Early detection of duodenal cancer by upper gastrointestinal‐endoscopy in Lynch syndrome

Abstract

Small bowel cancer (SBC) is the malignancy with the highest standardized incidence ratio in Lynch syndrome (LS) patients. Of all SBCs, about 50% are duodenal cancers (DCs), therefore being accessible by esophago-gastro-duodenoscopy (EGD) for surveillance. We asked whether early detection of DC is possible for LS patients undergoing surveillance by EGD and if surveillance should be limited to specific subgroups.Data for LS patients with DC were retrieved from the registry of the German Consortium for Familial Intestinal Cancer. Patients undergoing active surveillance by EGDs (surveillance group) were compared to those who did not (nonsurveillance group) regarding tumor stage at diagnosis. Union for International Cancer Control stages I-IIA were defined as early stage disease and IIB-IV as advanced stage disease. Statistical analysis was performed using Fisher's exact test. Among 2015 patients with pathogenic variants in any mismatch-repair-gene, 47 patients with 49 DCs were identified. In 10% of cases, patients were under 35 years at diagnosis; family and personal tumor history did not correlate with DC diagnosis. Pathogenic germline variants in MSH6, PMS2 or EPCAM were present in 10% of patients. Statistical analysis could be performed on 13 DC patients in the surveillance group

Upper Gastrointestinal Cancer Surveillance in Lynch Syndrome

“…It is known that colorectal and gynecologic-related cancers often develop at earlier ages in Lynch syndrome compared to the general population [ 7 , 70 ], and data confirm this in UGI cancers as well [ 49 , 54 , 65 ]. Therefore, we advocate for early initiation of UGI surveillance in Lynch syndrome beginning at age 30, or 2–5 years before the youngest UGI cancer in the family, whichever is earliest ( Figure 2 ).…”

“…A recent German study evaluating the detection of duodenal cancer in Lynch syndrome identified 49 duodenal cancers in 47 patients, with the majority (91%) of patients having a MLH1 or MSH2 pathogenic variant [ 65 ]. While the median age at diagnosis of duodenal cancer was 51.7 years, 10% of patients were less than 35 years old at the time of diagnosis.…”

The Approach to Performance of Quality Upper Endoscopy in Lynch Syndrome (QUELS)

“…(Table 1) Two studies comparing surveillance and nonsurveillance-based diagnostic EGDs reported that over two-thirds of UGI cancers identified on screening EGD were stage I while less than one-third of UGI cancers found on diagnostic EGDs were stage I 6,9. Although the results of these recent studies support EGD surveillance, study limitations include heterogeneity in study design, lack of systematic data reporting, a short length of follow-up, and no quality standards for EGD performance in LS 5–10…”

“…The majority (50% to 80%) of small bowel cancers in LS are reported to occur in the duodenum 46–48. Adenomas are the presumed precursor lesion for duodenal adenocarcinoma and have been reported in up to 2.8% of patients with LS; thus, identification and resection of these lesions are vital 4–8,10…”

“…Over the last 3 years, multiple studies have demonstrated that EGD surveillance in LS is associated with the detection of both precancerous lesions and early-stage cancers in the UGI tract. Six studies [5][6][7][8][9][10] of UGI surveillance spanning 3 countries and including 2069 patients with LS report findings, including Barrett's esophagus (BE), gastric intestinal metaplasia (GIM), H pylori, gastric and duodenal adenomas, and esophageal, gastric, and duodenal adenocarcinoma. (Table 1) Two studies comparing surveillance and nonsurveillance-based diagnostic EGDs reported that over two-thirds of UGI cancers identified on screening EGD were stage I while less than one-third of UGI cancers found on diagnostic EGDs were stage I.…”