Case of pediatric traditional serrated adenoma resected via endoscopic submucosal dissection

Traditional serrated adenoma(TSA)is a type of serrated polyp of the colorectum and is thought to be a precancerous lesion.There are three types of serrated polyps,namely,hyperplastic polyps,sessile serrated adenomas/polyps,and TSAs.TSA is the least common of the three types and accounts for about 5% of serrated polyps.Here we report a pediatric case of TSA that was successfully resected by endoscopic submucosal dissection(ESD).This rare case report describes a pediatric patient with no family history of colonic polyp who was admitted to our hospital with hematochezia.On colonoscopy,we found a polypoid lesion measuring 10 mm in diameter in the lower rectum.We selected ESD as a surgical option for en bloc resection,and histopathological examination revealed TSA.The findings in this case suggest that TSA with precancerous potential can occur in children,and that ESD is useful for treating this lesion.     

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.     

Serrated lesions of the colorectum: review and recommendations from an expert panel

Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid >5?mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.     

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.     

Long-term follow-up of patients with malignant pedunculated colon polyps after colonoscopic polypectomy

BACKGROUND:

Previously published studies have suggested that patients with resected colon cancer have an increased risk for early metachronous colon cancer. Current screening guidelines recommend intense surveillance by colonoscopy for the initial five years after the initial colon cancer has been resected. Information regarding endoscopically removed malignant polyps is limited.

METHODS:

In the present study, 25 consecutive patients (14 male, 11 female) with malignant pedunculated colon polyps treated with snare cautery polypectomy were followed for more than one decade up to 20 years. Five patients required an additional resection to ensure that removal of the original cancer was complete. Annual colonoscopies were planned for five years. If an adenoma was detected in the fifth year, colonoscopy was performed annually until no adenomas were detected. Otherwise, colonoscopy was planned every three years after five years.

RESULTS:

In the present study, there was no mortality from colon cancer and no patient developed either recurrent colon cancer or an early metachronous colon cancer during the initial five-year period of surveillance. Two patients (one male, one female) ultimately developed late cecal cancers almost one decade after the original colon cancers were resected. One had an early stage cancer that was resected, while the other had an infiltrating mucinous carcinoma complicating a small tubulovillous adenoma with extension to a single lymph node. After surgical removal and adjuvant chemotherapy, no further neoplastic disease has been detected.

CONCLUSIONS:

Overall, patients with malignant pedunculated polyps do extremely well if appropriately managed at the time of the initial polypectomy. Short-term outcomes after removal of a malignant polyp(s) appear to be similar to those with a nonmalignant polyp. However, late metachronous colon cancer may still occur. Long-term follow-up should be considered in each patient, assuming reasonable life expectancy, because risk of additional adenomas and metachronous colon cancer persists even after the initial five years of currently recommended surveillance. Patients with resected malignant polyps may represent a special patient subgroup that requires surveillance for more extended periods than current guidelines have recommended.     

Large sessile colonic adenomas: use of argon plasma coagulator to supplement piecemeal snare polypectomy

BACKGROUND: Residual adenoma is frequently found at the site of endoscopically resected large sessile adenomas on follow-up examination. We evaluated the efficacy of a thermal energy source, the argon plasma coagulator, to destroy visible residual adenoma after piecemeal resection of sessile polyps. METHODS: Seventy-seven piecemeal polypectomies with or without the use of argon plasma coagulator were analyzed retrospectively. All polyps were sessile, 20 mm or greater in size. The results from three groups of patients were compared. The study group was composed of patients who had visible residual adenoma after piecemeal polypectomy and had the base of the polypectomy site treated with the argon plasma coagulator. The first comparison group consisted of patients who underwent standard piecemeal polypectomy in whom the colonoscopist thought that all adenomatous tissue was removed and no further treatment was necessary. The second comparison group included patients in whom visible residual adenoma was left at the base after piecemeal resection of large adenomas. Follow-up colonoscopy was performed approximately 6 months after the initial procedure to check for recurrent/residual adenomatous tissue. RESULTS: The argon plasma coagulator was used after 30 piecemeal polypectomies in an attempt to eradicate visible residual adenomatous tissue; at follow-up, 50% of these cases had complete eradication of adenoma. The group in whom all visible tumor was removed by piecemeal polypectomy alone had an adenoma eradication rate of 54% on follow-up colonoscopy. In the patients in whom visible residual adenoma was left at the site the recurrence rate was 100% on the follow-up examination. Bleeding necessitating endoscopic therapy occurred once (3.3%) in the argon plasma coagulator group; there were four (12.5%) bleeding episodes and one (3.1%) confined retroperitoneal perforation in the complete piecemeal polypectomy group and no complications in the group in which polypectomy was incomplete. CONCLUSIONS: Argon plasma coagulator ablation of residual adenomatous tissue at the polypectomy base is safe and useful. It helps to complete the eradication of large sessile polyps when there is visible evidence of residual polyp.     

