Introduction

Patients with periampullary diverticulum (PAD) are often found accidentally and may increase the complication risk of endoscopic retrograde cholangiopancreatography (ERCP) or may decrease success cannulation rates.

Aims & Methods

We aimed to compare ERCP procedures and outcomes in naive patients with or without PAD. All ERCP procedure and outcomes data of 3072 patients between January 2021 and December 2023 referred to our tertiary center were retrospectively analyzed. ERCP procedures were divided into two groups based on the presence or absence of PAD.

Results

A total of 929 naive patients underwent ERCP, of whom 135 (14.5%) patients with PAD and 794 (85.5%) patients without PAD. Median age of the patients with PAD was significantly higher than the patients without PAD (73 years vs. 60 years, p<0.001), but the two groups had a similar regarding the genders.
The median ERCP procedure time (20 min vs. 18 min, P=0.410), cannulation time (8 min vs. 7 min, P=0.491) did not differ in patients with and without PAD respectively. Successful cannulation rate in the group with PAD was 134 (99.3%), and in the group without PAD was 791 (99.6%), there was no difference between the two groups (P=0.467). One of the indications of ERCP procedure, choledocholithiasis was a more common reason in patients with PAD than in those without PAD [116 (85.9%) vs. 551 (69.4%), p<0.001]. Indications of other ERCP procedures in patients without PAD, malignant biliary strictures [93 (11.7%) vs. 6 (4.4%), P=0.011] and biliary leak [94 (11.8%) vs. 6 (4.4%), P=0.010] were more frequent reasons than in the patients with PAD. There were no significant differences between the patients with PAD and without PAD in term of all ERCP-related complications [6 (4.5%) vs. 73 (9.2%) respectively, P=0.751].
Our results showed notable differences in cannulation techniques between the two groups. Rate of the selective cannulation technique in the patients with PAD was higher than the patients without PAD [102 (75.6%) vs. 506 (63.7%) respectively, P=0.008]. Needle knife fistulotomy in patients without PAD was a higher rate of using technique than in the patients with PAD [139 (17.5%) vs. 8 (5.9%) respectively, P=0.001]. In the Li-Tanaka classification, the distribution of the PAD types identified 9.6% type 1 diverticula, 20.7% type 2A diverticula, 35.6% type 2B diverticula, 18.5% type 3 diverticula, 9.6% type 4A diverticula and 5.9% type 4B diverticula. Li-Tanaka type 2B (35.6%) was the most common type of the diverticula. There was no significant difference seen in any parameter in the PAD subgroups.

Conclusion

Our study revealed that ages of the patients with PAD was significantly higher than the patients without PAD. In the presented study, the overall success rates and total durations of the ERCP procedures were unaffected by the presence of PAD. The overall cannulation rates and complications following the procedures were unaffected by the type of the diverticulum.
The periampullary diverticulum does not affect the success and duration of cannulation, while it may affect the type of cannulation.

Disclosure

The authors have no conflicts of interest to declare.

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

The role of capsule endoscopy (CE) for the surveillance of small-bowel (SB) cancer in asymptomatic Lynch syndrome (LS) patients has been questioned in recent years, with contradicting results. The overall lifetime risk of SB cancer in this population is around 4-5%, with an age-dependent pattern [1]. Besides, recent data highlight that, depending on the affected path_MMR gene, the frequencies of tumors other than colorectal cancer vary and that affected patients develop subsequent cancers later in life. The aim of this meta-analysis is to evaluate the diagnostic yield (DY) of CE as a screening tool in asymptomatic LS patients.

Aims & Methods

A systematic literature search was conducted in Pubmed, Embase and Web of Science to identify all studies evaluating SB cancer surveillance with CE in asymptomatic LS patients. The primary outcome was the evaluation of the DY of CE in consecutive screening rounds, for both CE-identified pathology and histologically-confirmed pathology (i.e., adenoma or adenocarcinoma). Pooled estimates of DY were calculated from random effects models.

Results

Five studies including 583 patients were identified for data extraction and statistical analysis [2-6] [Table]. The estimated pooled DY for CE-identified pathology was 8% in the first screening round (95% confidence interval [CI] 4-12%) and 6% in the second (95% CI 2-10%). Limiting the analysis to histologically-confirmed pathology, the pooled DY of the second-round screening dropped to 0% (95% CI 0-6%). The time interval between screening rounds was approximately 2 years.
Adenomas were detected in 8 patients (4 males) with a median age of 47.5 years (interquartile range [IQR] 19), while adenocarcinomas were diagnosed in 8 patients (5 males) with a median age of 62.5 years (IQR 17.25). MLH1 was the most involved path_MMR pathogenic variant (9 out of 16 patients), followed by MSH2 and MSH6 (5 and 2 patients, respectively). No adenocarcinomas were detected in MSH6 carriers, as only adenomas were found in 2 patients, with a considerably higher median age than MSH2 and MLH1 adenoma carriers (70.5 years versus 43.5 and 45). No predominance was observed according to the anatomical location (duodenum, n=6; jejunum, n=6; ileum, n=4).

