Treatment for gastric ‘indefinite for neoplasm/dysplasia’ lesions based on predictive factors

Abstract

BACKGROUNDGastric ‘indefinite for neoplasm/dysplasia’ (IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management.AIMTo determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions.METHODSIn total, 461 gastric lesions diagnosed via biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection (n = 134), surgery (n = 22), and follow-up endoscopic biopsy (n = 305) were performed to confirm the diagnosis. The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia (60%) or atypical epithelia (40%) at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases.RESULTSFour clinical factors [age ≥ 60 years (2.445, 95%CI: 1.305-4.580, P = 0.005), endoscopic size ≥ 10 mm (3.519, 95%CI: 1.891-6.548, P < 0.001), single lesion (5.702, 95%CI: 2.212-14.696, P < 0.001), and spontaneous bleeding (4.056, 95%CI: 1.792-9.180, P = 0.001)], and two pathologic factors [atypical epithelium (25.575, 95%CI: 11.537-56.695, P < 0.001], and repeated IFND diagnosis [6.022, 95%CI: 1.822-19.909, P = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were 91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change (5.594, 95%CI: 1.458-21.462, P = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review.CONCLUSIONMore than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.

Novel Pathologic Factors for Risk Stratification of Gastric “Indefinite for Dysplasia” Lesions

“…In the present study, 36/123 cases (29.3%) of IND lesions at initial biopsy were finally determined to be gastric cancers, which is similar to the rates observed in previous studies (22.6%–75.0%) [ 8 – 12 ]. Although currently, follow-up biopsy is usually recommended, recently, and ER has been proposed as a follow-up method because of high malignancy rates and diagnostic difficulty of IND [ 8 – 12 ]. Similarly, the diagnostic difficulty of IND in biopsy specimen was observed in the present study.…”

“…However, the use of ER as a follow-up method after IND diagnosis remains controversial because most tumors with IND are well-differentiated and slow growing [ 12 , 17 , 18 ]. Similar to previous findings, the present study showed that diagnostic delay did not affect the final pathological stage [ 12 ], and most tumors, even with false-negative diagnoses or persistent IND, were well-differentiated tumors that remained in the early gastric cancer stage ( Table 2 ).…”

“…Most previous studies about IND were focused on the clinical features suggesting malignancy [ 8 – 12 ], diagnosis agreements of pathologists [ 1 , 2 , 12 ], INDs of Barrett's esophagus [ 1 , 2 ], or diagnostic progress by additional immunohistochemistry [ 1 , 2 ]. Reportedly, ≥10 mm lesion size, depressed lesion, spontaneous bleeding, and surface nodularity on endoscopy were independent risk factors for gastric cancer [ 10 – 12 ]. However, other studies had shown that endoscopic lesion size, gross appearance, location, number of biopsies, and Helicobacter pylori infection were not predictive of gastric cancer [ 8 , 9 ].…”

“…With regard to the management of the IND, no definite criteria for selecting follow-up methods have been established. Although current guidelines advise follow-up biopsy for IND areas, a few endoscopists insist that endoscopic resection (ER) be used as a follow-up method because malignancy rates in IND areas are high (22.6%–75.0%) [ 8 – 12 ].…”

“…With regard to IND follow-up methods, ER has been recently suggested [ 8 – 12 ]. Only a few studies have investigated IND to attempt establishing the criteria of IND follow-up methods and have mostly focused on the clinical factors suggesting malignancy [ 8 – 12 ] or been studied in Barrett's esophagus [ 1 , 2 ]. The aims of this study were to investigate and quantify pathologic factors for predicting carcinoma in IND through the use of image analysis and thereby facilitate the subclassification of IND conditions and determine the proper follow-up methods.…”