Serrated polyps of the colon and rectum: Endoscopic features including image enhanced endoscopy

In this review, I outline the characteristic endoscopic findings of serrated lesions of the colorectum based on image enhanced endoscopy(IEE). Histopathologically, lesions with serrated structures are typically classified into the following three types based: hyperplastic polyps(HPs), traditional serrated adenomas(TSAs), and sessile serrated adenoma/polyps(SSA/Ps). Both HP and SSA/P often present as dark-green colors on auto fluorescence imaging(AFI) colonoscopy that are similar to the normal surrounding mucosa. In contrast, TSAs often have elevated shapes and present as magenta colors that are similar to the tubular adenomas. The superficial type of TSA also includes many lesions that present as magenta colors. When SSA/Ps are associated with cytological dysplasia, many lesions present with magenta colors, whereas lesions that are not associated with cytological dysplasia present with dark-green colors. When observed via narrow band imaging(NBI), many SSA/P include lesions with strong mucous adhesions. Because these lesions are observed with reddish mucous adhesions, we refer to them as "red cap sign" and place such signs among the typical findings of SSA/P. Because the dilatation of the pit in SSA/P is observed as a round/oval black dot on magnified observations, we refer to this finding as Ⅱ-dilatation pit(Ⅱ-D pit) and also positioned it as a characteristic finding of SSA/P. In contrast, dilatations of the capillary vessels surrounding the glands, such as those that occur in tubular adenoma, are not considered to be useful for differentiating HPs from SSA/Ps. However, in cases in which SSA/P is associated with cytological dysplasia, the dilatation of capillary vessels is observed in the same area. When submucosal layer invasion occurs in the same area, the blood flow presents with irregularities that are similar to those of common colorectal cancer at an early stage and disappears as the invasion proceeds deeply. The surface pattern of invasive cancer that is observed at the tumor surface is also likely to disappear. Based on the above results, we considered that the differentiations between HP and TSA, between TSA and SSA/P, and between HP and SSA/P might become easier due to the concomitant use of white light observation and IEE. We also concluded that AFI and NBI can be useful modalities for SSA/P lesions associated with cytological dysplasia.     

Sessile serrated adenoma/polyps: Where are we at in 2016?

It is currently known that colorectal cancers(CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway(50%-70%); the mutator "Lynch syndrome" route(3%-5%); and the serrated pathway(30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps(HP),sessile serrated adenomas/polyps(SSA/P) and traditional serrated adenomas(TSA),the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders,submucosal injection of a dye solution(for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions.     

Pathogenesis and Management of Serrated Polyps: Current Status and Future Directions

Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.     

Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma

Sessile serrated adenoma/polyps(SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a Cp G island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to "interval cancers". If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ‘‘mucus cap', and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions' endoscopic characteristics, which include their(semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates.     

Serrated polyps – a concealed but prevalent precursor of colorectal cancer

Serrated polyps have long been considered to lack malignant potential but accumulating data suggest that these lesions may cause up to one-third of all sporadic colorectal cancer. Serrated polyps are classified into three subtypes, including sessile serrated adenomas/polyps (SSA/Ps), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). SSA/P and TSA harbour malignant potential but TSA represents only 1–2%, wheras SSA/P constitute up to 20% of all serrated lesions. HPs are most common (80%) of all serrated polyps but are considered to have a low potential of developing colorectal cancer. Due to their subtle appearence, detection and removal of serrated polyps pose a major challenge to endoscopists. Considering that precancerous serrated polyps are predominately located in the right colon could explain why interval cancers most frequently appear in the proximal colon and why colonoscopy is less protective against colon cancer in the proximal compared to the distal colon. Despite the significant impact on colorectal cancer incidence, the aetiology, incidence, prevalence, and natural history of serrated polyps is incompletely known. To effectively detect, remove, and follow-up serrated polyps, endoscopists and pathologists should be well-informed about serrated polyps. This review highlights colorectal serrated polyps in terms of biology, types, diagnosis, therapy, and follow-up.     

Clinicopathological features,diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.     

IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions

AIM:To investigate insulin-like growth factor 2(IGF2)differentially methylated region(DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions.METHODS:To accurately analyze the association between the histological types and molecular features of each type of serrated lesion,we consecutively collected1386 formalin-fixed paraffin-embedded tissue specimens that comprised all histological types[hyperplastic polyps(HPs,n=121),sessile serrated adenomas(SSAs,n=132),traditional serrated adenomas(TSAs,n=111),non-serrated adenomas(n=195),and colorectal cancers(n=827)].We evaluated the methylation levels of IGF2 DMR0 and long interspersed nucleotide element-1(LINE-1)in HPs(n=115),SSAs(n=120),SSAs with cytological dysplasia(n=10),TSAs(n=91),TSAs with high-grade dysplasia(HGD)(n=15),non-serrated adenomas(n=80),non-serrated adenomas with HGD(n=105),and CRCs(n=794).For the accurate quantification of the relative methylation levels(scale 0%-100%)of IGF2 DMR0 and LINE-1,we used bisulfite pyrosequencing method.Tumor specimens were analyzed for microsatellite instability,KRAS(codons 12 and 13),BRAF(V600E),and PIK3CA(exons 9and 20)mutations;MLH1 and MGMT methylation;and IGF2 expression by immunohistochemistry.RESULTS:The distribution of the IGF2 DMR0 methylation level in 351 serrated lesions and 185 non-serrated adenomas(with or without HGD)was as follows:mean61.7,median 62.5,SD 18.0,range 5.0-99.0,interquartile range 49.5-74.4.The IGF2 DMR0 methylation level was divided into quartiles(Q1≥74.5,Q2 62.6-74.4,Q3 49.6-62.5,Q4≤49.5)for further analysis.With regard to the histological type,the IGF2 DMR0 methylation levels of SSAs(mean±SD,73.1±12.3)were significantly higher than those of HPs(61.9±20.5),TSAs(61.6±19.6),and non-serrated adenomas(59.0±15.8)(P<0.0001).The IGF2 DMR0 methylation level was inversely correlated with the IGF2 expression level(r=-0.21,P=0.0051).IGF2 DMR0 hypomethylation was less frequently detected in SSAs compared with HPs,TSAs,and non-serrated adenomas(P<0.0001).Multivariate logistic regression analysis also showed that IGF2 DMR0 hypomethylation was inversely associated with SSAs(P<0.0001).The methylation levels of IGF2 DMR0 and LINE-1 in TSAs with HGD(50.2±18.7and 55.7±5.4,respectively)were significantly lower than those in TSAs(61.6±19.6 and 58.8±4.7,respectively)(IGF2 DMR0,P=0.038;LINE-1,P=0.024).CONCLUSION:IGF2 DMR0 hypomethylation may be an infrequent epigenetic alteration in the SSA pathway.Hypomethylation of IGF2 DMR0 and LINE-1 may play a role in TSA pathway progression.     

Serrated adenoma prevalence in inflammatory bowel disease surveillance colonoscopy,and characteristics revealed by chromoendoscopy and virtual chromoendoscopy

BACKGROUND:

Sessile or nonpolypoid neoplastic lesions, including sessile serrated adenomas (SSAs), are difficult to detect in patients with inflammatory bowel disease (IBD).

OBJECTIVES:

To assess the prevalence and endoscopic features of SSA in IBD patients undergoing surveillance colonoscopy using novel endoscopic techniques.

METHODS:

Histology results of biopsies from a cohort of 87 patients (47 men; median age 51.4 years; median duration of disease 16.9 years; ulcerative colitis [n=40], Crohn disease [n=43], ischemic colitis [n=4]) with longstanding colonic IBD undergoing surveillance colonoscopy were reviewed. Lesions of dysplasia (adenoma-like mass, or dysplasia-associated lesion or mass), SSAs, adenoma-like polyps, hyperplastic polyps and inflammatory polyps were identified. Surveillance colonoscopy using high-definition alone, or with iScan (Pentax, USA) dye-sprayed or virtual chromoendoscopy was performed. Lesion characteristics were described before histological diagnosis.

