Role of video capsule endoscopy in patients with constitutional mismatch repair deficiency (CMMRD) syndrome: report from the International CMMRD Consortium
submitted 26. September 2017
accepted after revision 20. Februar 2018
10. August 2018 (online)
Background and study aims Constitutional mismatch repair deficiency (CMMRD) syndrome, also known as biallelic mismatch repair deficiency (BMMRD) syndrome is a rare autosomal-recessive genetic disorder that has a high mortality due to malignancy in childhood and early adulthood. The small bowel phenotype in CMMRD is not well described and surveillance protocols for small bowel cancer have not been well established. This study was conducted to evaluate the usefulness and clinical impact of video capsule endoscopy (VCE) for small bowel surveillance.
Patients and methods We retrospectively reviewed the prospectively maintained International CMMRD Consortium database. Treating physicians were contacted and VCE report data were extracted using a standardized template.
Results Among 58 patients included in the database, 38 VCE reports were collected from 17 patients. Polypoid lesions were first detected on VCE at a median age of 14 years (range: 4 – 17). Of these, 39 % in 7 patients (15/38) showed large polypoid lesions (> 10 mm) or multiple polyps that prompted further investigations. Consequently, three patients were diagnosed with small bowel neoplasia including one patient with adenocarcinoma. Small bowel neoplasia and/or cancer were confirmed histologically in 35 % of the patients (6/17) who had capsule surveillance and the lesions in half of these patients were initially visualized on VCE. Multiple polyps were identified on eight VCEs that were completed on three patients. Ten VCEs (28 %) were incomplete due to slow bowel transit; none required capsule removal.
Conclusions Small bowel surveillance in patients with CMMRD should be initiated early in life. VCE has the potential to detect polyps; however, small bowel neoplasias are often proximal and can be missed, emphasizing the importance of concurrent surveillance with other modalities.
Meeting presentations Digestive Disease Week 2017 and World Congress of Pediatric Gastroenterology, Hepatology and Nutrition 2016.
- 1 Raghav K, Overman MJ. Small bowel adenocarcinomas – existing evidence and evolving paradigms. Nature Rev Clin Oncol 2013; 10: 534-544
- 2 Schulmann K, Brasch FE, Kunstmann E. et al. HNPCC-associated small bowel cancer: clinical and molecular characteristics. Gastroenterology 2005; 128: 590-599
- 3 Offerhaus GJ, Giardiello FM, Krush AJ. et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 1992; 102: 1980-1982
- 4 Koornstra JJ. Small bowel endoscopy in familial adenomatous polyposis and Lynch syndrome. Best Pract Res Clin Gastroenterol 2012; 26: 359-368
- 5 Giardiello FM, Brensinger JD, Tersmette AC. et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000; 119: 1447-1453
- 6 Hata K, Yamamoto Y, Kiyomatsu T. et al. Hereditary gastrointestinal cancer. Surgery Today 2016; 46: 1115-1122
- 7 Durno CA, Sherman PM, Aronson M. et al. Phenotypic and genotypic characterisation of biallelic mismatch repair deficiency (BMMR-D) syndrome. European journal of cancer (Oxford, England: 1990) 2015; 51: 977-983
- 8 Lavoine N, Colas C, Muleris M. et al. Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort. J Med Genetics 2015; 52: 770-778
- 9 Elhasid R, Dvir R, Rosenfeld Keidar H. et al. Management of acute myeloblastic leukemia in a child with biallelic mismatch repair deficiency. J Ped Hem Onc 2015; 37: e490-493
- 10 Amayiri N, Tabori U, Campbell B. et al. High frequency of mismatch repair deficiency among pediatric high grade gliomas in Jordan. Int J Cancer 2016; 138: 380-385
- 11 Wimmer K, Kratz CP, Vasen HF. et al. Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘care for CMMRD’ (C4CMMRD). J Med Genetics 2014; 51: 355-365
- 12 Aronson M, Gallinger S, Cohen Z. et al. Gastrointestinal findings in the largest series of patients with hereditary biallelic mismatch repair deficiency syndrome: report from the International Consortium. Am J Gastroenterol 2016; 111: 275-284
- 13 Durno CA, Holter S, Sherman PM. et al. The gastrointestinal phenotype of germline biallelic mismatch repair gene mutations. Am J Gastroenterol 2010; 105: 2449-2456
- 14 Durno C, Boland CR, Cohen S. et al. Recommendations on surveillance and management of biallelic mismatch repair deficiency (BMMRD) syndrome: A consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2017; 152: 1605-1614
- 15 Enns RA, Hookey L, Armstrong D. et al. Clinical practice guidelines for the use of video capsule endoscopy. Gastroenterology 2017; 152: 497-514
- 16 Schulmann K, Hollerbach S, Kraus K. et al. Feasibility and diagnostic utility of video capsule endoscopy for the detection of small bowel polyps in patients with hereditary polyposis syndromes. Am J Gastroenterol 2005; 100: 27-37
- 17 Iaquinto G, Fornasarig M, Quaia M. et al. Capsule endoscopy is useful and safe for small-bowel surveillance in familial adenomatous polyposis. Gastrointest Endosc 2008; 67: 61-67
- 18 Tescher P, Macrae FA, Speer T. et al. Surveillance of FAP: a prospective blinded comparison of capsule endoscopy and other GI imaging to detect small bowel polyps. Hered Cancer Clin Pract 2010; 8: 3
- 19 Baichi MM, Arifuddin RM, Mantry PS. Metachronous small bowel adenocarcinomas detected by capsule endoscopy in a patient with hereditary nonpolyposis colorectal cancer. Dig Dis Sci 2007; 52: 1134-1136
- 20 Marmo R, Rotondano G, Riccio G. et al. Small-bowel adenocarcinoma diagnosed via capsule endoscopy in a patient found to have hereditary nonpolyposis colorectal cancer. Gastrointest Endosc 2007; 65: 524-525, discussion 525
- 21 Vasen HF, Ghorbanoghli Z, Bourdeaut F. et al. Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium “Care for CMMR-D” (C4CMMR-D). J Med Genet 2014; 51: 283-293
- 22 Anonymous. Update on the paris classification of superficial neoplastic lesions in the digestive tract. Endoscopy 2005; 37: 570-578
- 23 Haanstra JF, Al-Toma A, Dekker E. et al. Prevalence of small-bowel neoplasia in Lynch assessed by video capsule endoscopy. Gut 2015; 64: 1578-1583
- 24 Ross A, Mehdizadeh S, Tokar J. et al. Double balloon enteroscopy detects small bowel mass lesions missed by capsule endoscopy. Dig Dis Sci 2008; 53: 2140-2143
- 25 Baichi MM, Arifuddin RM, Mantry PS. Small-bowel masses found and missed on capsule endoscopy for obscure bleeding. Scand J Gastroenterol 2007; 42: 1127-1132
- 26 Chong AK, Chin BW, Meredith CG. Clinically significant small-bowel pathology identified by double-balloon enteroscopy but missed by capsule endoscopy. Gastrointest Endosc 2006; 64: 445-449
- 27 Clarke JO, Giday SA, Magno P. et al. How good is capsule endoscopy for detection of periampullary lesions? Results of a tertiary-referral center. . Gastrointest Endosc 2008; 68: 267-272
- 28 Ou G, Shahidi N, Galorport C. et al. Effect of longer battery life on small bowel capsule endoscopy. World J Gastroenterol 2015; 21: 2677-2682