Introduction

The risk of cancer in patients with solitary colorectal juvenile polyps is poorly investigated, but several studies have reported polyps with dysplastic and adenomatous alterations.

Aims & Methods

We aimed to investigate the long-term risk of cancer and mortality in these patients when merging data from national registers and comparing them to a matched control cohort. Patients with a solitary juvenile polyp were identified in The Danish National Pathology Register and Data Bank (DNPR). Included patients were matched on sex, age, and place of birth with 50 controls. The groups were then analyzed for risk of cancer using the Danish Cancer Registry and mortality using the Danish Cause of Death Registry.

Results

We identified 1,781 patients with solitary juvenile polyps and matched them to 83,713 controls. The mean follow-up time was 7.65 years for cases and 7.36 years for controls. The risk of cancer, including colorectal cancer, did not differ for the two groups and when adjusting for sex and year of birth the hazard ratio (HR) was: 1.15 (CI 95% 0.94-1.41, p=0.162). There was no increased risk of death (HZ: 1.07, CI 95% 0.88-1.30, p=0.486). The risk did not differ for different age groups or sex.

Conclusion

There is no increased risk of cancer or mortality for patients with solitary colorectal juvenile polyps. Thus, endoscopic follow-up may safely be omitted in these patients.

Disclosure

The authors declare that there is no conflict of interest

Introduction

Post-polypectomy guidelines classify individuals with polyps ≥10mm, in the absence of other high-risk features, as being at increased risk for developing colorectal cancer (CRC). Consequently, these individuals are recommended to undergo strict surveillance at three-year intervals. However, the necessity of such strict surveillance, particularly for polyps measuring between 10-20mm, remains a subject of ongoing debate. To shed light on this debate, this study aims to compare the risk of post-colonoscopy colorectal cancer (PCCRC) between individuals with polyps ≥10mm, in the absence of other high-risk features, and individuals without polyps.

Aims & Methods

For this study, data of quality-assured baseline colonoscopies performed between 2014 and 2020 as part of the Dutch fecal immunochemical test-based CRC screening program were used. In accordance with the guidelines in place at that time, a subset of individuals with adenomas ≥10mm without high-grade dysplasia and serrated polyps ≥10mm without dysplasia were advised a 5-year surveillance interval, rather than the currently recommended 3-year interval. For these individuals, the PCCRC-risk within 5 years was assessed and compared to that of individuals without polyps at baseline colonoscopy using multilevel cox regression analysis. Additionally, the adenoma detection rate (ADR) of endoscopists was categorized into tertiles to evaluate the impact of endoscopist quality on PCCRC-risk in individuals with polyps ≥10mm without other high-risk features.

Results

Among all included individuals in the Dutch screening program with high-risk polyps (n=74.289), 79% had polyps ≥10mm and 46% had polyps measuring 10-20mm as the sole high-risk feature. In total, 21.522 individuals with ≥10mm polyps without other high-risk features who were advised a 5-year surveillance, and 68.688 individuals without polyps who were referred back to the screening program after 10 years, were included in PCCRC-risk analysis. Within 5 years, there were 21 and 108 cases of PCCRC observed in these groups, respectively. Individuals with ≥10mm polyps at baseline colonoscopy had a comparable risk of PCCRC within 5 years to those without polyps (HR 0.67; CI95% 0.42-1.07). The PCCRC-incidence was 3.07 (CI95% 1.76-4.38) per 10.000 person-years of follow-up (PYFU) in individuals with ≥10mm polyps, and 5.02 (CI 95% 4.08-5.97) per 10.000 PYFU in individuals without polyps. PCCRC incidence in individuals with polyps ≥10mm without other high-risk features was lowest when colonoscopy was performed by endoscopists with high ADR, at 0.93 per 10.000 PYFU (CI95% 0.66-2.23), compared to 5.78 (CI95% 2.64-8.93) per 10.000 PYFU in those scoped by endoscopists with low ADR (HR 5.85 CI95% 1.28-26.55).

Conclusion

PCCRC-risk within 5 years among individuals with polyps ≥10mm as the sole high-risk feature is low and comparable to that of individuals without polyps at baseline colonoscopy. Notably, the risk for individuals with ≥10mm polyps significantly reduced when colonoscopies were performed by endoscopists with high ADR. Lengthening the surveillance interval from 3 to 5 years for individuals with polyps ≥10mm as their sole high-risk feature would concern 79% of all individuals with high-risk polyps, or 46% when limited to those with 10-20mm polyps. This could ease the burden on colonoscopy capacity and allow for more cost-effective use of resources.

Disclosure

ED: Honoraria for consultancy from Olympus, Fujifilm, Ambu, InterVenn, Norgine and Exact Sciences. Speakers' fees from Olympus, Norgine, IPSEN/Mayoly, FujiFilm, Steris and Pentax. Endoscopic equipment on loan of FujiFilm.
MS: received research support from Sysmex, Sentinel, Norgine and Medtronic
All other authors (NR and JIJ, ML) have nothing to disclose.

