Introduction

Serrated polyposis syndrome (SPS) is the most common polyposis syndrome found in approximately 1 in 125 screening colonoscopies and is associated with an increased risk of colorectal cancer (CRC).^1,2 Diagnosing SPS can be challenging due to cumulative polyp tracking and physician awareness.³ Serrated polyposis syndrome prevalence and patient outcomes, outside of established SPS cohorts, remains unclear.

Aims & Methods

We sought to explore the prevalence of SPS within academic gastroenterology practices and patient outcomes. Between 2013-2018, using an established histopathology database, patients who underwent colonoscopy with 1 of 11 academic gastroenterologists and with at least 1 serrated lesion underwent complete chart review. All patients were screened for SPS based on 2019 WHO criteria.³ Demographic, procedural and patient outcome variables were reviewed for all patients meeting SPS diagnostic criteria. Interim analysis (2013-2018) was conducted on the available dataset (2013-2023).

Results

From 2013-2018, 1800 patients with at least 1 serrated polyp underwent complete chart review; of which 83 (4.6%) met criteria for SPS (58 WHO I, 10 WHO II, 15 WHO I/II). Median age at first colonoscopy was 58 years (IQR 50-68 years) and 58 (69.6%) were female. Eighteen patients (21.7%) were referred with fecal immunohistochemistry test (FIT) positivity. Only twenty-eight (33.7%) patients were diagnosed by the clinician.
The median number of colonoscopies to diagnosis was 3 (IQR 2-4) over a median of 2 years (0-6 years). On index colonoscopy, patients with SPS had a median of 3 (IQR 2-5) serrated polyps with median largest size of 10mm (IQR 5-15), whereas patients without SPS had a median of 1 (IQR 1-2) serrated polyps with median largest size of 6mm (IQR 4-8) (both p<0.001).
CRC was found in 6 (7.2%) patients, either before or at diagnosis of SPS. Twelve (14.5%) patients underwent surgical resection; 5 (6%) for CRC and 7 (8%) for polyp burden. 71 (85.5%) patients with SPS were managed endoscopically.

Conclusion

In academic gastroenterology practices, the prevalence of SPS in patients with at least 1 serrated polyp was 4.6%; with only 33.7% receiving a formal diagnosis. This highlights the need for increased awareness and strategies for cumulative polyp burden tracking.

References

1. IJspeert JEG, Bevan R, Senore C, et al. Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview. Gut. 2017;66(7):1225-1232. doi:10.1136/gutjnl-2015-310784
2. IJspeert JEG, Rana S a. Q, Atkinson NSS, et al. Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis. Gut. 2017;66(2):278-284. doi:10.1136/gutjnl-2015-310630
3. Hui VW, Steinhagen E, Levy RA, et al. Utilization of Colonoscopy and Pathology Reports for Identifying Patients Meeting the World Health Organization Criteria for Serrated Polyposis Syndrome. Diseases of the Colon & Rectum. 2014;57(7):846-850. doi:10.1097/DCR.0000000000000140

Introduction

Fusobacterium nucleatum (Fn) and other species typical of the oral cavity are implicated in colorectal oncogenesis. The pathogenesis of serrated polyposis syndrome (SPS), the most common polyposis syndrome, remains unknown, and to date, the oral and gut microbiota of these patients has not been characterized.

Aims & Methods

The primary objective of this study was to describe and compare the composition of the oral and gut microbiota in individuals with SPS versus individuals without polyps, with sporadic serrated polyps, and with adenomas.
A prospective, observational, and bicentric study was conducted. Clinical and endoscopic data were collected, along with information obtained from a questionnaire on diet and dental health. Additionally, saliva and stool samples were obtained from 126 individuals divided into four groups: SPS (n=32), serrated (n=30), adenoma (n=32), and control (n=32). The microbiota was analyzed using 16S rRNA amplicon sequencing, and qPCR was performed for the detection of Fn.