RESULTS:

Fourteen SSAs were detected in 87 (11%) IBD patients. The endoscopic characteristics of SSA lesions were: nonpolypoid appearance (86%), predominant localization in the proximal colon (79%), >6 mm in size (79%), cloudy cover (64%), Kudo pit pattern modified type IIO (86%) and irregular spiral vascular pattern (79%). Among the 44 SSAs and hyperplastic polyps found in the present study, the above characteristics of SSA at colonoscopy had a sensitivity of 92.86% (95% CI 66.06% to 98.8%) and specificity of 93.33% (95% CI 77.89% to 98.99%) in predicting a histological diagnosis of SSA (positive predictive value 86.67%, negative predictive value 96.55%).

CONCLUSION:

SSAs are a common finding at surveillance colonoscopy in IBD and have several characteristic features. Further studies are needed to evaluate the natural history of these lesions in IBD patients.     

A significant number of sessile serrated adenomas might not be accurately diagnosed in daily practice

Background/Aims

The diagnosis of hyperplastic polyps (HPs) may involve a conglomeration of subgroups of serrated polyps. The diagnosis of HPs may therefore be revisited if this is sessile serrated adenoma (SSA). The aim of this study was to determine clinically and endoscopically relevant information associated with reclassification to SSA.

Methods

After reviewing the data from 1,372 patients who underwent colonoscopic polypectomy, 49 HPs larger than 10 mm were analyzed in this study. Two gastrointestinal pathologists reclassified each of the original 49 HPs as conventional HPs, SSAs, and others.

Results

Among the 49 initially diagnosed HPs, 18.4% were reclassified into SSAs or mixed polyps. Overall architectural features were useful for the diagnosis of SSA, but cytological features were less useful. The patient and polyp characteristics did not differ between HPs with and without reclassification of the initial pathological diagnosis.

Conclusions

A significant number of SSAs might not be accurately diagnosed in daily clinical practice without any predilection for size, shape, and location. Therefore, when large HPs are diagnosed in clinical practice, it is necessary for physicians to have greater awareness of the diagnosis of SSA and to individualize subsequent surveillance.     

Frequent somatic mutations of mitochondrial DNA in traditional serrated adenomas but not in sessile serrated adenomas of the colorectum

Background and Aim: Serrated adenomas (SAs), recently subdivided into traditional SAs (TSAs) and sessile SAs (SSAs), are recognized as a distinct form of neoplasia of the colorectum. One of the characteristics of SAs is hypermaturation of the gland epithelium due to the low extent of cell loss by apoptosis. Mutations of mitochondrial DNA (mtDNA) are closely associated with abnormality in apoptosis. We therefore examined mtDNA mutations in colorectal lesions including hyperplastic polyps (HPs), SSAs, TSAs, and carcinomas. Methods: Examined were 25 HPs, 32 SSAs, 19 TSAs, and 138 carcinomas. The D310 region of the mtDNAs was examined by microsatellite assay. Results: mtDNA mutations were detected in none of 25 (0%) HPs, one of 32 (3%) SSAs, six of 19 (32%) TSAs, and eleven of 133 (8%) carcinomas (five of the 138 carcinomas were not informative). The frequency of mtDNA mutations in the TSAs was significantly higher than that in the HPs, SSAs, and carcinomas (P = 0.004, P = 0.008, and P = 0.009, respectively). The frequency of mtDNA mutations in carcinomas was not significantly higher than that in HPs and SSAs (P = 0.14 and P = 0.28, respectively). Conclusion: Our data suggest that mtDNA mutations may play an important role in the development of TSAs and could be used as a genetic marker to aid in the diagnosis of colorectal lesions.     