Introduction

Familial adenomatous polyposis (FAP) is a dominantly inherited disorder that predisposes to colorectal cancer. However, after the introduction of prophylactic colectomy and endoscopic surveillance, as well as genetic screening of first-degree family members, the risk of CRC has decreased dramatically with subsequent prolonged expected life expectancy^.1 Current guidelines solely aim at preventing cancer, which has been the focus for decades.^2-3 From a patient perspective, mental aspects of the disease, which might decrease quality of life may be equally important. However, knowledge and focus on mental well-being in FAP patients is limited. If FAP patients are at increased risk of mental stress and ultimately of developing psychiatric disorders, a potential possibility of early intervention is missed. The Danish Polyposis Register has for over 40 years included data from all Danish FAP patients. Consequently, the register is free of referral and selection bias. We aimed this study at estimating the impact on educational level and risk of psychiatric disorders in a nationwide cohort of patients with FAP compared to a matched background population.

Aims & Methods

Known Danish FAP patients by April 2021 were identified from the Danish Polyposis Register and paired with four matched controls based on matched on sex, birth year, and zip code at birth. Using national registries, educational status, psychiatric contacts or diagnoses, and need for antidepressants, anxiolytics, or antipsychotics were compared between FAP patients and controls. Follow-up of patients started on the date of their first being identified as having FAP or on 1^st January 1996, whichever came last. Follow-up ended on the date of any of the listed outcomes, emigration, death, loss to follow-up or the end of the study on 1^st January 2020, whichever came first. Relative risk for any of the listed outcomes was quantified by hazard ratios (HR); these were estimated using Cox proportional hazards regression, with age as the underlying timescale, and used the variables of exposure status, year of outcome, sex, cancer, and education for the multiple regression model. Cancer was included as a time-varying covariate in the Cox proportional hazards regressions.

Results

The analysis included 445 FAP patients and 1,538 controls. The highest attained education was significantly lower for FAP patients (p<0.001). When comparing FAP patients and controls and adjusting for cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, CI 95%, 1.25–2.29, p<0.001), any psychiatric prescription (1.39, CI 95%, 1.17–1.66, p<0.001), receiving a psychiatric diagnosis (1.64, CI 95%, 1.19–2.26, p=0.002), as well as facing any psychiatric event (HR 1.55, CI 95%, 1.32–1.83, p<0.001). An increased risk was specifically seen for affective (1.76, CI 95%, 1.09–2.83, p=002) and behavioral disorders (2.01, CI 95%, 1.10–3.69, p=0.02) as well as prescription of antidepressants (1.59, CI 95%, 1.24–2.03, p<0.001) and antipsychotics (1.85, CI 95%, 1.26–2.70, p=0.002). For FAP patients, the median age for affective and behavioral disorders was 32.7 years (range 15.0–73.6 years) and 14.7 years (range 5.5–47.7 years), respectively, which did not differ from controls.

Conclusion

Compared to controls, FAP patients have a significantly reduced educational level and an increased risk of developing affective and behavioural disorders with increased needs for antidepressants and antipsychotics. This calls for further exploratory and interventional trials.

References

1 Karstensen JG, Burisch J, Pommergaard HC, et al. Colorectal Cancer in Individuals With Familial Adenomatous Polyposis, Based on Analysis of the Danish Polyposis Registry. Clin Gastroenterol Hepatol 2019; 17(11): 2294-300 e1.
2 Monahan KJ, Bradshaw N, Dolwani S, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut 2020;69(3):411-44.
3 van Leerdam ME, Roos VH, van Hooft JE, et al. Endoscopic management of polyposis syndromes: European society of gastrointestinal endoscopy
(ESGE) guideline. Endoscopy 2019;51:877–95.

Disclosure

JGK is consultant for SNIPR BIOME

Introduction

CDH1 gene mutations are associated with gastric and breast cancer. The risk of colorectal cancer may be increased in the presence of this mutation, although evidence is scarce.

Aims & Methods

Aims: To assess the presence of high-risk colorectal polyps (polyp with ≥10mm or with high-grade dysplasia, ≥5 adenomas, any serrated polyp ≥10mm or with dysplasia) and colorectal cancer in patients on surveillance program with mutation in CDH1 gene.
Methods: Retrospective study in patients with CDH1 gene mutation followed in a family risk appointment in a tertiary care hospital.

Results

Data from 36 patients with a mean age of 44.22±14.77 years, 20 males, with a mean follow-up of 5.5 years. Twenty-seven patients had family history of gastric cancer and 9 of gastric and breast cancer; twelve patients had never undergone colonoscopy (age ≤ 40 years). Of the 24 patients who had already undergone at least one colonoscopy, 12 (50%) never removed polyps. Only 4 patients had high-risk polyps (age 30, 52, 59 and 77 years) and no patient presented with colorectal cancer during follow-up.

Conclusion

Although this is a small sample, our study revealed a low percentage of patients with hereditary diffuse gastric cancer with high-risk colorectal polyps (and only one patient with a high-risk polyp aged <50 years) and no patients with colorectal cancer, similar to a population without a CDH1 mutation. Further studies with larger sample sizes are needed to clarify the impact of CDH1 mutation on colorectal cancer.