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.     

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.     

Current standards and new developments of colorectal polyp management and resection techniques

Introduction: Colonoscopy and endoscopic removal of precancerous polyps play an important role in colorectal cancer (CRC) prevention. Improved endoscopes and quality standards have led to an increasing polyp and adenoma detection rate. Optimal polyp resection techniques and management strategies are key for an effective colonoscopy practice.

Areas covered: Strategies for how to improve diminutive polyp (polyps up to 5 mm in size) management are discussed because of their high prevalence. Systematic removal of diminutive polyps leads to increasing costs of colonoscopy practice, while the effect on colorectal cancer prevention might be negligible. Furthermore, polypectomy recommendations for mid-size and large polyps are provided. For all larger polyps larger, complete and safe resection is mandatory to avoid post colonoscopy cancers. The focus for managing such larger polyps is to use new techniques (i.e. cold snares) and to attempt complete removal and to reduce post-polypectomy complications.

Expert commentary: The resect-and-discard strategy is a promising management strategy for diminutive polyps. However, modification of this approach might be required in order to make widespread adoption feasible. Cold snare polypectomy is a promising new approach for small polyp resection. For resection of large polyps adequate treatment recommendations with regard to endoscopic mucosal resection and complication prevention are provided.     

Clinicopathological features of serrated lesions of the colorectum

We reviewed 428 subjects with colorectal serrated lesions resected endoscopically or surgically at our institution. Colorectal serrated lesions were pathologically divided into 3 groups: hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA). SSA/P was detected frequently in the right colon and SSA/P was mainly flat-elevated. Cancers occurring in SSA/P were found more frequently than HP or TSA. The incidence of cancer in SSA/P was equivalent to that of cancer in traditional adenoma. Further studies are warranted to clarify clinicopathological features of serrated lesions of the colorectum.     

Serrated adenomas

Serrated adenomas are categorized as sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs). SSAs are more prevalent in the proximal colon and lack classic dysplasia, whereas TSAs are more prevalent in the rectosigmoid and have cytologic dysplasia. Serrated adenomas may progress to colorectal adenocarcinoma through diverse molecular alterations. Colonoscopy is the only test for the early detection of serrated adenomas that allows inspection of the entire colon and same-session biopsy sampling or polypectomy, if necessary. If an endoscopic biopsy at the right colon reveals SSA without cytologic dysplasia or biopsy at the rectosigmoid reveals SSA or TSA, those polyps should be excised or surgically resected as necessary. Postpolypectomy surveillance for removed SSAs without dysplasia and TSAs must be performed at 5- and 3-year intervals, respectively, with colonoscopy to prevent recurrence and progression to colorectal adenocarcinoma.     

Sessile serrated adenoma/polyp showed rapid malignant transformation in the final 13 months

Based on the concept of the adenoma-carcinoma sequence, most colorectal cancers are considered to arise from conventional adenomas. However, recent studies suggested that a subset of colorectal cancers develop through the serrated neoplastic pathway. It has also been documented that serrated polyps can rapidly transform into invasive cancers even when they are small in size. We now describe a case of a sessile serrated adenoma/polyp which had been followed up for 4 years but eventually showed rapid transformation into an advanced cancer accompanied by a remarkable morphological change within only 13 months. Retrospective genetic and epigenetic analyses showed microsatellite instability, CpG island methylator phenotype-positive, and BRAF mutation in the lesion, suggesting the tumor had developed through the serrated neoplastic pathway. This case may provide valuable information about the natural history of sessile serrated adenoma/polyps which eventually progress to advanced cancers.     