SUPERFICIAL TYPE SERRATED ADENOMA IN ULCERATIVE COLITIS RESECTED BY ENDOSCOPIC SUBMUCOSAL DISSECTION

A female patient with a 17‐year history of an entire type of ulcerative colitis (UC) showed a superficial elevated lesion in the rectum on surveillance colonoscopy. A standard colonoscopic picture showed a slightly red lesion in the background reticular mucosa in the remission stage of UC after a longstanding chronic inflammation. A chromoendoscopic picture using indigo carmine dye‐spraying showed a distinct superficial elevated lesion with slight marginal elevation of 12 mm in diameter. A magnified view showed a slightly irregular type II pit pattern (Kudo & Tsuruta's classification). Ultrasonographic view using a high frequency ultrasound probe (20 MHz) showed that this lesion was confined to the intramucosal layer. As submucosal fibrosis due to previous repeated inflammations made it difficult to perform strip biopsy, an endoscopic submucosal dissection (ESD) method using a Hook knife was undertaken. A completely resected histological specimen showed a serrated adenoma.     

Serrated polyps of the colon and rectum: Remove or not?

In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway. Colorectal serrated polyps are histopathologically classified into hyperplastic polyps(HPs), sessile serrated lesions, and traditional serrated adenomas; in the serrated neoplasia pathway, the latter two are considered to be premalignant. In western countries, all colorectal polyps, including serrated polyps, apart from diminutive rectosigmoid HPs are removed. However, in Asian countries, the treatment strategy for colorectal serrated polyps has remained unestablished. Therefore, in this review, we described the clinicopathological features of colorectal serrated polyps and proposed to remove HPs and sessile serrated lesions ≥ 6 mm in size, and traditional serrated adenomas of any size.     

Clinicopathological characteristics of serrated polyps as precursors to colorectal cancer: Current status and management

Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image‐enhanced endoscopic technique; and management of these lesions.     

Calcium and vitamin D in the serrated neoplastic pathway: Friends or foes?

Sessile serrated adenoma/polyps(known as SSA/Ps) may play an important role in the development of interval colorectal cancer(CRC). These lesions are more difficult to detect with conventional endoscopy and they may quickly turn into CRC, especially when dysplasia has developed. Therefore, primary or secondary chemoprevention may be an appealing strategy at a population level. Calcium and vitamin D have been shown in epidemiological studies to reduce the risk of CRC and conventional adenomas, but the evidence regarding their effect on SSA/Ps is controversial. In this editorial we comment on the results of a recent randomized controlled trial investigating the effect of calcium and vitamin D on the development of serrated lesions, summarizing the possible antineoplastic mechanisms of calcium and vitamin D, and discussing the differences found with previous observational reports.     

Endoscopic and histologic characteristics of serrated lesions

In recent years , a second pathway for colonic carcinogenesis , distinct from the adenomatous pathway, has been explored. This is referred to as serrated pathway and includes three types of polyp,characterised by a serrated appearance of the crypts:hyperplastic polyps(HP),sessile serrated adenomas(SSA)or lesions,and traditional serrated adenomas.Each lesion has its own genetic,as well as macroscopic and microscopic morphological features.Because of their flat aspect,their detection is easier with chromoendoscopy(carmin indigo or narrow-band imaging).However,as we show in this review,the distinction between SSA and HP is quite difficult.It is now recommended to resect in one piece as it is possible the serrated polyps with a control in a delay depending on the presence or not of dysplasia.These different types of lesion are described in detail in the present review in general population,in polyposis and in inflammatory bowel diseases patients.This review highlights the need to improve characterization and understanding of this way of colorectal cancerogenesis.     

High-definition colonoscopy with i-Scan: Better diagnosis for small polyps and flat adenomas