Results

The main clinical, dietary, and dental health characteristics of the groups are presented in Table 1. Regarding the oral microbiota, no differences were observed in alpha diversity (species variety) among the groups. However, the composition of the oral microbiota in the SPS group showed significant differences compared to the other groups, as evidenced by a greater unweighted UniFrac distance (differences in bacterial taxonomy) (p<0.001). In the gut microbiota, the adenoma group exhibited lower species richness than the control group, according to the Chao1 index (p=0.03), while no differences were found in the other groups. Statistically significant differences in beta diversity, measured using unweighted UniFrac distance, were observed between the SPS group and the adenoma and control groups (p<0.001).
Regarding taxonomy, Porphyromonas gingivalis, an oral bacterium associated with colorectal cancer (CRC) development and progression, showed higher oral abundance in the SPS group compared to the control and adenoma groups (p<0.05; FDR p=0.104). Treponema denticola and Prevotella intermedia, two oral bacteria related to CRC, were more abundant in the SPS group than in the control group (p<0.05; FDR p=0.09). Additionally, Peptoanaerobacter stomatis, an oral bacterium linked to CRC via the serrated pathway, was more prevalent in the SPS group compared to the serrated and adenoma groups (p<0.05; FDR p=0.26).
No differences in the abundance of Fn were found among the groups, either in saliva or stool samples.

Conclusion

The oral and gut microbiota of individuals with SPS exhibit a distinct bacterial composition compared to individuals without polyps and those with adenomas. Furthermore, certain oral bacteria associated with colorectal carcinogenesis are increased in SPS patients.

Disclosure

There are no conflicts of interest to declare.

Introduction

Serrated Polyposis Syndrome (SPS) is a disease characterized by multiple serrated lesions (SLs), such as sessile serrated lesions (SSL), traditional serrated adenomas (TSA), and hyperplastic polyps (HP). Although it has been suggested that SPS may be a high risk for developing colorectal cancer, it may have been frequently missed in the past due to low recognition and diagnostic complexity. Epidemiological investigations and studies on its pathogenesis are extremely limited, especially with the new WHO classification revised in 2019¹.

Aims & Methods

This study aimed to characterize the clinicopathological and molecular features of carcinogenesis in SPS. We retrospectively reviewed the findings of colonoscopy of 640 patients who underwent endoscopic/surgical resection of one or more serrated lesions at Okayama University Hospital between January 2012 and October 2023. Patients were classified into two groups: those matching the diagnosis of SPS (SPS group) and others (Sporadic SL group). The control group consisted of patients who underwent colonoscopy as a screening examination between January and December 2022 and had no serrated lesions. Patient background, incidence of colorectal cancer, and clinicopathological findings of all resected lesions including tubular adenoma (TA) were evaluated in the above three groups. Genomic DNA was extracted from FFPE tissues of all colorectal cancers, and mutation analysis of KRAS (codon 12 and 13) and BRAF (codon 600) were performed by direct sequencing of the PCR products. Microsatellite instability (MSI) analysis was performed by coelectrophoretic sequencing of five quasi-monomorphic mononucleotide markers (NR-21, NR-22, NR-24, BAT-25, and BAT-26).

Results

The subjects were 55 in the SPS group, 585 in the Sporadic SL group, and 368 in the control group. There were no significant differences in age, sex, or history of cancer in other organs. The incidence of colorectal cancer was 18 (32.7%) in the SPS group, 98 (16.8%) in the Sporadic SL group, and 20 (5.4%) in the control group, showing a significant difference among the three groups (p<0.001). Details of 21 colorectal cancer lesions in 18 patients in the SPS group were as follows: left/right side, 15 lesions/6 lesions; early/advanced cancer, 16 lesions/5 lesions. Four of the six (67%) right-sided lesions were MSI-high and/or had BRAF mutations, suggesting carcinogenesis via the serrated neoplasia pathway. In contrast, 12 of the 15 (80%) lesions on the left side were histologically coexistent with adenoma components and/or had KRAS mutations, suggesting carcinogenesis via the adenoma-carcinoma pathway. In addition, of the 640 patients with SLs (SPS group and Sporadic SL group), 458 (71.6%) had concomitant TAs and the incidence of colorectal cancer was significantly higher in patients with TAs (96/458, 21.0%) than in those without TAs (20/182, 11.0%) (p = 0.003).

Conclusion

SPS has a high incidence of colorectal cancer, and the coexistence of SLs and TAs is suggested to be a risk factor for cancer development. Interestingly, carcinogenesis via the adenoma-carcinoma pathway from comorbid TAs, rather than the serrated-neoplasia pathway, is dominant in SPS.