Korean guidelines for post-polypectomy colonoscopic surveillance

Post-polypectomy surveillance has become a major indication for colonoscopy as a result of increased use of screening colonoscopy in Korea. However, because the medical resource is limited, and the first screening colonoscopy produces the greatest effect on reducing the incidence and mortality of colorectal cancer, there is a need to increase the efficiency of postpolypectomy surveillance. In the present report, a careful analytic approach was used to address all available evidences to delineate the predictors for advanced neoplasia at surveillance colonoscopy. Based on the results of review of the evidences, we elucidated the high risk findings of the index colonoscopy as follows: 1) 3 or more adenomas, 2) any adenoma larger than 10 mm, 3) any tubulovillous or villous adenoma, 4) any adenoma with high-grade dysplasia, and 5) any serrated polyps larger than 10 mm. In patients without any high-risk findings at the index colonoscopy, surveillance colonoscopy should be performed five years after index colonoscopy. In patients with one or more high risk findings, surveillance colonoscopy should be performed three years after polypectomy. However, the surveillance interval can be shortened considering the quality of the index colonoscopy, the completeness of polyp removal, the patient's general condition, and family and medical history. This practical guideline cannot totally take the place of clinical judgments made by practitioners and should be revised and supplemented in the future as new evidence becomes available.     

Sessile serrated adenomas: Demographic, endoscopic and pathological characteristics

AIM:To study the demographic and endoscopic characteristics of patients with sessile serrated adenoma(SSA) in a single center.METHODS:Patients with SSA were identified by review of the pathology database of Mayo Clinic Arizona from 2005 to 2007.A retrospective chart review was performed to extract data on demographics,polyp characteristics,presence of synchronous adenomatous polyps or cancer,polypectomy methods,and related complications.RESULTS:One hundred and seventy-one(2.9%) of all patients undergoing co...     

Surveillance strategies in patients after polypectomy

Colorectal cancer (CRC) is a major cause of cancer death in the Western world. It develops slowly over several years from premalignant lesions (most prominently adenomatous polyps) to invasive cancer. The molecular basis of CRC pathogenesis has been well characterized. The most effective method to prevent CRC is endoscopic polypectomy. However, adenomatous polyps are known to recur at significant rates. The aim of surveillance programs after polypectomy is to further reduce the incidence of CRC in individuals where precancerous lesions have been identified and treated. However, the medical risks and the costs of repeated examinations must be kept as low as possible. Therefore, the identification of patient subgroups with a particular low cancer risk who may be followed-up less frequently seems important. There is recent evidence that other colorectal lesions, namely flat and depressed type adenomas (F&D adenoma) and possibly some hyperplastic polyps and serrated adenomas may also carry a malignant potential which could influence our screening, treatment and surveillance strategies for the colorectum in the future. General surveillance guidelines regarding these entities have not been issued to date. This article will first discuss the biology, natural history, present surveillance recommendations and future issues for sporadic adenomatous polyps. Then, recent literature on F&D type adenomas, hyperplastic polyps and serrated adenomas will be reviewed with respect to their malignant potential and the potential necessity for treatment and surveillance of these lesions.     

Patient,Physician, and Procedure Characteristics Are Independently Predictive of Polyp Detection Rates in Clinical Practice

Background

Variability in colon polyp detection impacts patient outcomes. However, the relative influence of physician, patient, and procedure-specific factors on polyp detection is unclear. Therefore, determining how these factors contribute to adenoma and sessile serrated polyp (SSP) detection is important to contextualize measures of colonoscopy quality such as adenoma detection rate and patient outcomes.

Aims

To determine the relative contribution of physician, patient, and procedure-specific factors in total polyp, adenoma, and SSP detection rates.

Methods

We performed a retrospective study of patients undergoing screening colonoscopy and used a two-level generalized linear mixed regression model to identify factors associated with polyp detection.

Results

7799 average risk screening colonoscopies were performed between July 2016 and October 2017. The patient factor most strongly associated with increased risk of adenoma and sessile serrated polyp detection was white race (OR 1.21, 95% CI 1.05–1.39 and OR 3.17, 95% CI 2.34–4.30, respectively). Adenomatous (OR 1.92, 95% CI 1.04–3.57) and sessile serrated polyps (OR 5.56, 95% CI 1.37–20.0) were more likely to be found during procedures performed with anesthesia care as compared to those with moderate sedation. Physician with a luminal gastrointestinal focus had increased odds of adenoma detection (OR 1.61, 95% CI 1.02–2.50).

Conclusions

In a multi-level model accounting for clustering effects, we identified patient, provider and procedural factors independently influence adenoma and sessile serrated polyp detection. Our findings suggest that to compare polyp detection rates between endoscopists, even at the same institution, risk adjustment by characteristics of the patient population and practice is necessary.