AIM:To investigate if high-definition (HD) colonoscope with i-Scan gave a higher detection rate of mucosal lesions vs standard white-light instruments. METHODS:Data were collected from the computerized database of the endoscopy unit of our tertiary referral center. We retrospectively analyzed 1101 consecutive colonoscopies that were performed over 1 year with standard white-light (n = 849) or HD+ with i-Scan (n = 252) instruments by four endoscopists, in an outpatient setting. Colonoscopy records included patients' main details and family history for colorectal cancer, indication for colonoscopy (screening, diagnostic or surveillance), type of instrument used (standard white-light or HD+ plus i-Scan), name of endoscopist and bowel preparation. Records for each procedure included whether the cecum was reached or not and the reason for failure, complications during or immediately after the procedure, and number, size, location and characteristics of the lesions. Polyps or protrudinglesions were defined as sessile or pedunculated, and nonprotruding lesions were defined according to Paris classification. For each lesion, histological diagnosis was recorded. RESULTS:Eight hundred and forty-nine colonoscopies were carried with the standard white-light video colonoscope and 252 with the HD+ plus i-Scan video colonoscope. The four endoscopists did 264, 300, 276 and 261 procedures, respectively; 21.6%, 24.0%, 21.7% and 24.1% of them with the HD+ plus i-Scan technique. There were no significant differences between the four endoscopists in either the number of procedures done or the proportions of each imaging technique used. Both techniques detected one or more mucosal lesions in 522/1101 procedures (47.4%). The overall number of lesions recognized was 1266; 645 in the right colon and 621 in the left. A significantly higher number of colonoscopies recognized lesions in the HD+ plus i-Scan mode (171/252 = 67.9%) than with the standard white-light technique (408/849 = 48.1%) (P 0.0001). HD+ with i-Scan colonoscopies identified more lesions than standard white-light imaging (459/252 and 807/849, P 0.0001), in the right or left colon (mean ± SD, 1.62 ± 1.36 vs 1.33 ± 0.73, P 0.003 and 1.55 ± 0.98 vs 1.17 ± 0.93, P = 0.033), more lesions 10 mm (P 0.0001) or nonprotruding (P 0.022), and flat polyps (P = 0.04). The cumulative mean number of lesions per procedure detected by the four endoscopists was significantly higher with HD+ with i-Scan than with standard white-light imaging (1.82 ± 2.89vs 0.95 ± 1.35,P 0.0001). CONCLUSION:HD imaging with i-Scan during the withdrawal phase of colonoscopy significantly increased the detection of colonic mucosal lesions, particularly small and nonprotruding polyps.     

Serrated pathway in colorectal carcinogenesis

Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC.Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps(HPs),sessile serrated adenoma(SSA),traditional serrated adenoma(TSA)and mixed polyps.HPs are the most common serrated polyp followed by SSA and TSA.This distinct histogenesis is believed to have a major influence in prevention strategies,patient prognosis and therapeutic impact.Genetically,serrated polyps exhibited also a distinct pattern,with KRAS and BRAF having an important contribution to its development.Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype.In the present review we will address the current knowledge of serrated polyps,clinical pathological features and will update the most recent findings of its molecular pathways.The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.     

Conventional endoscopic features are not sufficient to differentiate small,early colorectal cancer

AIM:To evaluate the depth of invasion of small,early colorectal cancers(ECCs)using conventional endoscopic features.METHODS:From January 2005 to September 2011,colonoscopy cohort showed that a total of 72 patients with small colorectal cancers with the size less than 20mm underwent colonoscopy at the Yonsei University College of Medicine,Seoul,South Korea.Among them,8 patients were excluded due to incomplete medical records.Finally,a total of 64 ECCs with submucosa(SM)invasion and size less than 20 mm were included.One hundred fifty-two adenomas with size less than 20 mm were included as controls.Nine endoscopic features,including seven morphological findings(i.e.,loss of lobulation,excavation,demarcated and depressed areas,stalk swelling,fullness,fold convergence,and bleeding ulcers),pit patterns,and non-lifting signs,were evalu-ated retrospectively.All endoscopic features were evaluated by two experienced endoscopists who have each performed over 1000 colonoscopies annually for more than five years without knowledge of the histology.RESULTS:Among the morphological findings,the size of deep submucosal cancers was bigger than that of superficial lesions(16.9 mm vs 12.3 mm,P<0.001).Also,demarcated depressed areas,stalk swelling,and fullness were more common in deep SM cancers than in superficial tumors(demarcated depressed areas:52.0%vs 15.7%,P<0.001;stalk swelling:100%vs4.2%,P<0.001;fullness:25.0%vs 0%,P=0.001).Among deep SM cancers,96%of polyps showed invasive pit patterns,whereas 19.4%of superficial tumors showed invasive pit patterns(P<0.001).A positive non-lifting sign was more common in deep SM cancers(85.0%vs 28.6%,P<0.001).Diagnostic accuracy of invasive morphology,invasive pit patterns,and nonlifting signs for deep SM cancers were 71%,82%,and75%,respectively.CONCLUSION:Conventional endoscopic findings were insufficient to discriminate small,deep SM cancers from superficial SM cancers by white light,standard colonoscopy.     