References

Dekker E, Bleijenberg A, Balaguer F. Update on the World Health Organization Criteria for Diagnosis of Serrated Polyposis Syndrome. Gastroenterology 2020; 158:1520-1523.

Introduction

Serrated polyps (in particular sessile serrated lesions and traditional serrated adenomas according to WHO classification) are recognized as premalignant lesions, responsible of a significant proportion of colorectal cancer via the serrated neoplasia pathway.

Aims & Methods

We aimed to study the prevalence and risk factors of serrated polyps, comparing them with adenomas and with patients with negative colonscopies in a colorectal italian screening population. A retrospective case-control study was performed in a secondary-referral center in Rome (San Filippo Neri Hospital). Data were collected on an Excel database and retrieved from pre-endoscopy questionairres, endoscopic and hystologic reports of screening colonscopies, performed from November 2021 to December 2024.

Results

Preliminary analysis was carried out on 700 screening subjects (331 male and 369 female of age between 50 and 74 years). including 274 subjects (39%) with adenomas and 33 subjects with serrated lesions (4,7%). Exclusion criteria were incomplete colonscopies, inadequate bowel preparation (Boston Bowel Preparation Scale < 6) and symptomatic subjects. In the group of subjects with serrated lesions, 23 (69,7 %) had dysplasia. About 70% of adenomas were in the left colon, while the prevalence of serrated lesions was similar in the left and right colon (51,5% and 48,5 % respectevely). People with hyperplastic polyps, although classified as serrated lesions by WHO classification, are generally considered as benign and were therefore not considered in our analysis. For multivariable analysis we considered 12 subjects that had only serrated lesions and 218 subjects that had only adenomas, comparing them to 339 subjects that had no polyps. Independent variable considered were: age, gender, smoking, Body Mass Index, hypertension, dyslipidemia and type 2 diabetes mellitus. From multivariable logistic regression resulted that smoking was significant indipendent risk factor for serrated lesions (OR: 3.646, 95 % CI 0.056-2.532), whilst male sex and smoking were significant indipendent risk factors for adenomas (male sex OR: 1.768, 95 % CI 0.217-0.923; smoking OR: 1.730, 95 % CI 0.196-0.900).

Conclusion

In our study population, the prevalence of colorectal serrated lesions was 4,7%. Risk factors associated with adenomas were male sex and smoking and with serrated lesions was only smoking. However, a larger sample of subjects with serrated polyps is needed to confirm these results.

References

-Lui RN, Kyaw MH, Lam TYT, Ching JYL et al. Prevalence and risk factors for sessile serrated lesions in an average risk colorectal cancer screening population. J Gastroenterol Hepatol. 2021 Jun;36(6):1656-1662. doi: 10.1111/jgh.15368. Epub 2021 Jan 6. PMID: 33617148.
-Zhang R, Ni Y, Guo CL et al. Risk factors for sessile serrated lesions among Chinese patients undergoing colonoscopy. J Gastroenterol Hepatol. 2023 Sep;38(9):1468-1473. doi: 10.1111/jgh.16200. Epub 2023 May 1. PMID: 37128710.

Introduction

Optical evaluation differentiating between adenomatous and serrated histopathology is the first step in management of large non-pedunculated colorectal polyps (LNPCP) as it informs appropriate endoscopic resection technique selection. Performance of optical evaluation is modest for diminutive polyps but has not been reported for LNPCP.¹

Aims & Methods

We sought to evaluate the performance of optical evaluation to differentiate between adenomatous and serrated histopathology for LNPCP. Consecutive patients > 18 years of age who underwent endoscopic resection for a LNPCP were enrolled in a prospective multi-center observation cohort study (ClinicalTrials.gov NCT05402696). Pre-resection optical evaluation was performed using high-definition white-light and narrow-band imaging (NBI) with or without near-focus. The Japanese NBI Expert Team (JNET) classification was used to differentiate between serrated (JNET I) vs. adenomatous (JNET IIA, IIB) LNPCPs. Traditional serrated adenomas (TSA) and cancers were excluded from analysis. Sensitivity, specificity, and accuracy were used to evaluate optical evaluation performance.

