Role of video capsule endoscopy in patients with constitutional mismatch repair deficiency (CMMRD) syndrome: report from the International CMMRD Consortium

Abstract

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.

High yield of surveillance in patients diagnosed with constitutional mismatch repair deficiency

“…In addition, benign duodenal lesions were detected and removed endoscopically in 27% of our patients. In the recent Consortium studies, no cancers of oesophagus or stomach were reported 9 10. We are not able to make conclusions on the value of VCE in the present study because in only 2 of 10 patients who underwent this procedure small polyps were detected and 1 patient developed a symptomatic SBC outside the programme.…”

“…The investigators concluded that although VCE was found to be effective to detect neoplasia of the small intestine, incomplete studies in 28%, false negative and positive results were found to be limiting factors of this screening modality. 10 Colonoscopic surveillance in our cohort led to the detection and removal of many adenomas including adenomas with highgrade dysplasia. One early asymptomatic CRC as well as one advanced CRC were found.…”

“…In our study, the four patients that developed gastric, oesophageal and SBC were between 10 and 26 years of age. In the VCE study by Shimamura et al ,10 three SBC were diagnosed at age 12, 15 and 20 years. The information on all known patients in the International Consortium study revealed that there were 10 patients with SBC of which 1 patient was diagnosed at age 9 and 2 patients with gastric cancer, of which 1 was diagnosed at age 9 8.…”

“…9 10 We are not able to make conclusions on the value of VCE in the present study because in only 2 of 10 patients who underwent this procedure small polyps were detected and 1 patient developed a symptomatic SBC outside the programme. However, the role of VCE in CMMRD surveillance has recently been studied in 17 patients by Shimamura et al 10 Polypoid lesions were detected in 63 % of VCEs (24/38) conducted on nine patients. Further investigation of three patients led to the detection of one adenocarcinoma in the jejunum in a patient aged 16 years.…”

“…During the programme, two other patients were diagnosed with SBC detected with magnetic resonance enterography and upper GI endoscopy, respectively. The investigators concluded that although VCE was found to be effective to detect neoplasia of the small intestine, incomplete studies in 28%, false negative and positive results were found to be limiting factors of this screening modality 10…”