Progress Report: New insights into the prevention of CRC by colonoscopic surveillance in Lynch syndrome

Abstract Background Regular endoscopic surveillance for Lynch syndrome is reported to reduce colorectal cancer (CRC)-related mortality. However, the appropriate surveillance intervals are still unclear. We evaluated the adequacy of annual colonoscopy and investigated the differences in tumor occurrence rates between individual patients. Methods In total, 25 patients with Lynch syndrome who underwent colonoscopic surveillance between 2007 and 2016 at the Iwakuni Clinical Center were included. We retrospectively investigated the surveillance frequency and the clinical features associated with tumor development. Results Colonoscopic surveillance was performed every 397 days on average. A total of 101 tumors, including 8 intramucosal carcinomas and 15 carcinomas, were observed within the study period. Annual colonoscopy detected six malignancies, including a carcinoma requiring surgery. Tumor incidence was associated with tumor existence in the initial colonoscopies (P = 0.018). Patients with a tumor occurrence rate of 0.4 tumors per year during our observation period were significantly more likely to have malignancies detected during regular surveillance than patients who had a lower occurrence rate (P < 0.001). Malignancy occurrence rate was strongly associated with tumor occurrence rate (P < 0.001, R2 = 0.44). Conclusions Annual colonoscopic surveillance for Lynch syndrome patients was effective in reducing the risk of CRC progression, but was insufficient to completely avoid surgery. Because the tumor occurrence rate differed substantially between individuals, more intensive surveillance was required for high-risk patients.

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Malignant potential of colorectal neoplasms in Lynch syndrome: an analysis of 325 lesions endoscopically treated at a single institute

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyab010 ◽

2021 ◽

Author(s):

Hiroyuki Hatamori ◽

Akiko Chino ◽

Masami Arai ◽

Daisuke Ide ◽

Shoichi Saito ◽

...

Keyword(s):

Lynch Syndrome ◽

Colorectal Neoplasms ◽

Distal Colon ◽

Lesion Size ◽

Proximal Colon ◽

Pathological Examination ◽

Low Grade ◽

Colonoscopic Surveillance ◽

Increased Risk ◽

Neoplastic Lesions

Abstract Background Patients with Lynch syndrome are at an increased risk of developing colorectal cancer, and the adenoma-carcinoma sequence is accelerated in these patients. However, the clinicopathological characteristics of colorectal neoplasms in Lynch syndrome patients are not well-known. Methods A total of 325 consecutive colorectal neoplasms were endoscopically removed from 68 patients with Lynch syndrome between June 2005 and May 2018 and retrospectively reviewed. Results Of the 325 lesions, 94 (29%), 220 (68%) and 11 (3%) were from patients with MLH1, MSH2 and MSH6 mutations, respectively. The median lesion size was 5 mm (range 2–40 mm), with 229 (71%) lesions having a non-polypoid morphology. The frequencies of advanced neoplasms, including high-grade adenomas, intramucosal carcinomas and submucosal invasive carcinomas were 14, 34, 97 and 93% for lesions with diameters of <5, ≥5 and <10, ≥10 and <20, and ≥20 mm, respectively. The frequencies of advanced neoplasms in the proximal colon, distal colon and rectum did not significantly differ (36, 35 and 41%, respectively). Conclusions Our results suggest that the malignant transformation interval from low-grade adenomas to advanced neoplasms is similar in all parts of the colon. Furthermore, since one-third of neoplastic lesions with diameters of ≥5 and <10 mm and most of those ≥10 mm were advanced neoplasms, we recommend that in Lynch syndrome patients, careful colonoscopic surveillance should be performed throughout the colon, and all neoplastic lesions, regardless of the size, should be subjected to detailed endoscopic examination, complete resection and detailed pathological examination.

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Impact of an optimized colonoscopic screening program for patients with Lynch syndrome: 6-year results of a specialized French network

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818775058 ◽

2018 ◽

Vol 11 ◽

pp. 175628481877505 ◽

Cited By ~ 10

Author(s):

Guillaume Perrod ◽

Elia Samaha ◽

Gabriel Rahmi ◽

Sherine Khater ◽

Leila Abbes ◽

...

Keyword(s):

Lynch Syndrome ◽

Detection Rate ◽

Screening Program ◽

Interval Cancer ◽

Surveillance Program ◽

Polyp Detection ◽

Colonoscopic Surveillance ◽

Polyp Detection Rate ◽

Adenoma Detection ◽

The Impact

Background: Despite colonoscopic screening, colorectal cancer (CRC) remains frequent in patients with Lynch syndrome (LS). The objective of this study was to evaluate the impact of an optimized colorectal screening program within a French dedicated network. Methods: All LS patients followed at our institution were consecutively included in the Prédisposition au Cancer Colorectal-Ile de France (PRED-IdF) network. Patients were offered an optimized screening program allowing an adjustment of the interval between colonoscopies, depending on bowel preparation, chromoendoscopy achievement and adenoma detection. Colonoscopies were defined as optimal when all the screening criteria were respected. We compared colonoscopy quality and colonoscopy detection rate before and after PRED-IdF inclusion, including polyp detection rate (PDR), adenoma detection rate (ADR) and cancer detection rate (CDR). Results: Between January 2010 and January 2016, 144 LS patients were consecutively included (male/female = 50/94, mean age = 51 ± 13 years and mutations: MLH1 = 39%, MSH2 = 44%, MSH6 = 15%, PMS2 = 1%). A total of 564 colonoscopies were analyzed, 353 after inclusion and 211 before. After PRED-IdF inclusion, 98/144 (68%) patients had optimal screening colonoscopies versus 33/132 (25%) before ( p < 0.0005). The optimal colonoscopy rate was 304/353 (86%) after inclusion versus 87/211 (41%) before, ( p < 0.0001). PRED-IdF inclusion was associated with a reduction of CRC occurrence with a CDR of 1/353 (0.3%) after inclusion versus 6/211 (2.8%) before ( p = 0.012). ADR and PDR were 99/353 (28%) versus 60/211 (28.8%) ( p > 0.05) and 167/353 (48.1%) versus 90/211 (42.2%) ( p > 0.05), respectively after and before inclusion. Conclusions: An optimized colonoscopic surveillance program in LS patients seems to improve colonoscopic screening quality and might possibly decrease colorectal interval cancer occurrence. Long-term cohort studies are needed to confirm these results.

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Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database

Gut ◽

10.1136/gutjnl-2015-309675 ◽

2015 ◽

Vol 66 (3) ◽

pp. 464-472 ◽

Cited By ~ 204

Author(s):

Pål Møller ◽

Toni Seppälä ◽

Inge Bernstein ◽

Elke Holinski-Feder ◽

Paola Sala ◽

...

Keyword(s):

Colorectal Cancer ◽

Ovarian Cancer ◽

Lynch Syndrome ◽

Retrospective Studies ◽

Cancer Surveillance ◽

Cancer Risks ◽

Colonoscopic Surveillance ◽

Robust Estimates ◽

Mutation Carriers

ObjectiveEstimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance.DesignWe undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affectingMLH1,MSH2,MSH6orPMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene.Results1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards inMLH1andMSH2mutation carriers, and from about 40 years inMSH6andPMS2carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% forMLH1, MSH2, MSH6andPMS2mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian.ConclusionsThe four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established athttp://LScarisk.orgenabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.

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