Results

Between June 2022 to April 2024, 440 patients underwent 476 procedures for 558 LNPCP. Median LNPCP size was 30 mm (IQR 20-40) and 404 (72.4%) LNPCP were proximal to the splenic flexure. Histopathology of all lesions included 365 (65.4%) adenomas, 137 (24.6%) serrated lesions, 34 (6.1%) cancers, and 22 (3.9%) other lesions, which included 6 (1.1%) TSA. Adenomatous histopathology was found predominantly in LNPCP with Paris 0-IIA+IS (107/136, 78.7%) and Paris 0-IS (70/82, 85.4%) morphology. Paris 0-IIA lesions were both adenomatous (184/328, 56.1%) and serrated (125/328, 38.1%). Of 137 serrated LNPCP, 133 (97.1%) were predicted as serrated, with sensitivity, specificity, and accuracy of 97.08% (95% CI 92.69-99.20), 99.45% (95% CI 98.03-99.93), and 98.80% (95% CI 97.42-99.56), respectively. Of 365 adenomatous LNPCP, 350 (96.0%) were predicted as adenomatous, with sensitivity, specificity, and accuracy of 95.89% (95% CI 93.31- 97.68), 97.08% (95% CI 92.69- 99.20), and 96.22% (95% CI 94.15- 97.71), respectively.

Table 1: Optical Performance

Conclusion

For LNPCP, optical evaluation had greater than 95% accuracy to differentiate between serrated and adenomatous lesions, forming the basis of a selective resection algorithm.

References

1. Yamada M, Sakamoto T, Otake Y, Nakajima T, Kuchiba A, Taniguchi H, et al. Investigating endoscopic features of sessile serrated adenomas/polyps by using narrow-band imaging with optical magnification. Gastrointestinal Endoscopy. 2015 Jul 1;82(1):108–17.

Introduction

Familial adenomatous polyposis (FAP) is a hereditary syndrome caused by a pathogenic variant in the APC gene, responsible for 1–2% of colorectal cancers (CRC) and associated with a near 100% lifetime CRC risk. Prophylactic colectomy or proctocolectomy reduces CRC incidence and mortality but does not eliminate the risk of rectal or pouch cancer (2–24%). The ESGE recommends endoscopic surveillance every 1–2 years, taking into account the number, size, and histological features of the polyps. However, these recommendations are mainly based on expert opinions, with limited current evidence available to optimize surveillance guidelines and define endoscopic quality standards.

Aims & Methods

To analyze the quality parameters of endoscopic surveillance and their association with the development of advanced neoplasia in the rectal remnant or reservoir among familial adenomatous polyposis (FAP) patients after prophylactic (procto)colectomy.
A retrospective observational study was conducted including FAP patients who underwent prophylactic colectomy or proctocolectomy and were registered between 1983 and 2022 at the Hospital Clínic de Barcelona. Numerical variables were analyzed using the Mann-Whitney U test, and categorical variables were evaluated with the Chi-square test. Logistic regression was performed to identify independent variables associated with the development of advanced neoplasia.

Results

Of the 85 eligible patients, 61 (64% women; median age, 53 years [range, 39–59]) met the inclusion criteria. Seven patients (11.5%) were diagnosed with advanced neoplasia (AN), of whom six had ileorectal anastomosis and one had ileoanal pouch anastomosis. Of these seven patients, three (43%) developed cancer, while four (57%) presented advanced adenomas in the rectal remnant or reservoir. Patients with AN underwent lower-quality endoscopic procedures compared to those without AN: the use of high-definition endoscopes was 42.9% vs. 94.4% (p=0.002), retroflexion was performed in 14.2% vs. 68.5% (p=0.005), adequate bowel preparation was achieved in 42.8% vs. 87% (p=0.004), procedures were performed in a dedicated endoscopy program in 28.5% vs. 79.6% (p=0.004), and the mean number of polyps removed was 1.1 ± 0.9 vs. 3.4 ± 4.2 (p=0.001), respectively. In the multivariable analysis, the only independent variable associated with the development of advanced neoplasia was the non-use of high-definition endoscopes.

Conclusion

The development of advanced neoplasia is associated with lower quality in endoscopic surveillance parameters among FAP patients who underwent prophylactic (procto)colectomy. These findings highlight the need to establish specific quality indicators to optimize endoscopic surveillance in this high-risk population.
In light of these preliminary findings, the study has been expanded to a European multicenter phase and is currently in the patient recruitment stage.