 25-32.
- Kudo S. Endoscopic mucosal resection of flat and depressed types of early colorectal cancer. Endoscopy 1993; 25: 455-61.
- The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 200. Gastrointest Endosc 2003; 58; S3-S43.
- Speake D, Biyani D, Frizelle FA, Watson AJ. Flat adenomas. ANZ J Surg 2007; 77:4-8.
- Goldstein NS. Serrated pathway and APC (conventional)-type colorectal polyps: molecular-morphologic correlations, genetic pathways, and implications for classification. Am J Clin Pathol 2006:125:146-159.
- Noffsinger AE, Hart J. Serrated adenoma: a distinct for m of non-polypoid colorectal neoplasia? Gastrointest Endosc Clin N Am 2010; 30: 543-63.
- Muto T, Bussey HJ, Morson BC. The evolution of cancer of the colon and rectum. Cancer 1975; 35: 2251-70.
- Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988, 319:525-32.
- Snover DC, Update on the serrated pathway to colorectal carcinoma. Hum Pathol 2011; 42: 1-20.
- Kambara T, Simms LA, Whitehall VL, et al. BRAF mutation is associated with DNA methylation on serrated polyps and cancers of the colorectum. Gut 2004; 53: 1137-1144.
- Jass JR. Serrated adenoma of the colorecturm and DAN-methylator phenotype. Nat Clin Pract Oncol 2005; 2: 398-405.
- Messick CA, Church J, Casey G, Kalady MF. Identification of the methylator (serrated) colorectal cancer phenotype through precursor serrated polyps. Dis Colon Rectum 2009; 52: 1535-41.
- Anderson JC, Rangasamy P, Rustagi T, et al. Risk factors for sessile serrated adenomas. J Clin Gastroenterol 2001 Feb 15. [Epub ahead of print]
- Park DH, Kim HS, Kim WH, et al. Clinicopathologic characteristics and malignant potential of colorectal flat neoplasia compared with that of polypoid neoplasia. Dis Colon Rectum 2008; 51:43-9.
- Cappell MS, Friedel D. The role of sigmoidoscopy and colonoscopy in the diagnosis and management of lower gastrointestinal disorders: endoscopic findings, therapy, and complications. Med Clin North Am 2002; 86:1253–88.
- Kudo S, Hirota S, Nakajima T, et al. Colorectal tumours and pit pattern. J Clin Pathol 1994; 47: 880-5.
- Su MY, Ho YP, Chen PC, et al. Magnifying endoscopy with indigo carmine contrast for differential diagnosis of neoplastic and nonneoplastic colonic polyps. Dig Dis Sci 2004; 49: 1123-7.
- Gujii T, Hasegawa RT, Saitoh Y, et al. Chromoscopy during colonoscopy . Endoscopy 2001; 33: 1036-41.
- Wada Y, Kashida H, Kudo SE, Misawa M, Ikehara N, Hamatani S. Diagnostic accuracy of pit pattern and vascular pattern analyses in colorectal lesions. Dig Endosc 2010; 22: 192-9.
- Lapalus MG, Helbert T, Napoleon B, et al. Does chromoendoscopy with structure enhancement improve the colonoscopic adenoma detection rate? Endoscopy 2006; 38: 444-8.
- Hurlstone DP, Cross SS, Slater R, Sanders DS, Brown S. Detecting diminutive colorectal lesions at colonoscopy: a randomized controlled trial of pan-colonic versus targeted chromoscopy. Gut 2004; 43: 376-80.
- Brown SR, Baraza W. Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum. Cochrane Database Syst Rev. 2010 Oct 6; (10): CD 006439.
- Gono K, Obi T, Yamaguchi M, et al. Appearance of enhanced tissue features in narrow-band endoscopic imaging. J Biomed Opt 2004; 9: 568-77.
- Machida H, Sano Y, Hamamoto Y, et al. Narrow-band imaging in the diagnosis of colorectal mucosal lesions: a pilot study. Endoscopy 2004; 36: 1094-8.
- Paggi S, Radaelli F, Amato A, et al. The impact of narrow band imaging in screening colonoscopy: a randomized controlled trial. Clin Gastroenterol Hepatol 2009; 7: 1049-54.
- Adler A, Aschenbeck J, Yenerim T, et al. Narrow-band versus white-light high definition television endoscopic imaging for screening colonoscopy: a prospective randomized trial. Gastroenterology 2009; 135: 410-6.e1.
- Kaltenbach T, Friedland S, Soetikno R. A randomized tandem colonoscopy trial of narrow band imaging versus white light examination to compare neoplasia miss rates. Gut 2008; 57: 1406-12.
- Rex DK, Helbig CC. High yields of small and flat adenomas with high-definition colonoscopes using either white light or narrow band imaging. Gastroenterology 2007; 133: 42-7.
- Chiu, H, Chang C, Chen C, et al. A prospective comparative study of narrow-band imaging, chromoendoscopy, and conventional colonoscopy in the diagnosis of colorectal neoplasia. Gut 2007; 56: 373-79.
- Tischendorf JJ, Wasmuth HE, Koch A, Hecker H, Trautwein C, Winograd R. Value of magnifying chromoendoscopy and narrow band imaging (NBI) in classifying colorectal polyps: a prospective controlled study. Endoscopy 2007; 39: 1092-6.
- Su MY, Hsu CM, Ho YP, Chen PC, Lin CJ, Chiu CT. Comparative study of conventional colonoscopy, chromoendoscopy, and narrow-band imaging systems in differential diagnosis of neoplastic and nonneoplastic colonic polyps. Am J Gastroenterol 2006; 101: 2711-6.