Introduction

Currently, gastric cancer screening is only cost-effective in countries with high incidence. Colorectal cancer screening is an effective method for the reduction of CRC incidence and receives high attendance rates. Integrated screening, where gastroscopy is performed in conjunction with colonoscopy, could help reduce the gastric cancer screening procedure burden in countries with low or intermediate incidence. However, there is a lack of population-based studies providing data on groups at high risk for mortality from gastric malignancies that might benefit from this approach.

Aims & Methods

In this retrospective analysis of a colorectal cancer screening program database, we used Cox proportional hazards model to identify an association of high-risk and low-risk finding (polyps ≥ 10mm or with high-grade dysplasia vs <10 mm and no high-grade dysplasia or advanced adenoma vs non-advanced adenoma) with time to death from
upper gastrointestinal (esophageal and gastric) cancer. To quantify the burden of deaths from upper GI cancer in screening participants with high-risk or low-risk polyps in relation to the general population, we calculated standardized mortality ratios.

Results

We included 331,284 CRC high-quality screening colonoscopies in our study. The median follow-up time was 5.04 years (95% CI 5.03-5.07). 4.4% of participants had polyps ≥10 mm or with HGD and 7.7% had advanced adenomas. At the end of the study period, 296 deaths of upper GI cancer had occurred, corresponding to a rate of 10.29 deaths per 100,000 person years in women and 26.61 deaths per 100,000 person years in men. In participants with non-advanced adenomas, hazards for upper GI cancer death were similar compared to participants with advanced adenomas (HR 1.37, 95% CI 1.01-1.72 and HR 1.35, 95% CI 0.94-1.95) when taking participants with a negative colonoscopy as the reference. However, in participants with polyps ≥10 mm or HGD, hazards for upper GI cancer death were higher (HR 1.70, 95% CI 1.07-1.66). Participants with polyps <10 mm and no HGD experienced significantly fewer deaths from upper GI cancer than the general population (SMR 0.71, 95% CI 0.61-0.83, p<0.001), however, participants with high-risk polyps had an upper GI cancer mortality which was similar to that of the population (SMR 0.90, 95% CI 0.60-1.29, p = 0.6).

Conclusion

CRC screening participants with polyps <10 mm and no HGD have a lower risk for mortality from upper gastrointestinal cancers compared to participants with polyps >10 mm and HGD or the general population. In these participants, additional upper GI screening efforts might not be useful. However, future studies will demonstrate whether integrated screening with additional gastroscopy is effective in CRC screening participants with large or highly dysplastic polyps.

Introduction

Patients with Serrated polyps are at increased risk for colorectal cancer (CRC) compared to those without polyps at screening colonoscopy. However, the burden of the serrated pathway by subtypes of serrated polyps (hyperplastic polyps, Sessile serrated lesions/traditional serrated adenomas) to long-term CRC mortality in screening patients is not well understood.

Aims & Methods

We conducted a retrospective cohort study where we included screening participants of the Austrian Quality Certificate for Screening Colonoscopy between 2010-2020. Data on CRC deaths by primary tumor location in the cohort was obtained by database linkage to the Austrian Death registry. We assessed cumulative incidence of CRC deaths after the diagnosis of SSL/TSA, HP and conventional adenomas with deaths from other causes as competing risk. Whether polyp size in HP, SSL/TSA, adjusted for polyp location, sex and age was associated with CRC death was assessed by Cox regression.

Results

321,964 participants were included in the final analysis. 10-year Cumulative incidence of CRC death was 0.13% (95% CI 0.12-0.14%) for participants with HP, 0.16% (95% CI 0.16-0.16%) for participants with SSL/TSA and 0.25% (95% CI 0.23-0.27%) after the diagnosis of conventional adenomas. 1,271 (95% CI 2.71%) HP were ≥10 mm, as compared to 1,354 (95% CI 18.65%) SSL/TSA and 9,576 (95% CI 13.26%) conventional adenomas. When adjusted for polyp location, the association of polyp size ≥10 mm with CRC death was of similar magnitude in participants with conventional adenomas (HR 3.69, 95% CI 2.45 - 5.55), SSL/TSA (HR 3.24, 95% CI 1.35 - 7.79) and HP (HR 5.08, 95% CI 2.42 - 10.65). Participants who had hyperplastic polyps at screening mostly died of cancers located in the distal colon (62.1%, n = 18), while only 10.3% (n = 3) of CRC deaths after the detection of hyperplastic polyps were of proximal tumors. In participants with SSL/TSA, 42.9% (n = 3) of deaths were from proximal tumors, only 14.3% (n = 1) were located in the sigmoid colon or rectum.

Conclusion

Across all histologic types, participants with a polyp sized ≥10 mm have higher hazards for CRC death after screening colonoscopy compared to polyps <10 mm. Although only few participants had large HP detected at screening, polyp size is associated with CRC mortality in participants with HP, when adjusting for of polyp location.