Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types

BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide,with the fourth highest mortality among all cancers.Reportedly,in addition to adenomas,serrated polyps,which account for 15%-30%of CRCs,can also develop into CRCs through the serrated pathway.Sessile serrated adenomas/polyps(SSAs/Ps),a type of serrated polyps,are easily misdiagnosed during endoscopy.AIM To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types.METHODS From January 2021 to December 2021,patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital,affiliated with Shanghai University of Traditional Chinese Medicine.Thirty cases each of large intestine damp-heat(Da-Chang-Shi-Re,DCSR)syndrome and spleen-stomach weakness(Pi-Wei-Xu-Ruo)syndrome were reported.Baseline comparison of the general data,typical tongue coating,colonoscopy findings,and hematoxylin and eosin findings was performed in each group.The expression of the Wnt pathway-related proteins,namelyβ-catenin,adenomatous polyposis coli,and mutated in colorectal cancer,were analyzed using immunohistochemistry.RESULTS Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types(P=0.001).The other aspects did not differ between the two groups.The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups,which was manifested asβ-catenin protein translocation into the nucleus.However,SSAs/Ps patients with DCSR syndrome had more nucleation,higherβ-catenin expression,and negative regulatory factor(adenomatous polyposis coli and mutated in colorectal cancer)expression(P<0.0001)than SSA/P patients with Pi-Wei-Xu-Ruo syndrome.In addition,the SSA/P size was linearly correlated with the related protein expression.CONCLUSION Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis.A high-quality colonoscopic diagnosis was essential.The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.

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 colonoscopy had a total of 226 SSAs.The mean(SE) size of the SSAs was 8.1(0.4) mm;42% of SSAs were ≤ 5 mm,and 69% were ≤ 9 mm.Fifty-one per cent of SSAs were located in the cecum or ascending colon.Approximately half of the patients had synchronous polyps of other histological types,including hyperplastic and adenomatous polyps.Synchronous adenocarcinoma was present in seven(4%) cases.Ninety-seven percent of polyps were removed by colonoscopy.CONCLUSION:Among patients with colon polyps,2.9% were found to have SSAs.Most of the SSAs were located in the right side and were safely managed by colonoscopy.

Improving sessile serrated adenoma detection rates with high definition colonoscopy:A retrospective study

BACKGROUND Sessile serrated adenomas(SSAs)are important premalignant lesions that are difficult to detect during colonoscopy due to poor definition,concealment by mucous caps,and flat appearance.High definition(HD)colonoscopy may uniquely aid in the detection of these inconspicuous lesions compared to standard definition(SD)colonoscopes.In the absence of existing clinical guidelines to obligate the use of HD colonoscopy for colorectal cancer screening in average-risk patients,demonstrating the benefit of HD colonoscopy on SSA detection rate(SSADR)may help strengthen the evidence to recommend its use in all settings.AIM To evaluate the benefit of HD colonoscopy compared to SD colonoscopy on SSADR in average-risk patients undergoing screening colonoscopy.METHODS Data from screening colonoscopies for patients aged 50-76 years two years before and two years after the transition from SD colonoscopy to HD colonoscopy at our large,academic teaching center were collected.Patients with symptoms of colorectal disease,positive occult blood test,history of colon polyps,cancer,polyposis syndrome,inflammatory bowel disease or family history of colon cancer or polyps were excluded.Patients whose endoscopists did not perform colonoscopies both before and after scope definition change were also excluded.Differences in individual endoscopist SSADR,average SSADR,and overall SSADR with SD colonoscopy vs HD colonoscopy were also evaluated for significance.RESULTS A total of 3657 colonoscopies met eligibility criteria with 2012 colonoscopies from the SD colonoscopy period and 1645 colonoscopies from the HD colonoscopy period from a pool of 11 endoscopists.Statistically significant improvements of 2.30%in mean SSADR and 2.53%in overall SSADR were noted with HD colonoscopy(P=0.00028 and P=0.00849,respectively).On the individual level,three endoscopists experienced statistically significant benefit with HD colonoscopy(+5.74%,P=0.0056;+4.50%,P=0.0278;+4.84%,P=0.03486).CONCLUSION Our study suggests that HD colonoscopy statistically significantly improves sessile serrated adenoma detection rate in the screening of average risk patients during screening colonoscopy.By improving the detection and removal of these lesions,adoption of HD colonoscopy may reduce the significant premalignant burden of sessile serrated adenomas.

Solitary rectal ulcer syndrome complicating sessile serrated adenoma/polyps: A case report and review of literature

Solitary rectal ulcer syndrome(SRUS) is a rare benign condition, which can mimic many other diseases because of their similarities in clinical, endoscopic and histological features. Sessile serrated adenoma/polyp(SSA/p) is a premalignant lesion in the colon and rectum. The misdiagnosis of SSA/p in SRUS patients has been noted, but the case of SRUS arising secondarily to SSA/p has been rarely reported. We herein report the case of a 59-year-old man who presented with an ulcerative nodular lesion in the rectum, accompanied by the symptoms of blood and mucus in the feces, diarrhea and constipation. Magnetic resonance imagining revealed thickening of the rectal mucosa-submucosa. Histologically, the lesion was characterized by the hyperplastic lamina propria and diffusely serrated crypts. Further immunohistochemical staining showed the loss of HES1 and MLH1 expression in the epithelial cells in the serrated area. The patient with SRUS had histological changes of SSA/p, suggesting a potential of tumor transformation in certain cases. SRUS uncommonly accompanied by serrated lesions should at least be considered by pathologists and clinicians.