     

Differential expression of p53 and p504s in hyperplastic polyp, sessile serrated adenoma and traditional serrated adenoma

Aims  

Known collectively as serrated polyps, hyperplastic polyps (HP), sessile serrated adenomas (SSA/SSP) and traditional serrated adenoma (TSA) may represent a spectrum of increasing malignant potential with characteristic immunological markers. There is increasing evidence that HP, SSA/SSP and TSA are biologically different and are likely to represent a spectrum along the serrated polyp pathway. Although there is general consensus about the diagnostic features of serrated polyps, the morphological differences between the categories are often subtle. This study compares the expression of p53 and P504S among serrated polyps. Sixty seven randomly selected biopsies (n = 59) and resection specimens (n = 8) histologically diagnosed for SSA/SSP, TSA and HP (19, 30 and 18 specimens, respectively) were obtained.     

Endoscopic snare resection of large colonic polyps: how far can we go?

BACKGROUND AND AIMS: Colonoscopic polypectomy is preventing colorectal cancer. Videoendoscopy and new perendoscopic hemostasis techniques make endoscopic polypectomy of large colonic polyps an alternative to the surgical approach. This study examined whether complete snare resection of giant colonic polyps is feasible and safe and for determining how often surgery is necessary due to invasive cancer detected histologically after polypectomy. PATIENTS AND METHODS: The study included 59 consecutive patients with 68 colonic polyps larger 30 mm in diameter. Snare polypectomy was performed after an endoscopic ultrasound with a miniprobe found no sign of invasive, or, depending on the appearance of the polyp, a bleeding prophylaxis had been carried out. Acute procedural or delayed bleeding was treated endoscopically. RESULTS: Of the 68 polyps 26, mostly pedunculated were resected en bloc (38%) and histologically ensured as completely resected; 42 polyps had to be resected by piecemeal technique (62%). Piecemeal resection was performed significantly more often in sessile polyps (38/41, 93%) than in pedunculated polyps (4/27, 15%, P<0.01). Follow-up colonoscopy after 3 months showed remaining adenomatous tissue of piecemeal-resected polyps in 12 cases (28%), which were 12 resected sessile polyps (29%) and no case of resected pedunculated polyp. To achieve complete resection of sessile polyps a second procedure was necessary significantly more often than for resection of pedunculated polyps (12 cases in sessile polyps, 18% vs. no case in pedunculated polyps). Remaining adenomatous tissue was removed in all 12 cases during the first follow-up colonoscopy after 3 months, confirmed by a biopsy 6 months after the initial procedure. Overall coexisting malignancy was found in only 7 polyps (12%). Due to high-risk factors only one of them underwent secondary surgical procedure. CONCLUSION: The present study shows that endoscopic snare resection of giant colonic polyps is a safe procedure, and that secondary operative measures for managing coexisting malignancy are rarely necessary.     

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.     

Case-control study supports extension of surveillance interval after colonoscopic polypectomy to at least 5 yr

OBJECTIVE: Colonoscopy with removal of polyps may strongly reduce colorectal cancer (CRC) incidence and mortality. Recommended time intervals to surveillance colonoscopy differ between countries and have recently been extended to 5 yr or longer for the majority of cases in the United States. Whereas previous evidence is mainly based on observations of adenoma recurrence, we aimed to assess risk of CRC occurrence according to time since polypectomy. METHODS: In a population-based case-control study conducted in Germany, detailed history and results of previous large bowel endoscopies were obtained by interview and from medical records. Risk of CRC among subjects with history of endoscopic polypectomy compared to subjects without previous large bowel endoscopy was assessed according to time since polypectomy among 454 cases with CRC and 391 matched controls. RESULTS: Odds ratios (95% confidence intervals) of CRC up to 2 yr, 3-5 yr, and 6-10 yr after polypectomy (using subjects without previous endoscopy as reference group) were 0.16 (0.09-0.69), 0.27 (0.08-0.87), and 1.90 (0.67-5.43), respectively. Risk was significantly reduced (odds ratio 0.27, 95% confidence interval 0.10-0.77) within 5 yr even after detection and removal of high-risk polyps (3+ polyps, at least 1 polyp > or =1 cm, at least 1 polyp with villous components). Odds ratios (95% confidence intervals) for the entire 10-yr time interval following polypectomy were 0.50 (0.23-1.12) and 0.36 (0.18-0.76) for patients with recorded high-risk adenomas and other patients, respectively. CONCLUSIONS: Our study provides empirical support for extension of the surveillance interval after colonoscopic polypectomy to at least 5 yr.