Serrated polyps of the large intestine: current understanding of diagnosis, pathogenesis, and clinical management

Approximately 30 % of colorectal carcinomas develop via the serrated neoplasia pathway characterized by widespread DNA methylation and frequent BRAF mutation. Serrated polyps represent a heterogeneous group of polyps which are the precursor lesions to serrated pathway colorectal carcinomas. The histological classification of serrated polyps has evolved over the last two decades to distinguish three separate entities: hyperplastic polyp, sessile serrated adenoma (SSA), and traditional serrated adenoma (TSA). The malignant potential of SSAs and TSAs has been clearly demonstrated. SSAs are more challenging to detect by colonoscopy and are likely to account for some interval carcinomas of the proximal colon. Serrated polyposis syndrome is now widely recognized as conferring a high risk of colorectal carcinoma although its cause remains elusive. The current understanding of the actual malignant potential of each serrated polyp subtype is still limited due to the lack of large-scale prospective studies. Patient management guidelines have been recently updated although high-level evidence to support them is still required.     

Endoscopic diagnosis for colorectal sessile serrated lesions

BACKGROUNDHyperplastic polyps are considered non-neoplastic, whereas sessile serrated lesions (SSLs) are precursors of cancer via the ‘‘serrated neoplastic pathway’’. The clinical features of SSLs are tumor size (> 5 mm), location in the proximal colon, coverage with abundant mucus called the ‘‘mucus cap’’, indistinct borders, and a cloud-like surface. The features in magnifying narrow-band imaging are varicose microvascular vessels and expanded crypt openings. However, accurate diagnosis is often difficult.AIMTo develop a diagnostic score system for SSLs.METHODSWe retrospectively reviewed consecutive patients who underwent endoscopic resection during colonoscopy at the Toyoshima endoscopy clinic. We collected data on serrated polyps diagnosed by endoscopic or pathological examination. The significant factors for the diagnosis of SSLs were assessed using logistic regression analysis. Each item that was significant in multivariate analysis was assigned 1 point, with the sum of these points defined as the endoscopic SSL diagnosis score. The optimal cut-off value of the endoscopic SSL diagnosis score was determined by receiver-operating characteristic curve analysis.RESULTSAmong 1288 polyps that were endoscopically removed, we analyzed 232 diagnosed as serrated polyps by endoscopic or pathological examination. In the univariate analysis, the location (proximal colon), size (> 5 mm), mucus cap, indistinct borders, cloud-like surface, and varicose microvascular vessels were significantly associated with the diagnosis of SSLs. In the multivariate analysis, size (> 5 mm; P = 0.033), mucus cap (P = 0.005), and indistinct borders (P = 0.033) were independently associated with the diagnosis of SSLs. Size > 5 mm, mucus cap, and indistinct borders were assigned 1 point each and the sum of these points was defined as the endoscopic SSL diagnosis score. The receiver-operating characteristic curve analysis showed an optimal cut-off score of 3, which predicted pathological SSLs with 75% sensitivity, 80% specificity, and 78.4% accuracy. The pathological SSL rate for an endoscopic SSL diagnosis score of 3 was significantly higher than that for an endoscopic SSL diagnosis score of 0, 1, or 2 (P < 0.001).CONCLUSIONSize > 5 mm, mucus cap, and indistinct borders were significant endoscopic features for the diagnosis of SSLs. Serrated polyps with these three features should be removed during colonoscopy.