How to"pick up"colorectal serrated lesions and polyps in daily histopathology practice:From terminologies to diagnostic pitfalls

Over the last decade,our knowledge of colorectal serrated polyps and lesions has significantly improved due to numerous studies on this group of precursor lesions.Serrated lesions were misleading as benign before 2010,but they are currently reclassified as precancerous lesions that contribute to 30%of colorectal cancer through the serrated neoplasia pathway.The World Health Organization updated the classification for serrated lesions and polyps of the colon and rectum in 2019,which is more concise and applicable in daily practice.The responsible authors prescribe that“colorectal serrated lesions and polyps are characterized by a serrated(sawtooth or stellate)architecture of the epithelium.”From a clinical standpoint,sessile serrated lesion(SSL)and SSL with dysplasia(SSLD)are the two most significant entities.Despite these advancements,the precise diagnosis of SSL and SSLD based mainly on histopathology remains challenging due to various difficulties.This review describes the nomenclature and the terminology of colorectal serrated polyps and lesions and highlights the diagnostic criteria and obstacles encountered in the histopathological diagnosis of SSL and SSLD.

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.

Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps

AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serrated adenomas(TSAs),and sessile serrated adenomas/polyps(SSA/Ps) has been proposed on the basis of recent molecular biological studies.However,few reports have examined the colonoscopic features of these divisions,including magnified colonoscopic findings.This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011.Patient characteristics(sex,age),conventional colonoscopic findings(location,size,morphology,color,mucin) and magnified colonoscopic findings(pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies,and were compared with histopathological diagnoses.The pit patterns were categorized according to Kudo's classification,but a more detailed investigation was also performed using the subclassification [type Ⅱ-Open(type Ⅱ-O),type Ⅱ-Long(type Ⅱ-L),or type Ⅳ-Serrated(type Ⅳ-S)] proposed by Kimura T and Yamano H.RESULTS:Lesions comprised 23 HPs(23/118:19.5%),39 TSAs(39/118:33.1%:with cancer in one case),50 SSA/Ps(50/118:42.4%:complicated with cancer in three cases),and six others(6/118:5.1%).We excluded six others,including three regular adenomas,one hamartoma,one inflammatory polyp,and one juvenile polyp for further analysis.Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs(SSA/P vs HP,13.62 ± 8.62 mm vs 7.74 ± 3.24 mm,P < 0.001;SSA/Ps vs TSA,13.62 ± 8.62 mm vs 9.89 ± 5.73 mm,P < 0.01);common in the right side of the colon [HPs,30.4%(7/23):TSAs,20.5%(8/39):SSA/P,84.0%(42/50),P < 0.001];flat-elevated lesion [HPs,30.4%(7/23):TSAs,5.1%(2/39):SSA/Ps,90.0%(45/50),P < 0.001];normal-colored or pale imucosa [HPs,34.8%(8/23):TSAs,10.3%(4/39):SSA/Ps,80%(40/50),P < 0.001];and with large amounts of mucin [HPs,21.7%(5/23):TSAs,17.9%(7/39):SSA/Ps,72.0%(36/50),P < 0.001].In magnified colonoscopic findings,17 lesions showed either type Ⅱ pit pattern alone or partial type Ⅱ pit pattern as the basic architecture,with 14 HPs(14/17,70.0%) and 3 SSA/Ps.Magnified colonoscopy showed the type Ⅱ-O pit pattern as characteristic of SSA/Ps [sensitivity 83.7%(41/49),specificity 85.7%(54/63)].Cancer was also present in three lesions,in all of which a type Ⅵ pit pattern was also present within the same lesion.There were four HPs and four TSAs each.The type Ⅳ-S pit pattern was characteristic of TSAs [sensitivity 96.7%(30/31),specificity 89.9%(72/81)].Cancer was present in one lesion,in which a type Ⅵ pit pattern was also present within the same lesion.In our study,serrated lesions of the colorectum also possessed the features described in previous reports of conventional colonoscopic findings.The pit pattern diagnosis using magnifying colonoscopy,particularly magnified colonoscopic findings using subclassifications of surface architecture,reflected the pathological characteristics of SSA/Ps and TSAs,and will be useful for colonoscopic diagnosis.CONCLUSION:We suggest that this system could be a good diagnostic tool for SSA/Ps using magnifying colonoscopy.

Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps

Background：Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries.However,few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations.The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population.Methods：Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed.Chi-square test or Fisher＇s exact test and logistic regression analysis were used for the data processing.Results：A total of 9191 （31.7%） patients were detected with at least one colorectal polyp.The prevalence of serrated polyps was 0.53% （153/28,981）.The proportions of hyperplastic polyp （HP）,sessile serrated adenoma/polyp （SSA/P）,and traditional serrated adenoma （TSA） of all serrated polyps were 41.2%,7.2%,and 51.6%,respectively,which showed a lower proportion of HP and SSA/P and a higher proportion of TSA.Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age.The proportions of large and proximal serrated polyps were 13.7% （21/153） and 46.4% （71/153）,respectively.In total,98.9% （89/90） serrated adenomas were found with dysplasia.Moreover,14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia,and large serrated polyps （LSPs） （odds ratio：3.446,95% confidence interval：1.010-11.750,P 〈 0.05）,especially large HPs,might have an association with synchronous advanced neoplasia （AN）.Conclusions：The overall detection rate ofcolorectal serrated polyps in Chinese symptomatic patient population was low,and distribution pattern of three subtypes is different from previous reports.Moreover,LSPs,especially large HPs,might be associated with an increased risk of synchronous AN.