Conclusion

The detection of adenocarcinoma appeared to have a 15-year delay compared to adenomas, supporting a rather slow adenoma to carcinoma transition.
A surveillance strategy starting from the age of 50, with a time interval between procedures lengthened to at least 5 years (instead of 2) could likely be more effective in reducing the burden of advanced disease, both in terms of cost-effectiveness and efficacy. Prospective data may reveal whether a potential SB surveillance might benefit from gene-associated differences in cancer risk, similar to the recent de-escalation of CRC screening recommendations in MSH6 and PMS2 carriers [7].
In conclusion, although the DY of CE is high in detecting SB lesions in LS, the low number of positive examinations eventually resulted in an even lower number of true-positive patients, with a pooled yield proximate to 0%.
The results of this study confirm that SB cancer surveillance with CE with a 2-year interval in asymptomatic LS individuals is not an effective screening strategy.

References

[1] Dominguez-Valentin M, Sampson JR, Seppälä TT, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med 2020;22:15–25.
[2] Saurin J-C, Pilleul F, Soussan EB, et al. Small-bowel capsule endoscopy diagnoses early and advanced neoplasms in asymptomatic patients with Lynch syndrome. Endoscopy 2010;42:1057–62.
[3] Haanstra JF, Al-Toma A, Dekker E, et al. Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy. Gut 2015;64:1578–83.
[4] Haanstra JF, Al-Toma A, Dekker E, et al. Incidence of small bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy. Endosc Int Open 2017;5:E622–E626.
[5] Perrod G, Samaha E, Perez-Cuadrado-Robles E, et al. Effectiveness of a dedicated small bowel neoplasia screening program by capsule endoscopy in Lynch syndrome: 5 years results from a tertiary care center. Ther Adv Gastroenterol 2020;13:1756284820934314.
[6] DeJesse J, Vajravelu RK, Dudzik C, et al. Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome. World J Clin Oncol 2021;12:1023–36.
[7] Peltomäki P, Nyström M, Mecklin J-P, et al. Lynch syndrome genetics and clinical implications. Gastroenterology 2023 Jan 24;S0016-5085(23)00050-1. doi:10.1053/j.gastro.2022.08.058 [Online ahead of print]

Introduction

Several therapeutics are in development for familial adenomatous polyposis (FAP) to reduce polyp burden, the incidence of cancer and prevent or postpone intestinal surgery. However, there is limited consensus on the optimal method for measuring intestinal disease activity in FAP.

Aims & Methods

We aimed to systematically review existing endoscopic severity indices for FAP.
We searched MEDLINE, EMBASE and the Cochrane Library from inception to February 2023 to identify studies that evaluated endoscopic disease activity and severity in children and adults with FAP.

Results

A total of 94 studies were included. We evaluated component items of scoring indices, such as polyp count, polyp size and histology, and the scoring indices for the upper- and lower gastrointestinal tract . Partial validation was observed for polyp count and size. The most common reported scoring index was the Spigelman classification system, which was used for assessing the severity of duodenal disease. A single study reported an almost perfect inter- and intra-observer agreement for this system. The InSIGHT polyposis staging system, which was used for assessing colorectal polyp burden has been partially validated. It showed substantial inter-observer agreement, however it lacked the analysis of the intra-observer agreement. The SPACE criteria is a novel system to identify high-risk gastric polyps and was assessed for the inter-observer agreement; however it showed a moderate level of inter-observer agreement.

Conclusion

There are no fully validated endoscopic disease severity indices for FAP. Development and validation of reliable and responsive endoscopic disease severity instrument will be useful for clinical care, research and to assess the impact of pharmacological therapies on polyp burden in FAP.

Disclosure

Hicham Bouchiba: nothing to disclose
Anna L. Silverman: nothing to disclose
Arthur S. Aelvoet: nothing to disclose
John K. MacDonald: nothing to disclose
Brian G. Feagan: BGF has received grant/research support from AbbVie Inc., Amgen Inc., AstraZeneca/MedImmune Ltd., Atlantic Pharmaceuticals Ltd., Boehringer-Ingelheim, Celgene Corporation, Celltech, Genentech Inc/Hoffmann-La Roche Ltd., Gilead Sciences Inc., GlaxoSmithKline (GSK), Janssen Research & Development LLC., Pfizer Inc., Receptos Inc./Celgene International, Sanofi, Santarus Inc., Takeda Development Center Americas Inc., Tillotts Pharma AG, and UCB; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport Inc., Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD Inc, JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd., and Zyngenia; speakers bureau fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG, and UCB Pharma; and is the Senior Scientific Officer of Alimentiv Inc. (formerly Robarts Clinical Trials, Inc.).
Vipul Jairath: has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi
CM: has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Takeda; royalties from Springer Publishing; research support from Ferring, Pfizer.
Evelien Dekker: Endoscopic equipment on loan of FujiFilm. Research grant FujiFilm. Honoraria for consultancy from Olympus, Fujifilm, Ambu and InterVenn, and speakers' fees from Olympus, GI Supply, Norgine, IPSEN, PAION and FujiFilm.
Jewel Samadder: Consulting or Advisory Role: Janssen Research & Development, Cancer Prevention Pharmaceuticals, Recursion Pharmaceuticals